Download Answers Oct 2004 - The Core Content Review of Family Medicine

VOLUME 35 • NO. 7 • OCTOBER 2004
ANSWER BOOKLET
The Core Content Review of Family Medicine Executive Board
Brian Bachelder, M.D., Mt. Gilead, Ohio
Jeffrey D. Bachtel, M.D., Tallmadge, Ohio
Joseph Cremé, M.D., Putnam, Connecticut
Paul Edelen, M.D., East Hartford, Connecticut
Drew Edwards, M.D., Prospect, Connecticut
James North, M.D., Toledo, Ohio
Linda Stone, M.D., Worthington, Ohio
Roy Zagieboylo, M.D., East Hartford, Connecticut
The Core Content Review of Family Medicine
Educational Staff
Administrative Officials
Linda Stone, M.D., Worthington, Ohio
Executive Board Chair
Kenneth Bertka, M.D., Holland, Ohio
Charlene Li, M.D., Windsor, Connecticut
Co-Editors and Education Directors
Arthur N. Schuman, Bloomfield, Connecticut
Executive Director
Donald Timmerman, M.D., Glastonbury, Connecticut
Assistant Education Director
Mark Schuman, Bloomfield, Connecticut
Assistant Executive Director
Michael Kazakoff, M.D., Middletown, Connecticut
Coordinator - Clinical Set Problems
Questions concerning production and distribution of the Review should be directed to Mr. Arthur Schuman.
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the Educational Staff. Please use the comment forms included in your Core Content Review
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Every effort has been made by the Executive Board, the contributing authors, and the editors of The Core Content Review
of Family Medicine to ensure that the medical and surgical concepts, drug dosages, drug recommendations, and other data and
information pertinent to clinical practice presented in The Core Content Review of Family Medicine are accurate and represent
the current practice standards in most areas of the United States at the time of publication. However, because the practice of
medicine is constantly evolving and because medical care must be individualized according to patient needs and wishes and both
local and regional standards of care, physicians and other healthcare personnel are advised to consult the prescribing information
of all drugs for recommendations of uses and dosages as approved by the Food and Drug Administration (FDA), to apply local
and regional standards in the care of patients, and to individualize care according to the needs and wishes of each patient.
Objectives
Upon completion of this program, you should be able to:
1. Discuss the diagnosis and management of medical and psychological disorders encountered by family physicians.
2. Identify areas of relative strengths and weaknesses in your core knowledge of family medicine.
3. Plan additional review in preparation for board certification examination if applicable.
娀2004 Connecticut Academy of Family Physicians and Ohio Academy of Family Physicians. All Rights Reserved.
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THE CORE CONTENT REVIEW OF FAMILY MEDICINE
11 A DISCUSSION
This patient has the typical lesions of psoriasis (thick,
silver scaling plaques) on his elbow and most likely
has psoriatic arthritis (PsA). Psoriasis is said to affect
approximately 2-3 percent of the population of the
United States. Of these patients, an estimated 5-8
percent have PsA, although some authorities feel
that the condition is underdiagnosed. It is found
equally in men and women. Usually (70 percent)
the skin lesions precede the arthritis, although simultaneous onset is seen in 10-15 percent of patients. The remaining 15-20 percent will have the
arthritis precede the skin lesions. Nail findings (pitting, ridging, onycholysis) are seen in 90 percent of
patients. There is a juvenile form, although it is an
uncommon childhood arthritis.
Five clinical patterns of presentation include
o Asymmetric, oligoarticular (43 percent)
o Symmetric polyarthritis – often with deformities
of the hands (33 percent)
o Distal – involving the distal phalangeal joints (816 percent)
o Axial – predominantly sacroiliitis (10 percent)
o Arthritis mutilans – destructive, deforming with
bone loss (2 percent)
Between 78 and 90 percent of patients will have
radiologic evidence of sacroiliitis. Patients with PsA
tend to have joints that are less tender and painful
than patients with rheumatoid arthritis so they may
present with joint deformities. The severity of joint
involvement does not necessarily mirror the severity
of skin lesions. Other clinical findings associated with
PsA include edema of the hands and feet, enthesitis
(inflammation at the site of tendon insertion), tenosynovitis and dactylitis (swelling of whole digit).
No specific laboratory tests make the diagnosis of
PsA. One third of patients will have an elevated
sedimentation rate and leukocytosis. Antinuclear antibodies and rheumatoid factor are found in only a
minority of patients. There may be an anemia, either of chronic disease or secondary to blood loss
from nonsteroidal antiinflammatory use.
A substantial minority of patients will have periods
of remission, although the majority of these patients
will experience at least one relapse. Male patients
with milder disease and disability from the arthritis
are more likely to have a remission. The majority of
patients will have a more chronic course. Patients
who are HLA-B27 positive, have more joint effusions, involvement of more than five joints and a
past history of high medication use (indicating more
active disease) are more likely to have disease progression. These patients are the ones who will most
likely require aggressive therapy.
Treatment of PsA begins with nonsteroidal antiinflammatory agents. Selective COX-2 inhibitors may
be used but do not have increased efficacy. Secondline therapies include methotrexate, cyclosporine,
azathioprine and sulfasalazine. Most recently, antitumor necrosis factor-alpha agents have been found to
be efficacious for PsA. Etanercept (Enbrel®) and
infliximab (Remicade®) are approved for use in PsA.
These agents are extremely expensive and are usually used when other agents have failed to successfully control disease.
References:
1. Gladman DD. Clinical manifestations and diagnosis of psoriatic
arthritis. In: Rose BD, ed, UpToDate. Wellesley, MA: UpToDate,
2003.
2. Gladman DD. Treatment of psoriatic arthritis. In: Rose BD,
ed, UpToDate. Wellesley, MA: UpToDate, 2003.
3. Mease PJ. Current treatment of psoriatic arthritis. Rheum Dis
Clin North Am 2003; 29(3):495-511.
4. Ruderman EM. Evaluation and management of psoriatic arthritis: the role of biological therapy. J Am Acad Dermatol 2003;
49(2 Suppl):S125-S132.
12 B DISCUSSION
The leading cause of death in the United States is
coronary heart disease (CHD). This is true for both
genders. Well-established risk factors for CHD for
both men and women include elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides and decreased highdensity lipoprotein cholesterol (HDL). Although several studies have shown clinical benefits from the use
of lipid-lowering drugs, primarily statins, for the primary and secondary prevention of CHD events and
CHD mortality, most of these studies have not specifically looked at the benefits of drug treatment of
hyperlipidemia in women. Often CHD studies have
an inadequate number of women participants to make
definite gender-based statements about the hypothesis being tested. A recent meta-analysis evaluated
gender-specific outcomes for women treated with
medication for hyperlipidemia.
While reviewing the benefits of drug treatment of
women with hyperlipidemia, it is important to remember that the most significant risk factor for CHD
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
205
in men and women is age. In premenopausal women,
the onset of CHD lags approximately 10 years behind the onset in men. After menopause, the risk of
CHD increases in women such that by age 75 years,
the overall risk in men and women is equal. This is
important for the evaluation of drug treatment of
hyperlipidemia because for men and women of the
same age with similar cholesterol and triglyceride
CHD risk factors, many more women would need
to be treated to prevent one CHD event.
In the meta-analysis, drug treatment of hyperlipidemia in women with a history of one or more
CHD events (secondary prevention) reduced the risk
of additional CHD events. However, the meta-analysis of studies involving drug treatment of hyperlipidemia in 11,435 women without a history of CHD
(primary prevention) did not show a definite reduction of CHD events. Likewise, regardless of CHD
event status, drug treatment of hyperlipidemia over
the 2.8- to 6-year range of the studies did not demonstrate a reduction of total mortality rates in women.
The authors of the meta-analysis conclude that future CHD studies should report gender-specific results, especially for women at intermediate (10-20
percent) 10-year risk.
References:
1. American Heart Association. Heart Disease and Stroke Statistics
Update 2002. Dallas: American Heart Association, 2002.
2. Walsh JME, Pignone M. Drug treatment of hyperlipidemia in
women. JAMA, 2004; 291:2243-2252.
Web site:
American Heart Association. Women and coronary heart disease.
http://www.american heart.org. Accessed May 2004.
13 D DISCUSSION
Until the late 1980s, leading obstetric textbooks recommended the routine use of episiotomy in vaginal
deliveries. This was especially true for nulliparous
women for whom episiotomy was thought to be necessary. Research in the past 20 years has made it clear
that routine episiotomy is unwarranted and that episiotomy should be reserved for only certain situations.
Currently, almost 40 percent of vaginal deliveries in
the United States are accomplished with an episiotomy.
Incidence varies greatly among hospitals and caregivers.
Some experts have suggested that a 20 percent episiotomy rate is reasonable and obtainable.
The use of elective episiotomy was believed to prevent the occurrence of third-degree (anal sphincter)
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and fourth-degree (rectum) lacerations. In fact, more
recent evidence demonstrates that midline episiotomy
actually increases the complications of third- and
fourth-degree perineal tears, which then predispose
women to fecal incontinence. Data indicate that episiotomy does decrease first- and second-degree
perineal tears and the rate of vaginal lacerations, but
no evidence suggests that these tears cause long-term
consequences. Studies are conflicting regarding
whether or not women who undergo episiotomy
are at higher risk for postpartum perineal pain and
dyspareunia. Generally, studies do not show an increased incidence of either of these problems in patients undergoing midline episiotomy. Mediolateral
episiotomy (incision at a 45º angle from the inferior
portion of the hymenal ring) is less likely to result in
anal sphincter injury but is associated with increased
postpartum pain and dyspareunia.
Another major proposed benefit of episiotomy is
that it prevents pelvic floor relaxation and its sequela. Reviewing the data from multiple recent studies, it has been shown that no conclusive evidence
supports the routine use of episiotomy to prevent
pelvic floor muscle damage, subsequent pelvic relaxation and its attendant complications of urinary incontinence, fecal incontinence and prolapse in the
form of cystocele or rectocele.
Episiotomy does not affect (improve) Apgar scores,
incidence of intraventricular hemorrhage or neonatal outcomes. It does reduce the duration of the
second stage in nulliparous women (approximately 9
minutes), but not in multiparous women. Infants
born after very long second-stage labors were no
more likely (and possibly less likely) to be admitted
to special care with asphyxia than were any other
infants. However, episiotomy is indicated in cases of
fetal distress/asphyxia where an expedited delivery is
needed.
The use of episiotomy in the case of shoulder dystocia is not routinely warranted, as shoulder dystocia is
the result of an anterior disproportion (fetus and
anterior bony pelvis) and not of fetal-perineal disproportion. Episiotomy may be indicated in some,
but not all, cases of operative (forceps, vacuum) vaginal delivery. Episiotomy is generally not needed with
outlet forceps, outlet vacuum or vacuum used to
assist in crowning. Rotational forceps, midforceps
and complete delivery with a vacuum extractor are
more likely to require episiotomy.
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
References:
1. Carroli G, Belizan J. Episiotomy for vaginal birth (review).
Cochrane Database Syst Rev 2000; (2):CD000081.
2. Cleary-Goldman J, Robinson JN. The role of episiotomy in
current obstetric practice. Semin Perinatol 2003; 27(1):3-12.
3. Klein MC. Reducing perineal trauma and pelvic floor relaxation. An evidence-based approach. Clin Fam Pract 2001; 3(2):365383.
4. Weber A. Who is at risk for severe perineal damage at vaginal
delivery? Evidence-based Obstet Gynecol 2002; 4(2):104.
14 C DISCUSSION
15 A With the increasing popularity of tattoos,
temporary, dye-based tattoos have been promoted as
a safer, nonpermanent alternative. Since temporary
tattoos do not employ the use of needles, the chance
of local skin infection or systemic inoculation with
hepatitis or HIV is all but eliminated. However,
dyes and color enhancers mixed with the dyes can
cause a delayed chemical dermatitis (type IV delayed
hypersensitivity reaction). One such dye, henna, is
commonly used in temporary tattoos. Single or repeated exposures to henna can lead to sensitization
and the development of dermatitis. The response
may be delayed in patients without prior sensitization and may be enhanced by the addition of such
chemicals as paraphenylenediamine that is often used
to darken the color of henna-based dyes. Neurodermatitis, on the other hand, develops as a result of
repetitive scratching of a skin area. The area often
looks excoriated but lacks deep erythematous borders. Erysipelas is a skin infection caused by Streptococcus species. Erysipelas is accompanied by red,
erythematous patches and crusted weeping sores. The
patient may or may not exhibit a fever, depending
on the extent of the infection. Although rare, cases
of atypical Mycobacterium have been reported with
permanent tattoos. The associated lesions are nodular and require biopsy and identification of acid-fast
bacteria and/or culture of Mycobacterium species.
Chronic hepatitis B may cause nonspecific dermatitis
lesions in infected individuals, but this is usually a
late manifestation of the disease in persons who are
already diagnosed.
Permanent tattooing is associated with a number of
complications related either to the use of needles or
to the type of dye used in the tattoo. Infectious
complications range from local cellulitis and viral
infections (verruca, molluscum contagiosum) to systemic infections with hepatitis B, hepatitis C, human immunodeficiency virus (HIV), syphilis and tu-
berculosis. The tattoo dye may cause local irritation
including keloid formation and the development of
eczema and chronic urticarial lesions. Interestingly,
many tattoo dyes contain iron, which may cause a
mild burning or tingling sensation during MRI examination. This is especially true of cosmetic tattoos
on the face that may be inadvertently scanned during an MRI of the head. Although malignancies
may develop in tattoos, making them difficult to
detect, there is no evidence that tattoos undergo
direct malignant transformation.
References:
1. Bowling JCR, Groves R. An unexpected tattoo. Lancet 2002;
359:649.
2. Breuner CC. The adolescent traveler. Prim Care 2002;
29(4):983-1006.
3. Leggiadro RJ, Boscamp JR, Sapadin AN. Temporary tattoo
dermatitis. J Pediatr 2003; 142(5):586.
4. Tope WD, Shellock FG. Magnetic resonance imaging and
permanent cosmetics (tattoos): survey of complications and adverse events. J Magn Reson Imaging 2002; 15(2):180-184.
5. Wolf R, Wolf D. A tattooed butterfly as a vector of atypical
Mycobacteria. J Am Acad Dermatol 2003; 48(5 Suppl):S73-S74.
16 E DISCUSSION
With the advances in human genetics, 100 primary
immunodeficiency diseases has now been described,
although less than 20 of them account for more than
90 percent of cases. All of these diseases are singegene disorders of the immune system. The defects
can result in a missing enzyme, a missing structural
component, a nonfunctional protein or developmental arrest at a specific differential stage of immune
development. While these may occur as a result of a
spontaneous de novo mutation, the majority are inherited (autosomal, x-linked) with dominant or recessive inheritance patterns and variable penetrance.
The majority of these disorders are diagnosed in
childhood, although some present in early adulthood. It is estimated that 500,000 Americans have a
primary immunodeficiency disease.
All primary immunodeficiency disorders result in an
increased susceptibility to infection, although the
types of infections and the severity depend on the
defect and what part of the host defense system is
affected. Regardless, these disorders share the common feature of unusual rate/frequency and severity
of infection as well as infection with unusual or
opportunistic organisms. In general, primary immunodeficiency diseases are associated with a higher
rate of immunologic/autoimmune disorders and malignancy.
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207
Primary immunodeficiency diseases have 4 major
subgroups:
Antibody deficiencies (inadequate or defective antibody
production) – account for 50 percent of these diseases;
onset after 6 months of age but can be in adulthood;
recurrent infections (sinusitis, otitis, bronchiectasis); Giardia lamblia and cryptosporidium species
Combined B- and T-cell deficiencies – account for
20 percent of these diseases; onset before 6 months
of age; opportunistic infections; failure to thrive; oral
candidiasis
Defective phagocytes – account for 18 percent of
these diseases; onset in infancy or childhood; unusually severe infections with common pathogens; granuloma formation; abscessed and skin infections
Complement system defects – onset at any age; recurrent and severe infections with encapsulated bacteria, Neisseria (meningococcal and gonococcal)
The National Institute of Child Health and Human
Development and the Jeffry Modell Foundation developed a list of warning signs that should alert physicians to consider the diagnosis of primary immunodeficiency.
• Eight or more new ear infections within 1 year
• Two or more serious sinus infections within 1
year
• Two or more months on antibiotics with little
effect
• Two or more pneumonias within 1 year
• Failure to thrive in an infant
• Recurrent deep skin or organ abscesses
• Persistent oral thrush after 1 year of age
• Need for intravenous antibiotics to clear infections
• Two or more deep-seated infections
• Family history of a primary immunodeficiency disease
Suggested evaluation (from reference 1) is shown in
Figure 1.
Figure 1: A diagnostic testing algorithm for primary immunodeficiency diseases
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THE CORE CONTENT REVIEW OF FAMILY MEDICINE
References:
1. Applying public health strategies to primary immunodeficiency
diseases. MMWR Morb Mortal Wkly Rep 2004; 53(RR-1):1-26.
2. Bonilla FA, Geha RS. Primary immunodeficiency diseases. J
Allergy Clin Immunol 2003; 111(2 Suppl):S571-581.
3. Cooper MA, Pommering TL, Koranyi K. Primary immunodeficiencies. Am Fam Physician 2003; 69(10):2001-2008.
Web site:
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5301a1.htm
Accessed June 2004
17 B DISCUSSION
IgA deficiency is the most common type of primary
immunodeficiency (between 1 in 333 and 1 in 700)
and is defined by an absence or near absence of IgA.
Its mode of inheritance is autosomal dominant with
variable penetrance. The majority of patients (85-90
percent) are asymptomatic. Diagnosis is made if a
person >4 years of age has an IgA serum level <7
mg/dL with normal serum IgM and IgG levels. Some
children <4 years of age may have transient IgA
deficiency that resolves spontaneously.
IgA limits the attachment of infectious agents to
mucosal surfaces and probably acts to prevent absorption of other foreign antigens, such as those in
the diet. IgA deficiency is associated with a host of
other conditions that can be classified into infections, autoimmune diseases and allergies. Some patients who have IgA deficiency concurrently have
low levels of the IgG2 and IgG4 subclasses and are
particularly prone to infections.
Infections occur predominantly in areas where secretory IgA is an important component of the immune
response, namely, the respiratory, urogenital and gastrointestinal tracts. Common infections include bacterial sinopulmonary infections, otitis and diarrhea
secondary to Giardia lamblia. The risk for viral infections is not increased
Autoimmune disorders, especially adult/juvenile
rheumatoid arthritis and systemic lupus erythematosus, may occur in conjunction with this condition;
however, autoantibodies may be present without
symptoms. Other disorders associated with IgA deficiency include Hashimoto’s thyroiditis, myasthenia
gravis, vitiligo, Sjögren’s syndrome, idiopathic thrombocytopenia and type 1 diabetes mellitus.
IgA deficiency may result in the failure to clear large
proteins from the gastrointestinal tract with resultant
antibody formation. This may account for the asso-
ciation of celiac disease and certain food intolerances
(e.g., milk). There is also an association with nodular lymphoid hyperplasia, chronic active hepatitis,
ulcerative colitis, Crohn’s disease and pernicious anemia. IgA deficiency is also associated with atopy.
Acquired IgA deficiency has been associated with
use of phenytoin (generic, Dilantin®), captopril (generic, Capoten®), valproic acid (generic, Depakote®,
Depakene®), sulfasalazine (generic, Azulfidine), gold
and D-penicillamine. The deficiency resolves once
the drug is discontinued. There are reports of IgA
deficiency associated with cyclosporine use that persisted even after discontinuation of the drug.
Severe anaphylactic reactions have been reported in
patients with IgA deficiency who receive transfusions containing plasma. This is due to the presence
of IgG anti-IgA antibodies in these patients. Approximately one third of IgA-deficient patients have
these antibodies. Therefore, blood products should
be washed prior to transfusing IgA-deficient individuals or obtained from IgA-deficient donors, including the recipient, prior to surgery.
Currently therapy for IgA deficiency is prompt identification and vigorous early treatment of specific
infections with appropriate antimicrobial agents. The
use of prophylactic antibiotics can also be considered. Intravenous gamma globulin may be considered if prophylactic antibiotic therapy does not
significantly decrease the frequency of infections,
although there is a risk of anaphylaxis as noted previously.
References:
1. Ballow M. Priamry immunodeficiency disorders: antibody deficiency. J Allergy Clin Innumol 2002; 109(4):581-591.
2. Cooper MA, Pommering TL, Koranyi K. Primary immunodeficiencies. Am Fam Physician 2003; 69(10):2001-2008.
3. Hostoffer R. IgA deficiency. In: Rose BD, ed, UpToDate.
Wellesley, MA: UpToDate, 2003.
18 E DISCUSSION
Cutaneous reactions to drugs are common and can
present in several forms. The most frequent of these
is the morbilliform, or maculopapular, eruption as
seen in this patient. It can occur with many antibiotics, especially semisynthetic penicillins and
trimethoprim/ sulfamethoxazole. Anticonvulsants,
thiazides, phenytoin and allopurinol are also commonly associated with this type of reaction.
This type of reaction to amoxicillin/ampicillin can
begin 2 days after treatment is initiated or may not
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209
occur until days after the medication is stopped. Some
other drugs (e.g., nitrofurantoin, phenytoin) may
have a latent period of 2-3 weeks. Characteristically,
the onset is day 7 or 8 of therapy. The rash consists
of erythematous macules and papules that start on
the trunk, are symmetric and may become confluent,
particularly in intertriginous areas. Spread to the extremities occurs over hours. The palms and soles are
usually spared and the face is less commonly affected. Varying degrees of pruritus are frequently
present. Fever and mucous membrane involvement
can occur but is less common. The rash generally
fades after 3 to 6 days even if the amoxicillin/ampicillin is continued.
Treatment consists of low-potency topical steroids
(if practical based on extent of the rash) and cool
compresses. The medication should be discontinued.
Antihistamines may be helpful for the itching
although the eruption is not histamine-mediated.
Oral steroids are generally not necessary for these
patients unless there is severe itching or an extensive
eruption.
Morbilliform eruptions are also very common in patients with infectious mononucleosis who are placed
on ampicillin or amoxicillin, so inquiry about symptoms of this illness, such as fatigue and lymphadenopathy, is warranted, especially as children approach
and enter the teenage years.
Distinguishing a drug-induced maculopapular rash
from an urticarial or anaphylactic drug reaction is
critical. The former may be mediated by helper T
cells, while the latter is an immediate IgE-mediated
reaction. This makes maculopapular reactions far
more benign and rechallenge with the drug may or
may not cause a similar reaction. Therefore, morbilliform eruptions are not an absolute contraindication
to future prescriptions, particularly in the case of
amoxicillin. Conversely, an urticarial or anaphylactic
reaction would mandate no future use of the inciting drug. Cross-reactivity with cephalosporins is a
well-recognized aspect of penicillin allergy. This occurs in approximately 10 percent of patients with
true anaphylaxis to penicillins but is not associated
with penicillin-induced maculopapular eruption.
References:
1. Barbaud AM, Bene MC, Schmutz JL, et al. Role of delayed
cellular hypersensitivity and adhesion molecules in amoxicillininduced morbilliform rashes. Arch Dermatol 1997; 133(4):481486.
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2. Habif TP. Drug eruptions. In: Habif TP, ed, Clinical Dermatology. 4th ed. St. Louis: Mosby Co., 2004:485-488.
3. Sanfillippo AM, Barrio V, Kulp-Shorten C, et al. Common
pediatric and adolescent skin conditions. J Pediatr Adolesc Gynecol
2003; 16(5):269-283.
19 D DISCUSSION
10 E Hypertension is twice as common in persons
with diabetes as those without. Diabetes increases
the risk for coronary artery disease fourfold for
women and twofold for men compared to control
subjects without diabetes. When associated with hypertension and/or dyslipidemia, the risk of coronary
artery disease is increased further. Patients with diabetes and hypertension have twice the risk of cardiovascular disease compared to hypertensive patients
without diabetes. Patients with diabetes and hypertension are also at greater risk for retinopathy and
nephropathy. Aggressive treatment of hypertension
in patients with diabetes can positively impact these
risks. In the United Kingdom Prospective Diabetes
Study (UKDPS), each 10 mmHg incremental decrease in systolic blood pressure was associated with
significant decreased risks for complications relating
to diabetes (12 percent reduction for any complication related to diabetes, 15 percent reduction for
deaths related to diabetes, 11 percent decreased risk
of myocardial infarction, 13 percent reduced risk for
microvascular complications).
While epidemiologic data indicate that blood pressure readings >120/70 are associated with increased
risk of cardiovascular events in patients with diabetes, the current target blood pressure goal for patients with diabetes is <130/80. Optimal target readings would be <120/80 and are especially important
for patients with proteinuria or renal insufficiency.
Lifestyle modifications should be initiated in all patients with hypertension regardless of whether or
not they have diabetes. Exercise, weight loss and a
diet high in potassium and low in sodium should be
encouraged, although these modifications alone are
usually not enough to attain the target blood pressure. Pharmacologic therapy is indicated for patients
who remain above target levels despite these modifications. Patients who present with systolic blood pressure readings of 130-139 or diastolic readings 80-89
may be given a 3-month trial of lifestyle modifications alone. Patients with systolic readings >140 or
diastolic readings >90 should be started immediately
on pharmacologic therapy.
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
Several classes of antihypertensive agents are suggested as first-line agents for patients with both diabetes and hypertension. The decision regarding which
class of agent to use is dependent on the patient’s
clinical status and associated medical problems. Many
patients will require multidrug therapy to attain target blood pressure.
Angiotensin-converting enzyme (ACE) inhibitors are
considered the preferred class of antihypertensive
agents in patients with diabetes by the American
Diabetes Association, National Kidney Foundation,
World Health Organization and JNC VI. ACE inhibitors have been shown to slow the progression of
diabetic renal disease and reduce cardiovascular events
(stroke, coronary events). A number of studies have
demonstrated a greater reduction in myocardial infarction risk compared to other agents, though one
study did not show a difference compared to atenolol
(generic, Tenormin®). ACE inhibitors may have
other benefits including increasing insulin sensitivity
as well as fibrinolysis and decreasing endothelial dysfunction. Consideration should be given to giving
an ACE inhibitor to a patient >55 years of age with
diabetes, regardless of the presence of hypertension,
if there is another cardiovascular risk factor, as the
addition of the agent can reduce the risk of cardiovascular events. Care should be taken when prescribing ACE inhibitors to patients with diabetes who
also have mild renal insufficiency (creatinine 1.4-2.3
mg/dL) and any additional cardiovascular risk factors, as this combination is associated with an increased risk of cardiovascular events. Angiotensin II
receptor blockers are also renoprotective and effective in controlling blood pressure. They are useful in
patients who can not tolerate ACE inhibitors.
Thiazide diuretics have been shown to be beneficial
in patients with diabetes and systolic hypertension.
In a study involving the elderly, diuretics were associated with a decrease in cerebrovascular and cardiovascular events. Loop diuretics, such as furosemide
(generic, Lasix®) and bumetanide (Bumex®), are more
effective in patients with renal insufficiency.
Traditionally the use of beta-blockers has been discouraged when treating patients with diabetes and
hypertension primarily because of the concern regarding masking of symptoms of hypoglycemia and
worsening metabolic parameters (elevation of glucose and lipid levels). However, the UKDPS dem-
onstrated similar reduction in macro- and microvascular disease compared with the ACE inhibitor
captopril (generic, Capoten®). There was no increase
in hypoglycemic episodes, although there was a
greater mean weight gain. Cardioselective betablockers are preferred. Beta-blockers may be a good
choice in a patient with preexisting atherosclerotic
disease.
Calcium channel blockers (CCB) and alpha-blockers
are considered second-line therapy for patients with
hypertension and concurrent diabetes. There is some
concern regarding the effectiveness of dihydropyridine CCBs (amlodipine [Norvasc®], diltiazem [generic, Cardizem®], nifedipine [generic, Procardia®])
in reducing cardiovascular events. Nondihydropyridine (verapamil [generic, Calan®]) CCBs do reduce
cardiovascular risk. Alpha-blockers may be useful in
the patient with concomitant prostatism.
References:
1. American Diabetes Association. Treatment of hypertension in
adults with diabetes. Diabetes Care 2003; 26:S80-S82.
2. Bakris GL. The importance of blood pressure control in the
patient with diabetes. Am J Med 2004; 116(Suppl 5A):30S-38S.
3. Konzem SL, Devore DS, Bauer DW. Controlling hypertension
in patients with diabetes. Am Fam Physician 2002; 66(7):12091214.
11 A DISCUSSION
Androgenetic alopecia, otherwise known as malepattern-baldness, results in hair loss at the crown or
vertex of the head and bitemporal areas. The areas
of hair loss correspond to the areas of the scalp that
contain the most androgen-sensitive hair follicles.
The onset of the hair loss is variable and appears to
be affected by genetic predisposition and circulating
androgens. In Caucasian males, 30 percent with have
some degree of androgenetic alopecia by age 30 years
and 50 percent will be affected by age 50 years.
Caucasian males are 4 times more likely to be affected than are African American males. While not a
serious problem medically, hair loss can affect a
person’s self-image and may cause considerable psychological distress.
The pathogenesis of androgenetic alopecia appears
to be a combination of an alternation in the normal
hair cycle and miniaturization of the hair follicles.
Normally the anagen (growth) phase is long, while
the telogen (rest) phase is short. In androgenetic
alopecia the anagen phase gradually shortens while
the telogen phase lengthens. Eventually the anagen
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
211
phase is so short that the hair never grows enough
to even reach the skin surface. Additionally, there is
a longer time span between telogen hair shedding
and anagen regrowth so that overall, the number of
hairs present is reduced. The hair follicle itself actually becomes smaller. All of these changes appear to
be in response to dihydrotestosterone (DHT).
Recent studies have indicated that patients with androgenetic alopecia have an increased risk for cardiovascular disease. However, there does not appear
to be an association with blood pressure or lipid
elevations. There also appears to be an increased risk
of benign prostatic hyperplasia and prostate cancer.
Two medication treatments have been approved for
androgenetic alopecia. Minoxidil (Rogaine™) is a
topical preparation available in 2 and 5 percent solutions that is applied to the scalp twice daily. It appears to lengthen the anagen phase but does not
affect the follicle itself. Treatment must be continued for 6-12 months before efficacy can be determined. Response is variable with approximately 40
percent of men having a small amount of hair growth
and 4 percent medium to dense growth. Once the
treatment is stopped, all of the medication-stimulated hair growth is lost. Few side effects are noted
and cost is between $10.00 and $15.00 per month.
There is some evidence that the efficacy of minoxidil
may be increased by the addition of tretinoin (generic, Retin-A™) applied once a day (at a different
time). Finasteride (Propecia™) is a potent and highly
selective 5␣-reductase type-2 inhibitor that inhibits
the conversion of testosterone to DHT. A 1 mg
dose reduces DHT levels in the scalp by 64 percent.
There is no increased response with higher doses. In
one study 66 percent of patients had 10-25 percent
regrowth of their hair with most of the remaining
patients having no further hair loss. Duration of
therapy longer than 2 years is not associated with
further hair growth but there is retention of the new
hair. If treatment is stopped, the hair loss resumes.
Cost per month is approximately $50.00.
References:
1. Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med 2002;
2002:1-11.
2. Rubin MB. Androgenetic alopecia. Postgrad Med J 1997;
102(2):electronic version.
3. Springer K, Brown M, Stulberg DL. Common hair loss disorders. Am Fam Physician 2003; 68(1):93-102.
212
12 B DISCUSSION
This patient has generalized anxiety disorder (GAD),
which is defined by the American Psychiatric
Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV™) as excessive worry and anxiety lasting for more than 6 months. The symptoms
must be severe enough to interfere with a patient’s
social life or occupation. Associated complaints include fatigue, sleep disturbance, difficulty concentrating, irritability and muscle tension. This condition is the most common of the anxiety disorders
and affects over 4 million Americans. Lifetime prevalence is estimated between 4.1 and 6.6 percent. Onset is usually in the early 20s and women are affected
more commonly than men. The course of the illness
tends to be chronic.
Of the options listed, the best choice is escitalopram
(Lexapro®), a selective serotonin reuptake inhibitor
(SSRI) that was approved for treatment of GAD by
the U.S. Food and Drug Administration (FDA) in
2004. Other SSRIs, paroxetine (generic, Paxil®) and
venlafaxine (Effexor®) are other agents that have been
FDA approved. As a class, the SSRIs have proven
effective for treatment of all the types of anxiety
disorders, including obsessive compulsive disorder,
social phobia and posttraumatic stress disorder.
Escitalopram is effective, well tolerated and nonaddictive. The starting dose is 10 mg. per day, which
may be increased to 20 mg. Like all SSRIs, the most
common side effects are nausea, jitteriness and sexual
dysfunction.
Alprazolam (generic, Xanax®) is a benzodiazepine.
This class of drugs traditionally has been the mainstay of treatment of GAD. The most common starting dose is 0.5 mg 3 times a day. Other medications
in this group include diazepam (generic, Valium®),
clonazepam (Klonopin®) and lorazepam (generic,
Ativan®). Although generally well tolerated, the side
effects of the benzodiazepines include sedation,
lightheadedness and fatigue. The biggest drawback is
the potential for addition and abuse. Patients may
develop tolerance to these drugs when they are used
long term. Cessation of these medications can result
in rebound anxiety and withdrawal symptoms.
Buspirone (generic, BuSpar®) is indicated for GAD,
but its onset of action is usually several weeks. Unlike the benzodiazepines there is no abuse potential
and there is no dependence or withdrawal symp-
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
toms. Headaches and dizziness may occur if the dose
is increased too quickly. Initial dose is 5 mg 3 times
a day with a maximum of 20 mg 3 times a day.
Buspirone may be less effective in patients who have
received benzodiazepines in the preceding 30 days.
Metoprolol (generic, Lopressor®) is a beta-blocker
generally used for hypertension and heart disease.
However, beta-blockers can help control the symptoms associated with performance anxiety such as
tachycardia, sweating and tremulousness. They have
been used for the treatment of the severe anxiety
associated with public speaking but would not be
useful in this patient with overwhelming daily symptoms.
Bupropion (Wellbutrin®) blocks the uptake of norepinephrine and dopamine. This drug is effective in
the treatment of depression but has not been approved for the treatment of anxiety.
Advising the patient to discuss her problems with a
supervisor at work will not address her generalized
anxiety. The most important thing is to alleviate her
symptoms as quickly as possible so she can perform
better on the job. Counseling can be an effective
treatment of GAD, both alone and in combination
with medical therapy. Relaxation therapy, biofeedback and cognitive therapy can be helpful. Enlisting
family members to participate in treatment is helpful.
References:
1. Ables AZ, Baughman OL. Antidepressants: update on new
agents and indications. Am Fam Physician 2003; 67(3):547-554.
2. Ciechanowski P, Katon W. Overview of generalized anxiety
disorder. In: Rose BD, ed, UpToDate. Wellesley, MA: UpToDate,
2003.
3. Gliatto MF. Generalized anxiety disorder. Am Fam Physician
2000; 62:1591-1600.
Website:
National Institute of Mental Health http://www.nimh.nih.gov/
publicat/anxiety.cfm. Accessed May 2004.
13 C DISCUSSION
Informed consent is a cornerstone of our health care
system. Consent for medical care becomes more
complicated when dealing with adolescents as they
can be at various stages of development and have
different levels of maturity and understanding of
health care issues that affect them. In the United
States the age of 18 years is considered the age of
majority, thus allowing those 18 years of age and
older the ability to direct their own health care decisions. However, there are three exceptions.
Emancipated minors – State criteria vary but generally include marriage, military service, parental consent (parents who have surrendered their rights and
responsibilities), parenthood, judicial order and financial independence
Mature minors – Those deemed by their physician
(or by a judge in certain circumstances) to be able to
understand the nature and consequences of medical
treatment; however, no definite guidelines exist for
assessing such maturiy
Special circumstances – Most states allow adolescents (13-18 years of age) to provide their own consent for contraception, sexually transmitted diseases,
pregnancy, alcohol and drug abuse and psychiatric
problems; no federally mandated age exists.
In the case of the patient described in the question,
the physician should be aware of the regulations
regarding this type of care for his/her state. The
biggest drawback to providing these services in the
office is financial. Insurance companies do not bill
services confidentially. Parents are not responsible
for payment when they did not consent to care.
Therefore, the adolescent is held responsible for payment. Although the physician may choose to write
off his/her office charges, the laboratory and pharmacy will not. Because of this, it is often in the
adolescent’s best financial interest to explore referral
to an agency such as a family planning clinic that has
a mechanism to bear these costs, or to encourage
her to involve a parent in her care. The physician
can provide guidance and support in this interaction.
Many adolescents are not aware of their rights regarding confidentiality. A discussion of confidentiality at the beginning of the office visit and providing
time without the parent in the room are often helpful in facilitating a frank discussion. Additionally, a
conversation with parent(s)/guardian(s) and the patient during early adolescence about how the physician will handle issues of adolescent confidentiality
can be very helpful before a situation such as the
one in the question arises.
The American Academy of Pediatrics (AAP) Committee on Bioethics suggests that the concept of informed consent (legal term) should probably be expanded for children, and particularly adolescents, to
include patient assent (approval but not legal consent) and parental permission. It is felt that it is important to include adolescents in decision-making
processes involving their own care. This empowers
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
213
the adolescent and promotes autonomy and decision-making skills. Great effort should be made to
obtain informed consent or assent from the adolescent involved before initiating any treatment, procedure or medication. Likewise, efforts should be make
to obtain parental permission when undertaking
medical interventions. Adolescents should be encouraged to involve their parents, but in situations where
they refuse to do so, the physician may provide the
services or refer the patient elsewhere for the service
if he/she feels uncomfortable about providing the
service without parental consent. Difficulty arises
when the adolscent and parents do not agree on
treatment. In such cases counseling and consultation
(e.g., mental health professionals, ethicists) may be
necessary. There is no precedent in favor of the
parental decision in all cases.
References:
1. Bartholome WG. Informed consent, parental permission and
assent in pediatric practice. Pediatrics 1995; 95(2):314-317.
2. Kuther TL. Medical decision-making and minors: issues of
consent and assent. Adolescence 2003; 38(150):343-358.
Web site:
http://www.ama-assn.org/ama/pub/category/8355.html Accessed
June 2004
14 E DISCUSSION
15 A Lyme borreliosis is a tickborne disease caused
16 C by the spirochete Borrelia burgdorferi and is
the most commonly reported vector-borne disease
in the United States. Borrelia burgdorferi is transmitted
by the usually asymptomatic bite of ticks of the genus Ixodes: I. Scapularis in the east and I. Pacificus in
the west.
The rising frequency of Lyme disease and its geographic spread have been linked to enlarging deer
populations and concurrent suburbanization. (See
Figure 2.)
Ticks search for host animals from the tips of grasses
and shrubs (not from trees) and transfer to animals
or persons who brush against vegetation. The transition zones from woods to well-kept suburban lawns
are common tick-infested areas and account for
Figure 2
From the Centers for Disease Control and Prevention
http://www.cdc.gov/ncidod/dvbid/lyme/index.htm
214
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
spread of the disease in people not active in outdoor
recreation. Ticks found on the scalp usually have
crawled there from lower parts of the body. Ticks
are most likely to transmit Lyme disease to humans
during the nymph stage. (See photograph.) Because
nymphs are very small (<2 mm), they are more
likely to feed on a person unnoticed. Ticks feed on
blood by inserting their mouth parts into the skin of
a host animal. They are slow feeders – a complete
blood meal can take several days. As they feed, their
bodies slowly enlarge. Infection is unlikely if the
tick is attached for 24 hours or less. However, tick
attachment of 72 hours or more has an infection rate
as high as 20 percent. Once transmission occurs, the
spirochete may be killed by host defenses, establish
local infection or disseminate to distant sites. The
attack rate for Lyme disease is highest in children
younger than 15 years of age and in adults older
than 29. Tick season is May through September.
Ixodes scapularis
From left to right: adult female, adult male, nymph, larva
Lyme disease affects many systems and has been classified into three stages: early localized (as in this
patient), early disseminated and late disseminated.
Signs and symptoms of this disease are variable and
dependent, to some extent, on the stage of the disease at presentation. Lyme disease can be difficult to
diagnose because its symptoms and signs mimic those
of many other diseases. The fever, muscle aches and
fatigue of early Lyme disease can easily be mistaken
for viral infections such as influenza or infectious
mononucleosis. Joint pain can be mistaken for other
types of arthritis such as rheumatoid arthritis. Upper
respiratory and gastrointestinal symptoms and signs
are uncommon in Lyme disease and, if present,
should suggest an alternate etiology. Nevertheless,
this disease presents a diagnostic challenge for clinicians since unrecognized and untreated early Lyme
disease can progress to disseminated or late disease
with arthritic, cardiologic and neurologic syndromes.
Early local disease has an incubation period from
infection to onset of erythema migrans of 7-14 days,
though it can as short as 3 days or as long as 30 days.
The characteristic rash is flat, uniformly red and
spreads out in a ring with central clearing, though
there is a great deal of variation on this pattern as in
the patient described. A vesicular form exists also.
The rash may burn or itch. Multiple secondary lesions may develop. The patient may have fever, malaise, fatigue, headache, myalgia, arthralgias and swollen lymph nodes. Some infected persons have no
symptoms at all (serologic evidence of disease without any clinical symptoms). On physical exam the
patient may have fever, neck stiffness and local adenopathy.
The diagnosis of early Lyme disease is clinical; since
Lyme disease mimics many other diseases, this may
not be an easy task. The goal of treatment of early
disease is to minimize the risk of development of
late Lyme disease and at the same time, minimize
unnecessary antibiotic prescriptions with possible adverse effects of unnecessary treatment.
In general, patients with a high risk of exposure in
an endemic area who have classic erythema migrans
can be treated empirically without any further testing. Since serologic testing has a low sensitivity in
early disease, serologic testing should be used only
to support a clinical diagnosis of Lyme disease, not
as the primary basis for making diagnostic or treatment decisions. Serologic testing may be more useful in later disease, at which time sensitivity and
specificity of the test are improved. A negative result
on the Western blot or ELISA indicates that no
serologic evidence of infection by B. burgdorferi at
the time the sample was drawn and has nothing to
do with whether the patient is infected with the
spirochete or not. The positive predictive value of
serologic testing is low in patients with vague symptoms unaccompanied by any objective signs of Lyme
disease, especially in those from less endemic areas.
Routine screening for Lyme disease with laboratory
testing in patients with vague symptoms is strongly
discouraged, as it can lead to a higher rate of false
positives than true positives, with subsequent inap-
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
215
propriate treatment and ‘labeling’ of patients with
Lyme disease.
A number of interventions have been shown to be
effective in the primary prevention of Lyme disease.
• Daily tick checks to minimize the length of time
the tick can feed
• Application of insect repellants containing DEET
• Tucking pant legs into socks to prevent contact
with ticks
• Tick control including creating a barrier (such as
with bark chips) between wooded areas and residential lawns, spraying with acaricides, removing
brush and leaf litter
• Prophylactic administration of doxycycline 200 mg
within 72 hours of recognized tick bite (efficacy
87 percent)
Treatment regimes are many and varied, but the
most commonly recommended regimens are doxycycline 100 mg twice daily for 14-21 days except for
children <8 years of age and pregnant women, in
whom amoxicillin, 500 mg 3 times daily (50 mg/
kg/day in children) for 14-21 days is recommended.
Pregnant women and children do not require a
longer course of therapy. Other antibiotics such as
cefuroxime axetil, ceftriaxone, erythromycin and
azithromycin can be used, but are not considered
first line.
References:
1. Brown SL, Hansen SL, Langone JJ. Role of serology in the
diagnosis of Lyme disease. JAMA 1999; 282(1):62-66.
2. Edlow JA. Lyme disease and related tick-borne infections. Ann
Emerg Med 1999; 33(6):680-693.
3. Hayes EB, Piesman J. How can we prevent Lyme disease? N
Engl J Med 2003; 348(24):2424-2430.
4. Steere AC. Lyme disease. N Engl J Med 2001; 345(2):115-125.
5. Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice
guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis 2000; 31Suppl1:1-14.
Web site:
http://www.cdc.gov/ncidod/dvbid/lyme/index.htm
May 2004
Accessed
17 B DISCUSSION
This patient has cutaneous larva migrans, one of the
most commonly acquired infections of travelers to
the tropics and subtropics of Latin America. It is
caused by the dog and cat hook worm, Ancylostoma
braziliense. Eggs are passed in the feces that then
hatch, giving rise to larvae that mature in soil and
sand. These filariform larvae penetrate the stratum
216
corneum of the skin via hair follicles, sweat glands
and fissures with the help of proteases produced by
the larvae. Once in the skin the larvae shed their
cuticles and produce more proteases that allow for
burrowing in the epidermis. People exposed to sand
and soil (travelers, children, laborers) are at higher
risk for acquiring the infection.
Clinically, the patient may feel a stinging sensation
when the larva initially penetrates the skin. A small
erythematous papule will develop at the entry site
within a few hours. The larva starts to migrate usually within 4 days of initial penetration, although
this can be delayed for weeks. Advancement may be
from several millimeters to up to 5 centimeters a
day. The resultant skin lesion is pruritic, erythematous, vesicular and serpiginous in pattern. The width
of the cord is usually 2-4 mm and the length is
variable. Secondary infection may occur. Lesions are
most commonly found on the feet, lower extremities, buttocks and genital area, corresponding to the
parts of the body most likely to be in contact with
the soil or sand containing the larvae. If a biopsy of
the lesion is performed, the larva is usually not found,
as it is often located 1-2 cm beyond the advancing
margin of the skin lesion. Patients may have a peripheral eosinophilia.
The cutaneous lesions usually persist for several weeks
to a month. There may be a recurrence of symptoms for a few days even after initial clearing. Even
without treatment, the larvae die and are eventually
resorbed, as they cannot complete their life cycle in
human hosts. On rare occasions, larvae may go to
the lungs via the blood stream. This can result in a
cough that usually manifests about a week after the
cutaneous lesion. Generally, the cough will last 1-2
weeks and will then resolve, although rarely it may
persist for up to 9 months. Chest x-ray may reveal
migratory infiltrates. Treatment of pulmonary involvement is not usually necessary, as it is a selflimited disease.
Treatment options for cutaneous larva migrans include
• Albendazole (Albenza®) 200 mg by mouth twice
daily for 3 days
• Ivermectin (Stromectol®) 150-200 mcg by mouth
once daily for 1-2 days
• Mebendazole (generic, Vermox®) 200 mg by
mouth twice daily for 3-4 days
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
• Thiabendazole (Mintezol®) suspension (500 mg/5
mL) applied twice daily for 2 weeks
• Thiabendazole 1500 mg by mouth twice daily for
4 days
Antihistamines may be helpful for the itching. Persons traveling to at-risk areas should be warned about
wearing shoes and avoiding direct skin contact with
sand and soil.
Jellyfish stings may give a similar-appearing serpentine rash but the rash will not extend in the days
following contact. Acute, intense stinging pain rather
than persistent pruritus is characteristic. Contact dermatitis is more likely to be linear rather than serpentine and usually becomes vesicular. Tinea pedis is
usually more erythematous and scaling and is generally not serpentine in distribution. Granuloma
annulare is not pruritic and is a circular lesion with
raised borders.
References:
1. Bravo S, Sanchez MR. New and re-emerging cutaneous infections in Latin America and other geographic areas. Dermatol Clin
2003; 21(4):665-668.
2. Joyce MP. Skin diseases of travelers. Prim Care 2002; 29(4):971981.
3. Weller PF. Cutaneous larva migrans (creeping eruption). In:
Rose BD, ed, UpToDate. Wellesley, MA: UpToDate 2002.
ralgia, multiple sclerosis, neuropathic head and neck
pain, phantom limb pain, Guillain-Barré syndrome,
spinal cord injury pain and human immunodeficiency
virus (HIV)-related sensory neuropathy. Controlled
studies are lacking to confirm these claims. In a randomized, double-blind study, gabapentin treatment
for migraine prophylaxis resulted in a 50 percent
reduction of migraine frequency. Gabapentin has also
been used for mood disorders, social anxiety disorder and attention deficit disorder but studies are lacking to document its effectiveness, if any, compared
to placebo.
Transient side effects during initial administration
include lethargy and dizziness. More persistent side
effects include ataxia, fatigue, edema, confusion and
depression. Stopping the medication abruptly can
result in lethargy, anxiety, insomnia, nausea, pain
and sweating.
For postherpetic neuralgia pain, gabapentin is started
at 300 mg/day and titrated up by 300 mg/day to a
level of 900 mg/day (in 3 daily doses). Further titrations up to 3,600 mg/day are possible. Lower doses
are recommended for patients with renal insufficiency.
References:
18 E DISCUSSION
Although only approved for the treatment of partial
seizures and postherpetic neuralgia by the Food and
Drug Administration (FDA), gabapentin (Neurontin®) is often prescribed for chronic pain, especially
neuropathic pain. Although its mechanism of action
is not known, gabapentin is an analog of the neurotransmitter gamma-aminobutyric acid (GABA) and
probably works at the level of the spinal cord where
it binds to voltage-sensitive calcium channels to block
pain stimuli.
In studies examining the effectiveness of gabapentin
for postherpetic neuralgia, pain scores were reduced
by approximately one third compared to placebo
after approximately 7-8 weeks of treatment. In a
randomized double-blind study for the treatment of
pain from diabetic neuropathy, 1,800-3,600 mg/day
of gabapentin resulted in significant improvement in
pain in approximately 60 percent of subjects. In another study, the effectiveness of gabapentin was found
to be equivalent to that of amitriptyline.
Gabapentin has also been reported to be effective for
the treatment of chronic pain from trigeminal neu-
1. Abrahm JL, Snyder L. Palliative care. Pain assessment and management. Prim Care 2001; 28(2):269-297.
2. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for
the symptomatic treatment of painful neuropathy in patients with
diabetes mellitus: a randomized controlled trial. JAMA 1998;
280(21):1831-1836.
3. Gabapentin (Neurontin) for chronic pain. Med Lett Drug Ther
2003; 46(1180):29-31.
4. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the
treatment of postherpetic neuralgia: a randomized controlled trial.
JAMA 1998; 280(21):1837-1842.
19 A DISCUSSION
Bell’s palsy is an acute, usually unilateral, facial paralysis
caused by inflammation and swelling of the seventh
cranial nerve. Although the etiology of the inflammation is unknown, many patients with Bell’s palsy have
serological evidence of a previous herpes simplex virus
infection. The lifetime risk of Bell’s palsy is approximately 1 percent with approximately 40,000 cases occurring annually in the United States. Men and women
are affected equally as are the two sides of the face. It is
most common between the ages of 15 and 60 years.
Groups at higher risk for Bell’s palsy include pregnant
women and individuals with diabetes or a history of a
recent upper respiratory infection.
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
217
The diagnosis of Bell’s palsy is primarily clinical – a
flaccid facial paralysis without sensory loss. Affected
individuals often describe hyperacusis (excessive sensitivity to sound), discomfort involving the ear, impaired taste and weakness of one side of the face.
Facial asymmetry is apparent on examination. Affected individuals usually have trouble closing the
involved eye completely, raising an eyebrow, smiling and chewing. Laboratory testing is usually unnecessary. Imaging with computed tomography (CT)
or magnetic resonance imaging (MRI) is also unwarranted in uncomplicated cases. A more extensive
work-up is recommended, however, in cases of bilateral Bell’s palsy, recurrent Bell’s palsy affecting the
same side of the face and Bell’s palsy associated with
other neuropathies. In these scenarios, Lyme disease,
meningitis, tumor, sarcoidosis and neuroma of the
seventh cranial nerve are some of the pathologies
that need to be ruled out. In areas of the country
where Lyme disease is prevalent, it has been suggested that Lyme disease testing may be prudent
even in cases of uncomplicated Bells’ palsy.
Spontaneous recovery of Bell’s palsy occurs over a
4-6 week period in approximately two thirds of patients; however, the majority of affected individuals
improve in the first three weeks. One third of patients have a more protracted course with recovery
taking 6 months. Some can have lingering problems
such as facial synkinesis (involuntary movement associated with a voluntary movement such as movement of the corner of the mouth when the individual attempts to close the eye on the affected side)
and crocodile tears.
Controversy exists regarding the treatment of Bell’s
palsy. The American Academy of Neurology has an
evidence-based practice parameter for Bell’s palsy
with the following conclusions:
• Early treatment with oral corticosteroids is probably effective to improve facial functional outcomes. Experts recommend steroids for patients
seen within the first 72 hours of the onset of
symptoms. Typically, prednisone 60-80 mg per
day is given for 4-7 days followed by a tapering
dose.
• Early treatment with an antiviral drug such as
acyclovir (generic, Zovirax®, 800 mg 5 times a
day), valacyclovir (Valtrex®, 1,000 mg 3 times
daily) or famciclovir (Famvir®, 500 mg 3 times
daily) in combination with prednisone is possi218
bly effective to improve facial functional outcomes.
• Evidence is insufficient to make recommendations regarding the use of facial nerve decompression to improve facial functional outcomes.
• The benefit of an antiviral medication alone has
not been established.
Protection of the involved eye, from drying out or
from erosion, is of paramount importance. The use
of ocular lubricants and possibly taping the eye shut
at bedtime can help prevent corneal problems. If
pain or redness of the eye develops, referral to an
ophthalmologist should be considered. Physical
therapy or massage and exercising of the facial
muscles may be helpful.
References:
1. Atkin PA. Diagnosis and management of Bell’s palsy. Practitioner 2003; 247:36, 39, 42-43.
2. Hato N, Matsumoto S, Kisaki H, et al. Efficacy of early treatment of Bell’s palsy with oral acyclovir and prednisolone. Otol
Neurotol 2003; 24(6):948-951.
3. Pascuzzi RM. Peripheral neuropathies in clinical practice. Med
Clin North Am 2003; 87:697-724.
Web site:
www.guideline.gov Accessed August 2004
National Guideline Clearinghouse. Practice parameter: Steroids,
acyclovir, and surgery for Bell’s palsy (an evidence-based review).
Report of the Quality Standards
20 C DISCUSSION
21 A Both of the patients in this series of ques22 E tions have forms of psoriasis. The 55-yearold woman has acrodermatitis continua of Hallopeau
(ACH) characterized by a chronic eruption of the
fingers and toes that may involve the entire hand or
foot. Tremendous scaling and fissuring is usual and
small lakes of pus may form underneath the scale.
For this reason, early cases in which only one or
two digits are involved are often mistaken for impetigo or a bacterial paronychia. Staphylococcus aureus
and Streptococcus pyogenes may occasionally be cultured from the debris, and it has been hypothesized
that a response to bacterial antigens may initiate or
worsen the condition. Antecedent trauma may also
play a role. ACH most often occurs in middle-aged
and older patients with a tendency to affect women
more than men.
Treatment of ACH can be very difficult. Even superpotent topical steroids are of limited value in such
patients because of the dense scale and intervening
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
purulence. Systemic therapy with a retinoid such as
acitretin (Soriatane®) or immune-suppressing medications such as methotrexate (generic, Rheumatrex®),
azathioprine (Imuran®) or cyclosporine (generic,
Sandimmune®, Neoral®) is usually necessary to control the lesions. Physical modalities such as ultraviolet radiation or superficial radiotherapy (Grenz rays)
may also play a role in therapy. A recent report suggested that tetracycline used in conjunction with a
topical corticosteroid might be helpful. The effect of
the tetracycline is probably due more to its antiinflammatory effect than its antimicrobial capabilities.
Other conditions included in the differential diagnosis of ACH include tinea corporis, chronic impetigo
and chronic contact dermatitis. Unless the patient
had some other long-standing immune-system-suppressing condition, it would be most unusual for a
tinea corporis to progress to this severity. A negative
potassium hydroxide preparation would help rule out
tinea corporis. It would be unlikely for chronic impetigo to spread over the entire hand but then remain confined to the hand. The patient described
has already been treated with several antibiotics that
should have diminished the severity of the disease if
infection was the primary cause. Bacterial culture
would help exclude this condition. A chronic contact dermatitis might show similar findings, but a
careful history would be expected to reveal the cause.
Allergy patch testing might help identify possible
offending allergens.
The second patient (son) in the clinical scenario has
classic nail findings of psoriasis. The nail changes of
psoriasis occur when the nail plate and nail matrix
are affected by the disease. Distal onycholysis, separation of the distal nail plate from the nail bed, is
common in psoriasis but is also seen commonly in
onychomycosis. Subungual debris may likewise occur in both psoriasis and fungal nails. A psoriatic nail
may be indistinguishable from a fungal nail. Complicating the situation further is the recent report
that patients with psoriatic nails may be more likely
to develop onychomycosis than patients with normal nails. Diagnosis of onychomycosis may be made
with a positive potassium hydroxide preparation,
growth of a dermatophyte on culture or with a histological exam in which fungal stains are employed.
Other characteristic psoriatic nail changes include
“oil drop” sign under the nail and pits in the nail
plate surface. The former is a brownish discoloration
of the underside of the nail resembling the color of
motor oil that may occur anywhere along the nail
and may be of varying size. Pits are tiny punctate
defects distributed on the surface of the nail plate.
Pitting can involve one or more nails with usually
no more than 10-15 pits per nail.
Treatment of psoriatic nails is similar to the treatment described above for ACH. Other treatments
include daily application of tazarotene gel (Tazorac®),
use of vitamin D 3 analogs such as calcipotriol
(Dovonex®) and 5-fluorouracil (Efudex®) cream or
solution. These topical treatments are applied to the
nail, resulting in less involvement of the new nail as
it emerges. Injection of the nail matrix with triamcinolone (generic, Kenalog®) may be helpful but is a
very uncomfortable procedure and is best done by
those trained in the technique.
Onychomycosis with a dermatophyte would not
likely show the oil spots and pits. Onychomycosis
with a mold usually presents with onychodystrophy
and subungual debris but may also cause apparent
pigmentation of the dystrophic nail plate. The classic
nail changes of lichen planus are a nail fold pterygium, caused by damage and eventual obliteration of
the nail matrix. This will appear to be an adherent
band of skin from the proximal nail fold and cuticle
to the nail surface. This is not a finding of psoriasis.
Trauma may be expressed in many ways on the
nails. Subungual hematoma may lead to nail loss,
nail dystrophy, or posttraumatic onychomycosis. The
nail may be fractured or split. Temporary injury to
the nail matrix may lead to the creation of a Beau’s
line, a horizontal groove that grows out with the
nail.
References:
1. Bianchi L, Soda R, Diluvio L, et al. Tazarotene 0.1% gel for
psoriasis of the fingernails and toenails: an open prospective study.
Br J Dermatol 2003; 149:207-209.
2. Piquero-Casals J, Fonseca de Mello AP, Dal Coleto C. Using
oral tetracycline and topical betamethasone valerate to treat acrodermatitis continua of Hallopeau. Cutis 2002; 70:106-108.
3.Salomon J, Szepietowski JC, Proniewicz A. Psoriatic nails: a
prospective clinical study. J Cutan Med Surg 2003; 7:317-321.
4. Yerushalmi J, Grunwald MH, Hallel-Halevy D, et al. Chronic
pustular eruption of the thumbs. Diagnosis: acrodermatitis continua of Hallopeau (ACH). Arch Dermatol 2000; 136:925-930.
23 C DISCUSSION
24 E Unfortunately, despite effective systemic therapy for metastatic breast cancer, randomized controlled trials present no evidence that systematic clini-
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
219
cal follow-up and surveillance testing of patients
treated for breast cancer results in improved survival.
Guidelines from the American Society of Clinical
Oncology (ASCO) regarding breast cancer surveillance after therapy include
1. Careful history and physical exam every 3 to 6
months for 3 years, then every 6 to 12 months
for 2 years, then annually
2. Monthly self-breast examination
3. For patients with breast conservation therapy, a
mammogram is recommended 6 months after
therapy. For all patients, including those with
modified radical mastectomy, a yearly mammogram is recommended.
4. Patients must be educated regarding symptoms of
recurrence since approximately 70 percent of patients with reoccurrence will present with symptoms between routine scheduled visits.
5. The available data show no difference in timeliness of discovery of recurrence or overall survival
based on whether a patient is followed by a family physician or a cancer specialist.
6. The following surveillance tests are NOT recommended:
a. Complete blood counts or chemistries
b. Chest X-ray
c. Bone scan
d. Liver ultrasound or computed tomography
e. Tumor markers (CA27.79, CA15-3, CEA)
Despite these guidelines many oncologists will follow patients at high risk for recurrence (≥ 4 positive
nodes, tumor size >5cm, Her2neu positive, hormone receptor negative) on a regular basis with blood
chemistries and tumor markers with the intent of
avoiding morbidity related to recurrence and to potentially extend survival.
Approximately 10-15 percent of patients with recurrent colorectal cancer will have localized, limited
disease that may be amenable to surgical resection
and possible cure. Most commonly resectable liver
lesions (≤4 in number and localized to one lobe) but
also local anastamotic recurrence and limited lung
metastasis can be resected, leading to a 10-year disease-free survival in the 20-40 percent range. ASCO
guidelines recommend CEA testing every 2-3 months
after initial curative surgery for at least 2 years and if
elevated, a work-up for metastatic disease is warranted. Colonoscopy should be done at 9-12 months
220
after curative surgery and, if negative, repeated in 3
years. If still negative, it should be repeated every 5
years. A meta-analysis involving 6 prospective trials
of systematic follow-up with CEA, liver panel and
CT scan versus evaluation for symptoms showed an
absolute improvement in 5-year disease free survival
of 10 percent.
Twenty-five to 40 percent of patients undergoing
radical prostatectomy for organ-confined prostate
cancer will eventually have recurrent disease. Risks
are increased by a preoperative prostatic specific antigen (PSA) >10 ng/ml and/or a Gleason Score ≥ 7.
(Editors’ note: For a discussion of prostate cancer, see
questions 12&13 in the January 2004 issue of The Core
Content Review.) Any rise in PSA following radical
prostatectomy reflects recurrence of prostate cancer.
Retrospective data evaluating salvage pelvic radiation in response to a rise in PSA has shown a significant percentage of patients who appear to be disease
free at 5 years after the diagnosis of the recurrence.
Whether these patients are actually cured is the subject of ongoing study. However, recommendations
based on the present data are to offer salvage radiation to appropriate patients with rising PSA after
radical prostatectomy. The surveillance recommendation is to check PSA every 4 months for 2 years
and then every 6 months for 3 years, then yearly.
Local pelvic irradiation should be started before the
PSA is >0.6 ng/ml as long as there is no evidence of
systemic metastasis.
Diffuse large cell lymphoma is a potentially curable
malignancy even in advanced stages. Complete response rates in patients treated with the anti-CD-20
antibody Rituxan® plus Cytoxan®, Adriamycin®, vincristine and prednisone (CHOP) are 70-75 percent.
Five-year disease-free survivals are in the range of
45 to 50 percent. Patients with complete remission
after initial chemotherapy must be followed closely
with evaluation every 2 months including history
and physical examination, CBC with platelets, lactate dehydrogenase (LDH), beta-2 microglobulin and
selected radiographic studies. Careful follow-up of
these patients is indicated to detect recurrent disease
at the earliest possible time. Patients who have chemotherapy-sensitive relapses (complete or near complete remission to standard dose salvage chemotherapy) can be treated with curative intent with
high-dose chemotherapy and autologous stem cell
rescue. The long-term disease-free survival in this
group of patients is approximately 40 percent.
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
Testicular cancer treatment is the prototype for successful chemotherapy of metastatic solid tumors.
Eighty-five to 90 percent of patients diagnosed with
testicular cancer can be cured with platinum-based
chemotherapy. In 2003, 7,000 patients were newly
diagnosed with testicular cancer and only 400 deaths
occurred. Salvage therapy including second-line standard chemotherapy and high dose treatment protocols with autologous stem cell rescue can cure 25-35
percent of relapsed or poorly responding patients.
Follow-up of patients after successful treatment of
testicular cancer should be compulsive and systematic. Tumor markers including alpha-fetoprotein
(AFP), beta-HCG and LDH should be measured
monthly for 2 years then less frequently out to 5
years. Chest x-rays are done at least every 2 months
for 2 years, then every 4 months for 1 year, every 6
months for 1 year, then yearly. Any abnormality of
tumor markers or chest x-ray should trigger an evaluation to confirm recurrent disease and to begin salvage therapy as soon the diagnosis is confirmed.
References:
1. Bast RC, Ravdin P, Hayes DF, et al. 2000 Update of recommendations for the use of tumor markers in breast and colorectal
cancer: clinical practice guidelines of the American Society of
Clinical Oncology. J Clin Oncol 2001; 19:1865-1878.
2. Benson AB, Desch CE, Flynn PJ. 2000 Update of American
Society of Clinical Oncology colorectal cancer surveillance guidelines. J Clin Oncol 2000; 18:3586-3588.
3. Fisher RI. Autologous bone marrow transplantation for aggressive non-Hodgkin’s lymphoma: lessons learned and challenges remaining. J Natl Cancer Inst 2001; 93:4-6.
4. Smith TJ, Davidson NE, Schapira DV, et al. American Society
of Clinical Oncology 1998 update of recommended breast cancer
surveillance guidelines. J Clin Oncol 1999; 17:1080-1082.
5. Stephenson AT, Shariat SF, Zelefsky MJ, et al. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.
JAMA 2004; 291:1325-1332.
25 D DISCUSSION
The patient described in this question has erythema
multiforme minor. There are two forms of erythema
multiforme, a major and minor form. The major
form, also known as Stevens-Johnson syndrome, is
usually secondary to a drug reaction. It is characterized by multiple bullae involving the mucous membranes and accompanied by systemic symptoms and
signs such as a harsh, hacking cough and evidence of
pneumonitis. The bullae are distributed widely and
affect many areas of the skin, the nares, the conjunctiva, mouth, vulvovaginal area, anorectal junction
and urethral meatus. Lesions in the mouth may cause
a severe stomatitis with hemorrhagic crusting. Con-
junctival lesions can lead to blindness. Medications
known to cause erythema multiforme major include
sulfonamides, phenytoin, barbiturates, penicillin, allopurinol and nonsteroidal antiinflammatory drugs.
Additionally, Mycoplasma pneumoniae infection may
precipitate erythema multiforme major.
Erythema multiforme minor does not involve mucous membranes, the lesions do not progress to bullae formation and there are no systemic symptoms.
The lesions of this condition appear suddenly, often
as target or iris lesions of erythematous papules with
central areas that may be cyanotic, purpuric or vesicular. The lesions vary from 1 to 3 cm in diameter
and typically involve the extensor surfaces of the
extremities and the palms and soles. Erythema
multiforme minor is usually associated with a preceding herpes simplex virus.
Erythema multiforme minor is a self-limited condition lasting 2-6 weeks. However, it may recur. Treatment is symptomatic. Secondary infection of skin
lesions may require the use of antibiotics. Oral
acyclovir may be used prophylactically to prevent
recurrence during herpes simplex infections.
In comparison, patients with erythema multiforme
major often require hospitalization. Corticosteroids
intravenously or orally are often used in severe cases,
although their use of is not supported by controlled
trials. Intravenous gamma globulin (0.75 g/kg/d for
4 days) has been effective.
References:
1. Ferri FF. Erythema multiforme. In: Ferri FF, ed, Ferri’s Clinical Advisor. Initial Disgnosis and Treatment. New York: Mosby,
2004:330.
2. Habif TP. Clinical Dermatology. 4th ed. St.Louis: Mosby,
2004:727-629.
3. Marx JA, Hockberger RS, Walls RM, et al. In: Marx JA, ed,
Rosen’s Emergency Medicine. 5 th ed. St. Louis: Mosby,
2002:1649-1653.
26 C DISCUSSION
Skin infections in wrestlers are a significant problem
and may contribute to loss of practice time, disqualification from competition and exposure of other athletes to potentially contagious illnesses. Compared to
other sports, infection transmission is a particular
concern in wrestling as the close skin contact between competitors increases risk. Cutaneous infections that frequently affect wrestlers fall into four
major categories: bacterial, viral, fungal and parasitic.
The National Collegiate Athletic Association
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
221
(NCAA) has developed guidelines regarding skin infections in wrestlers. The guidelines are outlined in
Table 1. No specific guidelines exist for high school
athletes.
Prevention of these infections should be the primary
intervention. Unfortunately, athletes often will not
notify coaches or physicians of skin conditions since
such identification will frequently preclude participation in their sport. Despite this barrier, efforts
should be aimed at having athletes seek early treatment for any of these skin conditions so that prompt
treatment can be initiated and return to participation
expedited. The following measures can help limit
the development and spread of infection:
• Encourage showers after every practice or competition
• Discourage the sharing of equipment of personal
items (e.g., towels, clothing)
• Plan routine cleaning of common equipment
• Education of coach regarding recognition of skin
conditions
• Education of athletes regarding skin conditions and
encourage early reporting
• Covering of skin lesions when appropriate
• Isolation of infected person until appropriately
treated
Recently, the Centers for Disease Control and Prevention (CDC) have received reports about methicillin-resistant staphylococcus aureus (MRSA) in athletes, particularly wrestlers. However, no new recommendations or guidelines have been added.
References:
1. Adams BB. Tinea corporis gladiatorum. J Am Acad Dermatol
2002; 47(2):286-290.
2. Dienst WL, Dightman L, Dworkin MS, et al. Pinning down
skin infections: diagnosis, treatment, and prevention in wrestlers.
Phys Sportsmed 1997; 25(12):45-56.
3. Eiland G, Ridley D. Dermatological problems in the athlete. J
Orthop Sports Phys Ther 1996; 23(6):388-402.
4. NCAA Guideline 2b: skin infections in wrestling. 2003-04
NCAA Sports Medicine Handbook (Revised June 2003):21.
5. Pratt MK, Mustafa MA, Stulberg D. Common skin conditions
in athletes. Clin Fam Pract 2003; 5(3):653.
Table 1 – NCAA Guidelines Regarding Skin Conditions in Wrestlers
Disorder
Recommendations
Furuncles, folliculitis, impetigo
- No new skin lesions for 48 hours before event
- Must have completed 72 hours of antibiotic therapy and have no moist or draining or
exudative lesions at the time of the event
Hidradenitis suppurativa
- Disqualification if extensive or draining lesions are present
Pediculosis
- Must be treated with appropriate pediculicidal agent and be examined for completeness of
response
Scabies
- Must be treated and negative for the infection at time of the event
Herpes simplex (primary
infection), also known as herpes
gladiatorum
-
Herpes simplex (recurrent infection)
- Must have no moist lesions; all lesions must be dry with firm, adherent crust
- Must have been on appropriate antiviral therapy for at least 72 hours prior to the time of the
event
Herpes zoster
- Must have firm, adherent crust
- No evidence of secondary bacterial infection
Molluscum contagiosum
- Lesions must be curetted or removed prior to event
- Localized or solitary lesions can be covered by a gas-permeable membrane followed by ProWrap and stretch tape
Verrucae
- Multiple digitate lesions of the face result in disqualification if they can not be covered with a
mask
- Multiple verruca vulgaris or verruca plana must be covered
Tinea corporis, also known as
tinea corporis gladiatorum
- Minimum of 72 hours of topical treatment; minimum 2-week treatment of scalp lesions
- Extensive or active lesions result in disqualification
222
Must be free of systemic viral symptoms
Must have developed no blisters for 72 hours before the event examination
Must have no moist lesions; all lesions must be dry with firm adherent crust
Must have been on appropriate antiviral therapy for at least 72 hours prior to the time of the
event
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
27 B DISCUSSION
28 C Basal cell carcinoma (BCC) is not only the
most frequently encountered type of skin cancer but
it is also the most common cancer, with up to
950,000 cases diagnosed annually in the United
States. Ultraviolet radiation plays a role in the development of basal cell carcinoma; however, sun exposure is more closely related to squamous cell carcinomas of the skin. The most common site for BCC
is the nose (30 percent), with 85 percent of BCC
located on the head and neck. Risk factors for BCC
include age >40 years, fair skin, use of tanning
booths, increased sun exposure, history of radiation
therapy, immunodeficiency and personal or family
history of skin cancer.
is dome-shaped and often has a rolled, pearly border. Telangiectasia may be noticed on the surface
and central ulceration of the nodule may occur.
Sometimes the nodule is pigmented, giving the appearance of a melanoma.
Although more than 25 microscopic types of BCC
have been identified, these can be categorized into
three histiologic types based on growth patterns:
nodular, superficial and morpheaform. As in this case,
these lesions are often translucent. The nodular BCC
The cure rate for BCC is approximately 90 percent.
The lesions at lowest risk for recurrence after treatment are those that are new lesions (not previously
treated) with well-defined margins and <1.5 cm in
diameter. Morpheaform lesions have less distinct
Morpheaform BCCs are usually flat or slightly raised
with a waxy consistency and a yellow or white color.
Often, morpheaform BCC looks like a scar in an
area of skin without a history of trauma.
Superficial BCC appears as a dark, circumscribed
scaling lesion, often with a pearly border similar to
that observed in nodular BCC. These lesions are
often crusted with areas of erosion and are most
often found on the trunk and extremities.
Figure 3: Mohs’ Micrographic Surgery Technique
(Reproduced with permission from Wolfe J. Nonmelanoma Skin Cancers: Basal Cell and Squamous Cell Carcinoma. In: Abeloff MD,
Armitage JO, Lichter AS, et al. eds. Clinical Oncology. 2nd ed. New York: Churchill Livingstone, 2000:1351-1358.)
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
223
margins and, hence, the highest recurrence rate after
treatment.
Treatment options for BCC are dependent upon the
type, size and location of the BCC. Options include
• Excision biopsy – Often used for lesions on the
trunk, legs, forehead and cheeks >5 mm in diameter
• Mohs’ micrographic surgery – Large tumors,
recurrent tumors, poorly differentiated tumors with
indistinct borders, cosmetically sensitive areas (e.g.,
nose, eyelid)
• Curettage with electrodesiccation – Nodular
BCC ≤5 mm in diameter
• Cryosurgery – Small, low-risk, well-demarcated
lesions
• Radiation surgery – Used when preservation of
surrounding tissue is crucial such as BCC around
the lips, large lesions, patients who cannot tolerate
surgery
BCC, especially morpheaform type, develop fingerlike projections into the surrounding dermis. Hence,
Mohs’ micrographic surgery is used to ensure that all
tumor is removed. Mohs’ technique consists of curetting out the visible tumor. Following this, successive
thin horizontal layers of tissue measuring 1-2 mm in
thickness are removed and examined microscopically, creating a map of the tumor. This is process
continues until a tumor-free plane is found. The
defect created by the procedure is allowed to heal
by secondary intention or can be closed primarily.
(See Figure 3.)
Topical chemotherapy with 5-fluorouracil is usually
used for the treatment of multiple actinic keratoses.
Occasionally, it is used for the treatment of superficial basal cell carcinomas when the conventional
methods described above are not practical because of
the location of the lesion.
References:
1. A Color Guide to Diagnosis and Therapy. Habif TP, ed, Clinical Dermatology. 4th ed. Philadelphia: Mosby, 2004:934-935.
2. Ferri FF. Basal cell carcinoma. In: Ferri FF, ed, Ferri’s Clinical
Advisor 2004. St. Louis: Mosby, 2004:132.
3. Wolfe J. Nonmelanoma skin cancers: basal cell and squamous
cell carcinoma. In: Abeloff MD, Armitage JO, Lichter AS, et al.,
eds, Clinical Oncology. 2nd ed. New York: Churchill Livingstone,
2000:1351-1358.
29 A DISCUSSION
Allopurinol is a xanthine oxidase inhibitor prescribed
to reduce the production of uric acid. It is indicated
224
in the management of gout as a preventive measure.
Similarly, it can be used to prevent uric acid kidney
stones and nephropathy. Patients who have recurrent calcium oxalate calculi and whose daily uric
acid excretion is high (> 800 mg/day in males or >
750 mg/day in females) have also received benefit
from allopurinol therapy for preventing future stones.
Allopurinol is also commonly prescribed during chemotherapy for patients with malignancies, particularly leukemia and lymphomas. During the tumor
lysis phase of chemotherapy, rising serum and
urinary uric acid can precipitate gout and nephrolithiasis.
While allopurinol is commonly prescribed and is
beneficial in each of the above circumstances, it is
not without side effects and potential significant toxicity. Approximately 20 percent of patients receiving
allopurinol will experience side effects of varying
severity. Side effects are dose-related and are more
likely in patients with renal insufficiency. The most
common side effects of allopurinol are dermatologic;
a pruritic maculopapular rash is the most frequent of
all adverse effects. The rash often involves the hands
and feet alone. Other nonserious skin problems include urticarial, erythematous, exfoliative, hemorrhagic or purpuric skin problems as well as alopecia.
More serious problems including desquamation and
Stevens-Johnson syndrome have occurred.
Allopurinol has hematopoietic side effects including
leukopenia, thrombocytopenia and eosinophilia.
More serious problems including fatal bone marrow
suppression and aplastic anemia have also occurred.
Hematopoietic side effects have been reported within
the first 6 weeks of therapy and, with continued
therapy, as late as 6 years after the initiation of
therapy. While no standard exists for monitoring, a
periodic complete blood count (CBC) has been advocated by some authors. Other side effects include
nausea, diarrhea or mild elevation of liver transaminases. Fever, weakness, malaise and peripheral neuropathy have also been reported.
The most serious complication of allopurinol therapy
is systemic toxicity. Allopurinol hypersensitivity syndrome is thought to be a cell-mediated response to
the allopurinol, oxipurinol (its major oxidative metabolite) or both. This toxicity can present with exanthematous rash, toxic epidermal necrolysis and/or
dermal vasculitis. Patients may have fever, eosino-
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
philia or leukocytosis. Severe hepatic and/or renal
dysfunction is possible along with gastrointestinal
bleeding. Pulmonary vasculitis, hypersensitivity angiitis, congestive heart failure and even acute onset
of permanent deafness have all occurred as part of
this syndrome.
Allopurinol has interactions with several commonly
used medications. Patients concurrently receiving
ampicillin/amoxicillin have a 10-fold increase in developing a rash from allopurinol therapy. Hypersensitivity reactions are increased for patients receiving
concomitant thiazide diuretic or angiotensin converting enzyme (ACE) inhibitor therapy; theophylline clearance may decrease, leading to increased
theophylline levels and possible toxicity; use with
Coumadin has yielded conflicting results, but several
reports have shown increased anticoagulant action
with prolonged prothrombin time and an increase in
the INR.
References:
1. Allopurinol. In: Hutchison TA, Shahan DR, eds, DRUGDEX
Drug Evaluations. Greenwood Village, CO: MICROMEDEX,
2004
2. Lacy CF, Armstrong LL, Goldman MP, et al. Drug Information
Handbook: Hudson, OH: Lexi-Comp Inc., 2003:52-54.
3. Roberts LJ, Morrow JD. Analgesic – antipyretic and antiinflammatory agents and drugs employed in the treatment of gout.
In: Hardman JG, et al., eds, Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York: McGrawHill, 2001:721-722
4. Schumacher HR, Fox IH. Antihyperuricemic Drugs. In: Kelley
WN, et al., Textbook of Rheumatology. 5th ed. Philadelphia: WB
Saunders, 1997:829-833.
30 B DISCUSSION
The pigmented lesions in this patient are caused by
oral minocycline. Minocycline 50-100 mg twice daily
is a very effective acne treatment. It has been found
to be effective in patients who have not responded to
oral tetracycline and to result in greater improvement
in patients switched from tetracycline. It is often effective in patients with pustular acne who may not
have responded to any other oral antibiotic therapy.
It is a lipophilic agent that has both antibacterial and
antiinflammatory actions. Unlike the other traditionally used antibiotics (e.g., tetracycline, clindamycin,
erythromycin), resistance to minocycline is rare. Inhibition of absorption related to food intake is significantly less than seen with tetracycline, therefore making dosing easier. However, the cost of minocycline
is greater than that of the other antibiotics.
There are four types of minocycline-induced cutaneous pigmentation:
• Blue/black pigmentation confined to sites of scarring and inflammation on the face
• Blue/gray circumscribed pigmentation of normal
skin involving the lower legs and forearms
• Diffuse muddy brown pigmentation of normal skin
accentuated in sun-exposed areas
• Blue/gray pigmentation within acne scars confined
to the back
While these pigmentary changes are usually seen only
after prolonged minocycline therapy, they have been
reported following only a few weeks of therapy.
Gradual resolution of these pigment changes does
occur after discontinuation of the medication, although the lesions may persist for a long time.
Discoloration of nails, bones, thyroid, oral mucosa
and sclera has been reported. Staining of the gingival
third of teeth occurs in children who are administered minocycline prior to the age of 7 years. Adults
administered minocycline for prolonged periods of
time may develop long-lasting staining of the teeth
involving the incisal one half to three quarters of the
crown.
In addition to pigment changes, minocycline has also
been associated with central nervous system side effects (ataxia, vertigo, nausea and vomiting) and
pseudotumor cerebri. It has been reported to result
in hypersensitivity syndromes consisting of a cutaneous reaction, eosinophilia and involvement of one
or more organs (hepatitis, nephritis, myocarditis, pericarditis, pneumonitis). Lupus-like and serum-sickness-like syndromes have also been seen. Patients
with preexisting renal insufficiency may suffer worsening of their renal function when administered
minocycline. Photosensitivity and hepatotoxicity may
also occur. Minocycline is category D in pregnancy
due to concerns regarding the development of teeth
and bones.
References:
1. Acne, rosacea and related disorders. In: Habif TP, ed, Clinical
Dermatology. 4th ed. St. Louis: Mosby Inc., 2004:181-182.
2. Minocycline hydrochloride. In: Nissen D, ed, Mosby’s Drug
Consult. St. Louis: Mosby 2004: online edition.
3. Mouton RW, Jordaan HF, Schneider JW. A new type of
minocycline-induced cutaneous hyperpigmentation. Clin Exp
Dermatol 2004; 29(1):8-14.
31 E DISCUSSION
A number of studies have shown that the risk of
depression is increased in patients with diabetes. One
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
225
meta-analysis suggests that the risk is twice that of
nondiabetic control populations. The prevalence of
depression in patients with diabetes is higher in
women than men and the odds ratio of developing
depression is 1.8 for women. Unfortunately, it is
estimated that only one quarter of depressed diabetic
patients are actually identified and started on appropriate treatment.
Diabetic patients who are depressed are less likely to
be adherent to diet, medication and exercise regimens. Accumulating research suggests that history of
depression is associated with poor glycemic control
as reflected in elevated glycosylated hemoglobin levels. Diabetic patients with depression are more likely
to develop diabetic complications at least in part
related to the poorer glycemic control. Additionally,
patients with diabetic complications are more likely
to become depressed. Patients with concomitant depression and diabetes have been found to have higher
health care costs and lower scores on quality-of-life
measures. It has even been suggested that major depression increases the risk for type 2 diabetes.
As in other medical illnesses, patients with diabetes
may report “depressive” symptoms such as weight
loss or gain, fatigue and hypersomnia that are actually a direct manifestation of their diabetes. Disordered sleep, a common depressive symptom, is often
a symptom of uncontrolled diabetes that causes nocturia. Patients with diabetes and concurrent depression may amplify somatic symptoms of physical illness and have difficulty adjusting to such aversive
symptoms. For example, patients with diabetes and
depression were found to report somatic symptoms
of poor glucose control, such as polydipsia, that were
not correlated with objective physiologic evidence
of poor glycemic control (i.e., elevated glycosylated
hemoglobin values).
Appropriate treatment of depression in the diabetic
patient has been shown to improve functioning and
the ability to manage the disease. Tricyclic antidepressants have been used, although hyperglycemic
effects have been reported. Also, side effects of particular concern for patients with diabetes include
weight gain, carbohydrate/sweet cravings and anticholinergic effects on bowel and bladder motility.
The latter may worsen diabetic gastroparesis and further disturb a neurologically impaired bladder. Enthusiasm for selective serotonin reuptake inhibitors
226
(SSRI) agents began with experimental evidence of
hypoglycemic and insulin-sensitizing effects.
Fluoxetine (generic, Prozac®) 60 mg/day has been
associated with improvement in weight and
glycosylated hemoglobin in subjects with type 2 diabetes. Of note, in one study, improvement was more
apparent at 3 and 6 months than at 9 and 12 months.
In a similar group of patients, 4 weeks of fluoxetine
60 mg improved insulin-mediated glucose disposal,
despite absence of weight loss. This supports a direct
fluoxetine effect on insulin sensitivity. Little research
has been conducted on the effects of SSRIs in subjects with both depression and diabetes. However,
an open, 10-week study of such patients given
sertraline (Zoloft®) 50 mg/day did reveal significant
improvement on two depression rating scales and
dietary compliance. Modest improvements of
glycosylated hemoglobin levels were also seen.
References:
1. Anderson RJ, Freedland KE, Clouse RE, et al. The prevalence
of depression in adults with diabetes. Diabetes Care 2001; 24:10691078.
2. Goldney RD, Phillips PJ, Fisher LJ, et al. Diabetes, depression
and quality of life: a population study. Diabetes Care 2004;
27(5):1066-1070.
3. Katon W, von Korff M, Ciechanowski P, et al. Behavioral and
clinical factors associated with depression among individuals with
diabetes. Diabetes Care 2004; 27(4):914-920.
4. Rubin RR, Ciechanowski P, Egede LE, et al. Recognizing and
treating depression in patients with diabetes. Curr Diab Rep 2004;
4(2):119-125.
32 C DISCUSSION
33 A This patient has nasal polyps, which appear
as outgrowths of the nasal mucosa on the lateral wall
of the nose. They arise most commonly from the
ethmoid sinus and clefts of the middle meatus and
protrude into the nose. The incidence of nasal polyps
is estimated to be between 1 and 4 percent in adults
and 0.1 percent in children. They are twice as common in men as in women, and the great majority
occur after the age of 40 years. In fact, nasal polyps in
a child (less than 10 years of age) or adolescent should
prompt an evaluation for cystic fibrosis.
The etiology of nasal polyps was thought to be allergic for many years. However, more recent studies
have implicated nonallergic mast cell degranulation
as the common pathway. Studies have shown that
patients with allergies are not at greater risk for polyps, and, in fact, atopic patients have a lower incidence of polyps compared to nonatopic patients. It
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
has been suggested that the edema from allergies,
inflammation of sinusitis or irritant reactions all lead
to swelling of the nasal mucosa. A focal accumulation of edema fluid with hyperplasia of submucosal
connective tissue creates a polyp.
The most common symptoms are nasal congestion,
sneezing, rhinorrhea, postnasal drip and anosmia. Pain
is rarely noted. On exam, patients present with a
grape-like projection in the medial meatus. The projections are commonly translucent, soft and do not
readily bleed. The differential diagnosis includes swollen turbinates and tumors. An important diagnostic
characteristic is that polyps are insensitive to pain.
The examiner should be able to manipulate them
with a cotton swab.
In addition to cystic fibrosis, other well-known associations with nasal polyps include
• Asthma: In a large series, 20-50 percent of patients
with nasal polyps had asthma and 32 percent of
asthmatics had nasal polyps. Asthma and nasal polyps share many pathologic features, suggesting a
common inflammatory process.
• The triad of asthma, aspirin sensitivity and nasal
polyps is known as Samter’s triad. The incidence
of nasal polyps in adult asthmatic patients with
aspirin sensitivity is approximately 49 percent. Vasomotor rhinitis associated with copious rhinorrhea generally occurs first, followed by the development of nasal polyps, then bronchial asthma and,
finally, aspirin sensitivity. These polyps are particularly resistant to treatment.
• Allergic fungal sinusitis often presents with nasal
polyps, chronic rhinosinusitis and, occasionally,
proptosis due to orbital involvement of the disease. The prevalence of nasal polyps is 66 percent
to 100 percent in patients with allergic fungal sinusitis. These patients are usually young, immunocompetent and atopic with or without asthma
and most often reside in the southern or southwestern United States.
• Primary ciliary dyskinesia is an autosomal recessive
inherited disease characterized by ultrastructural defects of cilia and spermatozoa that result in impaired motility. Clinically, these patients have recurrent upper and lower respiratory tract infections beginning in early childhood; chronic rhinorrhea; chronic sinusitis; chronic otitis media, often with a hearing deficit; and chronic bronchitis,
often leading to bronchiectasis by early adulthood.
Nasal polyps occur in 26 to 40 percent of these
patients.
• Churg Strauss syndrome (allergic granulomatosis
and angiitis) is characterized by asthma, eosinophilia, systemic vasculitis and pulmonary infiltrates.
Half of these patients will have nasal polyps.
Effective treatment consists of intranasal steroids.
Topical corticosteroids reduce the symptoms of rhinitis, improve nasal breathing, reduce the size of the
polyps and can reduce recurrence, although recurrences are common. Decongestants, antihistamines,
leukotriene modifiers and cromolyn sodium are ineffective. Resistant cases should be referred to an
otolaryngologist for endonasal sinus surgery. Even
following surgery, the recurrence rate is as high as
85 percent in patients followed for 20 years.
References:
1. Bachert C, van Cauwenberge. Nasal polyps and sinusitis. In:
Adkinson NF, ed, Middleton’s Allergy: Principles and Practice.
6th ed. Philadelphia: Mosby Year Book Inc. 2003:1421-1430.
2. Bikhazi NB. Contemporary management of nasal polyps.
Otolaryngol Clin North Am 2004; 37(2):327-337.
3. Blomqvist EH, Lundblad L, Anggard A, et al. A randomized
controlled study evaluating medical treatment versus surgical treatment in addition to medical treatment of nasal polyposis. J Allergy
Clin Immunol 2001; 107(2):224-228.
34 D DISCUSSION
Acute pyelonephritis is a major complication during
pregnancy with an overall incidence of approximately
1-2 percent. The incidence is 25 percent in women
with asymptomatic bacteruria. It may result in significant maternal and fetal morbidity including anemia, respiratory distress syndrome (ARDS), renal insufficiency or abscess and premature labor and lowbirth-weight infants. The pathogenesis of acute
pyelonephritis in pregnancy is related to the presence of bacteriuria, obstruction of the ureters caused
by the gravid uterus and its contents and ureteral
dilatation secondary to progesterone. Most cases of
acute pyelonephritis (up to three fourths) occur during the second and third trimesters and the rest during the postpartum period. The most common offending organisms are E. coli, and Klebsiella and
Enterobacter species.
The clinical diagnosis of acute pyelonephritis during
pregnancy is suggested by fever and flank pain. Other
features include nausea, vomiting, shaking chills and
costovertebral angle tenderness. The fever may be
high, with levels reaching 104ºF or higher in some
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
227
women. Blood cultures are positive in 10-20 percent of cases. A number of complications are associated with acute pyelonephritis in pregnancy. Septic
shock affects 1-2 percent. Endotoxin-mediated alveolar-capillary injury can lead to respiratory distress
and even adult respiratory distress syndrome (2-8
percent). Factors that are predictive of pulmonary
damage include tachycardia (>110 beats per minute),
tachypnea, blood transfusion, fever to 103ºF, use of
tocolytics and excessive hydration. Up to 25 percent
of women with acute pyelonephritis during pregnancy have reduced creatinine clearance (less than
80 mL/minute) that resolves over a few weeks with
appropriate treatment. Renal failure is infrequently
seen. The infection may cause hemolysis resulting in
anemia (hematocrit of less than 30 percent) in two
thirds of pregnant women. The anemia is thought to
be caused by endotoxin-mediated hemolysis. Acute
pyelonephritis in pregnancy is also associated with
preterm labor, preterm delivery and low birth weight.
Women with pyelonephritis during pregnancy are
generally hospitalized for aggressive hydration and
parenteral antibiotic therapy. Many women will actually experience uterine contractions with the initiation of antibiotic therapy, and the contractions
may continue for several hours. Antibiotic treatment
choices include ampicillin and gentamicin, cephalosporins, or extended spectrum penicillins.
Fluoroquinolones are avoided because of concerns
regarding their effects on growing bone and cartilage. Response to therapy is generally seen in 48 to
72 hours. Failure to respond to antibiotic therapy
suggests antimicrobial resistance (most common),
nephrolithiasis, obstruction or abscess. Some studies
suggest that some carefully selected patients may be
safely treated as outpatients (ceftriaxone [Rocephin®]
1 gram IM for 2 days followed by cephalexin [generic, Keflex®] 500 mg QID for 10 days) with outcomes equal to that of inpatient treatment. Outpatient treatment can be considered if the patient is
well-hydrated, can tolerate oral medication, has no
evidence of sepsis or organ dysfunction and is compliant with follow-up. Even following successful
treatment, up to 25 percent of women will have a
recurrence of pyelonephritis. Therefore, after an episode of pyelonephritis during pregnancy, monthly
urine cultures should be obtained to check for persisting bacteriuria or the affected patient should be
placed on antibiotic suppression, most commonly
228
with nitrofurantoin (generic, Macrodantin®) 100 mg
orally daily.
References:
1. Careno CA, Funai EF. Urinary tract physiology and urinary
tract infections in pregnancy. In: Rose BD, ed, UpToDate.
Wellesley, MA: UpToDate, 2003.
2. Delzell JE, Lefevre ML. Urinary tract infections during pregnancy. Am Fam Physician 2000; 61:713-721.
3. Gilstrap LC. Urinary tract infections in pregnancy. Obstet
Gynecol Clin North Am 2001; 28(3):581-591.
35 A DISCUSSION
Discoid lupus erythematosus is a chronic form of
cutaneous lupus. The disorder is seen more commonly in women, most commonly in the fourth
decade, although the age range is actually greater
than that of systemic lupus erythematosus (SLE). Initially, lesions are erythematous, round, scaling papules or plaques found most commonly on sun-exposed areas such as the malar prominences, bridge of
the nose, scalp and ears. An adherent scale extends
into the hair follicles creating follicular plugging.
The lesions tend to slowly expand in size with active inflammation at the margins of the lesion. The
central area will then heal with a depressed central
scar, atrophy, telangiectasias and altered pigmentation. Scalp lesions may result in alopecia and scarring. Mucus membrane involvement is often prominent, especially in the mouth.
Approximately 25 percent of patients with SLE will
develop chronic discoid lesions. However, some patients with discoid lesions will not have any other
signs or symptoms of systemic disease. Approximately
10 percent of these patients will eventually develop
SLE, although the systemic disease tends to be mild.
SLE is more likely to develop in patients with more
numerous and extensive lesions. Patients with discoid lupus generally are negative for antinuclear antibodies. Rarely anti-Ro antibodies are present in
low titer. All patients with discoid lesions should be
questioned regarding signs and symptoms of SLE.
Treatment should be initiated early to prevent atrophy and scarring. Topical steroid creams and ointments can result in resolution of lesions with more
potent steroid used for the thicker plaque-like lesions. Intradermal injections of steroid can be used
for resistant plaque lesions but are associated with
secondary atrophy. Some evidence indicates that
immunomodulatory therapy with agents such as
tacrolimus (Protopic®) and pimecrolimus (Elidel®)
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
may be helpful, but more study is needed.
Antimalarials, especially hydroxychloroquine (200400 mg/day), are helpful, with 50 percent of treated
patients having significant improvement or clearing
of their lesions.
References:
1. Jessop S, Whitelaw D, Jordaan F. Drugs for discoid lupus
erythematosus. Cochrane Database Syst Rev. 2001; (1):CD002954.
2. Schur PH, Moschella SL. Cutaneous manifestations of systemic
lupus erythematosus. In: Rose BD, ed, UpToDate. Wellesley,
MA: UpToDate, 2003.
Web site:
http://www.merck.com/mrkshared/mmanual/section5/chapter50/
50f.jsp. Accessed June 2004.
36 C DISCUSSION
37 A Pain management is a concern for pregnant
women as they approach the time for delivery of
their babies. Current common approaches to pain
management during labor include techniques learned
in childbirth classes (e.g., Lamaze method), opioid
analgesia and epidural analgesia. While techniques
for relaxation and concentration are sufficient for
some women for their entire labors, other women
request opioid or epidural analgesia as well. Opioid
analgesia can be easily administered and has a rapid
onset of action. However, it can decrease the
mother’s level of alertness and can suppress the neonate in utero as well as immediately after birth (sometimes requiring the administration of naloxone
[Narcan®]).
The primary advantage of epidural analgesia is the
excellent pain relief that patients experience during
the first (onset of labor to full dilatation) and second
(full dilatation to delivery of infant) stages of labor.
It can also allow for adequate anesthesia for operative vaginal deliveries and a possible Cesarean section. Side effects and complications associated with
epidural analgesia can be divided into those due to
the procedure itself and those affecting the labor
process.
Problems associated with the initiation of epidural
analgesia include hypotension (0-50 percent), pruritus (incidence variable depending on agent administered and dose), nausea and vomiting (7.5 percent)
and urinary retention (30-60 percent). Some patients
may not have complete pain relief, while others may
have a window (an isolated area where analgesic is
not effective). The most common procedural complication is inadvertent dural puncture (1-2 percent).
Following this, the risk for a postdural puncture headache is 31-75 percent. The headache is commonly
frontal in location, is most pronounced in the upright or sitting positions and is relieved by recumbency. It may be associated with visual changes, transient hearing loss and dizziness. Hydration, caffeine
and bed rest are the initial treatments. Epidural blood
patching (instillation of 2-3 mL of blood into the
epidural space) can be very effective (85 percent
relief after one patch, 98 percent after two). Low
back pain is a common complaint following the procedure but is probably unrelated. Infection is rare (<
0.1 percent), although spinal and paraspinal abscesses
have been described in patients with reduced immune response or associated malignant disease.
The major concern regarding epidural analgesia is the
effect on the labor process. Despite the general feeling
that epidural analgesia significantly prolongs labor and
increases the risk for an operative vaginal delivery for
dystocia and Cesarean section, a recent meta-analysis
does not bear this out. The first stage of labor does
not appear to be affected. The average prolongation
of the second stage is 15 minutes that, while statistically significant, is not clinically significant. The incidence of operative vaginal delivery for reasons other
than dystocia is increased. Multiple studies have shown
that the administration of epidural analgesia has no
effect on Apgar scores or cord pH.
Intrapartum fever, use of oxytocin and postdelivery
urinary incontinence are seen more frequently in
laboring women who receive epidural analgesia. The
fever is not indicative of infection and is thought to
be due to altered thermoregulation, although the
exact mechanism is unknown. The use of oxytocin
for perceived decrease in effective uterine activity
may account for the lack of prolongation of the first
stage of labor. Urinary incontinence, seen in the
immediate postpartum period, resolves spontaneously.
References:
1. Leighton BL, Halpern SH. The effects of epidural analgesia on
labor, maternal, and neonatal outcomes: a systematic review. Am
J Obstet Gynecol 2002; 186(5 Suppl Nature):S69-77.
2. Mayberry LJ, Clemmens D, De A. Epidural analgesia side effects, co-interventions, and care of women during childbirth: A
systematic review. Am J Obstet Gynecol 2002; 186(5 Suppl
Nature):S81-93.
3. Nishman R, Guinn D, Jones R. Epidural analgesia provides
more pain relief in labour than opioids, with no increase in cesarean section rate or adverse neonatal outcomes – meta-analysis.
Evidence-based Obstetrics and Gynecology 2003; 5(1):10-11.
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
229
38 B DISCUSSION
This patient has pityriasis rosea, a common skin condition seen in adults and children. It peaks in incidence between 20 and 29 years of age without gender preference. The exact etiology is unknown, but a
number of factors including clustering of outbreaks
and a prodromal illness (symptoms consistent with a
viral upper respiratory infection) in two thirds of
people suggest an infectious etiology. No specific tests
confirm the diagnosis that is made on a clinical basis.
The initial lesion, called the herald patch, is usually
on the trunk and measures 2-10 cm in diameter. It is
ovoid, slightly raised and erythematous, often with a
bit of scale along the outer margin. The differential
diagnosis at this point includes eczema. The herald
patch is followed in a few days or weeks by the
development of many more smaller lesions, also on
the trunk, although the proximal extremities may also
be involved. These smaller lesions are 5-10 mm in
size, are also raised and may be erythematous or
salmon-colored. They may also have some scale at
the margins like the herald patch. The differential
diagnosis at this stage includes nummular eczema, guttate psoriasis, secondary syphilis and tinea corporis.
The distribution of these lesions is generally along the
skin lines (Langer’s lines), giving the typical Christmas
tree appearance on the back. Generally, patients have
no systemic symptoms, although one quarter of patients may experience some pruritus.
Atypical presentations of pityriasis rosea include an
inverse form (involvement of extremities with sparing of trunk), localized form and gigantean form
(larger lesions but fewer in number). Children may
present with lesions limited to the face and scalp or
may have lesions that are folliculopapular, pustular,
vesicular, urticarial or purpuric. There are also cases
where no herald patch is identified.
The lesions typically remain for 5 to 8 weeks. Eighty
percent of patients will have cleared the lesions by 8
weeks. For this reason, treatment is not necessary
and the patient should be reassured. When the rash
is pruritic, oral antihistamines, topical steroids (medium potency) and antipruritic lotions (PrameGel®,
Sarna®, Prax®) may be helpful. Erythromycin 250
mg 4 times daily for 14 days was shown in one study
to reduce the severity and duration of the rash. (Rash
resolved in 73 percent of the test group by 6 weeks
compared to no resolution in patients receiving a
230
placebo.) This may be related to erythromycin’s antiinflammatory effects. Ultraviolet radiation (natural
or artificial) has been found to result in some initial
improvement in the lesions but ultimately has no
overall impact on the severity of the lesions or any
itching, if present.
References:
1. Chuh A, Chan H, Zawar V. Pityriasis rosea – evidence for and
against an infectious etiology. Epidemiol Infect 2004; 132(3):381390.
2. Goldstein AO, Goldstein BG. Pityriasis rosea. In: Rose BD, ed,
UpToDate. Wellesley, MA: UpToDate, 2003.
3. Stulberg DL, Wolfrey J. Pityriasis rosea. Am Fam Physician
2004, 69(1):87-92.
39 D DISCUSSION
Modafinil (Provigil®) was approved by the U.S. Food
and Drug Administration (FDA) in 1999 for the
treatment of daytime sleepiness secondary to narcolepsy. Recently, modafinil was approved for the treatment of excessive sleepiness from shift-work sleep
disorder and excessive sleepiness from obstructive
sleep apnea/hypopnea syndrome. The mechanism of
action of modafinil is not clear, but it appears to act
on the hypothalamus that is involved in maintaining
normal sleep and wake cycles.
Shift-work sleep disorder is a circadian-rhythm disturbance resulting from a change in the relationship
between the body’s internal biological clock and the
sleep-wake cycle resulting from shift work. The
suprachiasmatic nucleus of the hypothalamus appears
to function as the body’s biological clock. The severity of symptoms of shift-work sleep disorder depend upon the frequency of shift changes, the schedule during nights of work and daytime obligations
that interfere with the worker’s ability to sleep during the day. Nonpharmacological treatments for shiftwork sleep disorder include
• Maintenance of the same schedule for an entire
week
• Rotation schedule of day shift to evening shift
to night shift
• If unable to maintain a daytime sleep schedule
(when working nights) for the entire amount of
sleep needed, use of a biphasic sleep schedule
with 4-6 hour of nap in the morning after work
followed by 2-3 hours of nap in the afternoon
before returning to work.
For the treatment of excessive sleepiness, the dose of
modafinil is 200 mg given as a single dose in the
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
morning for patients with obstructive sleep apnea
and narcolepsy and 200 mg taken 1 hour before
work for patients with shift-work sleep disorder. In
clinical trials, the dose has been increased to 400 mg
daily for patients not responding adequately to a
lower dose. Modafinil is not an amphetamine, so it
does not have the cardiovascular side effects associated with amphetamines. Headache, nausea, anxiety,
nervousness and insomnia are the most frequently
reported side effects. In vitro, modafinil induces hepatic CYP3A4 enzyme that might decrease serum
concentrations of oral contraceptives. Conversely,
modafinil is a reversible inhibitor of CYP2C19 that
can increase the serum concentrations of benzodiazepines, beta-blockers and phenytoin (generic,
Dilantin®). Modafinil is pregnancy category C (safety
unknown; no human or animal studies show an adverse effect). It is a category IV drug (limited dependence liability)
In clinical trials for the treatment of obstructive sleep
apnea/hypopnea syndrome with modafinil, up to 70
percent of patients experienced a significant improvement of sleepiness symptoms. No controlled trials of
modafinil for use in patients with shift-work-related
disorder have been published.
References:
1. Consens FB, Chervin RD. Sleep disorders. In: Goetz CG,
Textbook of Clinical Neurology. 2nd ed. Philadelphia: WB
Saunders Co., 2003:1207-1224.
2. New indications for modafinil. Med Lett Drugs Ther 2004;
46(1181):34-35.
3. Reid KJ, Change AM, Zee PC. Circadian rhythm sleep disorders. Med Clin North Am 2004; 88(3):631-651.
40 C DISCUSSION
Periodic fever, aphthous stomatitis, pharyngitis and
cervical adenitis (PFAPA) syndrome was first recognized in 1987. Affected individuals present with recurring high fevers (40-40.6ºC) associated with aphthous oral ulcers (70 percent), cervical lymphadenopathy (88 percent) and pharyngitis (72 percent). It
is almost always seen in children under the age of 5
years. Symptoms are present for 3-6 days and then
spontaneously resolve. Events occur in cycles with
intervals of 2-9 weeks. Although the patients may
experience a mild leukocytosis and an elevation in
the sedimentation rate, no one lab test is specifically
associated with this disorder. The etiology of this
syndrome has not been identified. Although these
attacks are self-limited, 1 to 2 doses of oral pred-
nisone (1-2 mg/kg) seem to reduce the severity of
symptoms. Children are clinically well between episodes. Although prophylactic tonsillectomy has been
proposed as one treatment, the lack of an identifiable infectious etiology and lack of controlled trials
to evaluate this treatment has not supported this intervention. Usually these episodes will resolve after a
few years with no sequelae.
PFAPA is one of several causes of periodic fever in
children. Other causes include hereditary disorders
such as familial Mediterranean fever (FMF), hyperimmunoglobulin D periodic fever syndrome, TNF
receptor-1-associated syndromes (TRAPS) and systemic disorders like juvenile rheumatoid arthritis and
cyclic neutropenia.
In FMF, periodic fevers are associated with serositis
(arthritis, pleuritis and abdominal pain), an erysipelas-like skin rash, myalgias and the development
of amyloidosis in one third to one half of the patients. The disorder is thought to be due to complement C5a inhibitor disorder causing a complementmediated inflammatory process. Treatment consists
of prophylactic colchicine (0.02-0.03 mg/kg/24 hr,
to a maximum of 2 mg in 24 hours), used to prevent attacks. Colchicine not only prevents the development of fevers and symptoms but also reduces
the development of amyloidosis. The hyperimmunoglobulin D periodic fever syndrome presents with a
periodic fever associated with a rash, arthritis and
diarrhea. Symptoms often occur before the age of 1
year. The syndrome is associated with elevated levels
of IgD and, in some cases, IgA. No effective treatment currently exists, although corticosteroids may
help reduce symptoms. Cyclic neutropenia presents
with similar symptoms to PFAPA but is heralded by
neutropenia during the cyclic attacks. Sinusitis and
otitis media also may occur during attacks. This disorder is felt to be due to a defect in stem cell development. Although the neutrophil count recovers on
its own, any bacterial infectious noted during an
attack should be treated promptly. Juvenile rheumatoid arthritis is often accompanied by fever, but fevers often last longer than 6 days. The fevers are also
accompanied by arthritis and may be accompanied
by one or all of the following: erythematous rash,
generalized lymph node enlargement, hepatomegaly
or splenomegaly, or serositis.
References
1. Cazeneuve C, Genevieve D, Amselem S, et al. MEFV gene
analysis in PFAPA. J Pediatr 2003; 143(1):140-141.
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
231
2. Chesney PJ. Cervical lymphadenitis and neck infections. In:
Long SS, et al., eds, Principles and Practice of Pediatric Infectious
Diseases. 2nd ed. New York: Churchill Livingstone, 2003:170.
3. Gedalia A. Familial Mediterranean fever. In: Behrman RE, et
al., eds, Nelson Textbook of Pediatrics. 17th ed. Philadelphia: WB
Saunders Co., 2004:821-822.
4. Sadowitz PD, Amanullah S, Souid AK. Hematologic emergencies in the pediatric emergency room. Emerg Med Clin North
Am 2002; 20(1):177-198, vii.
5. Schneider R, Passo MH. Juvenile rheumatoid arthritis. Rheum
Dis Clin North Am 2002; 28(3):503-530.
41 D DISCUSSION
The patient described in the clinical scenario has a
subungual exostosis, a bony outgrowth of the tuft of
the distal phalanx. (See x-ray images of a similar
lesion of the toe.) This benign tumor probably begins as a fibrous growth that is replaced by cartilage
that eventually ossifies. The dorsal-medial hallux
(metatarsophalangeal joint) is the most common site,
although finger lesions are reported. This reactive
growth may begin as a response to minor trauma
but the exact etiology is uncertain. It is seen most
commonly in children and young adults with most
cases in the second or third decade of life.
(Reproduced from theFoot.org)
Other benign tumors such as pyogenic granulomas
and warts may present in a fashion similar to exostosis. However, serious conditions such as an osteochondrosarcoma are also part of the differential diagnosis, so indefinite observation is not advised. Definitive diagnosis requires biopsy performed after
doing an x-ray of the involved finger to determine
the bone anatomy. Radiologic imagining is also important look for signs of a subungual squamous cell
carcinoma that can present in a similar fashion as
232
subungual exostosis. In the case of a subungual squamous cell carcinoma, the x-ray might show evidence of bony destruction that would imply bony
invasion. This fact would be vital information both
for staging of the tumor and planning the definitive
therapy. The only effective treatment for subungual
exostosis is complete surgical excision.
Terbinafine (Lamisil®) is approved for treatment of
onychomycosis but does not have a role in the treatment of exostosis. Likewise, imiquimod (Aldara®) is
FDA-approved for the treatment of genital warts
and is used off-label for the treatment of other types
of warts, superficial basal cell carcinomas and lentigo
maligna melanoma. It has not been studied for the
treatment of exostosis.
References:
1. Davis DA, Cohen PR. Subungual exostosis: Case report and
review of the literature. Pediatr Dermatol 1996; 13:212-318.
2. Ilyas W, Geskin L, Joseph AK, et al. Subungual exostosis of the
third toe. J Am Acad Dermatol 2001; 45:S200-S201.
3. Letts M, Davidson D, Nizalik E. Subungual exostosis: diagnosis
and treatment. J Trauma 1998; 44:346-349.
42 B DISCUSSION
43 D Peripheral vascular disease (PVD) affects 810 million people in the United States. Claudication, defined as pain induced by walking (primarily
involving the calves) and relieved by rest, affects 1540 percent of patients with PVD. Men and women
are equally affected. Prevalence increases with age
with 20 percent of patients >70 years of age affected. Patients with PVD, regardless whether symptomatic, have an increased all-cause mortality rate.
Patients with PVD have the same increased risk of
death from cardiovascular disease as patients with a
past history of coronary or cerebrovascular disease
even if they do not personally have a past history of
myocardial infarction or stroke. Symptomatic PVD
is associated with a decreased ability to perform normal daily activities. Like diabetes mellitus, the National Cholesterol Education Program Adult Treatment Panel III identifies PVD as a risk equivalent to
established coronary artery disease for future coronary events.
As PVD is caused by atherosclerotic disease involving the peripheral vessels, initial medical treatment
involves modification of risk factors (see Table 2)
followed by pharmacologic intervention and exercise training.
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
Table 2 – Risk-Factor Modification for Persons with Peripheral Vascular Disease
Risk Factor
Goal
Effects of Modification
Smoking
Cessation
Slows progression to critical leg ischemia; lowers amputation rate; unknown whether
severity of claudication reduced
Hyperlipidemia
LDL <100 mg/dL
Can result in regression of femoral atherosclerosis; may lower rate of developing or
worsening claudication
Hyperglycemia
Hemoglobin A1c <7.0%
Slows progression of microvascular complications but does not have an effect on risk
of PVD
Hypertension
<130/85
No data regarding alteration in progression or risk of claudication; does decrease
coronary and cerebrovascular risk
Antiplatelet therapy, primarily aspirin, has been found
to reduce risk of nonfatal myocardial infarction, ischemic stroke and death from other vascular causes
in patients with cardiovascular disease. Aspirin (81325 mg/day) is recommended by the American College of Chest Physicians for patients with PVD.
However, the Food and Drug Administration expert
panel does not feel that there is adequate evidence
to approve labeling for this. There is evidence that
aspirin may reduce the need for subsequent surgery
for PVD and that it does improve graft patency after
surgery. Ticlopidine (generic, Ticlid®) may reduce
the need for vascular surgery and decrease the severity of claudication, but hematologic concerns (thrombocytopenia, neutropenia, thrombotic thrombocytopenic purpura) greatly limit its use. Clopidogrel
(Plavix®) is a similar drug but does not have the
hematologic concerns. It is indicated for the secondary prevention of atherosclerotic events in patients
with PVD. Pentoxifylline (generic, Trental®) has
antiplatelet effects and improves deformability of red
and white cells. While approved for the treatment of
claudication, studies reveal that its benefits are minimal. Cilostazol (Pletal®) suppresses platelet aggregation and is a vasodilator. It improves pain-free and
maximal walking distance in patients with PVD.
Benefit with this medication may be seen as early as
4 weeks after initiation of treatment.
Exercise training has been found to be of benefit to
patients with PVD, not only for the PVD itself, but
it also is beneficial in the management of comorbid
conditions (e.g., diabetes mellitus, hypertension, hyperlipidemia). In various studies exercise training has
been shown to improve pain-free walking time,
maximal walking time and ability to do routine daily
activities. Various potential mechanisms for this improvement have been proposed:
• Formation of collateral blood vessels and increased
blood flow
• Stimulation of endothelial-dependent vasodilatation
• Improved oxygen extraction from skeletal muscle
• Attenuation of inflammatory response that results
from ischemia
Patients undertaking an exercise training program
for PVD should be evaluated for their appropriateness to safely exercise. The recommended exercise
program consists of walking on a treadmill or a track.
The initial speed and grade of the treadmill should
be such that the patient develops symptoms of claudication within 3 to 5 minutes. The patient should
be instructed to continue walking until the claudication is of moderate severity. Once that point is
reached, the patient should rest to allow the symptoms to subside. This pattern (exercise-rest-exercise)
should be repeated during each session. Usually the
first session will have a duration of 35 minutes. This
amount of time is then increased by 5 minutes per
session until a total of 50 minutes is attained. Sessions should occur 3 to 5 times per week. Exercise
training such as this has been found to provide improvement in walking time over that seen with
antiplatelet therapy, or cilostazol therapy, alone. Exercise training can also augment the benefits seen
with angioplasty, bypass or pharmacologic therapy.
Improvement can be expected in 2 months. No evidence suggests that the patient “go home and walk”
is of any benefit. Exercise can be combined with
surgical intervention (bypass surgery or angioplasty)
or pharmacologic therapy. No evidence suggests that
exercise training will prevent the development of
claudication in asymptomatic patients with PVD.
References:
1. Hiatt WR. Medical treatment of peripheral arterial disease and
claudication. N Engl J Med 2001; 344(21):1608-1621.
2. Moeller ER. Medical management of claudication. In: Rose
BD, ed, UpToDate. Wellesley, MA: UpToDate, 2003.
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
233
3. Stewart KJ, Hiatt WR, Regensteiner JG, et al. Exercise training
for claudication. N Engl J Med 2002; 347(24):1941-1951.
44 A DISCUSSION
The patient described in this question has alopecia
areata. Affecting up to 0.2 percent of the population, this condition usually occurs in patients under
the age of 40 years with the majority of individuals
having their first episode prior to the age of 20
years. Patients with this type of hair loss typically
experience a sudden loss of hair in well-defined areas measuring up to 4 cm in diameter from any hairgrowing area of skin. The hairless areas usually involve the scalp and have well-demarcated edges.
When the scalp is involved, short stubs of hair may
appear on the surface but break off easily so the skin
remains smooth. Patients sometimes report itching,
tingling, burning or pain at the sites of hair loss.
Abnormalities of the nails, principally pitting but
also longitudinal striations, may develop prior to or
simultaneously with the appearance of alopecia areata.
Variations of the condition include alopecia totalis
(100 percent loss of scalp hair) and alopecia universalis
(100 percent loss of scalp and body hair).
Alopecia areata is an autoimmune disease. It is often
associated with other autoimmune conditions including autoimmune thyroiditis, vitiligo, systemic lupus
erythematosus, pernicious anemia and ulcerative colitis. Histologically, a lymphocytic infiltrate is found
around the hair bulbs. These are T-lymphocytes that
appear to down-regulate the proliferation of epithelial cells.
Anthralin (generic, Anthranol®) treatment (0.5 percent, topically) has been reported to result in improvement in approximately 25 percent of treated
patients. Combination anthralin and minoxidil treatment appears more effective than either drug used
alone.
The most effective treatment for more severe cases
is the use of contact sensitizers such as squaric acid
dibutyl ester (SADBE) and diphenylcyclopropenone
(DPCP). These agents appear to work as topical
immunomodulating agents.
References:
1. Habif TP. Hair diseases. Habif TP, ed, Clinical Dermatology.
4th ed. Philadelphia: Mosby, 2004:855-858.
2. Springer K, Brown M, Stulberg DL. Common hair loss disorders. Am Fam Physician 2003; 68:93-102, 107-108.
3. Thiedke CC. Alopecia in women. Am Fam Physician 2003;
67:1007-1014, 1017-1018.
45 B DISCUSSION
Tiotropium bromide inhalation powder (Spiriva
HandiHaler®) is the first long-acting (once daily)
inhaled anticholinergic medication approved by the
U.S. Food and Drug Administration (FDA) for use
in the treatment of chronic obstructive pulmonary
disease (COPD). Ipratropium bromide (generic,
Atrovent®) is a shorter acting anticholinergic medication for COPD that is used 4 times daily.
When hair loss is limited (<25 percent of scalp hair),
the prognosis for spontaneous resolution is excellent.
In these cases, regrowth of hair usually occurs within
1 to 3 months. Frequently, affective individuals will
have cycles of hair regrowth followed by hair loss in
the same or other areas.
In airway smooth muscle cells and mucous glands,
tiotropium binds to M1, M2 and M3 muscarinic receptors blocking the action of acetylcholine. Stimulation by acetylcholine of M1 and M3 receptors causes
bronchoconstriction. Tiotropium blocks these receptors for up to 24 hours, causing bronchodilation. M2
receptors, when stimulated, inhibit the release of acetylcholine. Although tiotropium blocks these receptors, that theoretically would increase bronchoconstriction, its action on M2 receptors is short-lived.
Commonly used therapies include both intralesional
injection and topical application of corticosteroids.
Antibiotics are not useful. High-dose systemic prednisone therapy can be effective but treatment usually
requires a 6-week burst and tapering. Minoxidil
(Rogaine®) solution (5 percent) applied topically
twice daily has been reported to result in hair regrowth in 20 to 45 percent of cases. However, initial hair regrowth may take 3 months of treatment.
Sustained treatment may be necessary, since minoxidil
does not change the natural course of the disease.
The recommended dose of tiotropium is 18 mcg
given by placing a powder-containing capsule in an
inhalation device that pierces the capsule to release
the powder. The medication is inhaled (2 inhalations) with the lips sealed tightly around the inhalation device’s mouthpiece. Tiotropium is poorly absorbed. Its action is topical beginning approximately
30 minutes after use, peaking in 3 hours and lasting
for more than 24 hours. With regular use, the bronchodilator effect of tiotropium reaches its maximum
steady state after approximately 8 days of use.
234
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
In clinical trials, tiotropium improved baseline FEV1
by an average of 22 percent measured 3 hours after
use and maintained an average improvement of 12
percent above baseline measured just prior to the
next day’s dose. In a trial comparing tiotropium
(daily) to ipratropium (4 times daily) for patients
with an exacerbation of COPD, tiotropium led to a
greater improvement in FEV1 (46 percent compared
to 35 percent). In a trials comparing tiotropium to
the long-acting beta2-agonist salmeterol (Serevent®),
tiotropium had a more sustained action. The most
common side effect is dry mouth. Other side effects
include tachycardia, urinary retention, blurred vision
and narrow-angle glaucoma.
Tiotropium is not approved as a treatment for asthma
and has not been studied in this potential role.
References:
1. Brusasco V, Hodder R, Miravitlles M, et al. Health outcomes
following treatment for 6 months with once daily tiotropium
compared with twice daily salmeterol in patients with COPD.
Thorax 2003; 58(5):399-404.
2. Tiotropium (Spiriva) for COPD. Med Lett Drug Ther 2004,
46(1183):41-42.
3. Vincken W, van Noord JA, Greefhorst AP, et al. Improved
health outcomes in patients with COPD during one year’s treatment with tiotropium. Eur Respir J 2002; 19:209-216.
46 B DISCUSSION
This patient demonstrates the typical signs and symptoms of nasal vestibulitis. This relatively common
condition of adults is a chronic inflammation of the
nasal vestibule. This area is laden with hair follicles,
and inflammation in this area provides an easy portal
of entry for bacteria. Staphylococcus aureus is the usual
pathogen associated with nasal vestibulitis. Any conditions that alter the normal mucosal barrier (e.g.,
frequent or recurrent blowing, picking or rubbing
of the nose) can predispose patients to this condition. Affected patients generally complain of a tender nose, sometimes associated with swelling. They
may report recurrent crusting of the vestibular area.
Physical examination usually reveals mild erythema
of the vestibular skin, with some small pustules and
occasionally a furuncle. Painful fissures may be noted
and even gentle manipulation of the area during the
exam may cause the patient to wince. Treatment
consists of the application of heat and topical antibiotics. Mupirocin (generic, Bactroban®) cream or ointment applied 3 times per day for 7 to 14 days seems
most cost effective. Alternatively, a course of
antistaphylococcal antibiotics such as dicloxacillin for
the same period of time can be used. In patients
who are suspected of being staphylococcus carriers,
adding rifampin 10 mg/kg twice daily for the last 4
days can help prevent recurrences. If a furuncle is
present, it should be gently incised and drained. It is
recommended the area not be squeezed or manipulated, as this can lead to rare but potentially serious
complications including spread of infection into the
cavernous sinus and other intracranial structures.
Of the other conditions listed, impetigo shares some
similarities but is more common in children, presents more acutely and extends more to the surrounding skin with honey crusted lesions. Nasal papillomata are small, fleshy, benign growths that can
be found around the external nostril. They can be
excised if patients find them troublesome or to be a
cosmetic problem. Acne rosacea also shares some of
the features (nasal sensitivity and pustules) of nasal
vestibulitis. However, it is not confined just to the
nostrils but is more common on the external nose,
sometime extending onto the face. Allergic rhinitis
may predispose a patient to nasal vestibulitis but does
not in itself cause this clinical picture.
References:
1. Ballenger JJ, Snow JB. Acute infections of the nose and face.
In: Ballenger’s Otorhinolaryngology. 15th ed. Baltimore: Williams
& Wilkins, 1996:127.
2. Jackler RK, Kaplan MJ. Ear, nose and throat. In: Tierney LM,
McPhee SJ, Papadakis MA, eds, Current Medical Diagnosis and
Treatment. 42nd ed. New York: Lange Medical Books/McGrawHill, 2003:195.
3. Mickelson SA, Benninger MS. The nose and paranasal sinuses.
In: Noble J, et al., eds, Textbook of Primary Care Medicine. 3rd
ed. St. Louis: Mosby, Inc., 2001:1751.
47 A DISCUSSION
It is important to remember that not all patients
with aneurysmal subarachnoid hemorrhage present
with “the worst headache of my life.” Furthermore,
the computed tomography (CT) brain scan is not
100 percent sensitive for the detection of aneurysmal
subarachnoid hemorrhage, especially when the bleed
is subtle. Features suggestive of a relatively minor
subarachnoid hemorrhage include atypical headache,
such as a headache that suddenly develops in a patient who has never had a significant headache before and reaches maximal intensity in minutes (thunderclap headache), atypical nature of the head pain,
the association with neck stiffness (meningismus), the
presence of an unexplained acute confusional state,
the presence of subhyaloid hemorrhage by fundus-
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
235
copic exam or the association of the bleeding event
with syncope. A negative CT brain scan accompanied by one or more of these features may represent
an opportunity to intervene before the patient experiences a potentially catastrophic outcome.
It is estimated that 25 percent or more of patients
with a major aneurysmal rupture will have at least
one minor event, the so-called warning leak, preceding the major event. Unfortunately, depending
on the study, almost half are misdiagnosed and the
potential for intervention prior to a major hemorrhage is missed. The majority of patients (75 percent
in one study) had the warning leak less than 2 weeks
prior to the major event. In general, patients with
warning leaks had worse outcomes than those without, especially when the interval between the warning leak and the rupture was less than 3 days.
The CT brain scan is roughly 90 to 95 percent
sensitive for detecting subarachnoid blood within the
first 24 hours. However, the finding can be subtle
and absence of subarachnoid blood by CT brain
scan does not rule out its presence. Therefore, if
there is clinical suspicion, a lumber puncture is indicated, as this test is essentially 100 percent sensitive
for the detection of blood in the subarachnoid space
related to aneurysmal rupture. The presence of elevated red blood cells and xanthochromia can persist
for a week or longer, while the sensitivity of CT
brain scan progressively falls within several days of
the bleed. Cerebral angiography remains the gold
standard for confirmation and localization of the cerebral aneurysm or aneurysms. This study not only is
pertinent for identification of the aneurysm, it can
also help to identify the most likely source of the
bleeding if multiple aneurysms are seen. Noninvasive
screening, especially in patients who are initially suboptimal surgical candidates, can include magnetic
resonance angiography (MRA) or spiral CT angiography. Not all cerebral aneurysms are identified on
the initial cerebral arteriogram, usually because of
vasospasm or the effects of edema. In that case, the
angiogram will need to be repeated within a few
days.
References:
1. Eldow JA, Caplan LR. Avoiding pitfalls in the diagnosis of
subarachnoid hemorrhage. N Engl J Med 2000; 342(1):29-36.
2. Mayer PL, Awad IA, Todor R, et al. Misdiagnosis of symptomatic cerebral aneurysm. Prevalence and correlation with outcome
at four institutions. Stroke 1996; 27(9):1558-1563.
236
3. Okahara M, Kiyosue H, Yamashita M, et al. Diagnostic accuracy of magnetic resonance angiography for cerebral aneurysms in
correlation with 3D-digital subtraction angiographic images: a study
of 133 aneurysms. Stroke 2002; 33(7):1803-1808
4. Reijneveld JC, Wermer M, Boonman Z, et al. Acute confusional state as a presenting feature in aneurysmal subarachnoid
hemorrhage: frequency and characteristics. J Neurol 2000;
247(2):112-116.
5. Schievink WI. Intracranial aneurysms. N Engl J Med 1997;
336(1):28-40.
48 D DISCUSSSION
It is estimated that 1 million burn injuries occur in
the United States annually, or about 4.2/100,000.
Approximately 45,000 hospitalizations and 4,500 fire
and burn deaths are recorded per year. Burns are
one of the leading causes of accidental death in the
United States.
In the past burns, were traditionally classified as first
degree (superficial, involving the epidermis), second
degree (partial thickness, extending into the superficial dermis) and third degree (full thickness, extending into the subcutaneous tissues). The depth of the
burn is presently designated as superficial, superficial
partial thickness, deep partial thickness and full thickness burn. (See Table 3.) Children <5 years of age
and adults >55 years of age are more likely to suffer
deeper burns, as their skin is generally thinner.
Some authorities include another category of burns,
described as fourth degree, that involve full thickness
of the skin and subcutaneous tissue plus damage to
underlying fascia, muscle, bones and/or other tissues.
The majority of burns are managed in the outpatient
setting by primary care physicians. Criteria to help
determine which patients require inpatient treatment
or referral to a burn center have been established by
the American Burn Association and can be found at
http://www.emedhome.com/resources/pdfdatabase/
57.pdf. This patient has a superficial partial-thickness
burn involving only a small area, so outpatient treatment is adequate.
A systematic approach to the treatment of burns can
be remembered by thinking of six Cs – clothing,
cooling, cleaning, chemoprophylaxis, covering and
comforting (pain management).
Clothing – Clothing that is hot, burned or has been
exposed to chemicals should be removed if this can
be done easily.
Cooling – Cooling of the tissue should be undertaken for several hours as this can decrease burn
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
Table 3 – Burn Classification Based on Depth
Classification
Appearance
Pain
Healing/Scarring
Comments
Superficial
(first degree)
Red and dry;
blanches with pressure
Painful
3-6 days; without
scarring
Ultraviolet radiation
(sunburn)
Superficial,
partial-thickness
(second degree)
Blisters; blanches
with pressure; red,
moist and weeping
Painful to air and
temperature
7-20 days; usually
without scarring,
although pigmentary
changes may occur
Scald or short-flash burns
Deep, partial
thickness
(second degree)
Blisters; wet or waxy dry;
does not blanch; variable
color (patchy to cheesy
white to red)
Sensation of pressure
only
>21 days; severe risk
of scar and
contracture
Scald (spill), flame, oil and
grease injuries; may be
difficult to differentiate
from full thickness
Full thickness
(third degree)
Variable color (waxy
white to leathery gray to
black and charred); does
not blanch
Sensation of deep
pressure only
Will not heal if
>2% of total body
surface area; very
severe risk of
contracture
Scald (immersion), flame,
oil, grease, chemical,
steam, high-voltage
electricity; likely requires
referral; may require skin
grafting
Adapted from Morgan ED, Bledsoe SC, Barker J. Ambulatory management of burns. Am Fam Physician 2000; 62:2015-2026.
pain. Cool (53.6ºF) sterile saline-soaked gauze should
be applied; ice should be avoided.
Cleaning – Current recommendations are to clean
with mild soap and water. The use of disinfectants
(e.g., povidone iodine [Betadine®], chlorhexidine
gluconate [Hibiclens®]) should be avoided as they
may actually inhibit the healing process. Whirlpool
debridement may be necessary in some cases. Removal of ruptured blisters is recommended. It is not
recommended to needle-aspirate blisters as this increases the risk of infection. It is generally suggested
that blisters containing cloudy fluid or over areas
where they are likely to rupture should be unroofed.
Chemoprophylaxis – Any burns deeper than superficial should have topical antimicrobial prophylaxis. Typically, silver sulfadiazine cream (Silvadene®)
is used, although is should not be used in pregnant
women, newborns or women nursing infants less
than 2 months of age. Bacitracin is a low-cost alternative that is especially useful around mucous membranes. Bismuth-impregnated petroleum gauze and
Biobrane dressings are also appropriate. Tetanus immunization should be updated.
Covering – Superficial burns to not require covering. Deeper burns should be covered with fine-mesh
gauze (e.g., Telfa®) that is held in place with a lightly
applied gauze wrap or a tubular net bandage.
Comfort – Generally, analgesics (acetaminophen, nonsteroidal antiinflammatory drugs) should be given
around the clock. Stronger narcotic medication may be
necessary, especially in preparation for dressing changes.
References:
1. Morgan ED, Bledsoe SC, Barker J. Ambulatory management of
burns. Am Fam Physician 2000; 62:2015-2026.
2. Moss LS. Outpatient management of the burn patient. Crit
Care Nurs Clin North Am 2004; 16(1):109-117.
3. Purdue GF, Hunt JL, Burris AM. Pediatric burn care. CPEM
2002; 3(1):76-82.
49 C DISCUSSION
50 C As the population of the United States ages,
51 B the incidence of both Alzheimer’s-type dementia and vascular dementia is increasing. As a result, increasing research is being conducted to develop new drugs that improve cognitive function
and/or slow progression of cognitive decline in individuals with dementia. The first class of agents
demonstrated to have a significant impact on both
Alzheimer’s disease and vascular dementia were the
anticholinesterase inhibitors. These agents include
donepezil (Aricept®), rivastigmine (Exelon®) and
galantamine (Reminyl®). These medications inhibit
the enzyme cholinesterase, thereby increasing acetylcholine concentrations at the neuronal synapses of
cholinergic neurons. These neurons are vital in
memory and in overall cognitive function (judgment, behavior, spatial relationships). In both
Alzheimer’s disease and vascular dementia, cholinergic neurons may decline in function. In Alzheimer’s
disease, the neurons begin to malfunction due to the
accumulation of beta-amyloid plaques, whereas in
vascular dementia, cholinergic neurons are damaged
by ischemic injury. The result in both forms of de-
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
237
mentia is a loss of cholinergic neurons and impaired
function in the remaining neurons. Anticholinesterase inhibitors improve the function of the remaining neurons, leading to improved memory, decreased
agitation and improvement in judgment. They are
not disease modifying. Typically, an anticholinesterase inhibitor is started and continued for approximately 2 months, at which time a review should be
done with the family for their assessment of symptomatic improvement. Side effects of these medications include anorexia, nausea, weight loss, abdominal discomfort, diarrhea, dizziness and headache. In
studies examining the benefit of cholinesterase inhibitors, improvements have been small but significant. In a meta-analysis of several trials, anticholinesterase inhibitors improved scoring on instrumental activity of daily living (IADL) scales by 0.09 standard deviations. In another meta-analysis comparing
cholinesterase inhibiters to placebo, improvement was
equivalent to preventing 2 months of decline over
the course of 1 year in the typical patient with
Alzheimer’s-type dementia.
Memantine (Namenda®) was approved by the United
States Food and Drug Administration (FDA) in 2004
for the treatment of Alzheimer’s-type dementia. In
clinical trials, memantine also improved clinical findings in patients with vascular dementia, particularly
those with small-vessel disease. Memantine is an Nmethyl-D-aspartate (NMDA) receptor antagonist. In
Alzheimer’s-type dementia, NMDA receptors appear
to become overstimulated by the action of glutamate,
an amino acid that appears to be involved in the
pathogenesis of Alzheimer’s dementia. Memantine
blocks overstimulation of neurons by glutamate and
blocks the abnormal influx of calcium, which is
thought to be neurotoxic. In this role, memantine
may be a disease-modifying agent. Research is ongoing regarding the neuroprotective actions of
memantine. When therapy with memantine is initiated, agitation may increase because of improved
neuronal transmission. Memantine may be used as
mono-therapy, or in combination with the anticholinesterase inhibitors. Memantine has been shown to
improve cognition in both types of dementia by
improving neuronal function and by slowing neuronal death. A study evaluating the use of memantine
and donepezil showed that combination therapy was
more effective than use of either agent alone.
Memantine has less frequent and less intensive side
238
effects than cholinesterase inhibitors. Its most frequent
side effects are headache, dizziness and confusion.
The calcium channel blockers nimodipine (Nimotop®) and nicardipine (generic, Cardene®) have been
shown to improve cognitive function in patients with
vascular dementia. These agents improve cerebral
blood flow to areas of ischemia, especially areas of
small-vessel disease. Like NMDA antagonists, these
calcium channel blockers may be neuroprotective,
preventing neuronal death by preventing abnormal
influx of calcium into neurons. However, these calcium channel blockers have not been demonstrated
to improve cognition in patients with Alzheimer’s
disease.
The herbal ginkgo biloba has been promoted for
many years for the treatment of various forms of
dementia and cognitive decline. It appears to have
antioxidant and antiplatelet actions that may have a
beneficial effect on various forms of dementia. To
date, studies evaluating this drug for Alzheimer’s disease and vascular dementia have been small and results have not been consistent. Currently, the NIH
is conducting a large patient study on ginkgo biloba
in various forms of dementia.
References:
1. Bonner LT, Peskind ER. Pharmacologic treatments of dementia. Med Clin North Am 2002; 86(3):657-674.
2. Hake AM, Farlow MR. On the horizon: pathways for drug
development in Alzheimer’s disease. Clin Geriatr Med 2004;
20(1):141-152.
3. Press D, Alexander M. Treatment of dementia. In: Rose BD,
ed, UpToDate. Wellesley, MA: UpToDate, 2004.
4. Román GC. Vascular dementia revisited: diagnosis, pathogenesis, treatment, and prevention. Med Clin North Am 2002;
86(3):477-499.
5. Sierpina VS, Wollschlaeger B, Blumenthal M. Ginkgo biloba.
Am Fam Physician 2003; 68(5):923-926.
6. Schneider LS. Cholinesterase inhibitors for vascular dementia?
Lancet Neurol 2003; 2(11):658-659.
7. Wilcock GK. Memantine for the treatment of dementia. Lancet Neurol 2003; 2(8):503-505.
8. Wilkinson D, Doody R, Helme R, et al. Donepezil in vascular
dementia: a randomized, placebo-controlled study. Neurology
2003; 61(4):479-486.
52 A DISCUSSION
53 B It is estimated that 1-6/1,000 newborns has
54 D hearing loss. Neonatal hearing screening has
55 D received increasing attention due to the
development of relatively inexpensive screening tests
and the recognition that treating hearing problems
before 6 months of age can prevent language delays.
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
The two screening tests most commonly used are
the otoacoustic emission (OAE) and the auditory
brain-stem response (ABR) tests. Both are used as
either primary or secondary screening tests, and both
are effective in evaluating the neonate. Both are tests
of auditory pathways rather than true tests of hearing. Normal hearing can not be definitively determined until a reliable audiogram is done. Therefore,
an infant whose parents voice concern about their
child’s hearing should receive further evaluation even
if a newborn screening test was normal.
The OEA test is based on the principle that the
cochlea generates sounds (generated by the outer
hair cells of the inner ear) in response to stimuli. It is
performed by placing a small probe with a sensitive
microphone in the ear canal for stimulus delivery
(clicks and tones) and response detection. The responsive cochlear sounds, when present, can be detected, suggesting normal hearing. Conversely, absence of the responsive cochlear sounds suggests hearing loss. The OEA test is usually abnormal if hearing
loss is evident at 30 db or greater. This test is relatively inexpensive to perform but does not clearly
define the cause or severity of the hearing loss. It is
effective in identifying inner and middle ear abnormalities but not problems related to transmission of
sound from the eighth nerve to the brainstem. While
there can be motion artifact, infants being tested do
not need to be sleeping or sedated.
ABR testing involves detecting nerve, brain stem
and brain wave activity in response to an auditory
stimulus. It is performed using ear phones and electrodes placed on the head to detect auditory stimuli.
The ABR is usually broken down into waveforms
labeled I-VII as follows: Wave I comes from the
distal 8th nerve; wave II, from the proximal portion
of the 8th nerve; wave III, from neurons of the
cochlear nucleus; wave IV, from the neurons of the
superior olivary complex; wave V, from the lateral
lemniscus and inferior colliculus; and waves VI and
VII, mainly from the inferior colliculus of the brain.
The ABR is a little more difficult to perform, as the
infant being tested must be quiet, asleep or sedated.
Although the ABR can be used as a primary screening test, it is often used in follow-up for an abnormal OEA test. ABR testing can provide information
about the location of hearing pathology and may be
able to detect hearing loss below the threshold of
the OEA test, if a hearing impairment is suggested
despite a normal OEA examination.
Although either test may be used for screening, falsepositive and false-negatives may occur. For this reason, some facilities recommend using both tests, particularly in high-risk infants, or repeating a single test
for high-risk infants. In addition, both tests are required to make the diagnosis of auditory dyssynchrony
(abnormal or absent ABR and normal OEA). Studies
have been done comparing the costs of ABR, OEA
and a two-step testing program (initial OAE followed
by ABR if OAE is abnormal). While ABR has higher
initial cost, overall cost is the same as OAE and the
two-step test since a lower posthospital discharge referral rate was noted with ABR.
Hearing screening in the newborn is now mandatory for all newborns in 32 states. Previously, only
high-risk infants were screened, but it has been noted
that up to 50 percent of hearing problems in infants
are not related to high-risk conditions. High-risk
conditions include family history of hereditary childhood sensorineural hearing loss, in utero infection,
ear/craniofacial anomalies, birth weight of less than
1,500 g, hyperbilirubinemia requiring exchange transfusion, bacterial meningitis, Apgar score of 0-3 at 1
minute or 0-6 at 5 minutes after birth, respiratory
distress, mechanical ventilation lasting 5 days or
longer, receipt of ototoxic medication (particularly if
for >5days) and stigmata or other findings associated
with a syndrome known to include a sensorineural
or conductive hearing loss.
References:
1. Bush JS. AAP issues screening recommendations to identify
hearing loss in children. Am Fam Physician 2003; 67(11):24092410.
2. Haddad J. Hearing loss. In: Behrman RE, et al., eds, Nelson
Textbook of Pediatrics. 17th ed. Philadelphia: WB Saunders, Co.,
2004:2130-2131.
3. Johnson KC. Audiologic assessment of children with suspected
hearing loss. Otolaryngol Clin North Am 2002; 35(4):711-732.
4. Kenna MA. Neonatal hearing screening. Pediatr Clin North
Am 2003; 50(2):301-313.
Newborn hearing screening: recommendations and rationale. Am
Fam Physician 2001; 64(12):1995-1999.
5. Vohr BR. Comparison of costs and referral rates of 3 universal
newborn hearing screening protocols. J Pediatr 2001; 139(2):238244.
56 C DISCUSSION
57 A The tests listed in this series of questions
58 E assesses the integrity of various components
59 B of the knee – medial and lateral collateral
60 D ligaments, the anterior and posterior cruciate
ligaments, the medial and lateral menisci and the
patella.
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
239
The lateral collateral and medial collateral ligaments
are evaluated using the varus (adduction) stress test
and the valgus (abduction) stress test respectively.
For each test, the examiner stands at the side of the
examination table closest to the knee being examined. Each test is first performed with the knee extended and then with the knee flexed to approximately 30 degrees. For the varus test, the examiner
places one hand on the medial aspect of the knee
and grasps the ankle with the other hand. While
applying a counter force to the medial aspect of the
knee, the lower leg is moved medially (varus stress)
placing stress on the lateral collateral ligament. Pain
or a soft or absent end point indicates rupture of the
lateral collateral ligament. For the valgus test, the
examiner places one hand on the lateral aspect of the
knee and grasps the ankle with the other hand. The
lower leg is abducted (valgus stress) while a counter
force is applied to the lateral aspect of the knee. This
places stress on the medial collateral ligament. If this
maneuver increases or causes pain at or just slightly
above or below the joint line, injury to the medial
collateral ligament should be suspected.
Varus Stress Test of the
Lateral Collateral Ligament
(All knee examination photographs are courtesy of Nicholas Institute of Sports Medicine and Athletic Trauma, New York, NY.)
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Valgus Stress Test of the
Medial Collateral Ligament
McMurray Test of the Lateral Meniscus
McMurray Test of the Medial Meniscus
The medial meniscus and lateral meniscus are tested
using the McMurray test. This test is performed with
the leg initially fully extended. The examiner holds
the ankle with one hand and then flexes both the
knee and the hip so that the hip is at 90 degrees and
the knee is at an acute angle with the back of the
heel approaching the buttock (almost maximum flexion of the knee). The examiner’s other hand is placed
over the knee so that the fingers are over the medical joint line and the thumb is over the lateral joint
line. To test the lateral meniscus, the tibia is rotated
internally then the knee is extended from the acute
angle to 90 degrees. A clicking or snapping sensation
or a thud as described by the examiner over the
lateral joint line indicates a tear of the lateral meniscus. To test the medial meniscus, the procedure is
repeated with the tibia placed in external rotation. A
similar sensation as described above over the medial
joint line indicates a tear of the medial meniscus.
Apley’s test assesses the integrity of the menisci and
the collateral ligaments. Consisting of four steps,
Apley’s test is performed with the patient lying prone
with both legs extended and the feet hanging over
the edge of the examination table. The examiner
anchors the patient’s thigh to the examination table
usually by placing his/her knee in the patient’s
popliteal space on the side being tested. (A towel or
pillow may be used for cushioning.) In the first step,
the examiner then grasps the foot and internally rotates the leg while flexing the knee past 90 degrees.
In the second step, the knee is extended and then
flexed to at least 90 degrees while the tibia is both
externally rotated and forced downward toward the
examination table through pressure placed on the
foot (compression). In the third step, the examiner
rapidly rotates the tibia medially and laterally while
applying a distraction force (forcefully lifting the
lower leg by grasping the ankle with both hands).
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
241
Finally, the examiner rapidly internally and externally
rotates the tibia on the femur. Symptoms of pain and
clicking with the Apley’s test suggest either a tear of a
collateral ligament or an injury to a meniscus. Forceful internal rotation of the tibia will stress the lateral
collateral ligament and cause pain if the ligament is
torn or injured. If a clicking sensation is noted when
the tibia is externally rotated with compression, a tear
of the medial meniscus is likely.
Of the two cruciate ligaments, the anterior cruciate
ligament (ACL) is most susceptible to injury. Two
tests – the Lachman test and the drawer test – are
used to evaluate the anterior cruciate ligament. The
Lachman test is more sensitive although it is also
slightly more difficult to perform than is the drawer
test. Performed by an experienced examiner, the
Lachman test can be as sensitive as magnetic resonance imaging (MRI) for detecting a tear of the
anterior cruciate ligament.
The Lachman test is performed with the patient lying supine with the involved knee slightly flexed
(<30 degrees). The examiner stabilizes the femur
with one hand placed around the lower thigh above
the knee with the other hand placed around the
lower leg just below the knee. Next, a posterior
force is applied to the femur while an anterior force
is applied to the tibia. Anterior displacement of the
tibia associated with a sense of a soft or indistinct
endpoint indicates a tear of the anterior cruciate ligament. Loss of the normal slope of the infrapatellar
tendon as the tibia is moved anteriorly also indicates
a tear of the anterior cruciate ligament.
The drawer test is performed with the patient lying
supine and the knee held in 90 degrees flexion. The
patient’s foot on the side being tested is held fixed
to the examination table usually by the examiner
sitting on the forefoot. The examiner’s hands encircle the lower leg just below the knee while ensuring that the hamstring muscles are relaxed. The
hamstring muscles must be relaxed in order to prevent a false-negative test. Anterior and posterior displacement of the tibia on the femur is then assessed.
The counter force to the movement is the patient’s
weight distributed through the femur. Anterior displacement of the tibia >6 mm is consistent with an
injury to the anterior cruciate ligament; however,
injury to the iliotibial band or the deep fibers of the
medial collateral ligament may cause similar findings.
During the drawer test if the tibia appears to be
posteriorly displaced (posterior sag sign) or if the
tibia displaces posteriorly when the examiner pushes
posteriorly on the tibial tubercle, injury to the posterior cruciate ligament should be suspected.
Posterior Drawer Test of the
Posterior Cruciate Ligament
Lachman Test of the
Anterior Cruciate Ligament
A direct blow to the anterior aspect of the knee may
cause a fracture of the patella. Often, the lateral region of the patella is fractured with this type of
injury because the bone is thinnest in this region.
An explosive fracture of the patella may occur if a
powerful, direct blow to the patella is sustained as
the quadriceps muscle is actively contracting. This
type of injury leads to a stellate type of fracture
which is extremely painful and which prevents complete extension of the knee. To test for a fracture of
the patella, Dreyer’s test may be used. The patient
lies supine and attempts to raise the affected lower
extremity with the knee extended. If the patella is
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fractured, any attempt to complete this motion is
painful and often the patient cannot lift the extremity. The action requires contraction of both the hip
flexor muscles and the knee extensor muscles. The
examiner then firmly grasps the thigh with both
hands just above the patella, completely encircling
the thigh. Because the examiner’s grasp of the thigh
prevents the full force of the quadriceps muscle from
being transmitted to the patella, the patient is now
able to lift the extremity with little pain or distress.
If the examiner relaxes the circumferential grasp of
the thigh and the patient again experiences pain with
attempting to raise the extended knee, a fracture of
the patella should be suspected.
References:
1. Calmbach WL, Hutchens M. Evaluation of patients presenting
with knee pain: part I. History, physical examination, radiographs,
and laboratory tests. Am Fam Physician 2003; 68:901-912.
2. Miller RH. Knee injuries. In: Canale ST, ed, Campbell’s Operative Orthopedics. 10th ed. Philadelphia: Mosby, 2003:21652180.
3. Mody EA, Greene JM. Disorders of the knee. In: Noble J,
Greene HL, Levinson W, et al., eds, Noble: Textbook of Primary
Care Medicine. 3rd ed. St. Louis: Mosby, 2001:1198-1206.
61 B
62 C
63 D
64 A
65 E
related
occur.
DISCUSSION
It is estimated that more than 11.5 million
units of blood will be transfused in the U.S.
in 2004. Although the blood supply is the
safest it has been in history, complications
to the administration of blood products still
The most feared immunologic complication is ABO
incompatibility. This occurs in 1 of every 100,000
units of blood transfused resulting in fatal acute
hemolytic reactions in approximately 1 of every
600,000 transfusions (approximately 20-30 deaths per
year in the U.S.). More than 80 percent of ABO
incompatible transfusions result from human clerical
errors; hence, hospitals are required to have a systematic, detailed approach to transfusion safety.
Immunologic reactions to minor red cell antigens
can cause delayed transfusion reactions. These occur
in approximately 1 of every 1,000 transfused units,
are usually mild and often occur several days after
transfusion. Rarely, these reactions can be severe
enough to resemble an ABO incompatibility. Patients with a delayed transfusion reaction will usually
complain of transient dark urine, low-grade fever
and mild back pain. A direct Coombs test that was
negative prior to transfusion will become positive
and the hemoglobin level, after transfusion, fails to
improve as expected. A work-up for the specificity
of the red cell antibody should be performed so that
appropriate cross matching for further treatment can
avoid rechallenging the patient. The most common
antigens involved in delayed transfusion reactions
include Rh e, kell and kidd system antigenic sites.
Today, many hematologists test patients who require
chronic transfusions for minor red cell antigens to
avoid sensitization. The diagnosis of delayed transfusion reaction may be difficult to make if a patient
delays seeking medical attention. The antibody is
produced transiently and may rapidly disappear as
transfused cells are destroyed through immune-mediated hemolysis. A urine hemosiderin stain may stay
positive for up to 2 weeks as intravascular hemolysis-related, iron-laden renal tubular cells are sloughed
into the urine.
Although there will always remain concern regarding microbial transmission from transfusion, recent
technical advances have further lowered this risk.
Nucleic acid testing for human immunodeficiency
virus (HIV), hepatitis C virus, human T-lymphotrophic virus (HTLV) and, most recently, West Nile
virus has reduced the window for transmission to
only a few days thereby decreasing the risk of acquiring one of these infections to 1 out of 1.5 to 2.0
million units transfused. Hepatitis B is not yet
screened by nucleic acid testing. Donor blood is
screened for hepatitis B surface antigen and antibodies to hepatitis B core antigen. The risk of acquiring
hepatitis B infection is 1 out of 250,000 units transfused. Potential transmission of protein prion particles associated with Creutzfeldt-Jakob Disease (Mad
Cow Disease) has raised much concern in the media. There have been a few patients in whom blood
product transmission of CJD was possible, but if
true, this occurrence is extraordinarily rare. Today,
CJD transmission is prevented by eliminating patients who have lived more than 3 months in the
United Kingdom during the last 5 years. No antibody or molecular studies available to screen donors
for CJD. Bacterial transmission, most commonly with
gram-negative bacteria such as Yersinia and
Pseudomonas, occur less than once in 1.1 million
units but gives rise to a severe sepsis syndrome with
a 25 percent mortality.
A relatively common but rarely recognized complication of transfusion is transfusion-related acute pul-
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
243
monary injury (TRAPI). This problem occurs in
approximately 1 in 5,000 transfusions and is characterized by respiratory distress, non-cardiogenic pulmonary edema, hypotension and fever occurring
within 6 hours after transfusion. This clinical presentation is often ascribed to fluid overload, but patients do not respond to diuretics, and mechanical
ventilation is often required (up to 70 percent of
patients). The symptoms usually resolve within 96
hours without sequelae, but the mortality rate is 510 percent. This problem is a neutrophil-mediated
increase in vascular permeability leading to pulmonary edema. In the majority of cases, donor plasma
is found to contain leukocyte antibodies, and all recipients of the affected donor’s blood products are at
increased risk for this syndrome. The blood bank,
therefore, should be notified of suspected TRAPI so
the donor can be tested for antigranulocyte antibodies. If a donor is positive for these antibodies, he
should be removed from the donor pool. Treatment
of TRAPI is supportive. There is no evidence that
steroid therapy is of any help.
The most commonly encountered transfusion problem is a febrile, nonhemolytic transfusion reaction.
The usual symptoms are fever and chills beginning 1
to 6 hours after the transfusion is started. Although
hemolytic transfusion must be considered, febrile,
nonhemolytic reaction is a benign reaction with no
sequelae. Fifteen percent of patients will have recurrent febrile reactions with subsequent transfusion.
This reaction is cytokine-mediated and is related to
the length of storage of blood and the presence of
white blood cells. Routine leukodepletion of packed
red cells either at the time of collection or with a
leukocyte filter at the time of transfusion markedly
reduces this complication.
An anaphylactic transfusion reaction can occur in
IgA-deficient patients. It begins within minutes of
transfusion with blood products that contain plasma.
The incidence is 1 in 35,000 infusions and can be
avoided by using ultrawashed red blood cells in susceptible patients.
An urticarial transfusion reaction occurs when soluble
antigen in donated blood reacts with existing IgE
antibodies in the recipient. This is treated with antihistamines, and once the urticaria regresses, transfusion can be safely continued.
Finally, some situations require irradiation of blood
products to protect the recipient from graft-versus244
host disease (GVHD). Candidates for blood product
irradiation include severely immunocompromised
patients such as allogenic bone marrow transplant
recipients, HIV-infected individuals, patients with
lymphoma or leukemia on aggressive chemotherapy
and patients undergoing autologous stem cell transplantation. Additionally, first-degree relatives are occasionally identified as directed donors. Since they
share HLA antigens with the recipient, the risk of
GVHD, which, unfortunately is almost always fatal,
is small. Therefore, blood products donated by firstdegree relatives for use in immunocompromised patients should be irradiated.
References:
1. Busch MP, Kleinman SH, Nemo GJ. Current and emerging
infection risks of blood transfusions. JAMA 2003; 289:959-962.
2. Kapko PM, Marshall CS, MacKenzie MR, et al. Transfusion
related lung injury: report of a clinical look back investigation.
JAMA 2002; 287:1968-1971.
3. Linden JV, Wagner K, Voytovich AE, et al. Transfusion errors
in New York State: an analysis of 10 years experience. Transfusion 2000; 40:1207-1213.
4. Pineda AA, Vamvaka EC, Gorden CD, et al. Trends in the
incidence of delayed hemolytic and delayed serologic transfusion
reactions. Transfusion 1997; 39:1097-1103.
5. Schreiber GB, Busch MR, Kleinman SH, et al. The risk of
transfusion-transmitted viral infection. N Engl J Med 1996;
334:1685-1690.
66 C DISCUSSION
67 A In 2002 more than 1,337 cases of malaria
68 D were reported in the United States or one of
69 B its territories. Of these, all but 5 patients
70 E were infected abroad, the majority from Asia
and Africa, with a smaller number from the Americas. Malaria in humans is caused by 4 species of
malaria parasites (Plasmodium falciparum, P. vivax, P.
ovale, P. malariae) and is spread by the bite of the
female Anopheles mosquito. Persons traveling abroad
to areas of malaria risk (see Figure 4) need to be
counseled regarding methods to reduce the likelihood of mosquito bites but should also be given
chemoprophylaxis against infection. It is important
for health professions to be aware that in 2002, 37
percent of the civilians who acquired malaria stated
that they had taken the appropriate chemoprophylaxis. Therefore, physicians and patients need to be
alert to any signs or symptoms that might indicate
malaria infection for up to a year following the
patient’s trip abroad, even when chemoprophylaxis
has been taken.
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Figure 4
Map from the World Health Organization http://www.who.int/ith/chapter05_m08_malaria.html
The choice of medication for malaria chemoprophylaxis depends on the area to which the person is
traveling, as the susceptibility of the organism to the
various agents (primarily chloroquine resistance) differs based on geography. The most up to date information on appropriate medication options can be
found at www.cdc.gov/travel.
Mefloquine (generic, Lariam™) administration should
begin 1-2 weeks before travel and continue with
weekly administration during travel and for 4 weeks
following return from the malarious area. It is effective against chloroquine-resistant P. falciparum. In
patients receiving this medication for prophylaxis,
the most common adverse reaction was vomiting (3
percent). Dizziness, syncope and extrasystoles were
very infrequently reported (1 percent). Mefloquine
has been reported to cause psychiatric symptoms
varying from anxiety, paranoia and depression to
hallucinations and psychotic behavior. While the
symptoms generally resolve with discontinuation of
the medication, there are reports of continuation of
psychiatric side effects even after the medication is
stopped. Therefore, it is recommended that
mefloquine not be administered to patients with active or recent history of depression or those with
generalized anxiety disorder, psychosis, schizophrenia or other major psychiatric disorders. Should any
psychiatric symptoms develop during administration
of the medication, discontinuation is recommended.
Mefloquine can also increase the risk of seizures in
patients with epilepsy by lowering plasma levels of
anticonvulsants, so its use in these patients should be
limited.
Chloroquine phosphate (generic, Aralen™) can only
be used for chemoprophylaxis in areas where there
is no resistance to the drug. The medication should
be started 1-2 weeks prior to travel and is taken
once a week during travel and for 4 weeks after
return from the malarious area. The medication is
generally well tolerated, although gastrointestinal disturbance, dizziness, headache, blurred vision, insomnia and pruritus are reported. While retinopathy and
hearing defects in patients with preexisting auditory
damage are associated with long-term or high-dose
administration, it is rarely seen with weekly administration for malaria prophylaxis. Chloroquine should
be used cautiously in patients with G6PD deficiency
and in patients with epilepsy, as it may provoke
hemolytic anemia and seizure activity, respectively.
Chloroquine can also cause a severe exacerbation of
ANSWER BOOKLET: VOLUME 35, NO. 7, OCTOBER, 2004
245
psoriasis, so it should be used with caution in affected patients. It is pregnancy category C.
Cimetidine can significantly increase chloroquine levels, so it should not be administered concomitantly.
Antacids and kaolin can reduce absorption of chloroquine, so a 4-hour interval should be maintained
between administration of these medications.
Primaquine can be used for primary prophylaxis if
no other medications can be used and in consultation with malaria experts (CDC Malaria Hotline 770488-7788). The medication is started 1-2 days before travel and is administered daily at 24-hour intervals during travel and for 7 days upon return from
the malarious area. While gastrointestinal adverse effects have been noted (nausea, vomiting, epigastric
distress, abdominal cramps), the most important adverse effects are hematologic. Primaquine is absolutely contraindicated in patients with G6PD deficiency. Additionally, it is contraindicated in acutely
ill patients with systemic disorders that are associated
with a tendency to granulocytopenia (e.g., rheumatoid arthritis, systemic lupus erythematosus) and in
patients who are receiving other drugs that can potentially cause hemolysis or depress myeloid elements
of bone marrow.
Malarone™ is a combination drug containing
atovaquone and proguanil hydrochloride. It is used
as primary prophylaxis in areas with chloroquineresistant or mefloquine-resistant P. falciparum. Administration should begin 1-2 days before travel and
the medication should be taken daily, at 24-hour
intervals, while in the malarious area and for 7 days
following return. The medication should be taken
with food or a milky drink. The most common
adverse reactions include abdominal pain (17 percent), nausea (12 percent), vomiting (12 percent),
headache (10 percent), diarrhea (8 percent), asthenia
(8 percent), anorexia (5 percent) and dizziness (5
percent). Should vomiting occur within an hour of
ingestion of a dose, a repeat dose should be taken. It
is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min). No
adjustments need to be made for mild to moderate
hepatic impairment. No studies are available in patients with severe hepatic dysfunction. It is not recommended for pregnant women (category C), for
children <11 kg or women nursing infants less than
<11 kg. Tetracycline, metoclopramide, rifampin and
rifabutin can significantly decrease bioavailability or
serum blood levels.
246
Doxycycline can be used as primary prophylaxis in
areas with chloroquine-resistant or mefloquine-resistant P. falciparum. Administration for prophylaxis
should begin 1-2 days before travel and continue at
24-hour intervals during travel and for 4 weeks following return from the malarious area. Doxycycline
is associated with photosensitivity, so patients receiving this medication should receive instruction
regarding ultraviolet radiation protection. It is also
associated with harmful effects on the fetus (permanent discoloration of teeth and retardation of skeletal development), so it is contraindicated in pregnant women (category D). It is also contraindicated
in nursing mothers and children <8 years of age
because of the dental discoloration. Absorption of
doxycycline may be impaired by antacids (containing aluminum, calcium or magnesium), bismuth
subsalicylate (Pepto-Bismol™) and also by iron-containing preparations.
References:
1. Nissen D, ed. Mosby’s Drug Consult. St. Louis: Mosby, Inc.,
2004:electronic version
2. Shah S, Filler S, Causer LM, et al. Malaria surveillance – United
States, 2002. MMWR Morb Mort Wkly Rep 2004; 53(SS01):2134.
Web sites:
http://www.cdc.gov/travel/malariadrugs2.htm. Accessed June
2004.
http://www.who.int/ith/chapter05_m08_malaria.html. Accessed
June 2004.
71 C DISCUSSION
72 A Hypokalemic periodic paralysis is the de73 B velopment of a generalized paralysis over a
74 D few hours or days. Patients may experience
75 A muscle weakness and respiratory difficulty and
may exhibit cardiac dysrhythmias. Attacks may occur after a large meal or after exercise and are often
associated with a family history of similar paralytic
events. The familial form has autosomal dominant
inheritance with variable penetrance and is thought
to be related to an abnormal gene of chromosome
1q. Diagnosis is based on the presence of low serum
potassium during an attack with normal levels between episodes. The low potassium results from intracellular migration of potassium from the intravascular space. As there is another entity called hypokalemia with paralysis that is characterized by excessive renal potassium loss, it is important to obtain
a spot urine potassium to differentiate the two, as
treatment differs. When intracellular shifts occur,
THE CORE CONTENT REVIEW OF FAMILY MEDICINE
urinary excretion of potassium is diminished as is
detected on a spot urine potassium. These patients
should be treated with oral potassium supplementation (60-120 meq) that will result in rapid resolution
of symptoms. A second form of hypokalemic periodic paralysis is associated thyrotoxicosis, especially
in Asian males. It is thought that the excess thyroid
hormone may increase susceptibility to the hypokalemic effects of epinephrine and insulin.
Botulism-related paralysis is due to a toxin released
by Clostridium botulinum, an anaerobic organism found
in the soil. The most common cause of botulism
toxin paralysis is from improperly cooked or canned
foods or from contact of the toxin, found in soil,
with a mucous membrane. Symptoms usually begin
12-36 hours after the introduction of the toxin. In
adults, gastrointestinal problems develop and are
quickly followed by paralysis of the cranial nerves
(leading to diplopia, dysphagia and dysarthria). The
paralysis then descends to involve the respiratory
muscles and muscles of the arms and legs. Motor
neurologic deficits are usually symmetric and sensory defects are absent. Fever is absent and vital signs
are generally normal. Patients remain responsive despite the neurologic deficits. Urinary retention and
constipation may occur. Diagnosis of the disorder is
made by identification of the bacteria or toxin, most
often in the stool. Initial treatment should be supportive in nature, including ventilatory support if
necessary. In adults, administration of equine-derived
botulism antitoxin has been shown to decrease fatality rates. As botulism toxin irreversibly binds to presynaptic cholinergic nerve fibers, supportive care must
be provided until new synaptic end-plates develop.
Patients with less severe disease and early treatment
with antitoxin have a good prognosis.
It may be difficult to differentiate tick paralysis from
Guillain-Barré syndrome (GBS), which may also
present with an ascending paralysis. GBS usually develops over a longer period of time (usually several
weeks versus days) and sensory nerves may be affected in some cases. A preceding infection, usually
an influenza-like upper respiratory infection or an
acute gastroenteritis with fever, is identified in two
thirds of patients. Influenza vaccination has been
implicated as an antecedent event in some cases,
although the judged risk associated with this vaccine
is extremely small. In the remaining patients, no
antecedent event is identified. It is felt that GBS is
an autoimmune process with development of antibodies to specific antigens or infectious organisms.
Symptoms are the result of inflammation and demyelination. GBS can occur at any age. Initial symptoms are weakness and paresthesias usually starting in
the legs and then progressing in an ascending pattern. In 90 percent of patients, progression of symptoms is complete after 4 weeks, followed by a plateau phase and then recovery. In severe cases respiratory and bulbar muscles may be affected and respiratory support is needed. Deep tendon reflexes are
decreased to absent. Diagnosis is based on clinical
findings, a history of an antecedent infection or vaccination and an elevated protein level in the cerebral
spinal fluid with a normal cell count. However, protein levels are not always elevated (20 percent of
cases), especially in the first week of the illness. Electromyography may help in the diagnosis. Treatment
consists of supportive care and the use of intravenous immunoglobulin and /or plasmapheresis.
Tick paralysis is transmitted by the bites of two species of ticks in North America – Dermacentor andersoni
and Dermacentor variabilis. Most cases are identified in
the western United States and Canada, although cases
have been reported elsewhere. Most cases occur in
spring and early summer. The majority of affected
individuals are children <10 years of age, probably
related to the smaller amount of neurotoxin needed
to cause symptoms. Girls are affected more often
than boys, perhaps because the ticks can remain undetected in long hair. Tick paralysis is due to the
release of a neurotoxin by female ticks. It leads to
progressive, ascending paralysis that spares the sensory nerves. Symptoms usually progress in a matter
of hours to days, often starting with paresthesias and
a feeling of fatigue or weakness. Respiratory function can be compromised with the paralysis and is
the major cause of death from this disorder. Despite
its rather rapid progression, no other systemic signs
like fever develop. The neurotoxin works by preventing the release of acetylcholine from presynaptic
neurons and is not associated with any infectious
process. Treatment consists of supportive therapy and
removal of the tick. Once the tick is removed, symptoms generally resolve quickly. Although an antitoxin does exist, it is not routinely used in humans
due to the potential for anaphylaxis and the fact the
paralysis resolves with removal of the tick
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247
Infant botulism is more prevalent than food-borne
and wound botulism. Ninety percent of recognized
worldwide cases are diagnosed in the United States
(approximately 250 cases per year). Affected infants
generally range from 6 weeks to 9 months of age
with 90 percent of affected infants <6 months of
age. Infant botulism presents differently, with constipation and cranial nerve palsies being the first clinical signs. Hypotonia and dehydration develop next,
with respiratory failure a late sign of this disorder. In
the past few years, infantile botulism has been associated with ingestion of raw honey, prompting physicians to recommend the avoidance of honey in
infants <1 year of age. Because infantile botulism
responds well to supportive care (respiratory support, nasogastric feeding, occupational and physical
therapy) antitoxin is not routinely used in infants, as
it has lead to anaphylaxis in up to 20 percent of
cases. Botulism immune globulin (a human-derived
antitoxin) may help hasten recovery in infants. The
average length of hospitalization for infant botulism
is 44 days.
References:
1. Cox N, Hinkle R. Infant botulism. Am Fam Physician 2002;
65(7):1388-1392.
2. Greenstein P. Tick paralysis. Med Clin North Am 2002;
86(2):441-446.
3. Lin SH, Chiu JS, Hsu CW, et al. A simple and rapid approach
to hypokalemic paralysis. Am J Emerg Med 2003; 21(6):487-491.
4. O’Brien KK, Higdon ML, Halverson JJ. Recognition and management of bioterrorism infections. Am Fam Physician 2003;
67(9):1927-1934.
5. Rose BD. Causes of hypokalemia. In: Rose BD, ed, UpToDate.
Wellesley, MA: UpToDate, 2003.
6. Shields RW. Demyelinating disorders of the peripheral nervous
system. In: Goetz CG, ed, Textbook of Clinical Neurology. 2nd
ed. Philadelphia: WB Saunders Co., 2003:1088-1090.
7. Wu CC, Chau T, Chang CJ, et al. An unrecognized cause of
paralysis in ED: thyrotoxic normokalemic periodic paralysis. Am J
Emerg Med 2003; 21(1):71-73.
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The Core Content Review of Family Medicine
Contributing Authors
The following list of authors contributed to the October 2004
Core Content Review of Family Medicine.
Richard Allen, M.D., Brookline, MA
Tony Miksanek, M.D., Benton, IL
Kenneth Bertka, M.D., Holland, OH
Laura Novak, M.D., Barberton, OH
Andreas Cohrssen, M.D., Brooklyn, NY
John O’Handley, M.D., Columbus, OH
Stephen Colameco, M.D., Haddonfield, NJ
T. Grant Phillips, M.D., Washington, PA
Joel Dickerman, D.O., Cascade, CO
Ronald Pies, M.D., Lexington, MA
Phillip Disraeli, M.D., Dallas, TX
Kalyanakrishnan Ramakrishnan, M.D.,
Oklahoma City, OK
Roger Kelley, M.D., Shreveport, LA
Gary Silko, M.D., Erie, PA
Charlene Li, M.D., Windsor, CT
Evan Slater, M.D., Ventura, CA
Jeffrey Meffert, M.D., San Antonio, TX
Kathy Soch, M.D., Corpus Christi, TX
Timothy Meneely, D.O., Urbana, IL
Cherie Zachary, M.D., Bloomington, MN
_________________________________
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