Download Case 1: Not all that swells ends well

Case 1: Not all that swells ends well
1.
What condition may explain the skin lesion of this patient?
The red skin lesion may be due to cellulitis, probably caused by penicillin hypersensitivity. Cellulitis is an acute inflammatory condition of the skin, manifested as localized pain,
erythema, swelling, and heat. It may be caused by the patient’s indigenous flora that colonizes the skin and appendages, most commonly Staphylococcus aureus. The most probable
portal of entry may be the rose thorn prick on the patient’s finger.
2.
What is the management of this lesion?
Primary treatment for cellulitis is cloxacillin, 2g IV q 4-6 hours. Alternative treatments can be cefazolin 1-3 g q 8 hours, ampicillin/sulbactam 1.5-3 g q 6 hours, erythromycin 0.5-1 g
IV q 6 hours, or clindamycin 600-900 mg IV q 6 hours.
3.
What additional problem does this patient have?
The patient is also suffering from tetanus, as evidenced by the lockjaw. Clostridium tetani, an obligate anaerobic gram-positive bacillus, causes tetanus. This bacterium is
nonencapsulated and forms spores, which are resistant to heat, desiccation, and disinfectants. The spores are ubiquitous and are found in soil, house dust, animal intestines, and human
feces. Spores that gain entry can persist in normal tissue for months to years. Under anaerobic conditions, these spores geminate and elaborate tetanospasmin and tetanolysin.
Tetanolysin is not believed to be of any significance in the clinical course of tetanus. Tetanospasmin that is released by the maturing bacilli is distributed via the lymphatic and vascular
circulations to the end plates of all nerves. Tetanospasmin then enters the nervous system peripherally at the myoneural junction and is transported centripetally into neurons of the
central nervous system (CNS).
These neurons become incapable of neurotransmitter release. The neurons, which release gamma-aminobutyric acid (GABA) and glycine, are particularly sensitive to
tetanospasmin, leading to failure of inhibition of motor reflex responses to sensory stimulation. This results in generalized contractions of the agonist and antagonist musculature
characteristic of a tetanic spasm. The shortest peripheral nerves are the first to deliver the toxin to the CNS, which leads to the early symptoms of facial distortion and back and neck
stiffness.
Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and
formation of new synapses.
What would be your management of this second problem?
Antibiotic therapy should be administered to eradicate vegetative cells. Penicillin 10-12 million units IV is given for 10 days. Metronidazole 500 mg q 6 hours can also be given.
Tetanus immunoglobulin 3000-6000 units RM is also given to neutralize the circulating antitoxin. To control the muscle spasms, diazepam is required.
Case 2: A Bump After The Bump
A 31 y/o M is seen because of a painless bump on the tip of his penis that he noticed a day prior to consultation. He admits to having unprotected sex with a female
commercial sex worker 3 weeks ago. He denies dysuria, frequency or hesitancy nor urethral discharge. PR: tender papule with an eroded center on the tip of the penis and absence of
inguinal lymphadenopathy.
1.
What sexually transmitted infections may give rise to genital ulcers or papules? How do you distinguish one from the other?
Haemophilus ducreyi is the etiologic agent of chancroid. This organism is a fastidious, Gram-negative rod that requires hemin.

The incubation period for chancroid ranges from 3 to 10 days.

The ulcers begin as small, inflammatory papules that develop into ulcers that have an undermined edge, contain purulent exudate and bleed easily.

Chancroid is a sexually transmitted disease that is more prevalent in males than females, with a ratio of approximately 8:1.

In men, the ulcer is located primarily on the prepuce and around the coronal sulcus.

In women, the forchette, labia and perianal area can be involved.

Multiple “kissing” ulcers (ulcers in direct opposition to each other) are common.

Approximately one-third of the patients with chancroid also have enlarged inguinal lymph nodes that are extremely tender. These lymph nodes may coalesce and rupture and
drain, forming buboes.
Treponema pallidum, a spirochete, is the agent of syphilis.

Syphilis usually presents as a small papule that develops into a painless, eroded, indurated ulcer.

The mean incubation period is 21 days.

If untreated, the genital ulcer disappears and, after a variable length of time, the patient may develop secondary syphilis with widespread, protean symptoms usually
involving the skin with disseminated diffuse papules.

The final stage of the disease, tertiary syphilis, can remain latent or appear as late syphilis consisting of neurosyphilis, cardiovascular syphilis, or gummatous syphilis.
Chlamydia trachomatis serovars L1, L2, and L3 are the agents of lymphogranuloma venereum. These strains of C trachomatis differ from ocular and nongonococcal urethritis in
being more invasive in a mouse model and more resistant to trypsin treatment.

Lymphogranuloma venereum, a disease due to restricted types of C trachomatis, usually begins as a painless papule that frequently goes unnoticed.

The second stage of the disease involves enlargement of regional lymph nodes and the third stage manifests as rectal strictures and fibrosis.
Granuloma inguinale is caused by Calmatobacterium granulomatis, which is usually demonstrated as intracellular Donovan bodies visualized by Warthin-Starry silver stain or
Giemsa stain of histologic sections. The disease is most prevalent in India, Papua, New Guinea, and the Caribbean.

Granuloma inguinale also begins as a painless papule that ultimately develops into a painless, raised, beefy-red lesion.
Herpes Simples Virus

The lesions of herpes simplex initially begin as small papules that develop into extremely painful vesicles or ulcers.
2.
What sexually transmitted infections must be screened for in individuals who practice high risk sexual behavior? What tests are ordered?
Screening Tests for High Risks
Collect cultures for N. gonorrhoeae from the pharynx and anus in both sexes, the vagina in girls, and the urethra in boys.
Collect cultures for Chlamydia trachomatis from the anus in both sexes and from the vagina in girls.
If a vaginal discharge is present, obtain cultures, wet mount, and KOH prep of vaginal swab specimens for bacterial vaginosis, Trichomonas vaginalis, and Candida
albicans.
3.
What additional test may increase the suspicion that this person has syphilis? What are the specific treponemal tests? Which test is used to determine response
to therapy?
Demonstration of the organism
Because T. pallidum cannot be detected by culture, dark-field microscopy examination of lesion exudates is used to evaluate moist cutaneous lesions such as the chancre
and condyloma lata.
If dark-field microscopy is not available, direct fluorescent antibody T. pallidum (DFA-TP) is an alternative exam. This uses fluorescein-conjugated polyclonal antitreponemal
antibody for the detectiondetection of T. pallidum in fixed smears from suspect lesions.
Treponemal test
There are two tests to confirm reactive non-treponemal results:
Fluorescent Treponemal Antibody-Absorbed (FTA-ABS) test. A blood serum screening test for syphilis designed to demonstrate the presence or absence of specific
antibodies directed against the organism (Treponema pallidum) responsible for syphilis.
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A negative FTA-ABS test result is consistent with a person not having syphilis. However, a person may have a negative FTA-ABS test result while in the early (primary) and late (tertiary)
stages of the disease. In the middle (secondary) stage of syphilis, the FTA-ABS test is most reliable and is reportedly positive in 100% of cases.
Agglutination assays for antibodies to T. pallidum
Response to therapy
Response of syphilis to treatment should be determined by monitoring the quantitative VDRL or RPR titer
VDRL is a screening test for syphilis that measures antibodies that can be produced by Treponema pallidum, the bacteria that causes syphilis.
The test is similar to the newer rapid plasma reagin (RPR) test.
A negative test is normal and means that no antibodies to syphilis have been detected. The screening test is most likely be positive in secondary and latent syphilis. During
primary and tertiary syphilis this test may be falsely negative.
A positive test result may mean you have syphilis. If the test is positive, the next step is to confirm the results with an FTA-ABS test, which is a more specific syphilis test.
The VDRL test's ability to detect syphilis depends on the stage of the disease. The test's sensitivity to detect syphilis nears 100% during the middle stages; it is less sensitive
during the earlier and later stages.
4.
What are the stages of syphilis and the corresponding manifestations?
Primary syphilis

Primary syphilis is typically acquired via direct sexual contact with the infectious lesions of a person with syphilis.

Approximately 10-90 days after the initial exposure(average 21 days), a skin lesion appears at the point of contact, e.g. the genitalia. This lesion, called achancre, is a firm,
painless skin ulceration localized at the point of initial exposure to the spirochete, often on the penis, vagina or rectum.

Rarely, there may be multiple lesions present although typically only one lesion is seen. The lesion may persist for 4 to 6 weeks and usually heals spontaneously.
Secondary syphilis

Secondary syphilis occurs approximately 1-6 months(commonly 6 to 8 weeks) after the primary infection.

There may be a symmetrical reddish-pink non- itchy rash on the trunk and extremities. The rash can involve the palms of the hands and the soles of the feet.

In moist areas of the body, the rash becomes flat broad whitish lesions known as condylomata lata. Mucous patches may also appear on the genitals or in the mouth.
Latent syphilis

Latent syphilis is defined as having serologic proof of infection without signs or symptoms of disease. It is further described as either early or late.

Early latent syphilis is defined as having syphilis for two years or less from the time of initial infection without signs or symptoms of disease.

Late latent syphilis is infection for greater than two years but without clinical evidence of disease.
Tertiary syphilis

Tertiary syphilis usually occurs 1-10 years after the initial infection, though in some cases it can take up to50 years.

This stage is characterized by the formation of gummas which are soft, tumor-like balls of inflammation known as granulomas. The granulomas are chronic and represent an
inability of the immune system to completely clear the organism.
5.
What is the drug of choice, dosage, and route of delivery for syphilis?
Stage of Syphilis
Primary, secondary or early
Late latent (or latent of uncertain
cardiovascular, or benign tertiary
Patients without Penicillin Allergy
Penicillin G benzathine (single dose of 2.4 mU IM)
duration),
Neurosyphilis (asympyomatic or symptomatic)
Syphilis in pregnancy
Lumbar puncture:
CSF normal: Penicillin G benzathine (single dose of 2.4
mU IM weekly for 3 weeks)
CSF abnormal: Treat as neurosyphilis
Aqueous penicillin G (18-24 mU/d IV, given as 3-4m mU
q4h or continuous infusion) for 10-14 days or
Aqueous penicillin G procaine (2.4 mU/d IM) plus oral
probenecid (500 mg qid), both for 10-14 days
According to stage
Patients with Confirmed Penicillin Allergy
Tetracycline hydrochloride (500 mg PO qid) or doxycycline
(100 mg PO bid) for 2 weeks
Lumbar puncture:
CSF normal and patient not infected with HIV: Tetracycline
hydrochloride (500 mg PO qid) or doxycycline (100 mg PO
bid) for 4 weeks
CFS normal and patient infected with HIV: Desensitization
and treatment with penicillin if compliance cannot be
ensured
CSF abnormal: Treat as neurosyphilis
Desensitization and treatment with penicillin
Desensitization and treatment with penicillin
Case 3: Line fever but armed with too few bullets
A 40 y/o female with Hodgkin’s lymphoma is admitted because of a one week history of fever and rash. She has been receiving chemotherapy via a Hickman catheter. Past
medical history is remarkable for a splenectomy 2 years ago. Temperature is 38.5C, PR 100/min, RR 20/min, BP 100/70. Palpebral conjunctivae pale, sclerae anicteric; no palpable
lymph nodes; heart and lungs unremarkable. There is a red streak over the subcutaneous portion of the Hickman catheter and a painless round necrotic lesion with eschar on the dorsum
of the left hand. The exit site of the central line at the left upper chest is nonerythematous and nontender. Hemoglobin is 98 g/L, platelet 110, WBC 800/ cu mm.
1.
What types of infection can this particular patient develop?
Generally, the patient is predisposed to infections due to her lack of a spleen. Specifically, she is predisposed to having skin-specific infections such as cellulitis since she is
neutropenic; or catheter-related infections due to her Hickman catheter. She may also have Salmonella infections as it is common in Hodgkin’s disease patients. Staphylocci,
streptococci, S. pneumoniae, H. influenzae, N. meningitides, Babesia, and Capnocytophaga canimorsus are the other microorganisms that may cause different infections in Hodgkin’s
lymphoma patients, especially those who have been splenectomized.
2.
What is the underlying immune abnormality of Hodgkin’s disease?
Hodgkin’s lymphoma is a malignancy of the lymphoid cells. It is of B cell origin, and mainly involves depletion of lymphocytes. In classic Hodgkin’s disease, the neoplastic cell is the
Reed-Sternberg (RS) cell. RS cells comprise only 1-2% of the total tumor cell mass. The remainder is composed of a variety of reactive, mixed inflammatory cells consisting of
lymphocytes, plasma cells, neutrophils, eosinophils, and histiocytes. Most RS cells are of B-cell origin, derived from lymph node germinal centers but no longer able to express
antibodies. Some Hodgkin disease cases have been identified in which the RS cell is of T-cell origin, but these are rare. The RS cells consistently express the CD30 (Ki-1) and CD15
(Leu-M1) antigens. CD30 is a marker of lymphocyte activation that is expressed by reactive and malignant lymphoid cells and was originally identified as a cell surface antigen on RS
cells. CD15 is a marker of late granulocytes, monocytes, and activated T cells that are not normally expressed by B-lineage cells. There is asymptomatic lymphadenopathy, with enlarged
and rubbery cervical and supraclavicular lymph nodes; splenectomy may also occur, as with other systemic symptoms (low-grade fever, night sweats, weight loss, etc.).
3.
What is the term used for the necrotic lesion on the arm? Name the most common cause if this lesion.
The necrotic lesion on the arm is called ecthyma gangrenosum. It is most often associated with Pseudomonas aeruginosa infection.
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4.
What is the appropriate management of this case?
The patient is presenting with ecthyma gangrenosum on the left hand probably caused by Pseudomonas aeruginosa, and a tunneled catheter. The Hickman catheter must be
immediately removed and changed with a new one to prevent progression to cellulitis and tissue necrosis.
The initial antibacterial therapy given to the patient must be active against both gram-positive and –negative bacteria such as a third-generation cephalosporin. Once the
bacterial culture becomes available, directed therapy must be given. If P. aeruginosa is indeed present, a synergistic combination of piperacillin plus an aminoglycoside may be
appropriate. Treatment must be continued until neutropenia resolves (granulocyte ct > 500/uL).
5.
What preventive measure may be offered to this patient?
Hand washing by all persons caring for the patient is vital to prevent spread of organisms. Sites of catheter insertions, as well as IV lines must always be cleaned and replaced if
needed.
Case 4: The “head cold” that refused to go away
A 50 year old microbiology laboratory technician has been complaining of a stuffy nose and productive cough for the past 2 days. He then suddenly developed high-grade
fever with chills and a severe headache, unrelieved by 2 tablets each of paracetamol and mefenamic acid. At the ER, he was toxic-looking with a temperature of 40C, RR 24/min, PR
100/min, BP 120/80. There was nuchal rigidity, no papilledema nor focal neurologic deficit. Except for occasional crackles, lung and heart findings were normal. Abdominal PE
unremarkable.
1.
What is your admitting diagnosis?
Acute Bacterial Meningitis is an acute purulent infection within the subarachnoid space. It is the most common form of suppurative CNS infection. In the past, most
meningitis cases occurred in children younger than 5 years. But as a result of the protection offered by current childhood vaccines, most meningitis cases now occur in young people
between the ages of 15 and 24. Older adults also tend to have a higher incidence of meningitis than do young children.
2.
What is the basis for your diagnosis?
Based on the history and physical findings of our patient, the most probable diagnosis is acute bacterial meningitis. The classic clinical triad of meningitis is Fever, Headache
and Nuchal Rigidity which are all present in our patient. His meningitis is Acute basically due to the fast onset of his symptoms which is only 2 days. The occupation of our patient as a
microbiology laboratory technician increases his risk for exposure to different pathogens like S. pneumoniae and N. meningitides, these two organisms may be the cause of his stuffy
nose and productive cough. Initially, these two bacteria colonize the nasopharynx then transported to the bloodstream and eventually reach the CSF. The findings of a negative
papilledema and focal neurologic deficit can rule out the presence of encephalitis or brain abscess. Other signs which could help confirm our diagnosis are Kernig’s and Brudzinski which
are also classic signs of meningeal irritation.
3.
What organisms may be involved?
Currently, the organisms most commonly responsible for community-acquired bacterial meningitis are Streptococcus pneumoniae (50%), N. meningitides (25%), group B
streptococci (15%), and Listeria monocytogenes (10%).
S. pneumoniae is the most common cause of meningitis in adults > 20 years of age. One predisposing condition that increases the risk of pneumococcal meningitis is
pneumococcal pneumonia. Mortality remains 20% despite antibiotic therapy.
N. meningitides accounts for 25% of all cases of bacterial meningitis and for up to 60% in children and young adults between ages 2 and 20. One important clue to the
diagnosis of meningococcal infection is the presence of petechial or purpuric skin lesion.
Enteric gram-negative bacilli are an increasingly common cause of meningitis in individuals with chronic and debilitating disease such as diabetes, cirrhosis/alcoholism and
with chronic urinary tract infection.
Group B streptococcus/ S.agalactiae was previously common in infants, it has been reported with increasing frequency in individuals >50 years old especially with
underlying disease.
L. monocytogenes has become an increasingly important cause of meningitis in neoates (<1 month of age), pregnant women, individuals >60 years and
immunocompromised individuals of all ages.
H. influenzae type b meningitis in children has declined dramatically since the introduction of the hib conjugate vaccine.
S. aureus and coagulase negative staphylococci are important cause of meningitis that follows invasive neurosurgical procedure.
4.
What is the typical CSF picture of acute bacterial meningitis?
Opening pressure
WBC
RBC
Glucose
CSF/serum glucose
Protein
Gram’s stain
Culture
Latex agglutination
Limulus lysates
>180 mmH2O
10/uL to 10,000/ uL, neutrophils predominate
absent in nontraumatic tap
<2.2 mmol/L (<40mg/dL)
<0.4
>0.45 g/L (>45 mg/dL)
(+) >60%
(+) >80%
may be (+) due to S. pneumoniae, N. meningitides, H.
Influenza, E.coli, group B streptococci
(+) gram-negative meningitis
5.
What is the management of this case?
Bacterial meningitis is a medical emergency. The goal is to begin antibiotic therapy within 60 min after arrival in the ER. Ceftriaxone or cefotaxime provide good coverage for
susceptible S. pneumoniae, group B streptococci and H. influenza. Vancomycin should be added due to the emergence of penicillin and cephalosphorin resistant S. pneumoniae.
Penicillin G is the antibiotic of choice for meningococcal meningitis. Although strains of penicillin resistant have been identified, success with penicillin treatment is still documented.
Empirical therapy is necessary in treatment of bacterial meningitis since the first 60 min is crucial. But still the result of the culture and sensitivity testing is an important guideline in
the management of our patient. Once resistant strains are identified then modification of antibiotics can be initiated.
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Case 5: The Burning Saga of a Market Vendor
45 y/o market vendor complained of fever, chills, and headache of 10 days duration. Consulted a local health center, given chloramphenicol 4g/day, was taken for 2 days.
Fever persisted and started to pass out bloody stools few hours PTA. Denied travel outside Manila, has not had any major illness and has not received blood transfusions. PE: toxic
looking, 39.8C, PR 101/min, BP 100/60, icteric sclera, subconjunctival hge. Liver span 12 cm Traube’s space obliterated. No rebound tenderness. In the hospital, she received several
untis of blood components and her GI bleeding eventually stopped; became afebrile. Later complained of calf muscle tenderness and decrease urine output. Given IV hydration plus
antibx therapy.
1.
What possible infectious diseases may explain the patient’s condition?
Leptospirosis is the working diagnosis for this case. The patient presents with fever, chills and a headache, which lasted for 10 days with the occurrence of tenderness in the calf
muscle. These are all classic signs and symptoms of the disease. The headache is described as frontal or retroorbital with the development of photophobia in some cases. Fever and
subconjunctival suffusion are frequent findings. Cough and chest pain with hemoptysis may also be present, although are less common.
After a week, a patient usually becomes asymptomatic with a recurrence in some within 1 to 3 days. This marks the beginning of the development of the antibodies. One should
note a recurrence of symptoms that herald this second phase of the disease because this is when a patient may develop aseptic meningitis.
A severe form of leptospirosis is Weil’s Syndrome. This is characterized by jaundice, renal dysfunction and hemorrhagic diathesis. This should be considered in our patient since
she presents with a decrease in her urine output, jaundice and subconjunctival hemorrhage and bloody stools. If left untreated, renal failure may develop, which can lead to oliguria or
acute tubular necrosis. Pulmonary involvement is sometimes noted with the development of cough, dyspnea, hemoptysis and chest pain.
Malaria is considered as a differential diagnosis to the case. Non specific symptoms include headache, fatigue, abdominal discomfort and muscle aches after a fever. However,
these muscle aches are described as non-tender, unlike the patient presented. Fever is of a spiking nature with regular intervals of lysis. Splenomegaly may also occur, as does
hepatomegaly which can lead to mild jaundice among adults.
Dengue is another consideration for this patient. It is clinically described as fever of abrupt onset accompanied by a frontal or retroorbital headache not unlike leptospirosis. It may
also be accompanied by a generalized macular blanching rash within the first 2 days of illness. These last for about a week and dissipate after 1 to 2 days. This is a biphasic disease
however and it recurs with a second rash although the symptoms mentioned are not as distinct. On PE one may note hemorrhagic manifestations such as petechiae, purpura, epistaxis,
gum bleeding or GI bleeding (possibly reflected in the passage of bloody stools or subconjunctival hemorrhage seen in our patient). Generalized lymphadenopathy is also appreciated.
2.
How are these diseases transmitted?
Leptospirosis can be transmitted through direct contact with urine, blood or tissue from an infected animal. Human to human transmission is a rare occurrence. The etiologic agent
can survive in water for many months. The rate of occurrence goes up during the rainy seasons due to flood water. This 45 year old market vendor might have been exposed to
substandard health conditions in her area of work which placed her at increased risk for becoming infected.
Malaria is caused by a bite from an infected female anopheles mosquito. It is endemic in some areas of the Philippines like Palawan but is quite rare in others like Manila.
Sporozoites are released into the human host and infect the hepatic cells where they mature, rupture and eventually release merozoites. Certain types (P. vivax and P. ovale) can
become latent within the liver and can cause relapse later in the future by invading the blood vessels. The parasite spreads hematogenously to produce its effects on the body.
Dengue is another mosquito borne infection caused by a flavivirus. Epidemics often begin in the rainy season when aedes aegypti, the etiologic agent, is most abundant. It breeds
in tropical and semi tropical areas in water receptacles. The female mosquito obtains the virus through its blood meals with an infected human. They remain infected for life, passing on
the virus during subsequent viremic feeding.
3.
What laboratory tests will help in the diagnosis of this case?
ESR is usually increased in leptospirosis. Leukocytosis is prominent in patients suffering from Weil’s syndrome. There is also a noted increase in levels of serum bilirubin and
alkaline phosphatase. Prothrombin time may be prolonged, easily correctible by the induction of Vitamin K, in patients with Weil’s.
An isolation of the organism or a rise in antibody titer helps determine etiology. The microscopic agglutination test (MAT) uses live leptospiral strains and ELISA makes use of
reacting antigens. These are both serologic procedures that can be done to determine the cause of illness.
Leptospires can be taken from the blood or CSF during the first 10 days. It is present in urine beginning on the first week of disease and can last a few more after that. If one does a
culture, it may become positive in as little as one week to as long as a month. One should also perform a serologic test for hantavirus in areas where this is known to reside due to their
close clinical correlation.
4.
What are the drugs of choice for these infections?
Our patient is presented as toxic like so one should provide her with IV penicillin G, amoxicillin, ampicillin or erythromycin. For a milder case, oral treatments with tetracycline,
doxycycline or amoxicillin can be given instead. Some with Weil’s syndrome may require dialysis due to their renal failure. At times, blood transfusions are necessary. Whole blood and
platelets (if needed) are given.
The drug of choice for malaria is dependent on which ones have no resistance within the area of procurement. The use of anti-malarial drugs are divided into two: prophylaxis and
treatment. For the former, chloroquine is used in areas without resistant P. falciparum. For areas with resistance, mefloquine is used. Multi drug resistant P. falciparum is given
doxycycline. Terminal prophylaxis of P. vivax and P. ovale infections are given primquine. This drug is now used as the last resort as to hinder the development of resistance.
In a clinical setting wherein P. falciparum and P. malaria are still sensitive to chloroquine, this drug is given. For P. vivax and P. ovale infections, chloroquine and primaquine are
given. One can only give the latter if the patient is G6PD normal. For severe or complicated infections by P. falciparum, quinidine gluconate is given.
Dengue is more of supportive therapy. No antiviral therapy is available for the treatment of this disease.
Case 6: Cold shivers after a hot trip
33 y/o news correspondent returns after a 3 month assignment in Palawan, complaining of fever and chills for 2 weeks, with headaches. Despite weekly chloroquine
prophylaxis he has had at least 2 previous bouts of fever and chills treated with Fansidar. Temp 40C, PR 110/min, RR 22/min, BP 120/60. Traube’s space obliterated.
1.
Explain the (positive and negative) PE findings.
The vital signs reveal high fever and an elevated pulse rate. The high fever is characteristic of the infectious process which is causing the patient’s signs and symptoms. It is an
inflammatory response mediated by cytokines and other inflammatory mediators which adjust the basal body temperature controlled by the thalamus. The elevated pulse rate, on the
other hand, may be a compensatory mechanism for the hemolytic anemia, which is characteristic of malaria. As more and more RBC cytolysis occurs due to intracellular replication of the
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protozoa, there are less blood cells delivering oxygen to various parts of the body. This leads to a state of relative hypoxia as tissues and organs receive less and less oxygen for aerobic
metabolism. The cardiovascular system tries to compensate for this by pumping more blood. This would manifest itself as an increased pulse rate.
The icteric sclerae may also be explained by the hemolysis caused by malaria. Plasmodia enter RBC’s and feed on hemoglobin and other proteins in the cell. They also
reproduce within the cell causing hemolysis.
The enlargement of the spleen is due to engorgement and edema as well as reticulo-endothelial hyperplasia. Later on, splenomegaly occurs due to increased hemolytic and
phagocytic function of the organ due to dysmorphic red blood cells infected with malaria.
The absence of skin lesions specifically petechiae are not present because thrombocytopenia shows a moderate decline during the paroxysms of fever, which the patient
has.
2.
If this is malaria, what are the probable reasons for this patient to have another episode of malaria?
Most patients re-infected with malaria are those that live in endemic areas, or those that travel repeatedly to these areas. Over time, these people may develop immunity to malaria
by acquiring mechanisms which can kill the parasites or stop the replication of these parasites. However, what is important is the ability of their immune system to regulate its response to
these infections, so as not to produce and overblown reaction to malaria.
This occurs as the first infection “primes” the immune system, while re-infection leads to an exaggerated, and very harmful response by the body.
3.
What processes are essential to the pathogenesis of malaria?
Most patients have been living or have recently visited an area which is endemic to malaria. The vector of the disease if the anopheles mosquito, which has plasmodia in its saliva.
While the mosquito bites into its host for a blood meal, the plasmodia is transferred into the vascular system. Then they enter circulating erythrocytes to feed on the hemoglobin and other
proteins, and they also replicate intracellularly thus destroying the RBC.
Most anopheles mosquitos are nocturnal, or are active only at night.
4.
What complications may develop in severe falciparum malaria?
The morbidity and mortality of P. falciparum species is greatest among the malaria species because of its increased parasetemia and its ability to cytoadhere- it produces
proteinacious knobs that bind itself to endothelial cells. This adherence causes RBC to clump together in some parts of the body leading to further damage due to vascular obstruction:
cerebral malaria, pulmonary edema, renal disfunction and anemia.
P. falciparum is also known for developing drug resistance to chloroquine, which is the treatment given to other species of malaria. It has also been known to develop resistance to
quinine and tetracycline.
5.
What drugs are used for uncomplicated/ complicated malaria?
Treatment for malaria should not be initiated until the diagnosis has been confirmed by laboratory investigations. Once confirmed, the treatment is based on the factors: the
plasmodium species, clinical status of the patient (uncomplicated or severe), and drug susceptibility.
Patients diagnoses with uncomplicated malaria may be treated with oral anti-malarials. However, patients diagnosed with complicated/sever malaria due to impaired
consciousness/coma, severe normocytic anemia, renal failure, pulmonary edema, acute respiratory distress syndrome, circulatory shock, disseminated intravascular coagulation,
spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated generalized convulsions, and/or parasitemia of > 5% should be treated with aggressive parenteral antimalarials.
Knowledge of the endemic area the patient recently visited or the patient is living in may provide clues which plasmodium species is infecting him/her.
Essentially, the drugs used for malaria are as follows:
a)
Chloroquine: inhibits parasite growth by inhibiting hemoglobin utilization by the parasites
b)
Primaquine: if uncomplicated infection is caused by P. ovale or P. vivax, this drug is important to use to prevent relapse. It binds to the parasite’s DNA and disrupts
its mitochondria
c)
Quinine: used for chloroquine- resistant infections. It intercalates with the parasite’s DNA preventing its growth.
d)
Quinidine: for complicated malaria, in conjunction with doxycycline, tetracycline, or clindamycin. It also intercalates with the DNA of the parasite preventing its
growth.
6.
How can malaria be prevented in adults?
Basically, prevention entails avoidance of endemic regions, taking proper prohylactic drugs before travel, using insect repellant to repel mosquitos especially at night, using
mosquito nets with permethrim for sleeping areas, and consulting with the physician right away when you suspect you have acquired the parasite.
Case 7: Break-bone fever
18 y/o student in Manila admitted d/t 4-day fever with headache and severe myalgia. No prior major illness and not on any maintenance medication. Occasionally buying food
from vendors and drinking iced beverages. PR: Temp 39C. CBC: leucopenia, slightly elevated transaminases. Patient defervesced on 2nd hospital day and follow up CBC showed
leucopenia, plt 80,000/cu.mm, increased Hct. VS remained stable; discharged after 3 days with improved hemogram. Final diagnosis: dengue hemorrhagic fever.
1.
-
Enumerate at least 3 factors that predispose a person with dengue fever to develop shock.
Presence of enhancing and nonneutralizing antibodies: Transplacental maternal antibody may be present in infants <9 months old, or antibody elicited by previous
heterologous dengue infection may be present in older individuals. T cell reactivity is also intimately involved.
Age: Susceptibility to DHF/DSS drops considerably after 12 years of age.
Sex: Females are more often affected than males.
Race: Caucasians are more often affected than blacks.
Nutritional status: Malnutrition is protective.
Sequence of infection: For example, serotype 1 followed by serotype 2 seems to be more dangerous than serotype 4 followed by serotype 2.
Infecting serotype: Type 2 is apparently more dangerous than other serotypes.
2.
Why is a second dengue infection said to be worse than primary dengue?
Second infection with a serotype of dengue virus different from that involved in the primary infection leads to dengue HF with severe shock.
Macrophage/monocyte infection is central to the pathogenesis of dengue fever and to the origin of DHF/DSS. Previous infection with a heterologous dengue-virus serotype may
result in the production of nonprotective antiviral antibodies that nevertheless bind to the virion’s surface and through interaction with the Fc receptor focus secondary dengue viruses on
the target cell, the result being enhanced infection. The host is also primed for a secondary antibody response when viral antigens are released and immune complexes lead to activation
of the classic complement pathway, with consequent phlogistic effects. Cross-reactivity at the T cell level results in the release of physiologically active cytokines, including interferon γ
and tumor necrosis factor α.
3.
How is dengue fever diagnosed?
5
After an incubation period of 2 to 7 days, the typical patient experiences the sudden onset of fever, headache, retroorbital pain, and back pain along with the severe myalgia that
gave rise to the colloquial designation “break-bone fever.” There is often a macular rash on the first day as well as adenopathy, palatal vesicles, and scleral injection. The illness may
last a week, with additional symptoms usually including anorexia, nausea or vomiting, marked cutaneous hypersensitivity, and – near the time of defervescence – a maculopapular rash
beginning on the trunk and spreading to the extremities and the face. Epistaxis and scattered petechiae are often noted in uncomplicated dengue, and preexisting gastrointestinal lesions
may bleed during the acute illness.
Laboratory findings include leucopenia, thrombocytopenia, and, in many cases, serum aminotransferase elevations. The diagnosis is made by IgM ELISA or paired serology during
recovery or by antigen-detection ELISA or RT-PCR during the acute phase. Virus is readily isolated from blood in the acute phase if mosquito inoculation or mosquito cell culture is used.
4.
What is the management of dengue infection? Is there a role for corticosteroids?
There is no specific treatment for classic dengue fever, and most people recover within 2 weeks. To help with recovery, health care experts recommend getting plenty of bed rest,
drinking lots of fluids, and taking medicine to reduce fever.
CDC advises people with dengue fever not to take aspirin. Acetaminophen or other over-the-counter pain-reducing medicines are safe for most people.
For severe dengue symptoms, including shock and coma, early and aggressive emergency treatment with fluid and electrolyte replacement can be lifesaving.
There is no good evidence that corticosteroids are helpful in dengue shock syndrome.
5.
How is this infection prevented from recurring?
The key to control of both dengue fever and DHF/DSS is the control of A. aegypti, which also reduces the risk of urban yellow fever and chikungunya virus circulation. Control
efforts have been handicapped by the presence of nondegradable tires and long-lived plastic containers in trash repositories, insecticide resistance, urban poverty, and an inability of the
public health community to mobilize the populace to respond to the need to eliminate mosquito breeding sites.
Case 8: A Little Bite Can Go a Long Way
A 72 year old male was admitted due to agitation. Two days prior to admission he was observed to have a sudden change of behavior characterized by periods of extreme
irritability. He started complaining of difficulty in swallowing solids 5 days ago and also experienced intense pain over the left arm. He had no fever, weakness, headache or vomiting. He
recalled having bitten by his month old puppy 2 months ago. No medications were taken at that time. The puppy died 7 days after the incident of unknown causes. On PE, the patient was
alert, oriented to 3 spheres and cooperative. Neurologic examination was unremarkable except for inability to swallow liquids and solids.
Salient features:
72 year old male
Sudden change of behavior and irritability
Difficulty in swallowing solids for 5 days and intense pain over the left arm
Recalled having bitten by month old puppy 2 moths ago
1.
Describe the pathogenesis of this infection
First event in rabies is the inoculation of virus through the skin, as for our case it was through a bite of a puppy that delivers virus-laden saliva. Initial virus replication appears
to occur within striated muscle cells at the site of inoculation.
Peripheral nervous system is exposed at the neuromuscular and/or neurotendinous spindles of unmyelinated sensory nerve endings, with neurotransmitter receptors such as
acetylcholine implicated in viral attachment and internalization. The virus spreads centripetally up the nerve to the CNS, probably through peripheral nerve axoplasm.
Once the virus reaches the CNS, it replicates almost exclusively within the gray matter and then passes centrifugally along autonomic nerves to other tissues. The salivary
gland, adrenal medulla, kidneys, lungs, liver, skeletal muscles, skin, and heart. Passage of the virus into the saliva glands and viral replication in mucinogenic acinar cells facilitate
further transmission via infected saliva.
The incubation period of rabies is exceedingly variable, ranging from 7 days to more than a year (mean, 1to 2 months) and depending on the amount of virus introduced, the
amount of tissue involved, host defense mechanisms, and the actual distance that the virus has to travel form the site of inoculation to the CNS. Rates of infection of mortality are
highest from bites on the face, intermediate from bites on the hands and arms, and lowest from bites on the legs.
2.
What are the 4 stages of this infection?
a.
Nonspecific Prodrome
Duration: 1-2 days to 1 week
Features: Fever, headache, anorexia, nausea, vomiting, focal pain, paresthesia, anxiety, agitation, depression
b.
Acute Neurologic (Encephalitis)
Duration: 1-2 days to <1 week
Features: Confusion, delirium, hallucinations, dysphagia, hypersalivatoin, aphasia, icoordination, marked hyperactivity, pharyngeal spasms, hydrophobia,
aerophobia, hyperventilation, hypoxia, seizures
c.
Profound dysfunction of brainstem centers
Features: Cranial Nerve involvement- diplopia, facial palsies, optic neuritis, and difficulty with deglutition. Also foaming of the mouth and hydrophobia.
Involvement of amygloid nucleus- priapism and spontaneous ejaculation.
Coma, death
Duration: Several days to 1 week
Features: Autonomic instability, hypoventilationm apnea, respiratory arrest, hypo/hyperthermia, hypotension, pituitary dysfunction, rhabdomyolysis, cardiac
arrhythmia, cardiac arrest.
d.
3.
How is this infection diagnosed?
Two laboratory methods are commonly used to detect rabies virus- specific antibodies.
a.
Indirect fluorescent antibody test
Involves the addition of dilutions of test serum to plates with wells containing rabies virus- infected cells. If rabies antigen-specific antibodies are present in the
serum, they bind to infected cells. The bound antibody is then detected with fluorescein-tagged antihuman antibodies. This rapid test predominantly detects
antibodies to the rabies virus bucleoprotein
b.
Rapid fluorescent focus inhibition test (RFFIT)
Is a valuable but labor intensive method that takes 1 day to complete. The RFFIT requires that a fixed amount of live rabies virus dilutions of test serum be added
to cell monolayers and allowed to incubate for 20 hours. If neutralizing antibodies to the rabies virus glycoprotein are present in the patient’s serum, few or no
6
infected foci are seen when the direct fluorescent antibody (DFA) test is applied to the cell monolayer, because the viral particles will have been neutralized by
antibodies and prevented from infecting cells.
Other Test
Reverse-Transcription Polymerase Chain Reaction (RT-PCR)
Presence of rabies virus nuclei acid in fresh saliva can be confirmed or ruled out
4.
How is this managed and prevented?
There is no specific treatment for clinical rabies. Medical management is supportive and palliative.
Human rabies postexposure prophylaxis consists of five doses of modern cell culture vaccine. Doses are administered on a schedule of 0, 3, 7, 14, and 28 days. In addition to
vaccine on day 0, one dose of human rabies immune globulin (20IU/kg) should be given; as much as the dose as is anatomically feasible should be administered intramuscularly at a
distant site.
Cell culture rabies vaccine widely available
Purified chick embryo cell vaccine (PCEC)
Purified Vero cell vaccine (PVRV)
Human diploid cell vaccine (HDCV)
Purified duck embryo vaccine (PDEV)
Rabipur
Verorab, Imovax-rabies vero, TRC
Rabivac
Lyssavac
verorab
Preexposure rabies vaccination is available to persons at risk of rabies exposure. It is recommended that a series of 1-ml doses of modern cell culture vaccine be administered
intramuscularly on days 0, 7, and 21 or 28. Once immunized against rabies with potent vaccines, individuals are primed against rabies for the rest of their lives. If an exposure occurs, a
previously immunized person should receive postexposure boosters consisting of two doses 3 days apart
5.
What is the prognosis?
If you get timely, appropriate wound care and rabies shots, you will be virtually 100% protected against rabies. Rabies is 100% fatal once symptoms develop.
RHEUMATIC DISEASES
Case 1: Hot knee while mending a broken heart
A 43 y/o lawyer with a 3-year history of hypertension has recently recovered from an acute MI. his current medications include furosemide, captopril and aspirin. Three days
ago, he developed acute painful swelling of the left knee. PE showed plethoric overweight male with stable VS. L knee was warm, effuse and tender.
1.
What factors can trigger an acute gouty attack?
Acute gouty attacks can be triggered by the following:
o
alcoholic beverage binges
o
certain drugs, ie. diuretics, aspirin, cytotoxics, cyclosporine, ethambutol
o
obesity
o
hypertension
o
middle-aged persons, especially males, are prone to have gout
2.
Outline therapy for acute gout.
o
o
o
o
3.
NSAIDS [indomethacin, ibuprofen] – for relief of pain
Colchicine – traditional and effective treatment for acute attacks
Hypouricemic agents

Uricosuric agents [probenecid] - increase renal clearance of uric acid by inhibiting the renal tubular reabsorption of uric acid

Allopurinol – xanthine oxidase inhibitor, best drug to lower serum urate in overproducers and stone formers.
Corticosteroids [prednisone] – for patients who cannot tolerate NSAIDS
Enumerate 3 indications to start treatment for hyperuricemia.
o
o
o
2-3 gouty attacks/year
Presence of tophaceous gout
Urine uric acid > 800 mg/dL
Case 2: Debilitating Polyarthritis
A 34 year old factory worker had noted gradually increasing pain and swelling in several metacarpophalangeal (MCPs) and proximal interphalangeal (PIPs) joints over ten
months. She had stiffness in those and other joints that seemed worse for the first 2 hours in the morning. She was easily fatigued and was finding it difficult to keep up right with the
work, having taken frequent sick leaves in the last month. She denied fever, rash, or any other clues to generalized disease. She tried aspirin, ibuprofen, and naproxen without any help.
She brought results of laboratory tests that showed ESR 88 mm/hr, normal complete blood count and chemical profile. Rheumatoid factor was positive up to 1:640.
Guide Questions:
1. What features in the case fulfill the classification criteria for R.A.?
Based on the 1987 Criteria for the classification of rheumatoid arthritis (see below), and in relation to the case, the patient has the following:

Morning stiffness

Arthritis of 3 or more joint areas

Arthritis of the hands

Symmetric arthritis
7

Positive serum rheumatoid factor
1987 Criteria for the Classification of Acute Arthritis of Rheumatoid Arthritis
Criterion
Definition
1. Morning stiffness
Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement
2. Arthritis of 3 or more joint areas
At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a
physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints
3. Arthritis of hand joints
At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint
4. Symmetric arthritis
Simultaneous involvement of the same joint areas (as defined in 2) on both sides fo the body (bilateral involvement of
PIPs, MCPs, or MTPs is acceptable without absolute symmetry)
5. Rheumatoid nodules
Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxtaarticular regions, observed by a
physician
6. Serum rheumatoid factor
Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in
<5% of normal control subjects
7. Radiographic changes
Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include
erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints (osteoarthritis
changes alone do not qualify)

For classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at least 4 or these 7 criteria. Criteria 1 through 4 must have been
present for at least 6 weeks. Patients with 2 clinical diagnoses are not excluded. Designation as classic, definite, or probable rheumatoid arthritis is not to be made.
2. What is the significance of an elevated ESR in R.A.?
The Erythrocyte Sedimentation Rate (ESR) is increased in nearly all patients with active RA. The levels of a variety of other acute-phase reactants including ceruloplasmin
and C-reactive protein are also elevated, and generally such elevations correlate with disease activity and the likelihood of progressive joint damage.
3. Enumerate other non-rheumatic conditions which can give a positive rheumatoid factor.

Infective endocarditis- is an infection of the lining of the heart chambers and heart valves, caused by bacteria, fungi, or other infectious agents. This is an
inflammation of the heart valves.

Osteomyelitis- is an acute or chronic bone infection, usually caused by bacteria. Affected bone may have been predisposed to infection because of recent trauma.

Tuberculosis- Pulmonary tuberculosis (TB) is a contagious bacterial infection that mainly involves the lungs, but may spread to other organs. caused by a bacteria
called Mycobacterium tuberculosis (M. tuberculosis). You can get tuberculosis by breathing in air droplets from a cough or sneeze of an infected person.

Syphilis- is an easily spread infection caused by the bacteria Treponema pallidum. The bacteria that causes it spreads through broken skin or mucous membranes. It
is most often spread by sexual contact.

Hepatitis- is a general term that refers to inflammation of the liver. This condition may result from various infectious and noninfectious etiologies. Infectious etiologies
include viral, bacterial, fungal, and parasitic organisms.

Mononucleosis- is a viral infection causing fevers, sore throat, and swollen lymph glands, especially in the neck. It is usually linked to the Epstein-Barr virus (EBV), but
can also be caused by other organisms such as cytomegalovirus (CMV).

Diffuse interstitial pulmonary fibrosis- is the name given to a group of disorders characterized by inflammation and eventually scarring of the deep lung tissues,
leading to shortness of breath.

Liver cirrhosis- Cirrhosis represents the final common histologic pathway for a wide variety of chronic liver diseases. Cirrhosis is defined histologically as a diffuse
hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. The progression of liver injury to cirrhosis
may occur over weeks to years.

Sarcoidosis- is a disease of unknown cause in which inflammation occurs in the lymph nodes, lungs, liver, eyes, skin, or other tissues. The cause of the disease is
unknown. Sarcoidosis is marked byabnormal inflammatory masses(granulomas)in certain organs of the body.
4. Aside from rashes, enumerate the potential side effects of methotrexate and hydroxychloroquine.
METHOTREXATE
Possible side effects can include :

anemia,

neutropenia,

increased risk of bruising,

nausea and vomiting,

dermatitis and

diarrhea.

A small percentage of patients develop hepatitis, and there is an

increased risk of pulmonary fibrosis.
Serious side effects include:

dry cough, shortness of breath;

diarrhea, vomiting, white patches or sores inside your mouth or on your lips;

blood in your urine or stools;

urinating less than usual or not at all;

fever, chills, body aches, flu symptoms;

sore throat and headache with a severe blistering, peeling, and red skin rash;

pale skin, easy bruising or bleeding, weakness; or

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
Less serious side effects may include:

nausea, vomiting, upset stomach;

dizziness, tired feeling;

headache;

bleeding of your gums; or

blurred vision.
8
The most common side effect of methotrexate is nausea. The nausea from methotrexate use often disappears on its own though and may be controlled by lowering the dose
or spreading the dose out.
The drug can cause hidden problems too and tests are done to monitor whether or not these problems are occurring. Complete blood counts are done since methotrexate
can suppress the production of new blood cells and lead to severe forms of anemia. Liver-chemistry profiles are done to watch for possible effects on the liver. Liver damage is among
the worst potential problems since once the damage is done it is irreversible. Since most serious damage to the liver is not revealed in a blood test, a liver biopsy may be recommended
periodically.
Another potential threat from methotrexate use is lung disease. Dry cough accompanied by fever and shortness of breath could indicate such a problem. Hair loss is seen in
some patients. Some people who use methotrexate develop sores on their skin and inside their mouths. These are signs of a toxic reaction to the drug and its use may need to be
discontinued.
According to the American College of Rheumatology, "the use of folate supplements (folic and folinic acid), which are B vitamins, can decrease side effects during
methotrexate treatment."
HYDROXYCHLOROQUINE
Hydroxychloroquine may cause side effects.

headache

dizziness

loss of appetite

upset stomach

diarrhea

stomach pain

vomiting

skin rash
More serious side effects include:

reading or seeing difficulties (words, letters, or parts of objects missing)

sensitivity to light

blurred distance vision

seeing light flashes or streaks

difficulty hearing

ringing in ears

muscle weakness

bleeding or bruising of the skin

bleaching or loss of hair

mood or mental changes

irregular heartbeat

drowsiness

convulsions
Case 3: What goes up must come down
A 34-y/o male felt something snapped over his lumbosacral spinal area as he was bending to pick up a pail of water. Immediately after, he fell on his back because of severe
pain in the midgluteal region, posterior region of the right thigh and calf radiating to the heel. On examination, there was tenderness over the sacroiliac and posterior thigh areas on the R.
pain was reproduced during hip flexion as the right leg was raised. Paresthesias were present in the R lower leg and outer toes. The ankle jerk on R was diminished. Patient had difficulty
walking on toes.
1.
Enumerate 5 sources of low back pain.
o
Age-related degenerative disk and facet processes
o
Muscle- or ligament-related injuries
o
Nerve root syndromes
o
Musculoskeletal pain syndromes -myofascial pain syndromes and fibromyalgia
o
Skeletal causes - osteomyelitis, sacroiliitis, and malignancy
2.
What is the most likely source of this patient’s back pain? Explain the neurological findings.
The patient might be having a herniated disk in the lumbosacral area, causing impingement of the nerve. Impingement pain tends to be sharp, well localized, and can be associated
with paresthesia. It is associated with a positive straight leg raising sign. Neurologic deficits and pain radiation below the knee are common. Herniated disks are produced as the spinal
disks degenerate. After growing thinner, the nucleus pulposus herniates out of the central cavity against a nerve root. Intervertebral disks begin to degenerate by the third decade of life,
and herniated disks are found on autopsy in one third of adults older than 20 years. Only 3% of these, however, are symptomatic. The most common locations for herniation are L4, L5,
and S1.
 L5 nerve impingement from a herniated disc can cause weakness in extension of the big toe and potentially in the ankle (foot drop). Numbness and pain can be felt on top
of the foot, and the pain may also radiate into the rear.
 S1 nerve impingement from a herniated disc may cause loss of the ankle reflex and/or weakness in ankle push off (e.g. patients cannot do toe rises). Numbness and pain
can radiate down to the sole or outside of the foot.
3.
Is a plain spine radiograph useful? Explain your answer.
Nerve impingement is rarely seen on X ray films, thus offer little value in directing therapy. It also exposes the reproductive organs to unnecessary radiation.
Case 4: An unfortunate cascade of events
A 29 year-old bank teller presented with fever, hair loss, malaise, and joint pain. PE showed mild alopecia, tender proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints
and a malar rash.
9
Laboratory investigation indicated anemia, ANA of 1:640, elevated anti-dsDNA antibodies, low C3 complement, negative VDRL, and a normal urinalysis. A diagnosis of SLE was made
and prednisone was initiated at 40 mg/day with good response. The patient was lost to follow-up until she presented a year later with malaise, visual complaints and difficulty with thought
processes. After extensive evaluation, a diagnosis of CNS involvement secondary to SLE was made. The patient was begun on prednisone 60 mg/day to which she responded quickly.
Six months later, while on prednisone 10 mg/day, she developed fever and lethargy. Chest radiographs showed bilateral mid and lower lung field infiltrates. A diagnosis of pulmonary
hemorrhage was confirmed by lung biopsy. Because of progressive respiratory distress, she was intubated and maintained on mechanical ventilation for a brief period. Pulse
methylprednisolone therapy consisting of 1 g/day for 3 days was administered. A month after extubation, she began to complain on both hips. Hip radiographs showed evidence of
osteonecrosis.
1.
Enumerate rheumatic diseases which can present with arthritis and rash.




Systemic Lupus Erythematosus
Psoriatic arthritis
Reiter’s Syndrome
Systemic Vasculitis
o
Disseminated gonococcal infection
o
Henoch-Schönlein purpura
2.
Outline the various organ/system involvement in SLE and give an example of each.
SLE may involve virtually any organ system and have a wide range of disease severity. Common involvement are:









Constitutional – fatigue, fever, malaise, weight loss.
Cutaneous – malar rash, discoid rash, photosensitivity, alopecia, oral ulcers, vasculitis
Musculoskeletal – non-erosive, inflammatory, symmetrical polyarthritis
Hematologic – anemia (may be hemolytic), neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly, venous or arterial thrombosis
Pulmonary – pleuritis
Cardiovascular – pericarditis, pericardial effusion, myocarditis, endocarditis e.g. Libmann-Sacks (non-infective) endocarditis
Gastrointestinal – peritonitis, vasculitis, serositis manifesting as ascites, pancreatitis, nausea, abdominal pain, diarrhea
Renal – glomerulonephritis, nephritic syndrome
Neurologic – organic brain syndromes, seizures, psychosis, cerebritis
3.



What basic laboratory tests are useful in the initial diagnosis of SLE?
Complete Blood Count and ESR – anemia, neutropenia, thrombocytopenia
Urinalysis – it may show hematuria, proteinuria, cylindruria
Creatinine – useful in patients with renal manifestations
4.

Give the clinical associations of specific autoantibodies e.g. dsDNA
Antinuclear Antibodies (ANAs). A primary test for SLE checks for antinuclear antibodies (ANA), which attack the cell nucleus. In general, the ANA test is considered a
screening test. High levels of ANA are found in more than 98% of patients with SLE. A number of other conditions, however, also cause high levels of ANA, so a positive test
is not a definite diagnosis for SLE:
o
Antinuclear antibodies may be strongly present in other autoimmune diseases (such as scleroderma, Sjögren syndrome, or rheumatoid arthritis).
o
They also may be weakly present in about 20 - 40% of healthy women.
o
Some drugs can also produce positive antibody tests, including hydralazine, procainamide, isoniazid, and chlorpromazine.
Generally, the higher the titer, the more strongly lupus should be considered.
ANA Subtypes. In some cases, doctors may test for specific ANA subtypes.
o
Anti-double stranded DNA (Anti-ds DNA) is usually found only in patients with SLE. It may play an important role in injury to blood vessels found in SLE and
high levels often indicate kidney involvement. Anti-ds DNA levels tend to fluctuate over time and may even disappear.
o
Anti-Sm antibodies are also usually found only with SLE. They are more constant and are more likely to be detected in African-American patients.
o
When the ANA is negative but the diagnosis is still strongly suspected a test for anti-Ro (also called anti-SSA), and anti-La (also called anti-SSB) antibodies
may identify patients with a rare condition called ANA negative, Ro lupus.
Antibodies to SR Proteins. An advance in diagnosing SLE has been the detection of antibodies to molecules called SR proteins, which are carried by most patients. The
test accurately detects lupus in 50 - 70% of patients who test positive for these antibodies.
Antiphospholipid antibodies. In patients with SLE in whom blood abnormalities are suspected, tests will be administered to detect the presence of the two major
antiphospholipid antibodies:
o
The test for the lupus anticoagulant antibody measures the time it takes blood to clot. A longer than normal blood clotting time indicates a higher chance for
clotting in the body and, therefore, the presence of lupus anticoagulant.
o
An ELISA test (enzyme-linked immunosorbent assay) is performed to detect the anticardiolipin antibody.
As with the ANA, these antibodies also have a tendency to appear and disappear in a single patient. Patients who have these autoantibodies as well as blood clotting
problems or frequent miscarriage are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.
Complement. C3 is the most widely available. Low levels are expected in active disease. It may also portend a "flare" in a diagnosed case of lupus.
Autoantibody
Disease/s



Anti-ssDNA
Anti-Ro/SSA
Anti-histone
Anti-U1RNP
5.
SLE, RA, DM
SLE, Sjogrens syndrome, neonatal lupus
Drug-induced lupus
SLE, progressive systemic sclerosis,
polymyositis
What are some non-life threatening, and some life-threatening SLE manifestations.
10
Some non-life threatening SLE manifestations










6.
Some life-threatening SLE manifestations






Fever
Fatigue
Rashes
Alopecia
Myalgia
Arthritis
Oral ulcers
Lymphadenopathy
Anemia
Mild headache
Sepsis
Severe pulmonary hypertension
Myocardial infarction
Congestive heart failure
Acute renal failure
Intractable seizures
Differentiate the various steroid preparations. Enumerate the side effects of long term steroid therapy.
AGENT
ANTI-INFLAM.
TOPICAL
SALT-RETAINING
EQUIVALENT
DOSE
ORAL
FORMS AVAILABLE
SHORT - MEDIUM ACTING
Hydrocortisone
1
1
1
20
Oral, Injectable, topical
Cortisone
0.8
0
0.8
25
Oral, injectable, topical
Prednisone
Prednisolone
4
5
0
4
0.3
0.3
5
5
Oral
Oral, injectable, topical
Methylprednisolone
5
5
0
4
Oral, injectable, topical
Meprednisone
INTERMEDIATE ACTING
Triamcinolone
5
-
0
4
Oral, injectable
5
5
0
4
Oral, injectable, topical
Paramethasone
Fluprednisolone
LONG ACTING
Betamethasone
10
15
7
0
0
2
1.5
Oral, injectable
Oral
25-40
10
0
0.6
Oral, injectable, topical
Dexamethasone
30
10
0
0.75
Oral, injectable, topical
Side Effects of Long-Term Oral Corticosteroids.
Unfortunately, serious and even life-threatening complications have been associated with long-term steroid use. The bone-thinning condition osteoporosis is a common and particularly
severe long-term side effect of prolonged steroid use.
Other side effects associated with prolonged use of oral steroids include:
 Weight gain, centripetal fat deposition (leading to moon facies and cervical fat pad)
 Susceptibility and increased risk of bacterial and opportunistic infections such as tuberculosis and fungal infections
 Cataracts, glaucoma
 Excess hair growth / hirsutism
 Hypertension, myopathy, accelerated atherosclerosis, dyslipidemia
 Diabetes / hyperglycemia / glucose intolerance
 Fluid retention leading to edema, electrolyte abnormalities (hypokalemia)
 Wasting of the muscles
 Osteonecrosis, osteoporosis
 Menstrual irregularities
 Irritability, insomnia, psychosis
7.
Outline the simple "do's and "don'ts" for any patient with SLE.
"Do's" in patients with SLE.

Patients should exercise. And it would be best if they do it in a daily basis. Exercise is safe, but patients should not expect it to improve symptoms, including joint aches and
fatigue.

Patients should have a healthy and a balanced diet.
o
Eat a diet low in saturated fats. Not all fats are unhealthy. Some studies suggest that omega-3 fatty acids, which are fat compounds found in fish oil, black currant
or primrose seed oils, and flax seed, have anti-inflammatory and nerve protecting actions.
o
Choose whole grains and fresh vegetables and fruits.
o
Get most proteins from vegetables, particularly soy.
o
Avoiding dairy and meat products may help protect the kidneys.
o
Take extra calcium and vitamin D (this is particularly useful for patients taking corticosteroids).
o
Supplements of vitamins B12, B6, and folate may be necessary, especially in people whose blood tests show high levels of homocysteine.
o
Restrict salt (particularly for patients with signs of high blood pressure and kidney disease).
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





Avoid SLE triggers. Simple preventive measures include avoiding overexposure to ultraviolet rays and wearing protective clothing, and sunscreen lotions/sunblocks. You can
also wear a hat or use umbrella if patients must be out in the sun. There is some concern that allergy shots may cause flare ups in certain cases. Patients who may benefit
from them should discuss risks and benefits with an SLE specialist. In general, patients with SLE should use only hypoallergenic cosmetics or hair products.
Patients should be compliant and take their medications regularly.
Patient should have awareness on prevention of infections. Patients should minimize their exposure to crowds or people with contagious illnesses. Careful hygiene, including
dental hygiene, is also important.
Patients should also try their best in reducing stress. Chronic stress has profound physical effects and influences the progression of SLE. According to one study, patients
with SLE differ from healthy individuals in their immune responses to stress, and psychological stress can induce flare-ups in patients with SLE. Patients should try to avoid
undue emotional or physical stress. Getting adequate rest of at least 8 hours and possibly napping during the day may be helpful. Maintaining social relationships and healthy
activities may also help prevent the depression and anxiety associated with the disease.
Patients should be aware about SLE so they will be able to understand it better.
Patients should see their doctors regularly.
"Don'ts" in patients with SLE.




Patients should avoid too much outdoor activities during noon/peak sunlight hours usually during 10AM – 4PM.
They also shouldn't miss their regular medications.
They should not eat too much salty and fatty foods, so they should restrict it (particularly salt for patients with signs of high blood pressure and kidney disease).
Women with SLE should not get pregnant if their lupus is active. And they shouldn't take contraceptive pills either.
8.
What are other causes of osteonecrosis?
The causes of osteonecrosis are divided into two categories: post-traumatic osteonecrosis and non-traumatic osteonecrosis.
Post-traumatic osteonecrosis refers to the onset of the bone condition after experiencing a significant trauma. A severely broken bone or dislocated joint is typically the underlying cause
behind the development of osteonecrosis.
Non-traumatic osteonecrosis refers to the onset of the bone condition for reasons unrelated to a physical trauma. People may be more susceptible to development of the bone condition if
they have a history of diseases or activities known to disrupt blood supply, such as:

alcoholism, smoking

pregnancy

dysbarism (the “bends” that occur with scuba-diving)

embolism

hematologic disorders/blood clotting disorders such as thalassemia and sickle cell disease

kidney disease

connective tissue disease such as vasculitis and rheumatoid arthritis

proliferative disorders (such as solid tumors)

metabolic disorders such as gout

treatment with high levels of corticosteroids

use of cytotoxic drugs e.g. vincristine, cisplatin, 5-fluorouracil

radiation therapy
Oftentimes the condition has unknown causes and is referred to as an idiopathic case of osteonecrosis.
More recently, a family of drugs called bisphosphonates has been linked with the development of non-traumatic osteonecrosis. It may be that bisphosphonate medications, such as
alendronate or risedronate, when used to treat osteoporosis, interfere with the body’s ability to repair bone after dental trauma/surgery, or infection.
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