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A N E V I D E N C E - B A S E D A P P ROAC H T O E M E RG E N C Y M E D I C I N E
September 2002
Dermatologic Emergencies:
Diagnosing And Managing
Life-Threatening Rashes
Volume 4, Number 9
Authors
Thomas Nguyen, MD
Assistant Professor of Emergency Medicine, Mount Sinai
School of Medicine, New York, NY.
Jessica Freedman, MD
Assistant Professor of Emergency Medicine, Associate
Residency Director and Mount Sinai Residency Site
Director, Mount Sinai School of Medicine, New York, NY.
March 15, 2001: You see a patient for “fatigue.” This 52-year-old man was
recently discharged from the hospital on ticlopidine and methyldopa. When you
enter the room, he is fully clothed in a suit and tie—another violation of the ED’s
“get naked” policy (which is more honored in breach than observance). He looks
okay—he’s certainly well-dressed, and through his coat, his lungs sound clear.
Looks like another “viral syndrome.”
February 25, 2002: You receive an ominous-looking certified letter. The
complaint is lengthy but you understand the gist. A patient you had seen almost a
year ago died two days after his visit from an intracerebral bleed. The plaintiff’s
lawyers cite a triage note that documented complaints of “fatigue and rash”; your
record did not mention a rash. The attached pathology report listed the cause of
death as “medication-induced TTP.”
Peer Reviewers
Marianne C. Burke, MD
Consultant, Burke Emergency Medicine Consultants,
Glendale, CA.
Stephen J. Playe, MD, FACEP
Assistant Professor, Emergency Medicine, Tufts
University School of Medicine; Residency Program
Director, Department of Emergency Medicine, Baystate
Medical Center, Western Campus of Tufts University
School of Medicine, Springfield, MA.
W
HILE most rashes seen in the ED are benign, some indicate a serious
or even life-threatening medical illness. This issue of Emergency
Medicine Practice provides a systematic approach to managing dangerous
dermatologic complaints.
CME Objectives
State Of The Literature
Guidelines and evidence-based literature regarding dermatologic emergencies are sparse. An extensive search using MEDLINE, the Cochrane Collaboration, and www.guidelines.gov (the National Guideline Clearinghouse)
yielded no guidelines on life-threatening rashes. While specific guidelines
exist for “mycotic infections” or “psoriasis,” the only relevant guideline
regards cutaneous adverse drug reactions.1
The classification of various skin diseases has changed over time,
further confounding the literature. Many of the earlier studies on StevensJohnson syndrome and toxic epidermal necrolysis erroneously grouped
Editor-in-Chief
Stephen A. Colucciello, MD, FACEP,
Assistant Chair, Department of
Emergency Medicine, Carolinas
Medical Center, Charlotte, NC;
Associate Clinical Professor,
Department of Emergency
Medicine, University of North
Carolina at Chapel Hill, Chapel
Hill, NC.
Associate Editor
Andy Jagoda, MD, FACEP, Professor
of Emergency Medicine; Director,
International Studies Program,
Mount Sinai School of Medicine,
New York, NY.
Editorial Board
Judith C. Brillman, MD, Residency
Director, Associate Professor,
Department of Emergency
Medicine, The University of
New Mexico Health Sciences
Center School of Medicine,
Albuquerque, NM.
W. Richard Bukata, MD, Assistant
Clinical Professor, Emergency
Medicine, Los Angeles County/
USC Medical Center, Los Angeles,
CA; Medical Director, Emergency
Department, San Gabriel Valley
Medical Center, San Gabriel, CA.
Francis M. Fesmire, MD, FACEP,
Director, Chest Pain—Stroke
Center, Erlanger Medical Center;
Assistant Professor of Medicine,
UT College of Medicine,
Chattanooga, TN.
Valerio Gai, MD, Professor and Chair,
Department of Emergency
Medicine, University of Turin, Italy.
Michael J. Gerardi, MD, FACEP,
Clinical Assistant Professor,
Medicine, University of Medicine
and Dentistry of New Jersey;
Director, Pediatric Emergency
Medicine, Children’s Medical
Center, Atlantic Health System;
Vice-Chairman, Department of
Emergency Medicine, Morristown
Memorial Hospital.
Michael A. Gibbs, MD, FACEP, Chief,
Department of Emergency
Medicine, Maine Medical Center,
Portland, ME.
Gregory L. Henry, MD, FACEP,
CEO, Medical Practice Risk
Assessment, Inc., Ann Arbor,
MI; Clinical Professor, Department
of Emergency Medicine,
University of Michigan Medical
School, Ann Arbor, MI; President,
American Physicians Assurance
Society, Ltd., Bridgetown,
Barbados, West Indies; Past
President, ACEP.
Jerome R. Hoffman, MA, MD, FACEP,
Professor of Medicine/Emergency
Medicine, UCLA School of
Medicine; Attending Physician,
UCLA Emergency Medicine Center;
Co-Director, The Doctoring
Program, UCLA School of Medicine,
Los Angeles, CA.
Francis P. Kohrs, MD, MSPH, Associate
Upon completing this article, you should be able to:
1. describe indicators that a rash may have a potentially
life-threatening cause;
2. list aspects of the history and physical examination
that may help identify life-threatening rashes;
3. discuss the differential diagnosis for maculopapular,
petechial/purpuric, diffuse erythematous, and
vesiculo-bullous rashes, emphasizing life-threatening
causes of each; and
4. describe the proper disposition for patients with lifethreatening rashes.
Date of original release: September 1, 2002.
Date of most recent review: August 7, 2002.
See “Physician CME Information” on back page.
Professor and Chief of the Division
of Family Medicine, Mount Sinai
School of Medicine, New York, NY.
John A. Marx, MD, Chair and Chief,
Department of Emergency
Medicine, Carolinas Medical
Center, Charlotte, NC; Clinical
Professor, Department of
Emergency Medicine, University
of North Carolina at Chapel Hill,
Chapel Hill, NC.
Michael S. Radeos, MD, MPH,
Attending Physician, Department
of Emergency Medicine,
Lincoln Medical and Mental
Health Center, Bronx, NY;
Assistant Professor in Emergency
Medicine, Weill College of
Medicine, Cornell University,
New York, NY.
Steven G. Rothrock, MD, FACEP, FAAP,
Associate Professor
of Emergency Medicine, University
of Florida; Orlando Regional
Medical Center; Medical Director of
Orange County Emergency
Medical Service, Orlando, FL.
Alfred Sacchetti, MD, FACEP,
Research Director, Our Lady of
Lourdes Medical Center, Camden,
NJ; Assistant Clinical Professor
of Emergency Medicine,
Thomas Jefferson University,
Philadelphia, PA.
Corey M. Slovis, MD, FACP, FACEP,
Professor of Emergency Medicine
and Chairman, Department of
Emergency Medicine, Vanderbilt
University Medical Center;
Medical Director, Metro Nashville
EMS, Nashville, TN.
Mark Smith, MD, Chairman,
Department of Emergency
Medicine, Washington Hospital
Center, Washington, DC.
Charles Stewart, MD, FACEP,
Colorado Springs, CO.
Thomas E. Terndrup, MD, Professor
and Chair, Department of
Emergency Medicine, University
of Alabama at Birmingham,
Birmingham, AL.
evolution or various external factors such as scratching,
healing, medications, and infections transform primary
lesions into secondary lesions.
Pattern recognition is the key to the correct diagnosis
of an unknown rash. Peter Lynch developed a taxonomy
in which an unknown rash is classified based on its major
these conditions as variants of erythema multiforme.
Epidemiology
Dermatologic complaints account for approximately 5%
of all ED visits. However, there are limited epidemiologic
data that analyze the types of rashes seen in EDs. One
pediatric ED reported that 31% of the cases primarily
involved the skin. Most cases were classified as contusions, lacerations, and burns; non-traumatic causes
included viral exanthems, bacterial infections, and
contact dermatitis.2 In one survey, the most common skin
complaints diagnosed by internists were dermatitis (16%
of all diagnoses), bacterial skin infections (14%), fungal
infections (5%), and acne vulgaris (5%).3 The emergency
physician is more likely to encounter the life-threatening
rashes, such as meningococcemia, toxic epidermal
necrolysis, or toxic shock syndrome.
Table 1. Common Skin Lesions.
“A thick skin is a gift from God.”
—Konrad Adenauer (1876-1976), German statesman
Lesion type
Macule
Description
Circumscribed area of change in normal
skin color with no skin elevation
Papule
Solid, raised lesion up to 0.5 cm in
diameter; variable color
Nodule
Similar to papule but located deeper in
the dermis and subcutaneous tissue;
more than 0.5 cm in diameter
Plaque
Circumscribed elevation of skin more
than 0.5 cm in diameter; often a
confluence of papules
Pustule
Circumscribed area of skin containing
purulent fluid
Vesicle
Circumscribed, elevated, fluid-filled
lesion up to 0.5 cm in diameter
Bulla
Circumscribed, elevated, fluid-filled
lesion greater than 0.5 cm in diameter
Petechiae
Small red or brown macules up to 0.5
cm in diameter that do not blanch
with pressure
Purpura
Circumscribed petechiae more than
0.5 cm in diameter
Scales
Excess dead epidermal cells produced
by abnormal keratinization; scaling in
sheets is desquamation
Pathophysiology
The skin is comprised of three layers: the epidermis, the
dermis, and the subcutaneous layer. The epidermis
contains basal cells and keratinocytes, which form a
protective barrier. Melanocytes produce the pigment that
filters ultraviolet radiation. The dermis is comprised of
connective tissues—collagen, elastin, and reticular
fibers—which provide strength and elasticity to the skin.
The subcutaneous layer contains mostly fat cells and
connective tissue. Sweat glands, hair follicles, nerves,
capillaries, and veins are dispersed within these
three layers.
When these capillaries leak blood into the skin,
petechiae appear. Leakage results from perivascular
inflammation and/or thrombocytopenia. Petechiae are
often first seen in dependent areas such as the ankles and
wrists. If the petechiae are greater than 0.5 cm in size,
they become purpura. In vasculitis, the purpura can
become palpable.
The dermal-epidermal junction deserves special
mention. It is the site of immunoglobulin and complement deposition and is the origin of blisters in diseases
such as pemphigus and Stevens-Johnson syndrome.
Immunofluorescence assays performed at the dermalepidermal junction can help diagnose vesiculo-bullous
skin disease.
Table 2. Secondary Skin Lesions.
Differential Diagnosis And Terminology
Common terminology is essential to describe cutaneous
lesion, categorize rashes, and facilitate communication
among clinicians. These descriptive terms are also crucial
in developing a differential diagnosis.
A lesion is a general term for a single, small area of
skin disease. A rash is the result of a more extensive
process and generally involves many lesions. Table 1 lists
some common terminologies for primary skin lesions,
while Table 2 addresses secondary skin lesions. Disease
Emergency Medicine Practice
2
Lesion type
Erosion
Description
Focal loss of epidermis; heals
without scarring
Ulcer
Focal loss of epidermis and dermis;
heals with scar
Excoriation
Linear or angular erosions due
to scratching
Crust
A collection of dried serum and
cellular debris
Lichenification
Area of thickened epidermis that
results from habitual rubbing
Atrophy
A depression in the skin resulting
from thinning of the epidermis
or dermis
Scales
Shedding of excess dead epidermal
cells that are produced by keratinization
and shedding
www.empractice.net • September 2002
Emergency Department Evaluation
morphology, which has since been adopted by many
clinicians.4,5 The Clinical Pathway on page 13, “Evaluating The Unknown Rash,” presents a modified Lynch
algorithm using six major morphological groups and lists
the differential diagnoses of potentially life-threatening
rashes according to the clusters.
Triage/Initial Nursing Interventions
The triage nurse should rapidly identify those patients
with a rash who appear seriously ill or likely to decompensate. High-risk patients include those with abnormal
vital signs, altered mental status, or potential airway
compromise. A petechial rash should also prompt early
physician involvement, especially when accompanied by
fever or confusion. In some hospitals, patients with fever
and a rash are placed in respiratory isolation, especially if
the patient is immunocompromised. The triage nurse
should ensure early isolation of patients with lesions
compatible with chickenpox or meningococcemia.
All toxic-appearing patients with a rash require IV
access, an ECG, and pulse oximetry monitoring. Oxygenation, perfusion, and a bedside blood sugar must be
assessed in all patients with altered mental status.
Prehospital Care
As a general rule, prehospital care providers should
always use standard precautions and assume all bodily
fluids or weeping lesions are infectious. In a patient with
a fever and a petechial/purpuric rash (i.e., suspected
meningococcemia or viral hemorrhagic fever), respiratory
and contact isolation are advised, including a properly
fitting mask for both the healthcare provider and the
patient. The ambulance should be well-ventilated in
order to eliminate potentially infectious airborne droplets.6 All equipment contaminated with blood or bodily
fluids should be wiped down with a disinfectant solution, such as bleach diluted with water. These same
protocols are used to disinfect a hospital room occupied
by a patient with meningococcemia. If the patient is
hypotensive, medics should give IV normal saline while
en route to the hospital.
Red Flags
Look for the following “red flags” when evaluating a
patient with an unknown rash, as these may indicate
serious illness. (See Table 3.)
Fever suggests that an infectious or inflammatory
process may be present. Infants and the elderly are more
Table 3. Red Flags That A Rash May Potentially Be Life-Threatening.
History or physical findings
Significance
Fever
Viral exanthem, septicemia, Rocky Mountain spotted fever, toxic shock syndrome,
erythema multiforme, Kawasaki disease, Stevens-Johnson syndrome, toxic
epidermal necrolysis
Age: Very young
Meningococcemia, Kawasaki disease, viral exanthem
Age: Elderly
Meningitis, pemphigus vulgaris, sepsis, meningococcemia, toxic epidermal
necrolysis, Stevens-Johnson syndrome, hypersensitivity syndrome, toxic
shock syndrome
Toxic-appearing
Necrotizing fasciitis, meningococcemia, toxic epidermal necrolysis, StevensJohnson syndrome, hypersensitivity syndrome, toxic shock syndrome, Rocky
Mountain spotted fever
Immunocompromised
Meningococcemia, herpes zoster, septicemia, necrotizing fasciitis, (asplenia,
alcoholic, debilitated)
Adenopathy
Drug reaction, hypersensitivity syndrome, viral illness
Diffuse erythroderma
Staphylococcal scalded skin syndrome, toxic shock syndrome, streptococcal toxic
shock syndrome, necrotizing fasciitis
Petechiae/purpura
Meningococcemia, necrotizing fasciitis, vasculitis, disseminated intravascular
coaugulopathy, Rocky Mountain spotted fever
Mucosal/oral lesions
Erythema multiforme major, toxic epidermal necrolysis, Stevens-Johnson
syndrome, pemphigus vulgaris
Hypotension
Toxic shock syndrome, meningococcemia, Rocky Mountain spotted fever,
toxic epidermal necrolysis, Stevens-Johnson syndrome
Severe localized pain/tenderness in extremity
Necrotizing fasciitis, cellulitis
Recent new drug use (1-4 weeks)
Cutaneous drug reaction, photosensitivity, erythema multiforme, toxic epidermal
necrolysis, Stevens-Johnson syndrome, hypersensitivity syndrome
Arthralgias
Rocky Mountain spotted fever, drug reaction, viral illness
September 2002 • www.empractice.net
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Emergency Medicine Practice
4. Is the lesion pruritic? Itching is probably a primitive
form of pain, mediated by histamine released by
mast cells. Other mediators of itch include opioid
peptides, prostaglandins, and tachykinins. Diffuse
pruritus without a rash can be seen in biliary
cirrhosis or certain cancers, especially lymphomas.
Pruritus with a diffuse rash may be from an acute
allergic reaction or other inciting agents, such as
dermatitis herpetiformis from gluten sensitivity.
Scabies and poison ivy, in particular, usually present
with a profound itch, although the most common
reason for pruritus is xerosis (dry skin).10
5. Has there been any recent travel? Travel to certain
geographical regions may expose the patient to
organisms not typically seen in your ED. For
example, a petechial rash in someone who has been
to a wooded area may be Rocky Mountain spotted
fever or ehrlichiosis. Lyme disease is endemic in the
Northeast, mid-Atlantic, north Central, and far West
regions of the United States.11 Consider typhus if
there is a history of flea bites, travel to the southwestern United States, and a maculopapular rash
that spreads from the trunk to the extremities.
Hemorrhagic fevers present with a maculopapular
rash and recent travel; dengue fever is endemic to
parts of the Caribbean, while Ebola is found in subSaharan Africa.
6. What is the patient’s past medical history? A person’s
medical history may predispose him or her to certain
dermatologic findings. For example, patients with an
artificial heart valve, cardiac valvular lesions, or IV
drug use may have endocarditis. Certain cutaneous
conditions tend to recur in the same patient, such as
herpes zoster associated with HIV or recurrent
erythema multiforme following herpes simplex or
mycoplasma infections.
Inquire about the patient’s immune status. An
asplenic or immunocompromised patient is susceptible to encapsulated organisms such as meningococcemia. HIV disease and chemotherapy predispose to
thrombotic thrombocytopenic purpura, while those
who are diabetic, debilitated, or alcoholic are
vulnerable to necrotizing fasciitis.
7. What is the patient’s occupation? Daycare workers,
college students, and military personnel are susceptible to outbreaks of meningococcemia, while postal
workers or healthcare professionals may be exposed
to anthrax. Consider tularemia in a game trapper
who presents with regional adenopathy, an ulcerated
lesion, and flu symptoms.
8. What medications is the patient taking? Cutaneous drug
reactions occur in about 2%-3% of hospitalized
patients and 1% of outpatients.12 While most reactions are benign maculopapular or fixed eruptions,
life-threatening presentations may occur. Such
potentially lethal conditions include StevensJohnson syndrome and toxic epidermal necrolysis.
Immediate life-threatening drug reactions include
anaphylaxis and angioedema, both of which can
prone to infections due to a decrease in their immune
status. While most patients with rash and fever have a
benign viral exanthem, fever will also accompany lethal
conditions such as Rocky Mountain spotted fever and
meningococcemia. Other causes of fever include malignancy and certain medications.
Petechiae or purpura can be seen in some benign
conditions; however, their presence should “raise the
antennae” of the emergency physician.
Lesions of the oral or genital mucosa, as seen in
Stevens-Johnson syndrome, may suggest that a severe
systemic process is present, usually due to drugs or an
infectious process.
Altered mental status or confusion should alert the
emergency physician to the possibility of sepsis,
hypoperfusion, and central nervous system involvement,
as seen in meningococcemia.
Most rashes are not significantly painful, nor are
they exquisitely tender to the touch. Patients who have
pain out of proportion to tenderness of an extremity may
have necrotizing fasciitis. (Necrotizing fasciitis is discussed in further detail in the January 2001 issue of
Emergency Medicine Practice, “Skin And Soft-Tissue
Infections: The Common, The Rare, And The Deadly.”)
History
Gathering data about the character and progression
of the rash, along with other key elements of the patient
history, is essential to detect life-threatening rashes.
The following key questions should be a part of every
patient history:
1. When did the rash appear, and how quickly did it
progress? The most lethal rashes often progress
rapidly. Acute urticaria with anaphylaxis can start
within minutes after contact with the inciting agent.
(See the April 2000 issue of Emergency Medicine
Practice, “Allergic Emergencies And Anaphylaxis:
How To Avoid Getting Stung.”) The petechial rash of
Rocky Mountain spotted fever generally occurs four
days after exposure but will then spread swiftly.7 In
meningococcemia, the rash can progress over hours.
A non-allergic drug-induced rash can take days or
weeks to evolve.8
2. Did the rash change over time? Certain rashes change
their morphology over time. For example, the
lesion of anthrax begins as a pruritic papule that
then forms an ulcer over 24-48 hours, finally becoming a black eschar after seven days. (See the July
2002 issue of Emergency Medicine Practice,
“Bioterrorism And The Emergency Physician:
On The Front Lines.”)
3. What was the progression of the rash? Where did the
rash start? Vasculitic rashes generally spread in a
peripheral-to-central pattern, whereas viral rashes
(e.g., varicella) start centrally and spread peripherally.9 A localized rash that does not progress may
mean a contact dermatitis depending on the
situation (e.g., dermatitis on both hands after
wearing latex gloves).
Emergency Medicine Practice
4
www.empractice.net • September 2002
General Appearance And Vital Signs
compromise the airway.13
Determine whether the patient used any creams
or medications that may have altered the morphology of the rash. Diphenhydramine or topical
corticosteroids may decrease the erythema or
urticaria of a histamine-mediated rash.
Before closely examining the rash, assess the general
appearance of the patient. Abnormal vital signs or
evidence of toxicity should prompt interventions and
accelerate the evaluation.
Head-To-Toe Examination
Physical Examination
• Head: Look at the patient’s scalp, conjunctiva, and
oral mucosa. Oral ulcers or blisters imply a serious
systemic reaction, as seen, for example, in StevensJohnson syndrome or pemphigus vulgaris. The
presence of oral thrush suggests HIV-related disease
(although it can be seen in patients with uncontrolled
diabetes and those who have recently completed a
course of antibiotics). Conjunctival injection is found
in Kawasaki disease and viral syndromes. When
endocarditis is a possibility, a funduscopic exam may
reveal Roth’s spots, which appear as white-centered
retinal hemorrhages.
• Neck: In the ill-appearing patient, check for nuchal
rigidity and other meningeal signs. In potential cases
of anaphylaxis, look for signs of airway compromise,
such as stridor, drooling, or laryngeal swelling.
• Lymph nodes: Adenopathy is a nonspecific finding
seen with drug reactions such as serum sickness and
hypersensitivity syndrome. Adenopathy may be
associated with infections, including viral, bacterial,
rickettsial, and spirochetal disease. Mononucleosis is
a common cause of generalized adenopathy. The
acute retroviral syndrome that occurs with the initial
Perform the physical examination in a systematic fashion
from head to toe, paying special attention to abnormal
vital signs. When evaluating a rash, the “get naked”
policy should be enforced (for the patient). Patients often
remain blissfully unaware of a rash on their back,
buttocks, perineum, or soles. Look carefully for involvement of the mucous membranes (mouth, lips, conjunctiva, anus, and vagina). Adequate exposure and good
lighting are important when looking at a rash; natural
light or white light is recommended. Touch the rash
(with gloved hands, as lesions of secondary syphilis
are contagious and no one knows how far scabies can
jump). Press on lesions to see whether they blanch to
better diagnose petechiae. Rub erythematous skin to
see if it sloughs. This result, known as Nikolsky’s sign,
signifies a potentially life-threatening diagnosis such
as toxic epidermal necrolysis.
The goal of the physical examination is not
necessarily an instant diagnosis. In many cases, it
is enough to detect toxicity and categorize the rash
so that it can be identified with the aid of books or
a consultant.
Pearls And Pitfalls In Patients With Rashes
members) and certain medical personnel (those in
contact with respiratory droplets). Contact the local
health department to assist in notification.
1. In Rocky Mountain spotted fever (RMSF), don’t just give
just any broad-spectrum antibiotic. Give doxycycline (or,
if it is contraindicated, as in pregnancy,
chloramphenicol). Other regimens will not work. If you
cannot quickly distinguish RMSF from
meningococcemia, treat for both.
5. For patients with meningococcemia, a skin biopsy and
Gram’s stain of the cutaneous lesion are much more
sensitive than CSF analysis. While CSF analysis is the
gold standard for meningitis, for meningococcemia,
it’s blood cultures .
2. If a drug is suspected as the cause for a severe
cutaneous drug reaction, stop it immediately.
Withdrawal of the offending drug reduces the risk of
death by about 30% a day. Do not start a chemically
related drug.
6. EM minor and major usually occur secondary to
infection. Drugs commonly cause toxic epidermal
necrolysis and Stevens-Johnson syndrome.
3. Consider infections as a cause for a “drug allergy.” Viral
exanthems are by far more common than true drug
allergies, especially in the pediatric population. The
“ampicillin rash” is a classic example. This prevents the
patient having an extensive list of “drug allergies.”
7. Toxic shock syndrome (caused by Staphylococcus or
Streptococcus) presents with high fever, rash, hypotension,
and mucous membrane involvement. Streptococcal toxic
shock has a higher morbidity and mortality and is
associated with bacteremia in 60% of cases.
4. Remember to give antibiotic prophylaxis to contacts of
patients with meningococcemia. These include close
contacts (school mates, dorm mates, household
September 2002 • www.empractice.net
8. About 80% of streptococcal toxic shock syndrome cases are
associated with a soft-tissue or skin infection. ▲
5
Emergency Medicine Practice
•
•
•
•
•
•
around the ankles and wrists. The petechial rash
of Rocky Mountain spotted fever spreads from the
wrists and ankles toward the body (centripetal
spread). Pain out of proportion to tenderness is
found with necrotizing fasciitis; in this case, the
affected limb may become tense with shiny
erythema. (See the January 2001 issue of Emergency
Medicine Practice, “Skin And Soft-Tissue Infections:
The Common, The Rare, And The Deadly.”) Sparse
hemorrhagic pustules about the hands and feet
imply gonococcemia.
• Joints: Arthralgias are thought to be the result of
antibody-antigen deposits in joints and may be a
sign of serum sickness. Arthralgias with a rash are
seen in Rocky Mountain spotted fever, drug reactions, and bacterial and viral illnesses. Disseminated
gonococcal infection may present with frank arthritis
and a meager hemorrhagic-pustular rash.
• Palms and soles: Involvement of the palms and soles
usually signifies inflammation of the small vessels
and can be drug-induced or pathogen-induced.8 The
classic target lesions of erythema multiforme are
often found on the palms and soles. The “nickel and
dime” lesions of secondary syphilis are similarly
prominent in these areas. In secondary syphilis, these
symmetric lesions begin as faint papulosquamous
macules that darken over time. In toxic epidermal
necrolysis, Kawasaki disease, scarlet fever, and toxic
shock syndrome, there is late desquamation of the
hands and feet. However, since desquamation
usually occurs 7-10 days after the acute illness, this
finding is usually not helpful in the ED.
• Nails and fingers: These areas provide important clues
to the diagnosis of endocarditis. Splinter hemorrhages are found under the nails, while Osler’s
nodes are pea-sized subcutaneous nodules in the
pulp of the fingers or toes. Janeway lesions are nontender erythematous, hemorrhagic macules on the
palmar aspect of the fingers.
infection of HIV presents as a “mono-like” illness
with diffuse rash and generalized lymphadenopathy.
Look for regional lymphadenopathy as well.
Patients with Kawasaki disease usually demonstrate
cervical lymphadenopathy, with at least one lymph
node measuring 1.5 cm or more in diameter. Postauricular nodes accompany adenovirus infection. In
addition to the cervical nodes, evaluate for adenopathy proximal to an extremity lesion. The axillary
nodes are often swollen in cutaneous anthrax of the
upper extremity.
Lung: Observe for signs of bronchial constriction
and edema, such as tachypnea, wheezing, and
retractions that may accompany acute allergic
reactions or early sepsis.
Cardiovascular: While most heart murmurs are
either functional or benign, they may be associated
with endocarditis—especially in the setting of IV
drug abuse.
Abdominal: Palpate for hepatosplenomegaly, which
can occur with drug hypersensitivity or viral illness.
Non-surgical diffuse abdominal pain may occur with
allergic angioedema, while dull right upper quadrant
pain suggests a hepatitis-related rash. Look for a
laparotomy scar. If present, ask the patient, “Are you
sure you still have your spleen?”
Trunk and chest: Most viral exanthems start on the
trunk and then spread to the extremities (centrifugal
spread). These rashes are fine, macular papular
erythematous eruptions that usually become
confluent. Drug allergies usually begin on the trunk
as discrete macules/papules, which spare the face,
and then spread to the extremities. Bullous lesions in
a dermatomal pattern are likely to be herpes zoster.
Fine, scaling, faint pink papules in a “Christmas
tree” pattern in the trunk may be pityriasis rosea,
especially if accompanied by a “herald patch.” This
oval lesion marks the first appearance of pityriasis
rosea and is usually found on the trunk. It measures
1-2 cm in diameter and has central pink area,
sometimes lined with small scales, surrounded by a
darker peripheral zone.
Genital: Look in the mucosal areas of the anus and
scrotum or vulva for target lesions and bullous
lesions characteristic of erythema multiforme or
Stevens-Johnson syndrome.
Tinea cruris and erythrasma are also found in
the genitocrural area. Both conditions present with a
finely wrinkled, scaly rash that is reddish-brown in
color. When erythrasma is viewed under a Wood’s
lamp, it fluoresces a bright coral red. Diffuse tender
erythema around the scrotal and perineal areas
(especially if associated with subcutaneous air) may
represent Fournier’s gangrene. (See the November
2000 issue of Emergency Medicine Practice, “Male
Genitourinary Emergencies: Preserving Fertility And
Providing Relief.”)
Extremities: Palpable purpura and petechiae
usually present in the extremities, especially
Emergency Medicine Practice
“I’m tired of all this nonsense about beauty being only
skin-deep….What do you want—an adorable pancreas?”
—Jean Kerr
The Skin Examination
First, the clinician should get an overall view of the rash,
and then the primary lesion can be closely examined. A
magnifying glass may be helpful when looking at a single
lesion. The lesion should be palpated with a gloved
finger to assess its texture and to see if the lesion
blanches. If it is unclear whether a lesion blanches, use a
glass slide to compress the area.
The following four major skin signs should be noted
during the evaluation of any skin lesion or rash:14
1. Type of lesion: This description should be for the
representative lesion, as described in Table 1. Note if
there are any secondary changes or if there are
scaling, crusts, or fissures, as described in Table 2.
Determine the color of the lesion and assess for
6
www.empractice.net • September 2002
cian believes the patient has a 20% or greater chance of
harboring active disease.16
erythema, desquamation, and tenderness.
2. Shape of the individual lesion: Is the lesion round, oval,
annular (ringed-shaped as in anthrax), iris-shaped
(as in erythema multiforme), umbilicated (molluscum), or irregular (petechial)?
3. Arrangement of multiple lesions: Are the lesions
isolated, grouped (linear, annular, serpiginous),
or disseminated (scattered discrete lesions, or
diffuse involvement as in viral exanthem or drug
allergy)? Linear patterns not in a dermatomal
distribution usually signify contact dermatitis
(e.g., poison ivy) and, when located in the finger
web spaces, scabies. A scattered, diffuse macular
rash suggests a drug allergy.
4. Pattern of the rash: Pattern is the functional/physiologic arrangement of the lesion, such as sunexposed area, flexor/extensor surface, or hairbearing areas. Also, note if the distribution is
symmetrical or unilateral. Bilateral symmetry
usually signifies a systemic internal event, whereas
isolated lesions indicate a local process such as
contact dermatitis. A rash in a sun-exposed distribution is compatible with a photosensitive drug
reaction (e.g., tetracycline).
Scrapings
In certain cases, aspirates or scrapings of pustular fluid
may be obtained for Gram’s stain (useful in suspected
cases of anthrax or gonococcemia). When evaluating an
unknown ulceration, Tzanck smears are 74% sensitive to
herpes infections.17 Potassium hydroxide preparations to
look for hyphae are sometimes useful in the diagnosis of
yeast infections.
Punch Biopsies
Punch biopsies are relatively simple to do. A circular
cutting instrument called a trephine is pushed vertically
into the skin with rotational movements until the
instrument sinks into subcutaneous tissue. The operator
then lifts the specimen with a toothless forceps, and the
base is cut with iris scissors. Specimens can then be sent
in a sterile container for Gram’s staining or other tests
(e.g., immunofluorescence).18
Emergency physicians familiar with the technique
can use punch biopsies to identify a variety of lesions.
For example, a febrile patient with a petechial/purpuric
rash may have either meningococcemia or Rocky
Mountain spotted fever. A Gram’s stain of a punch
biopsy specimen may identify the organism and streamline antibiotic selection. The sensitivity for punch biopsy
in meningococcemia is approximately 72%.19
General Diagnostic Testing
Blood Tests
There are few studies that provide an evidence-based
approach to laboratory testing in patients with a rash.
Furthermore, with the exception of secondary syphilis,
blood tests will almost never supply the etiology of a rash
in the ED. In patients who are not toxic or febrile,
laboratory testing is driven by clinical suspicion. If the
rash appears benign, then laboratory studies are generally unnecessary.
This said, toxic-appearing patients with an unexplained rash and fever may benefit from a complete
blood count with differential, along with a platelet count,
chemistry panel, liver function tests, and blood cultures.
The platelet count may implicate thrombocytopenia as a
cause of petechiae. In the patient with unstable vital signs
or who appears dehydrated, a chemistry panel will detect
acidosis as well as renal or electrolyte abnormalities.
Patients with Stevens-Johnson syndrome or toxic
epidermal necrolysis, in particular, may have electrolyte
abnormalities from fluid losses through the disrupted
skin. Liver function tests may tell the clinician if there is
hepatitis, which is occasionally seen with some drug
hypersensitivity reactions.15
Serology is occasionally useful. A Venereal Disease
Research Laboratory (VDRL) or fluorescent treponemal
antibodies (FTA) test for syphilis can be diagnostic in a
person with papulosquamous lesions suggestive of the
disease. If Lyme disease is suspected, then an IgM
antibody to Lyme or rising IgG titers may be sent for
confirmation. However, the sensitivity and specificity are
not perfect, and a positive test does not discriminate
between previous and current infection. Serologic testing
for Lyme disease is recommended only when the physi-
September 2002 • www.empractice.net
Diagnostic Decision Making
After the initial stabilization, history, and physical
examination, formulate a differential diagnosis using the
modified Lynch algorithm presented in the Clinical
Pathway on page 13, “Evaluating The Unknown Rash.”
The unknown lesion is classified into one of six major
categories, as described in the Pathway. In the sample
case mentioned at the beginning of this paper, our patient
(a 52-year-old man on ticlopidine and methyldopa)
presented with a petechial rash and underlying
erythema. Following the Lynch algorithm, the lesion
would be classified first as solid, meaning not vesicular
or bullous. Going down the algorithm, the lesion would
then be assessed as having erythema, then as petechial/
purpuric. The differential diagnosis to entertain would
include vasculitis, thrombotic thrombocytopenic purpura, meningococcemia, Rocky Mountain spotted fever,
and endocarditis. A history of taking ticlopidine and
methyldopa moves thrombotic thrombocytopenic
purpura to the top of the list. A platelet count in the ED
would have been diagnostic—and possibly life-saving.
Maculopapular Rashes
Maculopapular rashes are the most common types of
rash and have the broadest differential diagnosis. They
are usually seen with viral illnesses, bacterial infections,
drug reactions, and other immune-related syndromes.
It is probably easiest to categorize maculopapular
7
Emergency Medicine Practice
rashes as either principally centrally or peripherally
distributed. (See Table 4 and the Clinical Pathway on page
14, “Evaluating The Maculopapular Rash.”) Important
historical questions would address sick contacts, travel, and
new medications (within 1-4 weeks).
Viral illnesses—especially mumps, measles, and
rubella—generally begin as central lesions. Other viral
culprits include Epstein-Barr virus, enteroviruses, and
adenoviruses. In children, roseola (human herpes virus
6), erythema infectiosum (fifth disease), and parvovirus
B19 are frequent causes of maculopapular rash.
The lesions of Lyme disease (termed erythema
migrans) usually begin in the proximal extremities, chest,
and body creases.20 The primary lesion is an expanding
erythema with a central pallor, sometimes with a central
necrosis. Arboviruses (dengue fever, West Nile virus)
cause fever, chills, myalgias, and a dense maculopapular
rash on the trunk.21
Ehrlichiosis is a tick-borne disease caused by an
obligate intracellular bacteria commonly seen in the midAtlantic and central Southwest states. In 30% of the cases,
there is a central-appearing maculopapular rash. Patients
may present with fever, headaches, abdominal pain,
leukopenia, lymphopenia, and thrombocytopenia.
The most serious diseases to consider with peripheral
maculopapular rashes include the early stages of meningococcemia and Rocky Mountain spotted fever (which
are described in further detail in a later section) as well as
the early stages of anthrax (as described in the July 2002
issue of Emergency Medicine Practice.)
ampicillin. This type of rash is self-limited and usually
resolves without permanent sequelae after the offending
agent is discontinued.
A drug hypersensitivity syndrome is a severe,
idiosyncratic systemic reaction. The patient has a severe
exanthematous rash that may exfoliate, often combined
with fever, hepatitis, nephritis, carditis, facial swelling,
and/or lymphadenopathy. The hypersensitivity syndrome usually develops 2-6 weeks after a drug is started,
vs. 1-3 weeks as seen in TEN or SJS. Drugs commonly
implicated are phenytoin, carbamazepine, phenobarbital,
sulfonamides, allopurinol, and dapsone. The incidence
may be higher in blacks and in people who have slow
N-acetylation of sulfonamides.23 Drugs with a long halflife are more likely to result in a fatal outcome than
reactions from drugs with a short half-life.24
Diagnosis
The diagnosis is essentially clinical. While a skin biopsy
does not help identify the offending agent, it can assist
the consultant in defining the reaction pattern.8,14,22 (See
Table 5, Table 6, and Table 7 on page 9.)
Treatment
The first step in managing a suspected cutaneous drug
reaction is removing the drug. In one retrospective study,
withdrawal of the offending drug reduced the risk of
death by about 30% per day.24 If possible, all drug therapy
should be stopped in a patient who develops an unexplained syndrome of blisters or substantial epidermal
erosions accompanied by fever. The need for drug
withdrawal is less clear in patients who present with a
minor maculopapular eruption with or without pruritus.
Routine use of corticosteroids is not indicated.25,26 Oral
antihistamines (diphenhydramine 25-50 mg PO q6h prn)
may alleviate pruritus. Alternatives include hydroxyzine,
certirizine, or loratadine, which have the advantage of
less sedation. An evidence-based review on the efficacy
of antihistamines in relieving pruritus showed no
Cutaneous Drug Reactions
Etiology
Cutaneous drug reactions commonly present as a
maculopapular rash. The most commonly involved drugs
are sulfonamides, penicillins, anticonvulsants, and
nonsteroidal-anti-inflammatory drugs.12
Epidemiology
Cutaneous allergic reactions to drugs are reported
in about 1%-3% of hospitalized patients and 1% of
outpatients.1,8 Fortunately, most drug reactions are not
serious, though life-threatening reactions can occur. The
most severe reactions include the hypersensitivity
syndrome, Stevens-Johnson syndrome (SJS), and toxic
epidermal necrolysis (TEN).
Table 4. Differential Diagnosis
Of Maculopapular Rashes.
Centrally distributed rash
• Viral exanthem: Rubela, rubeola, roseola,
erythema infectiosum, Epstein-Barr virus,
enterovirus, adenovirus, arboviruses
• Lyme disease
• Typhus fever
• Ehrlichiosis
• Meningococcemia (early)
• Cutaneous drug allergy eruptions
Pathophysiology
Cutaneous drug reactions can be immunologic or nonimmunologic. Non-immunologic causes account for more
than 75% of cutaneous drug reactions.12
Clinical Presentation
Peripherally distributed rash
• Rocky Mountain spotted fever
• Secondary syphilis
• Erythema multiforme
• Meningococcemia (early)
• Hand-foot-mouth disease (coxsackie 16)
• Cutaneous anthrax
Most cutaneous drug eruptions are morbilliform (meaning it looks like measles) or exanthematous. The rash is
comprised of brightly erythematous macules and
papules, mostly on the trunk and extremities, discrete in
some areas and confluent in others.14 A morbilliform rash
often erupts in patients with mononucleosis who take
Emergency Medicine Practice
8
www.empractice.net • September 2002
SJS and TEN.
Seven factors distinguish EM minor and major from
SJS and TEN. They are: 1) the etiology; 2) the underlying
pathology; 3) the degree of mucosal involvement (mouth,
conjuctiva, rectum, vagina, respiratory tract); 4) the
presence or absence of a “classic rash”; 5) the degree of
epidermal detachment; 6) the degree of multisystem
involvement; and 7) the morbidity and mortality.8,28,29 (See
Table 8 on page 10.)
Unlike SJS and TEN, EM minor and major are not
characterized by epidermal detachment. EM minor presents
with the “classic rash” and has no mucosal involvement.
EM major also presents with the “classic rash” but has
only one mucous membrane involved. Neither SJS nor
TEN demonstrate the classic target lesions, but both are
characterized by mucous membrane involvement and
epidermal detachment. (Because SJS and TEN produce
widespread purpuric macules and mucosal erosions,
along with epidermal detachment, they are discussed in
more detail in the section on vesiculo-bullous rashes.) EM
minor and major usually occur after an infection (when a
cause can be identified), whereas SJS and TEN usually
occur after drug exposure. In one retrospective study of
76 cases, the authors reported that cases could be
classified as either EM or SJS/TEN based on the inciting
cause.30 SJS and TEN have greater morbidity and mortality than EM minor and major.
differences in the effectiveness of non-sedating antihistamines vs. diphenhydramine. However, the non-sedating
antihistamines cost about 27 times more than over-thecounter diphenhydramine.27
Distinguishing Between Erythema Multiforme,
Stevens-Johnson Syndrome, And Toxic
Epidermal Necrolysis
Erythema multiforme (EM) is the archetypal maculopapular rash of the extremities. The rash typically begins
as a macular eruption that then progresses to a papule
with a dusky center—the classic “target” lesion.
In the past, EM major and minor, Stevens-Johnson
syndrome (SJS), and toxic epidermal necrolysis (TEN)
were all believed to be part of the same clinical spectrum.
Now, EM minor and major are considered distinct from
Table 5. Red Flags That A Cutaneous Drug Reaction
May Be Serious.
Clinical findings
Cutaneous
• Confluent erythema
• Facial edema or central facial involvement
• Skin pain
• Palpable purpura
• Skin necrosis
• Blisters or epidermal detachment
• Positive Nikolsky’s sign
• Mucous membrane erosions
• Urticaria
• Swelling of the tongue
Erythema Multiforme
Etiology
EM is a common acute inflammatory disease that is
usually self-limited. Many factors have been implicated
in the etiology, including infectious agents, drugs, and
malignancy. (See Table 9 on page 10.) However, in up to
50% of cases no etiologic agent can be identified. In
children, EM commonly follows a herpes simplex or
mycoplasma infection. A recurrent form of EM may
General
• High fever (>40ºC)
• Enlarged lymph nodes
• Arthralgias or arthritis
• Shortness of breath, wheezing, hypotension
Laboratory results
• Eosinophil count >1000/mm3
• Lymphocytosis with atypical lymphocytes
• Abnormal liver function tests
Table 7. Drugs Commonly Implicated In Cutaneous
Allergic Reactions.
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Table 6. Guidelines For The Assessment Of A Possible
Adverse Drug Reaction.
1.Alternative causes should be excluded, especially
infection. Many infections (especially viral) are difficult to
distinguish clinically from adverse drug reactions.
2.The interval between introduction of a drug and the
onset of a reaction should be examined (e.g., 1-3 weeks
for TEN/SJS, 2-6 weeks for hypersensitivity syndrome).
3.Any improvement after drug withdrawal should
be noted.
4.The caregiver should determine whether similar reactions
have been associated with the same compound.
5.Any reaction on re-administration of a drug should
be noted.
Source: Bigby M, Jick S, Jick H, et al. Drug-induced cutaneous
reactions. A report from the Boston Collaborative Drug Surveillance
Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA 1986
Dec 26;256(24):3358-3363.
Adapted from: Roujeau JC, Stern RS. Severe adverse cutaneous
reactions to drugs. N Engl J Med 1994;331:1272-1285.
September 2002 • www.empractice.net
Aminopenicillins
Sulfonamides
Cephalosporins
Allopurinol
Phenobarbital
NSAIDs
Quinolones
Phenytoin
Valproic acid
ACE inhibitors
Thiazide diuretics
Beta-blockers
Oral contraceptives
Phenothiazines
Corticosteroids
9
Emergency Medicine Practice
develop after each episode of herpes simplex.
malaise, fever, and arthralgias. Target lesions are the
hallmark of EM minor and major. (See Figure 1.) Dusky
red macules and papules appear suddenly on the palms,
soles, and extensor surfaces of the extremities, especially
the knees and elbows. They are usually symmetrical and
evolve over 24-48 hours. As the maculopapular lesions
enlarge, the central area becomes cyanotic, appearing as
annular papules or plaques with dusky centers. Vesicles
and bullae may form in the center of the lesion. Plaques
may also develop without the classic target lesions. These
lesions are uniform in size (averaging 1-2 cm in diameter), non-pruritic, and may remain unchanged for up to
two weeks.
Lesions develop in crops for up to 2-4 weeks and
heal without scarring in 1-2 weeks. The entire episode
lasts for one month. In EM minor, mucous membrane
involvement is absent; bullae and systemic symptoms
do not develop. EM minor becomes EM major if a
single mucous membrane is involved; erosions may
occur on the lips, in the oral cavity, or on the
Pathophysiology
The pathogenesis of EM is not clearly understood but is
most likely caused by an immune complex-mediated
hypersensitivity reaction.31
Epidemiology
The true incidence of EM is not known. It occurs in all
age groups but is more common in those 20-40 years old.
Morbidity And Mortality
Death from EM is rare. However, if patients have ocular
involvement, disabling and permanent visual sequelae
may occur. Scarring of the skin is unusual except in
hyper-pigmented patients.
Clinical Presentation
Most patients with EM present to the ED with a chief
complaint of rash. They often have a prodrome of
Table 8. Classification Of Erythema Multiforme, Stevens-Johnson Syndrome, And Toxic Epidermal Necrolysis.
Entity
Erythema multiforme minor
Most common etiologic agent/rash
Infectious/classic target lesion without mucous membrane involvement (no
epidermal detachment)
Erythema multiforme major
Infectious/classic target lesions with mucous membrane involvement (no
epidermal detachment)
Stevens-Johnson syndrome
Drug induced/widespread purpuric macules and mucosal erosions with 10%
epidermal detachment, plus Nikolsky’s sign
SJS/TEN transition
Drug induced/widespread purpuric macules and mucosal erosions with 10%-30%
epidermal detachment, plus Nikolsky’s sign
Toxic epidermal necrolysis
Drug induced/widespread purpuric macules and mucosal erosions with more than
30% epidermal detachment, plus Nikolsky’s sign
Sources: Bastuji-Garin S, Rzany B, Stern RS, et al. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and
erythema multiforme. Arch Dermatol 1993 Jan;129(1):92-96; Roujeau JC. The spectrum of Stevens-Johnson syndrome and toxic epidermal necrolysis:
a clinical classification. J Invest Dermatol 1994 Jun;102(6):28S-30S.
Table 9. Etiologies Of Erythema Multiforme.
Figure 1. Erythema multiforme.
Idiopathic (50% of cases)
Infectious
• Herpes simplex virus
• Epstein-Barr virus
• Adenovirus
• Coxsackievirus
• Vaccinia virus
• Mycoplasma
• Chlamydia
• Salmonella typhi
Medications
• Penicillin
• Sulfonamides
• Phenytoin
• Barbiturates
• Phenylbutazone
Emergency Medicine Practice
Reproduced with permission from: Habif T, ed. Clinical Dermatology:
A Color Guide to Diagnosis and Therapy. 3rd ed. St. Louis: Mosby; 1996.
10
www.empractice.net • September 2002
conjunctiva. Up to 10% of patients with EM major
have ocular involvement.32
and allopurinol in three.37 Fewer than 5% of patients with
TEN report no drug use.38
Diagnosis
Pathophysiology
The diagnosis of EM is clinical. The diagnosis is most
ensured when classic target lesions are present. If the
patient does not have target lesions, another diagnosis
should be considered. Similarly, if the patient looks toxic,
has systemic complaints, or has abnormal vital signs,
consider an alternative diagnosis.
The pathophysiology of SJS and TEN is not completely
understood. Some studies suggest it is the result of an
altered metabolism and immune-mediated response.39,40
Epidemiology
The incidence of TEN varies from 0.4-1.2 cases per
million per year.38 TEN occurs in all age groups but is
more common in adults over 40. SJS commonly occurs in
children and young adults. While HIV patients are
predisposed to TEN, HIV is not considered to be a
causative factor.41
Management
EM minor and major generally resolve without treatment
in 2-3 weeks. Any underlying infection should be treated.
While many physicians treat EM with prednisone,
supporting data remain weak to nonexistent, involving
just a handful of patients. A prospective study of 16
children with EM major treated with steroids showed a
significant reduction in the period of fever and reduction
in the period of the eruption.33 Another prospective study
of three patients with EM minor showed a rapid response
to steroid therapy.34 However, other larger studies
suggest minimal to no benefit from treatment with
steroids.35,36 Based on a review of the literature, there is no
strong evidence that steroids are beneficial in EM minor or
major. The best ED intervention is to determine (and if
possible treat) the cause of the rash and provide
symptomatic relief using systemic antihistamines
and possibly analgesia.
Morbidity And Mortality
The leading causes of death in TEN are sepsis from
Staphylococcus aureus or Pseudomonas aeruginosa and
fluid/electrolyte abnormalities.38,42 The severity of
complications is proportional to the extent of skin
necrosis. Massive transepidermal fluid losses can
produce significant electrolyte imbalance; prerenal
azotemia is common. Bacterial colonization of the skin
and decreased immune responsiveness leads to sepsis.
The mortality rate is 5%-10% for SJS and 23%-30%
for TEN.42 The mortality rate is higher still in elderly
patients—51% in one retrospective study of 77 elderly
patients with TEN.43 Variables associated with a poor
prognosis include increased age, extent of disease, extent
of disease at time of transfer to a burn center, azotemia,
multiple medication use, thrombocytopenia, and neutropenia.38,44 Ophthalmologic sequelae such as keratitis and
corneal ulcerations, cornel scarring, and blindness occur
in 40%-50% of patients.45
Disposition
Essentially all patients diagnosed with EM minor or
major can be safely discharged home. Follow-up with
the primary medical doctor or dermatologist is
helpful. Patients must return to the ED if there is
rapid progression of the rash or new systemic
symptoms. Follow-up with an ophthalmologist is
essential in cases of ocular involvement.
Clinical Presentation
In both SJS and TEN, patients present with a chief
complaint of a rash. Some experience prodromal symptoms similar to a viral illness such as myalgias, fever,
cough, or sore throat. If a new drug is the cause, the
prodrome usually begins within days of ingestion. Skin
lesions then develop suddenly, after 1-2 weeks of
prodromal symptoms.
Skin lesions in SJS look like atypical target lesions or
purpuric macules on the trunk. (This is in contrast to EM
minor and major, where the majority of the distribution is
“You know what happens to scar tissue.
It’s the strongest part of your skin.”—Michael R. Mantell
Vesiculo-Bullous Rashes
Vesicles and bullae appear in many disorders. Some of
these disorders are benign—such as poison ivy or a mild
case of varicella zoster—whereas others are potentially
life-threatening, such as SJS, TEN, and pemphigus
vulgaris (PV).
Table 10. Etiologic Agents In Stevens-Johnson
Syndrome And Toxic Epidermal Necrolysis.
Stevens-Johnson Syndrome
And Toxic Epidermal Necrolysis
Etiology
•
•
•
•
•
•
•
•
SJS and TEN are related to the use of certain medications.
Anticonvulsants, sulfonamides, other antibiotics, and
non-steroidal anti-inflammatory drugs (NSAIDs) are the
main offenders.22 (See Table 10.) In one retrospective
study, sulfonamides were found to be the etiology in 30
cases, NSAIDs in 29 cases, anticonvulsants in seven cases,
September 2002 • www.empractice.net
11
Sulfonamides
Penicillins
Quinolones
Phenytoin
Phenobarbital
Carbamazepine
NSAIDs
Allopurinol
Emergency Medicine Practice
on the face and extensor surfaces of the extremities.)
Patients commonly develop oropharyngeal lesions
causing an erosive stomatitis. A purulent conjunctivitis
can lead to ocular erosions and blindness. SJS is a selflimited disease; new lesions may appear, but they usually
resolve in one month.
In contrast to SJS, patients with TEN complain of
skin tenderness, pruritus, and pain. Onset is more rapid
with repeated ingestion of the inciting agent. Objective
skin findings are characterized by a warm and tender
erythema that first affects the face around the eyes, nose,
and mouth. Erythema then extends to the shoulders and
trunk and proximal extremities in a symmetric fashion.
All areas become confluent over several hours to days.
Small, irregularly confluent bullae form within the areas
of erythema. Lateral pressure on normal skin adjacent to a
bullous lesion dislodges the epidermis. (This is known as
Nikolsky’s sign.) (See Figure 2.) Bullae form between the
epidermis and dermis, leading to widespread sloughing
of the epidermis in large sheets and resulting in sizeable
areas of exposed dermis.
Mucous membrane involvement is characteristic of
TEN. Stomatitis or conjunctivitis may precede the
generalized erythematous rash by 24-48 hours. Most
patients have erythema and sloughing of the lips and
buccal mucosa. In about three-quarters of patients, the
eyes are also affected, producing conjunctivitis or painful
erosions. These lesions can form synechiae between the
eyelids and the conjunctiva, causing blindness. Up to half
of patients develop genital and anal lesions.46 Respiratory
failure can also occur.
The appearance of dermatologic manifestations of
TEN is variable and unpredictable, ranging from 24
hours to two weeks. Re-epithelialization begins after
several days, and most of the skin surface is re-epithelialized in three weeks. Mucosal lesions may remain crusted
for two or more weeks.
The clinically distinguishing features of SJS and TEN is
the degree of epidermal detachment. SJS involves mucosal
erosions and less than 10% of epidermal detachment.
TEN is defined by more than 30% of epidermal detachment. (See Figure 3.) Between 10%-30% is considered the
overlap zone of SJS and TEN.
Figure 2. A positive Nikolsky’s sign in toxic epidermal
necrolysis.
Figure 3. Toxic epidermal necrolysis.
Diagnosis
As with most rashes, the diagnosis SJS and TEN is
clinical. However, it can be confirmed by biopsy, which
will demonstrate detachment of the epidermis from the
dermis. The visual appearance of TEN is very similar to
that of staphylococcal scalded skin syndrome (SSSS).
Biopsy distinguishes these conditions, as the split in SSSS
is high in the epidermis below the stratum corneum. SSSS
also tends to occur in infants and children less than five
years of age and is rare in adults.
Treatment
Treatment for SJS and TEN is supportive. Management
focuses on removal of the offending agent and replacement of fluid losses. Patients are treated in a manner
similar to burn victims. They should have two IV lines in
place and be placed on a monitor. IV fluid repletion with
large volumes of colloids and crystalloids is essential,
with special attention to electrolyte balance. Provide
liberal doses of analgesics; oral symptoms can be relieved
with viscous lidocaine. All drugs started within the past
month should be discontinued. Avoid topical sulfacontaining preparations such as Silvadene (silver
sulfadiazine) due to possible cross-reactivity.
The role of corticosteroids in SJS and TEN is
highly controversial. In one retrospective study of 32
children with SJS, systemic corticosteroid therapy did
not affect the course of disease.36 One prospective study
showed higher rates of morbidity and mortality in
Continued on page 16
Reproduced with permission from: Habif T, ed. Clinical Dermatology:
A Color Guide to Diagnosis and Therapy. 3rd ed. St. Louis: Mosby; 1996.
Reproduced with permission from: Habif T, ed. Clinical Dermatology:
A Color Guide to Diagnosis and Therapy. 3rd ed. St. Louis: Mosby; 1996.
Emergency Medicine Practice
12
www.empractice.net • September 2002
Clinical Pathway: Evaluating The Unknown Rash
Possible life-threatening rash
➤
➤
Solid
Fluid-filled
➤
➤
➤
Non-erythematous
(see below
for differential
diagnosis)
Clear
Pustular
(see below
for differential
diagnosis)
➤
➤
➤
Maculopapular
(see below
for differential
diagnosis)
Petechial/purpuric
(see below
for differential
diagnosis)
Diffuse
erythematous
(see below for
differential
diagnosis)
➤
➤
Erythematous
Vesiculo-bullous
(see below
for differential
diagnosis)
Adapted from: Lynch PJ, Edminster SC. Dermatology for the nondermatologist: a problem-oriented system. Ann Emerg Med
1984 Aug;13(8):603-606.
Differential Diagnosis Of Rash By Morphology Types.
Rash type
Differential diagnosis
Maculopapular
Meningococcemia (early), Rocky Mountain spotted fever (early), toxic shock syndrome,
erythema multiforme, cutaneous drug reactions, systemic lupus erythematosus, viral
exanthems (rubeola, rubella, Epstein-Barr virus, adenovirus, enterovirus), Lyme disease
Petechial/purpuric
Meningococcemia, Rocky Mountain spotted fever, vasculitis(Henoch-Schönlein purpura,
hypersensitivity drug reactions, necrotizing fasciitis), gonococcemia, enteroviral
infection, rubella, Epstein-Barr virus, thrombocytopenia, systemic lupus erythematosus,
idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura,
endocarditis, purpura fulminans
Diffuse erythematous
Necrotizing fasciitis, toxic shock syndrome, streptococcal toxic shock syndrome,
staphylococcal scalded skin syndrome, Kawasaki disease, erythema multiforme,
hypersensitivity drug reactions, cellulitis, viral exanthems, enteroviral infection
Vesiculo-bullous
Erythema multiforme major, Stevens-Johnson syndrome, toxic epidermal necrolysis,
pemphigus vulgaris, varicella zoster, herpes simplex virus, necrotizing fasciitis (late)
Pustular
Bacterial folliculitis, gonorrhea
Non-erythematous
Secondary syphilis, anthrax (ulcerated lesions)
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright ©2002 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format
without written consent of EB Practice, LLC.
September 2002 • www.empractice.net
13
Emergency Medicine Practice
Clinical Pathway: Evaluating The Maculopapular Rash
Maculopapular rash
➤
➤
Peripheral
➤
➤
Sick contact?
Sick contact?
Yes
No
Consider:
• Meningococcal disease
• Hand-foot-mouth
disease
Consider viral exanthem
➤
Has there been any travel, or local incidence
of tick-borne disease?
No
➤
➤
Possible cutaneous drug
reaction
➤
Has the patient been using a new drug?
Yes
No
➤
➤
Yes
Central
Consider:
• Rocky Mountain
spotted fever
• Ehrlichiosis
No
➤
Yes
➤
Consider:
• Lyme disease
• Arboviruses
• Pityriasis rosea
Consider:
• Erythema
multiforme
• Secondary syphilis
• Anthrax
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright ©2002 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format
without written consent of EB Practice, LLC.
Emergency Medicine Practice
14
www.empractice.net • September 2002
Clinical Pathway: Evaluating The Petechial Rash
Petechial rash
➤
If the patient is ill-appearing, consider empiric treatment
for meningococcemia and Rocky Mountain spotted fever
➤
Does the patient have any sick contacts?
No
Has there been any travel, or local incidence of tick-borne disease?
➤
Yes
➤
Consider:
• Meningococcemia
• Rubella
• Epstein-Barr virus
• Enterovirus
• Hepatitis B
• Gonococcemia
• Rheumatic fever
➤
➤
Yes
No
Is there palpable purpura?
Consider vasculitis
➤
Yes
➤
Consider:
• Rocky Mountain
spotted fever
• Dengue fever
• Typhus
• Rat bite fever
No
Possible
thrombocytopenia:
• Idiopathic
thrombocytopenic
purpura
• Thrombotic
thrombocytopenic
purpura
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright ©2002 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format
without written consent of EB Practice, LLC.
September 2002 • www.empractice.net
15
Emergency Medicine Practice
Continued from page 12
year with a mean age of onset in the sixth decade.
Because of a genetic predisposition, patients with PV
may report a family member who once had “bad blisters.”54 If not recognized and treated early, PV can lead
to significant morbidity (due to pain and disfigurement)
and mortality (due to loss of protective barrier and
secondary infection). The natural course of PV is
relentless and progressive over months to years.55 In
some cases, patients may have a rapid progression
with extensive involvement.56
patients treated with corticosteroids—66% survival in
the group treated without corticosteroids vs. 33% in
those treated with corticosteroids. Other trials suggest
that steroids increase the risk of sepsis and delay epithelialization,44,45,47 although one prospective trial of 67
consecutive patients with SJS treated with steroids
reported no fatalities or adverse affects.48 Based on a
review of the literature, there does not appear to be a
consensus on the use of steroids in the treatment of SJS and
TEN. Since there is no evidence to support their use,
and because steroids may increase morbidity and
mortality, avoid using them.
Cyclosporin is occasionally used to treat SJS and
TEN, based on very small case series.49,50
As with the burn patient, those with SJS or TEN
require aseptic technique to avoid infection. Use of
adhesive material, ointments, and creams should be
avoided. Patients should be covered in a clean white
sheet. Debridement of necrotic tissue may be necessary
(usually after the patient is admitted). Prophylactic
antibiotic therapy is no longer given for fear of crossreactivity with the drug that initiated the TEN and
because of the risk of selecting for resistant organisms.51
Pathophysiology
PV is characterized by circulating IgG autoantibodies that
bind to the surface of the keratinocytes. This results in the
loss of cohesion between the epidermal cells (acantholysis), while cells in the basement membrane remain
intact.57 Clinically, this means that blisters form within in
the epidermal layer of the skin.
Clinical Presentation
Initially, blisters localize to the oral mucosa weeks to
months before the skin blisters appear. These oral lesions
rupture and create painful erosions. Over several weeks,
non-pruritic skin blisters erupt over the rest of the body,
ranging in size from one to several centimeters in
diameter. (See Figure 4.) These blisters may be localized,
usually affecting the head and trunk first. If left untreated, they generalize over months.58 With pressure, the
thin roof of the bullae may rupture or the fluid may
dissect laterally into the mid-epidermal areas (a positive
Nikolsky’s sign).
Ruptured blisters develop into painful erosions that
may become secondarily infected. Prior to the availability
of corticosteroids, mortality ranged from 50% to 90%;
currently, the mortality is approximately 10%-20%. Most
of the complications are due to infections.59 Some patients
can develop extensive fluid, protein, and electrolyte loss
in association with extensive blistering.
Disposition
Some patients diagnosed with SJS can be safely
discharged from the ED if all of the following criteria
are met: 1) the patient is non-toxic and has stable vital
signs; 2) the patient is tolerating oral fluids; 3) the rash
is not rapidly progressing; 4) the patient is not
immunocompromised; and 5) close follow-up is ensured.
All patients with ocular involvement should be evaluated
by an ophthalmologist soon after discharge.
If these criteria are not met, patients with SJS should
be admitted to the hospital for 24-hour observation, IV
hydration, local skin care, and nutritional support. If
there is any progression of lesions, transfer to a burn or
intensive care unit should be considered.
All patients suspected of having TEN should be
admitted to an intensive care unit. Depending on hospital
resources, early transfer to a burn unit may be necessary.
In one retrospective review, patients who were treated in
a burn unit had lower rates of bacteremia, septicemia,
and mortality if transfer was done early in the hospital
course (less than seven days).52 An earlier study yielded
similar results.53
Figure 4. Pemphigus vulgaris.
Pemphigus Vulgaris
Etiology
Pemphigus vulgaris (PV) is a rare but potentially lethal
blistering condition predominantly seen in the elderly.
This autoimmune disease is characterized by erosions
and blistering of epithelial surfaces of the oral mucosa
and skin.
Epidemiology
Reproduced with permission from: Habif T, ed. Clinical Dermatology:
A Color Guide to Diagnosis and Therapy. 3rd ed. St. Louis: Mosby; 1996.
The incidence of PV is estimated to be about 4500 cases a
Emergency Medicine Practice
16
www.empractice.net • September 2002
Diagnosis
General Approach
The diagnosis of PV is made by biopsy of the skin
adjacent to the blister. Light microscopy will show
intraepidermal blister, acantholysis of the epidermal cell,
and a slight eosinophilic infiltrate. Direct immunofluorescence demonstrates IgG on the surface of keratinocytes.
Circulating autoantibodies can be found in 80%-90% of
PV patients.60
For the emergency physician, the skin biopsy and
immunofluorescence may not be practical. Therefore, the
emergency physician must act based on the clinical
scenario—for example, an elderly patient who complains
of oral blisters for a few months and now has generalized
vesicles on the body. In the case of SJS or TEN, bullous
lesions progress faster, the patient will look more toxic,
and he or she may have recently taken a suspect drug.
First, consider isolating the patient with a rapidly
progressive petechial rash who looks ill and has a fever.
In such cases, the examiner should wear a fitted respiratory mask until meningococcemia can be ruled out. As a
rule, whenever confronted with a petechial rash, consider
the worst-case scenario—that is, meningococcemia and
Rocky Mountain spotted fever—as both of these diseases
can be rapidly progressive and fatal if not treated
aggressively. (See the Clinical Pathway on page 15,
“Evaluating The Petechial Rash.”) It is prudent to
rapidly (and empirically) treat the ill-appearing
patient for these conditions, especially if the work-up
will take several hours.
History
In a patient with petechiae, it is important to elicit any
sick contacts (especially those with meningococcemia).
Patients with viral infections may have upper respiratory
illnesses, body aches, and fever. It is also important to
elicit a travel history. Dengue fever should be suspected
for those who have traveled to Central or South America
(although recent outbreaks have erupted in Puerto Rico,
Hawaii, and the South Pacific). The petechial/purpuric
rash will appear in about 30%-50% of patients and will
materialize a few days after initial symptoms of malaise,
cough, and fever.62 Rocky Mountain spotted fever is
associated with tick bites and is most often acquired in
Treatment
A low daily dose of prednisone (1 mg/kg/d) is the initial
treatment for cutaneous PV.54 Steroids are given until
remission (defined as a state of no new blisters for one
week). If new lesions appear after 1-2 weeks of treatment,
the dose of prednisone is increased.61
In general, begin the first dose of prednisone (1 mg/
kg PO or IV) in the ED after consultation with a dermatologist. (Alternatively, the dermatologist can begin
steroids as indicated if close follow-up is ensured.) Most
cases of PV can be treated at home as long as the patient
is not toxic-appearing and has only a few blisters.54 A
dermatologist should see the patient within days. The
consultant can then perform an outpatient biopsy and
adjust corticosteroids as indicated.
Patients with extensive blisters, erosions of the skin,
or who are toxic-looking should be admitted. Once in the
hospital, they can be monitored and treated for fluid or
electrolyte imbalances and observed for potential
infection. If there are overt signs of infection in the ED,
start antibiotics immediately.
Table 11. Causes Of Petechial/Purpuric Rashes.
Bacterial
• Meningococcal disease
• Rocky Mountain spotted fever
• Gonococcemia
• Pneumococcal sepsis
• Haemophilus influenzae sepsis
• Rat bite fevers (Spirillum minor and Streptobacillus
moniliformis)
• Epidemic typhus
Petechial/Purpuric Rashes
Certain petechial eruptions are among the most rapidly
fatal of the rashes. Prompt and accurate diagnosis and
proper treatment may be life-saving, especially in
patients with meningococcal disease or Rocky Mountain
spotted fever.
Viral
• Dengue
• Hemorrhagic fevers (Ebola, Lassa, etc.)
• Enteroviral infections
• Epstein-Barr virus
• Rubella
• Hepatitis B
Etiology
There are many causes of petechial rashes. It may be
easier to separate petechial rashes into bacterial, viral,
and non-infectious causes. (See Table 11.) While
petechial rashes caused by bacteria are usually the
most lethal, they are potentially treatable. Viral causes
include Epstein-Barr virus, rubella, hepatitis B,
and enteroviruses. Enteroviruses (e.g., echo 9 and
coxsackie 9) more commonly occur in summer and fall
seasons. Affected patients may have disseminated
petechial rash and aseptic meningitis, mimicking
meningococcal disease.9
September 2002 • www.empractice.net
Noninfectious
• Coughing, sneezing, strangulation, Valsalva (mostly
petechiae in face or above nipple line)
• Thrombocytopenia
• Idiopathic thrombocytopenic purpura
• Thrombotic thrombocytopenic purpura
• Vasculitis (Henoch-Schönlein purpura, hypersensitivity)
• Systemic lupus erythematosus
Adapted from: Schlossberg D. Fever and rash. Infect Dis Clin North Am
1996;10:101-110.
17
Emergency Medicine Practice
bacteremia, then sepsis and/or CNS invasion. Untreated,
meningococcemia is invariably fatal. Even with prompt
treatment, the mortality rate is about 10%-20%.67
There are about 3000 cases of meningococcal disease
per year in the United States; about 50% of these involve
meningitis.68 Most cases occur sporadically, but outbreaks
arise in crowded environs such as dormitories or military
settings.69 Most cases develop during the winter and
spring months. Children from 6 months to 1 year of age
are at highest risk, followed by adults under 20 years.
Persons with complement deficiencies, protein C&S
deficiency, or who are asplenic are at higher risk than the
rest of the population.67
rural parts of the central and eastern United States.
Ask the patient regarding a history of thrombocytopenia, systemic lupus erythematosus, scurvy, or HIV
disease. HIV patients are prone to idiopathic thrombocytopenia purpura (ITP) and thrombotic thrombocytopenic
purpura (TTP).
On physical examination, determine whether the
purpura are palpable. Palpable purpura is seen in
vasculitis due to Henoch-Schönlein purpura, essential
mixed cryoglobulinemia, hypersensitivity vasculitis,
and secondary vasculitis from connective tissue disease.63
Note the location of the petechiae. Coughing, sneezing,
and other Valsalva maneuvers will produce petechiae
limited to above the nipple line—a finding especially
likely in children. In one study, no febrile child with
petechiae limited to above the nipple line had
invasive disease.64
Clinical Presentation
The incubation period varies from two to 10 days, but the
disease usually begins 3-4 days after exposure. Symptoms usually begin with an upper respiratory infection.
The patient can have fever, chills, malaise, myalgias,
headaches, nausea, and vomiting. A rash is seen in more
than 70% of people with meningococcemia.70 Petechiae,
which develop on the wrist and ankles, are the first sign
of impending septicemia. At this stage, the rash may be
mistaken for Rocky Mountain spotted fever. The petechiae then spread to the rest of the body, becoming
confluent and eventually developing into purpuric
macules. This process can be very rapid—with as little as
12 hours between onset of fever until death.67
In certain people, the rash of meningococcemia can
also be described as faint pink macules or erythematous
papules in addition to the classic petechiae and purpuric
lesions.71 Some petechiae may appear “smudged,” and
the purpura can appear “gun metal gray” in the center.
Look for signs of meningeal irritation—neck soreness or
stiffness, photophobia, and headaches.
The clinical manifestations of meningococcemia are
those of septic shock, with acute renal failure, hypoxia,
hypotension, multi-organ failure, and disseminated
intravascular coagulopathy. This fulminating septicemia
is termed Waterhouse-Friderichsen syndrome, accompanied by hemorrhagic destruction of the adrenal glands.
Early diagnosis and treatment are crucial. The
diagnosis of meningococcemia must rest on clinical
findings and is confirmed by positive cultures of the skin
or blood. In meningococcal sepsis, a Gram’s stain of a
skin biopsy specimen is significantly more sensitive
(72%) than Gram’s-stained cerebrospinal fluid (22%).
Also, a Gram’s-stained punch biopsy can be positive up
to 45 hours after antibiotics, compared to 13 hours for
blood cultures.19 Patients should only have a punch
biopsy when blood cultures results are negative for
suspected N. meningitidis and a definitive diagnosis needs
to be made. This decision is usually in the hands of the
consultant and not the emergency physician.
General Diagnostic Tests
In toxic-appearing patients, draw a CBC with platelets,
blood cultures, chemistries, and PT/PTT. These tests may
help to determine if the patient has multi-organ failure
and/or disseminated intravascular coagulopathy.
Consider thrombotic thrombocytopenic purpura in a
patient with petechiae, mental status change, renal
insufficiency, hemolysis, and thrombocytopenia.
Order a urine assay to look for casts, red blood
cells, and protein (as glomerulonephritis is seen with
Henoch-Schönlein purpura).65 A lumbar puncture
should be performed on those who have fever,
headache, or meningeal signs. Additional tests that
may aid in the diagnosis include hepatitis B and
hepatitis C antibodies, an HIV test, an antinuclear
antibody test, and a skin biopsy. If you are not sure
whether meningococcemia or Rocky Mountain spotted
fever is the cause of the rash in a toxic-appearing
patient, then a biopsy of the petechial/purpuric lesion
for Gram’s staining may be helpful. (A simpler solution is
to give antibiotics that will cover both diagnoses—that
is, ceftriaxone plus doxycycline—and let the consultant
worry about further diagnostic testing.)
General Treatments
Administer antibiotics as soon as possible for suspected
meningococcemia or Rocky Mountain spotted fever: IV
ceftriaxone (Rocephin) 2 g for meningococcemia and
doxycycline 100 mg IV for suspected Rocky Mountain
spotted fever. Give these antibiotics before the results of
tests return if the patient is ill-appearing or the rash is
progressing rapidly. Be aggressive with IV fluids in toxic
and hypotensive patients; pressors may be necessary.
Meningococcemia
Acute meningococcemia and meningococcal meningitis
are caused by Neisseria meningitidis, an encapsulated
gram-negative diplococcus.66 Most cases of meningococcemia begin with colonization of the nasopharynx and
then progress to systemic invasion, ultimately leading to
Emergency Medicine Practice
Treatment
In cases where the organism has not yet been identified,
ceftriaxone (2 g q12h) is the initial antibiotic of choice to
18
www.empractice.net • September 2002
Subsequently, the rash spreads centrally to the trunk and
proximal extremities.78 The rash begins as reddish
macules that blanch with pressure, eventually becoming
petechial and purpuric. (See Figure 5.) In approximately
10%-15% of the cases, a rash does not appear (producing
“spotless” fever).75 In darker-skinned people, the rash
may be difficult to see, which may contribute to the
higher mortality rate in blacks (16%) as compared to
whites (3%).71,79 Most patients with RMSF complain of
fever, headaches, myalgias, and malaise.74 Pain in the
calves and abdomen is common. In severe cases of
RMSF, multiple organs can be involved. CNS involvement may range from headaches (very common) to
coma and even seizures. Disseminated intravascular
coagulopathy is a predictor for mortality. Third spacing
of fluids and concomitant edema, hypoalbuminemia,
and hypovolemia may occur secondary to increased
capillary permeability. In severe cases, the syndrome
of inappropriate secretion of antidiuretic hormone can
produce hyponatremia.80
The diagnosis of RMSF is empiric and is initially based on
clinical and epidemiologic findings. Serologic testing will be
negative in the acute period.81 As a general rule, a patient
with a history of possible tick exposure in an endemic
area during the months of April to September who
presents with fever, headaches, and a rash should be
treated for RMSF. Unfortunately, this triad of fever, rash,
and a history of tick bite is found in only 60%-70% of
patients on initial examination.75 Serologic testing is
confirmatory about two weeks after the tick bite but
generally unnecessary.82 The Weil-Felix agglutination
test is no longer used because of its low sensitivity
and specificity.78,83
cover the most common bacterial causes of purpuric
disease: N. meningitidis, H. influenzae, and S. pneumoniae.
Once a definitive diagnosis of N. meningitidis is made in
the hospitalized patient, ceftriaxone can be continued or
the patient can be switched to IV penicillin G (4 million
units q4h). An alternative regimen is ampicillin (2 g q6h);
for those who are penicillin-allergic, ceftriaxone (2 g
q12h) or cefotaxime can be used. In cases of severe
penicillin allergy, IV chloramphenicol 4 g/d is indicated.72 Supportive care involving IV fluids is crucial in
the patient with overt or incipient shock. Patients with
suspected meningococcemia should be admitted to an
isolation room.
Close contacts, such as daycare center personnel,
household members, or ED personnel who have been in
contact with the patient’s oral secretions should receive
antibiotic prophylaxis. Others who should receive
prophylaxis include those with prolonged contact (for at
least 4 hours in the week before onset of illness). In the
case of healthcare workers, prophylaxis is indicated for
those involved with intubation, nasotracheal suctioning,
or resuscitation efforts. (A housekeeper who inadvertently walks into an isolation room to change the garbage
bag does not need prophylaxis.) The recommendation for
prophylaxis is a single dose of ciprofloxacin 500 mg PO.
An alternative is rifampin 600 mg q12h PO for two days
or ceftriaxone 250 mg IM.73
Rocky Mountain Spotted Fever
Rocky Mountain spotted fever (RMSF) is an acute
infectious disease caused by Rickettsia rickettsii, an
obligate intracellular coccobacillus. This organism is
transmitted by the bites of several species of ticks, mostly
Dermacentor variabilis (American dog tick) in the eastern
United States and Dermacentor andersoni (Rocky Mountain
wood tick) in the western United States. The term “Rocky
Mountain” spotted fever is misleading because the
majority of the cases occur in the eastern part of the
United States (although the first cases were described in
Idaho and Montana).66,74
There are about 1000 cases of RMSF a year, most of
which occur between April and September, when the
ticks are most active. However, cases have been reported
year-round. The mortality rate for the untreated exceeds
30%.71,75 Risk factors for mortality include delay in
treatment and advanced age.76
It is thought that the tick must be attached for a
prolonged period (hours) in order for the rickettsii to be
released into the bloodstream; however, a tick bite is
recalled in only 50% of patients.77 After the tick bite, the
R. rickettsii organism disseminates into the bloodstream
and invades the endothelium of blood vessels. The
resulting vasculitis produces the characteristic rash of
petechiae, hemorrhage, and edema.
Treatment
The recommended treatment for RMSF in adults is
doxycycline 100 mg BID PO or IV for seven days or
for two days after temperature has normalized.
Figure 5. Rocky Mountain spotted fever.
Clinical Presentation
The rash typically appears on the fourth day after the bite
(range, 1-15 days), erupting first on the wrist and ankles.
September 2002 • www.empractice.net
Reproduced with permission from: Habif T, ed. Clinical Dermatology:
A Color Guide to Diagnosis and Therapy. 3rd ed. St. Louis: Mosby; 1996.
19
Emergency Medicine Practice
to die than those who receive treatment after the fifth
day (6.5% vs 22.9%; P < 0.03).81 The need for hospitalization depends on the severity of the illness. Long-term
sequelae from severe illness due to RMSF include
hearing loss, peripheral neuropathy, bladder and
bowel incontinence, and cerebellar, vestibular, and
motor dysfunction.89 Lifelong immunity appears to
develop after infection.80
While chloramphenicol is also active against the
rickettsia, doxycycline is associated with fewer
fatalities.84 In the past, doxycycline was not often used in
children under 8 years because of the presumed risk of
dental staining that occurs with tetracycline, a related
drug. For this reason, some physicians prescribe chloramphenicol for young children in whom RMSF is suspected.
However, a number of authorities strongly recommend
doxycycline even in children under 8, arguing for its
documented effectiveness, broad margin of safety,
minimal risk of dental staining, and convenient dosing
schedule.85 Evidence suggests that the short courses of
doxycycline used to treat RMSF do not cause clinically
significant staining of teeth.86 The recommended treatment for pregnant women is chloramphenicol 500 mg
QID PO or IV for seven days or for two days after the
temperature has normalized.87,88
Patients who receive antirickettsial therapy within
five days of symptom onset are significantly less likely
Henoch-Schönlein Purpura
“Numerous smaller, and larger, dark red, or bluish, round
patches are especially noticed on the legs and feet, while the
upper portions of the body are free, or present but a few specks.
They are not changed by pressure....The purpura in these cases
was always combined with colic, tenderness of the colon,
vomiting, intestinal hemorrhage, and, with one exception, with
rheumatic pains, with swelling of the joints being less constant.”—Eduard Heinrich Henoch, Lectures on Diseases of
Children: A Handbook for Physicians and Students, 1882
Ten Pitfalls To Avoid
1. “I didn’t think Mr. Smith had Rocky Mountain spotted
fever—he had no rash!”
Well, he had “Rocky Mountain spotless fever.”
Approximately 10%-15% of people diagnosed with
RMSF have no rash. It can be fatal to presume otherwise.
The index of suspicion should be high in individuals
with fever, headache, myalgias, and possible tick exposure
from April to September. Treat liberally and empirically
with doxycycline.
him on IV penicillin G. He got worse, developing
hepatitis and nephritis. Then his skin began to exfoliate
for no reason.”
There was a reason. You neglected to elicit that he had selfmedicated with his girlfriend’s “antibiotic pill” for a sore
throat. This pill turned out to be penicillin VK. Facial swelling
and erythema without pain in a person with
lymphadenopathy and a diffuse body erythema should
raise suspicion for a hypersensitivity syndrome.
2. “That elderly fellow kept returning to the ED with mouth
sores and complained it was painful to eat. I referred him to
his dentist.”
Well, you neglected to check out the rest of his body for
lesions or ask about personal or family history of bullous
diseases. This patient had pemphigus vulgaris. Early
treatment can significantly improve outcome.
5. “I didn’t think about antibiotic prophylaxis for his
dorm mates.”
You did a splendid job in quickly diagnosing and treating
the index case of meningococcemia, but you neglected to
prophylax his roommates with ciprofloxacin or rifampin.
Now two other students have contracted meningitis.
6. “I diagnosed the patient with Stevens-Johnson syndrome
because he came in with denuded skin and lesions of the
mouth, eyes, and rectum. I put silver sulfadiazene on the
denuded areas, but he got worse.”
Drugs are usually the inciting agent in SJS and TEN. This
patient was started on sulfonamides the week he
developed symptoms. You should have stopped the drug
(and not given silver sulfadiazene) as soon as the diagnosis
of SJS was considered.
3. “I thought that alcoholic, drug-abusing homeless person
was seeking narcotics. He kept on saying he had severe
pain in his leg, but I didn’t see any physical signs that
anything was wrong. He was probably drunk.”
Pain out of proportion to physical examination in a “toxic”
person should raise suspicion for early necrotizing fasciitis.
This patient was toxic with altered mental status—not
drunk. History of alcohol abuse, diabetes, peripheral
vascular disease, and a debilitated state are all risk factors
for necrotizing fasciitis.
7. “I thought the patient might have TEN because she had a
really bad rash that was sloughing off and fever. It was 3:00
a.m. and I didn’t want to wake up the dermatologist, so I
4. “I thought the patient might have had cellulitis of his face
and chest. He had fever and lymphadenopathy, so I started
Emergency Medicine Practice
Continued on page 21
20
www.empractice.net • September 2002
Henoch-Schönlein purpura is a vasculitis that primarily
affects children. It is a constellation of cutaneous purpura, arthritis, abdominal pain, gastrointestinal bleeding,
and nephritis. Immunoglobulin A (IgA) plays an important role in the development of this syndrome.90 Patients
present with palpable purpura on the legs and buttocks
and often complain of joint pain. Abdominal pain is also
common, and some children go on to develop intussusception. Nephritis occurs in 40% of patients, usually
associated with gross or microscopic hematuria and
frequently proteinuria.
Henoch-Schönlein purpura is an acute, self-limited
disease of approximately one month’s duration. Corticosteroids are effective in treating the arthritis and abdominal pain.91,92 Consult a specialist if nephritis is suspected.
is broad. Some of these diagnoses are not immediately
life-threatening, such as a viral exanthema, staphylococcal scalded skin syndrome, and Kawasaki disease. Others
are rapidly lethal, such as the toxic shock syndromes
(TSS) and necrotizing fasciitis.
Staphylococcal Toxic Shock Syndrome
And Streptococcal Toxic Shock Syndrome
For the purposes of this article, staphylococcal toxic
shock syndrome (TSS) and streptococcal toxic shock
syndrome (STSS) will be discussed together, since
they are similar in etiology, clinical presentation,
and treatment.
Etiology
TSS and STSS are exotoxin-mediated diseases with
dramatic clinical presentations. First described by Todd et
al in 1978, TSS is characterized by fever, rash, mucous
membrane involvement, and hypotension. Initially, toxic
Diffuse Erythematous Rashes
The differential diagnosis for diffuse erythematous rashes
Ten Pitfalls To Avoid
(continued)
just started the steroids in the ED. I admitted the patient
to the floor and figured the dermatologist could see her
in the morning.”
This emergency physician made two big mistakes: 1) He
should have called the on-call dermatologist. 2) The patient
should have been admitted to the ICU. Retrospective
studies have shown that steroids may increase the rate
of morbidity and mortality of patients with TEN. Steroids
are generally not given for TEN and should only be given
in consultation with a dermatologist. Patients with TEN
should be treated like burn patients and admitted either
to a burn unit or an ICU setting. The mortality rate from
TEN is 25%-30%.
9. “She was 68 years old and had a high fever and a red
rash on her trunk. She said she had decreased energy
and myalgias for the past few days with low-grade
fever. She had a past medical history of hypertension.
I thought she had a viral syndrome and sent her home
with follow-up with her primary care physician the
next day.”
This patient’s rash worsened, and when she went to her
primary care physician the next day, the patient was found
to have a high fever, hypotension, and upon admission to
the hospital she had increased BUN/Cr, CPK, and bilirubin.
The patient had a nosebleed approximately one week prior
to presentation that required nasal packing. The emergency
physician failed to obtain this history. She was admitted to
the hospital with the diagnosis of staphylococcal toxic
shock syndrome.
8. “The patient came in complaining of severe leg pain and
malaise. He was febrile and hypotensive but responded to
fluids and acetaminophen. I diagnosed him with cellulitis,
started him on cefazolin, and admitted him to the floor. I
had no idea he would deteriorate so quickly and require
transfer to the ICU.”
This patient had streptococcal toxic shock syndrome.
STSS often presents with pain out of proportion to
physical exam findings. About 80% of patients with
STSS have an associated soft-tissue infection, and
60% develop bacteremia. The emergency physician
must have a high index of suspicion for STSS when
patients present with a soft-tissue infection or injury,
high fever, and hypotension. IV penicillin combined
with clindamycin is the initial treatment of choice.
Get a surgical consult if there is suspicion of a
necrotizing infection.
September 2002 • www.empractice.net
10. “I suspected meningococcemia from the start. It takes
time to get blood and urine cultures. I also needed to get a
CT before I did the lumbar puncture. Plus, the nurses
couldn’t find a vein to stick.”
This child arrested before antibiotics were ever given. When
you suspect meningococcemia, set a timer. If the cultures,
bloodwork, lumbar puncture, etc., are not done by 30
minutes, give the antibiotics anyway (the lesions can be
biopsied and successfully Gram’s-stained the next day—
and the cerebrospinal fluid will not be sterilized for hours).
Can’t get a peripheral IV or a central line? If you can’t get
access within a reasonable time, consider IM or
intraosseous antibiotics for the first dose and give the IV
dose as soon as a line is established. ▲
21
Emergency Medicine Practice
STSS tend to be young and healthy, the morbidity and
mortality are higher in STSS than TSS.103 Patients develop
profound shock, renal failure, sepsis, and adult respiratory distress syndrome. The overall mortality is 30%, and
mortality rates can reach 80% in the elderly.104-106 Between
1990 and 1994, 29 cases of STSS were reported in children
up to 14 years of age, and five of these children died.107
The mortality rate for TSS is 2%-5%.108
shock syndrome was thought to be associated only with
staphylococcal infection, but it has since been found to be
associated with streptococcal infection as well.93
Pathophysiology
TSS is caused by colonization of toxin-producing strains
of S. aureus. The systemic manifestations of the illness
arise from a staphylococcal toxin and other mediators.
Unlike TSS, STSS is caused by a local tissue
invasion of the infecting organism S. pyogenes (group
A Streptococcus). Unlike TSS, a bacteremia ensues.94
Clinical Presentation
Patients report a prodrome of low-grade fever, malaise,
myalgias, and vomiting.109 Symptoms may occur within
2-3 days of tampon use, soft-tissue infection, or within a
week of other inciting factors.110
The onset of the major symptoms of TSS and STSS
(high fever, rash, and hypotension) begins abruptly after
the prodrome. Hypotension develops rapidly, leading to
tissue ischemia and subsequent multisystem involvement. An endotoxin-induced vasculitis contributes to the
systemic failure.
Rash is a characteristic feature of TSS and usually
develops 1-3 days after other major symptoms. The rash
is a diffuse, non-pruritic, blanching, and macular erythroderma. It generally erupts on the trunk, where it remains
most prominent, although scattered erythematous
papules may coexist. If the patient is thrombocytopenic,
purpura may develop. The initial rash may be subtle or
even overlooked (especially in dark-skinned individuals)
and generally resolves in 3-5 days. Half of patients
develop a pruritic, diffuse, maculopapular eruption,
usually on the hands and feet.78 If the patient survives the
initial episode of TSS, full-thickness desquamation of the
palms and soles occurs 5-12 days after the onset of
Epidemiology
When TSS was first discovered, 85%-90% of the cases
were in young, healthy women who used hyper-absorbent tampons, which resulted in vaginal colonization of
toxin-producing strains of S. aureus.95 Increased patient
and physician awareness, along with removal of these
tampons from the market, has decreased the incidence of
TSS in menstruating women. Currently, TSS occurs in all
age groups but still occurs more commonly in women.96
Up to 45% of cases of TSS are non-menstrual.97 Nonmenstrual cases of TSS occur with abscesses, bursitis,
surgical wounds, indwelling foreign bodies such as nasal
packing, and in post-partum patients.98-101
In STSS, most patients are 20-50 years old,78 and 80%
of patients have an associated soft-tissue infection or
minor skin trauma.94 In contrast to TSS, where blood
cultures are usually sterile, more than 60% of patients
with STSS develop bacteremia.102
Morbidity And Mortality
Even though most individuals who are susceptible to
Cost-Effective Strategies For Patients With Rashes
Caveat: Certain patients will require laboratory evaluation,
including those who are ill-appearing (and especially if
they have petechiae). In such patients, a CBC, with special
attention to the platelet count, is useful. Order a VDRL for
those with a papulosquamous rash, particularly if it
involves the palms or soles.
1. Discharge appropriately.
Patients with erythema multiforme minor and major, and
even some with Stevens-Johnson syndrome, can be
discharged home with timely follow-up.
Caveat: Patients who are discharged should return
immediately for any worsening of their rash or if they
start to feel worse. Individuals with significant epithelial
loss, the very young or very old, and those with
comorbidities or no follow-up require admission to the
hospital. Those with TEN require intensive care and
possibly transfer to a burn unit.
3. Do a good physical examination.
Nothing will provide as much “bang for the buck” as a superb
physical examination. While the best way to examine a rash is
to take a naked patient out into the afternoon sun, this is not
always practical. At least make sure every patient is in a gown
and touch the rash. Does the patient have palpable purpura
or a positive Nikolsky’s sign? If there are “spots,” do they
blanch? Always look in the mouth and at the eyes, as well as
the palms and soles; if erythema mulitforme or StevensJohnson syndrome is possible, look at the genitalia and
rectum as well. ▲
2. Limit laboratory studies.
The diagnosis of most rashes is clinical. If the patient is not illappearing, most patients with rash will not require
bloodwork. Confused about a rash? Get out a book or talk to
a consultant instead of ordering gazillions of tests that will
only further muddy the waters.
Emergency Medicine Practice
22
www.empractice.net • September 2002
lin, nafcillin, cefoxitin, vancomycin, or clindamycin)
should be started as soon as the diagnosis is considered.
Antibiotics are unlikely to alter the course of TSS but may
decrease the rate of recurrence.111 All potential sites of
infection should be cultured. However, the initial site of
infection (for example, the upper respiratory or genital
tract) is often colonized with S. aureus, which may make
test interpretation difficult.
The use of steroids in TSS and STSS is controversial;
some believe that patients in severe shock who do
not respond to initial antibiotic therapy may benefit
from them.112 In severe cases of TSS and STSS,
immunoglobulins can also be considered, but this,
too, is contentious.113,114
Antibiotic treatment in STSS is essential. If suspicion
of STSS is high, a broad-spectrum antibiotic coverage is
recommended until a specific organism is identified (e.g.,
penicillin G or ampicillin, plus clindamycin, and possibly
an aminoglycoside). Culture all potential sites of infection, and debride necrotic tissue.
symptoms, as well as a fine desquamation of the face
and trunk.
A key distinguishing factor of STSS, present in 85% of
patients, is extreme localized pain at the site of infection that is
out of proportion to physical findings. Desquamation is less
common than in staphylococcal toxic shock syndrome.104
Diagnosis
The diagnosis of TSS and STSS is clinical and requires the
presence of high fever, rash followed by desquamation,
mucous membrane involvement, and the involvement of
three or more organ systems. (See Table 12.) In patients
less than 10 years of age, the diagnosis of Kawasaki
disease should be considered.
In making the diagnosis of STSS, the clinician should
search for a site of infection. Soft-tissue infection may
progress to necrotizing fasciitis or myositis.94 One
retrospective study of 20 patients with STSS found that
55% of patients had necrotizing fasciitis.104 Diagnosis of
STSS requires isolation of group A Streptococcus from a
normally sterile body site.
Disposition
Treatment
All patients who are suspected of having TSS or STSS
should be admitted. Those at the extremes of age, and
patients with unstable vital signs, rapidly progressing
disease, or significant comorbidities, may benefit from
ICU admission.
Patients with TSS and STSS often require aggressive
resuscitation. Some will need vasopressors, inotropic
agents, and mechanical ventilation. In TSS, remove the
source of staphylococcal colonization, such as vaginal
tampons, nasal packing, or breast implants (involve a
plastic surgeon with this last one). Antibiotic therapy
with anti-staphylococcal coverage is recommended.
Intravenous beta-lactamase-resistant antibiotics (oxacil-
Conclusion
In the diagnosis of rashes, clinical acumen and physical
findings far outweigh laboratory evaluation. Take a
careful history with special attention to the patient’s
immune status and any recent medications. Finding out
where on the body the rash started and the presence of
any associated symptoms may provide important clues.
The physical examination should target involvement of
mucous membranes, the presence of petechiae, and
determination of toxicity. Ultimately, pattern recognition
is often crucial to making the correct diagnosis of an
unknown rash.
Using clinical skills, the emergency physician must
quickly recognize potentially lethal conditions and
administer empiric therapy. Certain etiologies, such as
meningococcemia, require immediate antibiotics, while
others, such as TEN and TSS, require aggressive supportive care. ▲
Table 12. Toxic Shock Syndrome Case Definition.
Major criteria (all criteria must be present):
• Fever: Temperature >102ºF
• Rash:
• Erythroderma followed by desquamation
• Mucous membrane: oral, conjunctival, and vaginal
• Hypotension: Systolic blood pressure < 90 mmHg
Multisystem manifestations (three or more):
• CNS: Altered mental status without focal neurologic
symptoms
• Cardiovascular: distributive shock, heart failure,
arryhthmias, AV blocks, non-specific ST changes
• Pulmonary: advanced respiratory distress syndrome,
pulmonary edema
• Gastrointestinal: vomiting and diarrhea
• Hepatic: increased bilirubin, alkaline phosphatase,
or transaminases
• Renal: azotemia
• Hematologic: thrombocytopenia, anemia, leukopenia
• Musculoskeletal: creatine phosphokinase more than two
times upper limit normal
• Metabolic: hypocalcemia, hypophosphatemia
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23
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95. Broome CV. Epidemiology of toxic shock syndrome in the
United States: overview. Rev Infect Dis 1989 Jan;11 Suppl
1:S14-S21. (Review)
96. Manders SM. Toxin-mediated streptococcal and staphylococcal disease. J Am Acad Dermatol 1998 Sep;39(3):383-398;
quiz 399-400. (Review)
97. Herzer CM. Toxic shock syndrome: broadening the
differential diagnosis. J Am Board Fam Pract 2001
Mar;14(2):131-136. (Review, case report)
98. Reingold AL, Hargrett NT, Dan BB, et al. Nonmenstrual
toxic shock syndrome: a review of 130 cases. Ann Intern
Med 1982 Jun;96(6 Pt 2):871-874. (Retrospective; 130 cases)
99. Andrews MM, Parent EM, Barry M, et al. Recurrent
nonmenstrual toxic shock syndrome: clinical manifestations, diagnosis, and treatment. Clin Infect Dis 2001 May
15;32(10):1470-1479. (Review, case report; 3 patients)
100. Arnold J, Lucarelli M, Cutrona AF, et al. Toxic shock
syndrome originating from the foot. J Foot Ankle Surg 2001
Nov;40(6):411-413. (Case report)
101. Davis D, Gash-Kim TL, Heffernan EJ. Toxic shock
syndrome: case report of a postpartum female and a
literature review. J Emerg Med 1998 Jul;16(4):607-614.
(Review, case report)
102. Stevens DL. The toxic shock syndromes. Infect Dis Clin
North Am 1996 Dec;10(4):727-746. (Review)
103. Chesney PJ. Clinical aspects and spectrum of illness of toxic
shock syndrome: overview. Rev Infect Dis 1989 Jan;11 Suppl
1:S1-S7. (Review)
104.*Stevens DL, Tanner MH, Winship J, et al. Severe group A
streptococcal infections associated with a toxic shock-like
syndrome and scarlet fever toxin A. N Engl J Med 1989 Jul
6;321(1):1-7. (Retrospective; 20 patients)
105. Stevens DL. Invasive group A streptococcus infections. Clin
Infect Dis 1992 Jan;14(1):2-11. (Review)
106. Davies HD, McGeer A, Schwartz B, et al. Invasive group A
streptococcal infections in Ontario, Canada. Ontario Group
A Streptococcal Study Group. N Engl J Med 1996 Aug
22;335(8):547-554. (Population surveillance; 323 patients)
107. Conway E. Streptococcal toxic shock: A race against time.
Contemp Pediat (Res Ed) 1995;2:5-10. (Review)
108. Gannon T. Dermatologic emergencies. When early
recognition can be lifesaving. Postgrad Med 1994
Jul;96(1):67-70, 73-75, 79 passim. (Review)
109. Wright SW, Trott AT. Toxic shock syndrome: a review. Ann
Emerg Med 1988 Mar;17(3):268-273. (Review)
110. Kain KC, Schulzer M, Chow AW. Clinical spectrum of
nonmenstrual toxic shock syndrome (TSS): comparison
with menstrual TSS by multivariate discriminant analyses.
Clin Infect Dis 1993 Jan;16(1):100-106. (Comparative;
45 patients)
111. Norman GR, Rosenthal D, Brooks LR, et al. The development of expertise in dermatology. Arch Dermatol 1989
Aug;125(8):1063-1068. (Comparative)
112. Todd JK, Ressman M, Caston SA, et al. Corticosteroid
therapy for patients with toxic shock syndrome. JAMA
1984 Dec 28;252(24):3399-3402. (Comparative, retrospective; 45 patients)
113. Todd JK. Therapy of toxic shock syndrome. Drugs 1990
Jun;39(6):856-861. (Review)
zation Practices (ACIP) and the Hospital Infection Control
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Mortal Wkly Rep 1997 Dec 26;46(RR-18):1-42. (Guideline)
Weber DJ, Walker DH. Rocky Mountain spotted fever. Infect
Dis Clin North Am 1991 Mar;5(1):19-35. (Review)
Spach DH, Liles WC, Campbell GL, et al. Tick-borne
diseases in the United States. N Engl J Med 1993 Sep
23;329(13):936-947. (Review)
Dalton MJ, Clarke MJ, Holman RC, et al. National surveillance for Rocky Mountain spotted fever, 1981-1992:
epidemiologic summary and evaluation of risk factors for
fatal outcome. Am J Trop Med Hyg 1995 May;52(5):405-413.
(Population surveillance; 7650 patients)
Kirk JL, Fine DP, Sexton DJ, et al. Rocky Mountain spotted
fever. A clinical review based on 48 confirmed cases, 19431986. Medicine (Baltimore) 1990 Jan;69(1):35-45. (Review,
retrospective; 48 patients)
Drage LA. Life-threatening rashes: dermatologic signs of
four infectious diseases. Mayo Clin Proc 1999 Jan;74(1):6872. (Review)
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spotted fever—United States, 1990. MMWR Morb
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(Epidemiologic data)
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Jun;37(6):95-104. (Review)
Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic
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(Retrospective cohort)
Kostman JR. Laboratory diagnosis of rickettsial diseases.
Clin Dermatol 1996 May;14(3):301-306. (Review)
Kaplan JE, Schonberger LB. The sensitivity of various
serologic tests in the diagnosis of Rocky Mountain spotted
fever. Am J Trop Med Hyg 1986 Jul;35(4):840-844. (Comparative; 4141 cases)
Holman RC, Paddock CD, Curns AT, et al. Analysis of risk
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Dec 1;184(11):1437-1444. (Comparative; 6388 patients)
Cale DF, McCarthy MW. Treatment of Rocky Mountain
spotted fever in children. Ann Pharmacother 1997
Apr;31(4):492-494. (Review)
Lochary ME, Lockhart PB, Williams WT Jr. Doxycycline
and staining of permanent teeth. Pediatr Infect Dis J 1998
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Stallings SP. Rocky Mountain spotted fever and pregnancy:
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Surv 2001 Jan;56(1):37-42. (Review, case report)
Thorner AR, Walker DH, Petri WA Jr. Rocky mountain
spotted fever. Clin Infect Dis 1998 Dec;27(6):1353-1359; quiz
1360. (Review)
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Mountain spotted fever. Clin Infect Dis 1995 May;20(5):11221125. (Follow-up study; 25 patients)
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Rheumatol 2001 Jan;13(1):35-40. (Review)
Rosenblum ND, Winter HS. Steroid effects on the course of
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Emergency Medicine Practice
26
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114. Barry W, Hudgins L, Donta ST, et al. Intravenous immunoglobulin therapy for toxic shock syndrome. JAMA 1992 Jun
24;267(24):3315-3316. (Case report)
40. Maculopapular rashes:
a. are the most common types of rash.
b. have the broadest differential diagnosis.
c. are usually seen with viral illnesses, bacterial
infection, drug reactions, and other immunerelated syndromes.
d. should prompt questions about sick contacts,
travel, and new medications.
e. all of the above.
Physician CME Questions
33. When triaging patients with rashes, any of
the following would qualify the patient as
high-risk except:
a. abnormal vital signs.
b. altered mental status.
c. a localized rash that does not progress.
d. potential airway compromise.
e. a petechial rash.
41. Appropriate treatment of cutaneous drug reactions
include all of the following except:
a. removing the offending drug.
b. a short course of steroids.
c. diphenhydramine to alleviate pruritus.
d. non-sedating antihistamines (instead of diphenhydramine if sedation would be a problem) to
alleviate pruritus.
34. The most common cause of pruritus is:
a. scabies.
b. lymphomas.
c. an acute allergic reaction.
d. poison ivy.
e. dry skin.
42. A target lesion is typically associated with:
a. erythema multiforme.
b. pemphigus vulgaris.
c. Rocky Mountain spotted fever.
d. toxic shock syndrome.
35. Recent travel can be associated with all of the
following life-threatening rashes except:
a. toxic epidermal necrolysis.
b. Rocky Mountain spotted fever.
c. Lyme disease.
d. hemorrhagic fevers.
36. Oral ulcers or blisters can imply a serious systemic
reaction, such as Stevens-Johnson syndrome or
pemphigus vulgaris.
a. True
b. False
43. Which of the following would be the
proper disposition of the patient with
erythema multiforme?
a. immediate admission to the ICU.
b. discharge home with a two-week course
of prednisone.
c. discharge home with antihistamines and
analgesia for symptomatic relief as needed.
d. admission for a day of observation.
37. A patient who presents with a rash and fever:
a. should receive a full, head-to-toe examination.
b. only requires a skin examination.
c. should receive acetaminophen for presumed
viral syndrome.
d. is considered low-risk unless he or she also has
difficulty breathing.
44. Diseases that produce diffuse erythematous rashes
include all of the following except:
a. staphylococcal scalded skin syndrome.
b. toxic epidermal necrolysis.
c. Kawasaki disease.
d. the toxic shock syndromes.
e. necrotizing fasciitis.
38. When performing the skin examination, the
emergency physician should evaluate:
a. the type of lesion.
b. the shape of the individual lesion.
c. the arrangement of multiple lesions.
d. the pattern of the rash.
e. all of the above.
45. Antibiotic prophylaxis for all close contacts of
patients with meningococcemia, including household members and medical personnel in contact
with respiratory droplets, is mandatory.
a. True
b. False
46. Henoch-Schönlein purpura:
a. rarely affects children.
b. is a constellation of cutaneous purpura,
arthritis, abdominal pain, gastrointestinal
bleeding, and nephritis.
c. requires hospital admission.
d. treatment should include antibiotics and
not corticosteroids.
39. Patients who are not toxic or febrile and who have
a rash that appears benign should receive:
a. a CBC.
b. a CBC, chemistry panel, and liver function tests.
c. a Gram’s stain.
d. a punch biopsy.
e. none of the above.
September 2002 • www.empractice.net
27
Emergency Medicine Practice
Physician CME Information
47. Which of the following is/are a risk factor(s)
associated with toxic shock syndrome?
a. Soft-tissue infection
b. Surgical wounds
c. Indwelling foreign bodies such as
nasal packing
d. Use of hyper-absorbent tampons
e. All of the above
This CME enduring material is sponsored by Mount Sinai School of Medicine and
has been planned and implemented in accordance with the Essentials and
Standards of the Accreditation Council for Continuing Medical Education. Credit
may be obtained by reading each issue and completing the printed post-tests
administered in December and June or online single-issue post-tests
administered at www.empractice.net.
Target Audience: This enduring material is designed for emergency medicine
physicians.
Needs Assessment: The need for this educational activity was determined by a
survey of medical staff, including the editorial board of this publication; review
of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and
evaluation of prior activities for emergency physicians.
48. All of the following are true of petechial/
purpuric rashes except:
a. They can be due to viral, bacterial, or
non-infectious causes.
b. They include some of the most rapidly
lethal rashes.
c. They are usually caused by toxic
shock syndrome.
d. They should be presumed to be caused
by Rocky Mountain spotted fever or
meningococcal disease until ruled out.
Date of Original Release: This issue of Emergency Medicine Practice was published
September 1, 2002. This activity is eligible for CME credit through September
1, 2005. The latest review of this material was August 7, 2002.
Discussion of Investigational Information: As part of the newsletter, faculty may
be presenting investigational information about pharmaceutical products that
is outside Food and Drug Administration approved labeling. Information
presented as part of this activity is intended solely as continuing medical
education and is not intended to promote off-label use of any pharmaceutical
product. Disclosure of Off-Label Usage: This issue of Emergency Medicine Practice
discusses the use of doxycycline in young children with Rocky Mountain
spotted fever. Although it is not approved for this use, clinical studies indicate it
is safe and effective for this condition. (See text.)
Faculty Disclosure: In compliance with all ACCME Essentials, Standards, and
Guidelines, all faculty for this CME activity were asked to complete a full
disclosure statement. The information received is as follows: Dr. Nguyen, Dr.
Freedman, Dr. Burke, and Dr. Playe report no significant financial interest or
other relationship with the manufacturer(s) of any commercial product(s)
discussed in this educational presentation.
Class Of Evidence Definitions
Each action in the clinical pathways section of Emergency Medicine Practice
receives an alpha-numerical score based on the following definitions.
Class I
• Always acceptable, safe
• Definitely useful
• Proven in both efficacy and
effectiveness
Level of Evidence:
• One or more large prospective
studies are present (with
rare exceptions)
• High-quality meta-analyses
• Study results consistently
positive and compelling
Class II
• Safe, acceptable
• Probably useful
Level of Evidence:
• Generally higher levels
of evidence
• Non-randomized or retrospective studies: historic, cohort, or
case-control studies
• Less robust RCTs
• Results consistently positive
Class III
• May be acceptable
• Possibly useful
• Considered optional or
alternative treatments
Level of Evidence:
• Generally lower or intermediate
levels of evidence
Accreditation: Mount Sinai School of Medicine is accredited by the Accreditation
Council for Continuing Medical Education to sponsor continuing medical
education for physicians.
• Case series, animal studies,
consensus panels
• Occasionally positive results
Credit Designation: Mount Sinai School of Medicine designates this educational
activity for up to 4 hours of Category 1 credit toward the AMA Physician’s
Recognition Award. Each physician should claim only those hours of credit
actually spent in the educational activity. Emergency Medicine Practice is approved
by the American College of Emergency Physicians for 48 hours of ACEP Category
1 credit (per annual subscription). Emergency Medicine Practice has been reviewed
and is acceptable for up to 48 Prescribed credit hours by the American Academy
of Family Physicians. Emergency Medicine Practice has been approved for 48
Category 2B credit hours by the American Osteopathic Association.
Indeterminate
• Continuing area of research
• No recommendations until
further research
Level of Evidence:
• Evidence not available
• Higher studies in progress
• Results inconsistent,
contradictory
• Results not compelling
Earning Credit: Two Convenient Methods
• Print Subscription Semester Program: Physicians with current and valid
licenses in the United States who read all CME articles during each
Emergency Medicine Practice six-month testing period, complete the posttest and the CME Evaluation Form distributed with the December and June
issues, and return it according to the published instructions are eligible for
up to 4 hours of Category 1 credit toward the AMA Physician’s Recognition
Award (PRA) for each issue. You must complete both the post-test and CME
Evaluation Form to receive credit. Results will be kept confidential. CME
certificates will be delivered to each participant scoring higher than 70%.
Significantly modified from: The
Emergency Cardiovascular Care
Committees of the American Heart
Association and representatives
from the resuscitation councils of
ILCOR: How to Develop EvidenceBased Guidelines for Emergency
Cardiac Care: Quality of Evidence
and Classes of Recommendations;
also: Anonymous. Guidelines for
cardiopulmonary resuscitation and
emergency cardiac care. Emergency
Cardiac Care Committee and
Subcommittees, American Heart
Association. Part IX. Ensuring
effectiveness of community-wide
emergency cardiac care. JAMA
1992;268(16):2289-2295.
• Online Single-Issue Program: Physicians with current and valid licenses in
the United States who read this Emergency Medicine Practice CME article
and complete the online post-test and CME Evaluation Form at
www.empractice.net are eligible for up to 4 hours of Category 1 credit
toward the AMA Physician’s Recognition Award (PRA). You must complete
both the post-test and CME Evaluation Form to receive credit. Results will
be kept confidential. CME certificates may be printed directly from the Web
site to each participant scoring higher than 70%.
Emergency Medicine Practice is not affiliated with any
pharmaceutical firm or medical device manufacturer.
Publisher: Robert Williford. Executive Editor: Heidi Frost.
Direct all editorial or subscription-related questions to EB Practice, LLC: 1-800-249-5770 • Fax: 1-770-500-1316 • Non-U.S. subscribers, call: 1-678-366-7933
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Emergency Medicine Practice (ISSN 1524-1971) is published monthly (12 times per year) by EB Practice, LLC, 305 Windlake Court, Alpharetta, GA 30022. Opinions expressed are not necessarily
those of this publication. Mention of products or services does not constitute endorsement. This publication is intended as a general guide and is intended to supplement, rather than
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Emergency Medicine Practice
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www.empractice.net • September 2002