Bryan Cairns, MD;

Fever, rash, and peeling skin Megan Rich, MD

University of Cincinnati
(Dr. Cairns); Inpatient Family
Medicine, University
Our hospital was the third one this patient had visited of Cincinnati/The Christ
Hospital (Drs. Cairns and Rich)
for a rash and other symptoms that had developed after Bryancairns@gmail.com
having an abscess drained. The authors reported no
potential conflict of interest
relevant to this article.

CASE 䉴 A 21-year-old woman sought care
at our emergency department (ED) for an
extensive rash that began approximately
1 week earlier and hurt “like a sunburn.” She
said that 2 weeks earlier, she’d been seen at an-
other hospital for an incision and drainage of a
thigh abscess. She was started on sulfamethox-
azole/trimethoprim (Bactrim) at that time.
She returned to that ED several times,
complaining of headache and fever, then
went to a different ED because her lips
were swollen and she was developing a rash
(FIGURES 1A AND 1B ). Initially the rash was red,
slightly rough, and covered most of her body
(except for her palms and soles). Providers at
the second ED discontinued the Bactrim, start-
ed her on a course of steroids by mouth, and
sent her home.
On this particular morning, she woke up
feeling that her mouth was burning and her
throat was “closing up.” She was admitted to
our intensive care unit (ICU) for monitoring of
respiratory compromise related to angioede-
ma. She did not require intubation, but her
skin began to desquamate.
● WHAT IS THE MOST LIKELY
EXPLANATION FOR HER
CONDITION?

FIGURE 1

Swollen lips and rash

A B
PHOTOS COURTESY OF MEGAN RICH, MD

This 21-year-old patient had swollen lips and a rash that hurt “like a sunburn.” She said that when she woke up that morning, her mouth
was burning and her throat felt like it was “closing up.”

JFPONLINE.COM VOL 60, NO 1 | JANUARY 2011 | THE JOURNAL OF FAMILY PRACTICE 9

 Stevens-Johnson syndrome
A painful rash involving mucous membranes,
along with fever, should alert the clinician to
the possibility of Stevens-Johnson syndrome
(SJS) or toxic epidermal necrolysis (TEN). The
2 conditions are distinguished by how much
of the body surface area (BSA) is involved:
If the rash covers <10% of the BSA (as it did
with our patient), the condition is called SJS;
if >90%, it’s referred to as TEN.1 Skin involve-
ment that falls between these 2 parameters is
referred to as SJS/TEN overlap syndrome.
Mucous membranes are involved in
more than 90% of SJS cases and in virtually
all cases of TEN.1 Illnesses on this spectrum
typically start with prodromal fever and mal-
aise, followed by the onset of a maculopapu-
lar rash. The rash then becomes vesicular and
eventually progresses to desquamation and
Patients with epidermal necrolysis.2
HIV, cancer, ❚ Common inciting factors. SJS/TEN is
systemic lupus most commonly caused by an infection or a
erythematosus, reaction to medication. In adults, medication
and radiation reaction is the more common etiology. In chil-
exposure are at dren, medications are still the leading cause
higher risk for but a larger proportion of pediatric cases are
Stevens-Johnson associated with infection. Multiple drug clas-
syndrome and sifications can lead to the disorder, including
toxic epidermal anti-gout agents, anti-epileptics, nonsteroi-
necrolysis. dal anti-inflammatory drugs (NSAIDs), and
certain antibiotics—sulfonamides, penicil-
lins, and cephalosporins (TABLE ).3
Slow metabolizers may be at risk
The pathophysiology that underlies these
conditions is not entirely understood. Recent
research indicates a possible role of granuly-
sin, a product of cytotoxic T and natural killer
cells.4 People with slow medication metabo-
lism due to lower rates of N-acetylation may
be at increased risk because of the greater ac-
cumulation of potentially toxic metabolites.5
In addition, the risk for SJS/TEN is
3 times higher in patients who are positive
for human immunodeficiency virus (HIV).
If an HIV patient is exposed to Bactrim—the
offending agent in this case—the relative risk
increases to 40-fold.6 (Our patient was not in-
fected with HIV.)
Other conditions associated with higher
risk are malignancy, systemic lupus erythe-
matosus (SLE), rapid titration or high dos-
10 THE JOURNAL OF FAM ILY P R A C TIC E | J A N U A RY 2011 | VOL 60, N O 1
TABLE
Agents implicated in SJS/TEN
Allopurinol
Amoxicillin
Ampicillin
Lamotrigine
Phenylbutazone
Piroxicam
Sulfadiazine
Trimethoprim/sulfamethoxazole
SJS/TEN, Stevens-Johnson syndrome/toxic epidermal
necrolysis.
Adapted from: Sharma VK et al. Indian J Dermatol
Venerol Leprol. 2008.3
es of medication, and radiation exposure.
Patients with HLA B 1502 haplotype are at
increased risk when exposed to aromatic
anticonvulsant agents, such as phenobarbi-
tal and phenytoin.7
The differential was large,
but the diagnosis was clear
Conditions with a presentation similar to SJS/
TEN include erythema multiforme, erythem-
atous drug reaction, pustular drug eruptions,
sunburn, toxic shock syndrome, staphylococ-
cal scalded skin syndrome, and paraneoplas-
tic pemphigus.
While the differential diagnosis for acute
rash is large, the diagnosis in this case was
clear because of the combination of prodro-
mal symptoms, pain that was out of propor-
tion to the appearance of the skin, and skin
sloughing. In addition, a classic inciting drug
(Bactrim) was easily identified and the timing
of the drug exposure—1 to 3 weeks before the
onset of the rash—was consistent with SJS/
TEN. Sparing of the palms and soles helped
us differentiate SJS/TEN from toxic shock
syndrome.
Why so long to diagnosis?
We suspected that the diagnosis was missed
during our patient’s earlier ED visits because
she initially had nonspecific symptoms and
 FEVER, RASH, AND PEELING SKIN

did not have mucosal involvement early on.
Further complicating matters: She went to
multiple EDs.
Labwork is of limited value
No laboratory values or pathologic tests
are pathognomonic for SJS/TEN. Anemia
and lymphopenia are possible findings,
and neutropenia is an indicator for a poor
prognosis.8 Elevated liver enzymes are
common, reaching levels approximately
2 to 3 times the upper limit of normal.8
All of these laboratory findings become
increasingly more likely as BSA involved
increases.8 Our patient’s laboratory values
were unremarkable.
Tx: Discontinue drug, replace fluids
This syndrome is potentially deadly and must
be treated as an emergency as soon as it is
recognized. The mortality rate is 1% to 3% for
SJS and 25% to 35% for TEN.9
Discontinuing the causative agent is the
first step in treatment. In our patient’s case,
Bactrim had been discontinued before she
came to our ED. The next step, ideally, is to
transfer the patient to a burn unit where she
can receive the same type of supportive care
burn victims require. Diligent wound care,
fluid replacement, electrolyte monitoring,
and raised ambient temperature are vital ele-
ments in proper care. The patient should also
be evaluated throughout the treatment pe-
riod for any ocular involvement, such as con-
junctivitis, keratitis, or severe dryness.10
As is the case with burn victims, the ma-
jor risks are secondary infection and sepsis.
Skin, blood, and access-line cultures should
be gathered throughout the hospitalization
to evaluate for infection. Some authorities
believe glucocorticoids are helpful in chil-
dren with SJS/TEN, but the adverse effects
are sufficiently significant that the risks
may outweigh the benefits. In adults, the
evidence favors the use of glucocorticoids in

OCTOBER 2010 • VOLUME 20, NUMBER 10

www.clinicianreviews.com

This woman’s lesions started on her legs, then spread to

her trunk. What is the underlying cause?
see DermaDiagnosis, page 5 >>

xcellence
of E
Years
A PEER-REVIEWED JOURNAL

THE CLINICAL RESOURCE FOR NP AND PA PRACTICE

FROM THE NP EDITOR-IN-CHIEF

CE/CME
Influenza The Family
2010-2011 Finishes the
Dissertation
A peer-reviewed journal dedicated to keeping
A
s health technology
and methodology
advance, the need
for continued learn-

Nurse Practitioners and Physician Assistants up-to-date in clinical ing and scholarly activities has
driven many of us to pursue
advanced degrees. Many are
poised in various states of com-
pletion, with as many reasons

practice and important trends in health care delivery.

© Courtesy of CDC

for being stalled in one stage

THE MANDATE DEBATE

as there are degree programs.
Recently, in a conversation with
friends, we reminisced about
Laura M. Gunder, DHSc, MHE, PA-C
Bonnie Dadig, EdD, PA-C
How Can We Increase Clinicians’ our “all-but-dissertation” days.
While the pain of the process

Pretest probability, rapid flu

Flu Vaccination Rates? has finally become a mere wince
in recollection, the memory of
how much support we each re-

h h
testing, antiviral therapy,

 I
f the golden rule of medi- for Healthcare Epidemiology of

CME/CE article
see Family, page 2 >>

Interviews with PA and

vaccination—will these tools
cine is “First, do no harm,”
help reduce last season’s
some experts in infectious
flu-related hospitalization
diseases think the major-
and mortality rates?
ity of clinicians are dropping the
ball—at least when it comes to
influenza vaccination. For years,
America (SHEA), “despite Her-
culean efforts to increase it.”
Clinician Reviews
Now, SHEA and other pro-
is endorsed by the
fessional medical organizations American Society
think it may be time to take the of Endocrine PAs
gloves off (figuratively, of course).

h

Intriguing NP thought leaders see Influenza, page 32
the rate of vaccination against
flu among health care person-
nel has been “unacceptably low,”
in the words of Neil Fishman,
MD, President of the Society
The organization recently pub-
lished a position paper in Infec- IN THIS ISSUE
tion Control and Hospital Epide- Your Turn . . . . . . . . . . . . . . . . 1
miology in which it “endorses a
policy in which annual influenza
ECG Challenge . . . . . . . . . . . . 6
vaccination is a condition of both Malpractice Chronicle. . . . . . 7

h
initial and continued [health care Grand Rounds . . . . . . . . . . . 13

self-assessment Malpractice Chronicle

personnel] employment and/
or professional privileges.” The
Case Studies: Toxicology . . 16
recommendation applies to all Endocrine Consult. . . . . . . . 21
health care providers (and other Radiology Review. . . . . . . . 30
workers) in all settings, as well as
students and volunteers. Infection in RA Patients . . . 38

quizzes see Mandate, page 24 >> Classifieds . . . . . . . . . . . . . . 45

hhh
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JFPONLINE.COM VOL 60, NO 1 | JANUARY 2011 | THE JOURNAL OF FAMILY PRACTICE 11

 SJS, but not in TEN, where the increased risk
of sepsis following immunosuppression may
outweigh the benefits.11
Intravenous immunoglobulin (IVIG)
may benefit both children and adults, and
the benefit appears to outweigh risks asso-
ciated with this therapy.12 Plasmaphoresis to
remove toxic metabolites from the circula-
tion is an additional treatment option, but
there is no strong evidence to support this
approach.13
A positive outcome for our patient
Our patient was transferred to a facility with
an inpatient burn unit and a consulting der-
matology service. She was maintained on
steroids, but neither plasmapheresis nor IVIG
was necessary.
She was discharged to her home with
A burn unit prescriptions for topical emollients and an
is the most oral steroid solution for her mouth irritation.
appropriate Systemic steroids were not continued, as the
place for relatively small area of desquamation made
inpatient this unnecessary.
treatment ❚ Staying safe hinges on education. Our
of a patient patient was advised that going forward, she
with SJS/TEN. needed to avoid Bactrim and any other sulfa
drugs. She was told that when medications
References
1. 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;129:92-96.
2. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to
drugs. N Engl J Med. 1994;331:1272-1285.
3. Sharma VK, Sethuraman G, Minz A. Stevens Johnson syn-
drome, toxic epidermal necrolysis, and SJS-TEN overlap: a
retrospective study of causative drugs and clinical outcome.
Indian J Dermatol Venereol Leprol. 2008;74:238-240.
4. Chung WH, Hung SI, Yang JY, et al. Granulysin is a key me-
diator for disseminated keratinocyte death in Stevens-Johnson
syndrome and toxic epidermal necrolysis. Nat Med. 2008;14:
1343-1350.
5. Dietrich A, Kawakubo Y, Rzany B, et al. Low N-acetylating ca-
pacity in patients with Stevens-Johnson syndrome and toxic
epidermal necrolysis. Exp Dermatol. 1995;4:313-316.
6. Rotunda A, Hirsch RJ, Scheinfeld N, et al. Severe cutaneous
reactions associated with the use of human immunodeficien-
cy virus medications. Acta Derm Venerol. 2003;83:1-9.
7. US Food and Drug administration. Information for healthcare
professionals: dangerous or even fatal skin reactions—carba-
mazepine (marketed as Carbatrol, Equetro, Tegretol, and ge-
nerics). Available at: http://www.fda.gov/Drugs/DrugSafety/
PostmarketdrugsafetyinformationforPatientsandProviders/
Visit us online at jfponline.com
12 THE JOURNAL OF FAM ILY P R A C TIC E | J A N U A RY 2011 | VOL 60, N O 1
are prescribed for her in the future, she must
consult with the pharmacist to make sure sul-
fonamides are not included.11 JFP
CORRESPONDENCE
Bryan Cairns, MD, 2123 Auburn Avenue, Cincinnati, OH
45219; Bryancairns@gmail.com
PRACTICE POINTERS
䉴 Ask about inciting factors for SJS/TEN—
anti-gout agents, anti-epileptics, NSAIDs,
sulfonamides, penicillins, and cephalospo-
rins—when a patient seeks care for a painful
rash involving mucous membranes.
䉴 Rule out look-alike conditions, including
erythema multiforme, sunburn, toxic shock
syndrome, staphylococcal scalded skin syn-
drome, and paraneoplastic pemphigus.
䉴 Withdraw the causative agent as the first
step in the treatment of SJS/TEN.
䉴 Refer patients with SJS/TEN to a burn unit
for supportive treatment, including wound
care, fluid replacement, and electrolyte and
ocular monitoring.
ucm124718.htm. Page last updated: January 25, 2010. Ac-
cessed December 20, 2010.
8. Roujeau JC, Chosidow O, Saiag P, et al. Toxic epidermal
necrolysis (Lyell syndrome). J Am Acad Dermatol. 1990;
23:1039-1058.
9. Letko E, Papaliodis GN, Daoud YJ, et al. Stevens-Johnson syn-
drome and toxic epidermal necrolysis: a review of the litera-
ture. Ann Allergy Asthma Immunol. 2005;94:419-436.
10. Williams PM, Conklin RJ. Erythema multiforme: a review and
contrast from Stevens-Johnson syndrome/toxic epidermal
necrolysis. Dent Clin North Am. 2005;49:67-76, viii.
11. Nirken M, High W. Stevens-Johnson syndrome and toxic epi-
dermal necrolysis: clinical manifestations, pathogenesis, and
diagnosis. In: Ofori A, Levy M, Adkinson NF, eds. UpToDate
[online database]. Version 18.2. Waltham, Mass: UpToDate;
2010.
12. French LE, Trent JT, Kerdel FA. Use of intravenous immuno-
globulin in toxic epidermal necrolysis and Stevens-Johnson
syndrome: our current understanding. Int Immunopharma-
col. 2006;6:543-549.
13. Furubacke A, Berlin G, Anderson C, et al. Lack of significant
treatment effect of plasma exchange in the treatment of
drug-induced toxic epidermal necrolysis? Intensive Care Med.
1999;25:1307-1310.