30024569.pdf

REVIEW ARTICLE

Stevens-Johnson syndrome: Pathogenesis, diagnosis, and management

RIBHI HAZIN1, OMAR A. IBRAHIMI2, MOUSTAFA I. HAZIN3 & ARASH KIMYAI-ASADI4

1Harvard University, Faculty of Arts and Sciences, Cambridge, MA, USA, 2Harvard Medical School, Department of

Dermatology, Massachusetts General Hospital, Boston, MA, USA, 3Department of Internal Medicine, St. Joseph’s Hospital

& Medical Center, Phoenix, AZ, USA, and 4DermSurgery Associates, Houston, Texas, USA

AbstractCutaneous drug reactions are the most common type of adverse drug reaction. These reactions, ranging from simple pruriticeruptions to potentially life-threatening events, are a significant cause of iatrogenic morbidity and mortality. Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening cutaneous drug reaction. Although progress has beenmade in the management of SJS through early detection, prompt hospitalization, and immediate cessation of offendingagents, the prevalence of permanent disabilities associated with SJS remains unchanged. Nevertheless, despite being aproblem that is global in scope, government and health care agencies worldwide have yet to find a consensus on eitherdiagnostic criteria or therapy for this disorder. Here, we provide the internist and emergency room physician with a briefreview the SJS literature and summarize the latest recommended interventions with the hope of improving early recognitionof this disease and prevention of permanent sequelae and mortality that frequently complicate SJS.

Key words: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, intravenous immunoglobulins,adverse drug reaction, drug hypersensitivity, dermatological emergencies, mucocutaneous lesions, HLA B1501/HLA B1502,keratinocyte apoptosis

Introduction

Stevens-Johnson Syndrome (SJS) is a life-threaten-

ing inflammatory mucocutaneous drug reaction (1–

3). SJS, also known as erythema multiforme major,

lies on a continuum between erythema multiforme

minor, characterized by targetoid cutaneous lesions

encompassing less than 10% of the body surface

area, and toxic epidermal necrolysis, characterized

by widespread mucocutaneous involvement affect-

ing 30%–100% of the skin surface (Table I) (4). The

initial diagnosis of SJS is based on clinical presenta-

tion, but skin biopsies and direct immunofluores-

cence studies of the skin are essential to rule out

other conditions such as autoimmune bullous dis-

ease (5,6).

Clinical manifestations

SJS characteristically begins with vague upper

respiratory tract symptoms lasting up to 2 weeks.

During this period, patients may complain of fever,

sore throat, chills, headaches, and malaise (7).

Persistent fever lasting longer than 4 weeks should

raise suspicion of a concomitant infection, but

studies have demonstrated that continued fever

may occur in up to 85% of cases even in the absence

of an associated infection (8). This is followed by the

rapid onset of mucocutaneous lesions. Painful

erosions of the mucous membranes are common

and may affect any combination of the lip, oral

cavity, conjunctiva, nasal cavity, urethra, vagina,

gastrointestinal tract, and respiratory tract during

the course of the illness (9–11). Involvement of

mucous membranes is evident in approximately 90%

of affected patients, and the absence of mucous

membrane involvement should cast doubt on the

diagnosis of SJS. Mucous membrane involvement

can result in both short-term dysfunction and

morbidity, as well as long-term complications due

to fibrosis and strictures. The characteristic skin

lesions seen in SJS are diffuse erythematous macules

Correspondence: Arash Kimyai-Asadi MD, DermSurgery Associates, 7515 Main, Suite 210, Houston, Texas 77030, USA. Fax: +1-713 791-9927. E-mail:

[email protected]

Annals of Medicine. 2008; 40: 129–138

ISSN 0785-3890 print/ISSN 1365-2060 online # 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)

DOI: 10.1080/07853890701753664

with purpuric, necrotic centers and overlying blister-

ing (Figure 1). These cutaneous lesions often

become confluent in some areas, and often demon-

strate a positive Nikolsky sign, which is further

detachment of the epidermis with slight lateral

pressure. Targetoid lesions are typically present

and are caused by epidermal necrosis in the center

of lesions (4,12). As involvement progresses,

affected portions of the skin slough, resulting in

widespread superficial ulcers and loss of the epider-

mal barrier (13).

The characteristic mucocutaneous lesions

(Figure 1) tend to develop suddenly during the

prodrome, and new lesions may continue to erupt for

up to 4 weeks. Thereafter, the lesions reepithelialize.

The mucocutaneous lesions seen in the prodromal

period are often the predominant feature and may exist

in the absence of skin lesions. Arriving at an accurate

diagnosis can be challenging in cases that lack notice-

able skin lesions (14). Thus, cultures of oral mucosa

are indicated to help differentiate SJS from other

causes of sore lesions in the oral mucosa including

stomatitis, or virus-induced sloughing (15,16).

For most patients, the most clinically significant

elements of SJS are the sequelae of mucosal

ulceration followed by scarring and stricture, result-

ing in significant deterioration of function of the

affected organ systems. The organ most commonly

affected in this manner is the eye, where corneal

involvement affects the majority of patients and may

result in corneal ulceration, perforation, and perma-

nent sclerotic changes (17–19). Indeed, the majority

of patients with SJS have long-term ocular compli-

cations. Less common and generally less debilitating

ocular complications of SJS include anterior uveitis,

iritis, keratitis, and conjunctivitis (17). Early con-

sultation with and continued care by an ophthalmol-

ogist is critical in all patients with significant ocular

involvement or injury (17–19). Urethral erosions are

another common complication of SJS and may result

in genitourinary strictures (15,20–22). In the acute

setting, placement of a Foley catheter to maintain a

patent urinary tract should be considered.

Figure 1. SJS in a patient on carbamazepine: Skin lesions demonstrating characteristic diffuse erythematous macules seen in SJS. The

macules are typically targetoid with necrotic centers, and overlying flaccid blisters.

Key messages

N Early recognition and immediate withdrawal

of offending agents are critical to minimizing

debilitating or potentially life-threatening

consequences of Stevens-Johnson syndrome

(SJS).

N Pharmaceutical treatment of SJS remains

controversial, although intravenous immuno-

globulins (IVIg) are thought to hold promise

for the management of SJS.

N A multidisciplinary approach, including

prompt transfer to a burns unit in severe

cases, is key to reducing the morbidity and

mortality associated with SJS.

Table I. Classification of Stevens-Johnson syndrome and toxic

epidermal necrolysis (48,49).

Classification

Body surface area

involved

Stevens-Johnson syndrome v10%

Overlap Stevens-Johnson syndrome/Toxic

epidermal necrolysis

10%–29%

Toxic epidermal necrolysis w30%

130 R. Hazin et al.

Consultation with a urologist for evaluation and

management of urethral ulceration and strictures is

therefore warranted in patients with SJS (19–23).

Gastrointestinal involvement has also been

described, primarily affecting the esophagus, and

often results in the development of esophageal

webbing or stricture (24–26). In rare cases SJS

may cause ulceration of the mucosa of other

gastrointestinal organs such as the colon (27).

Respiratory involvement in SJS has been reported

in rare cases and is associated with poor prognosis

(28,29). Pulmonary restriction may develop second-

ary to SJS-induced scarring of the pulmonary tract

(30,31).

Incidence

SJS occurs at a rate of approximately 1–7 cases per

million people per year (32–34). The risk of Stevens-

Johnson syndrome remains low with any of its

associated causes (32). SJS is fatal in approximately

5%–15% of cases (35). Both the incidence of the

condition and the associated mortality rate appear to

be elevated in immunocompromised patients with

these risks correlating with worsening immune func-

tion (36,37). Chronic viral infections, such as Epstein

Barr virus and Human Immunodeficiency Virus

(HIV), may also increase the risk of SJS indepen-

dently of the degree of immunosuppression (38–40).

Autoimmune disorders, such as systemic lupus

erythematosus, have also been reported to predispose

to the development of SJS (1,41,42).

A certain genetic predisposition may also confer

increased risk of developing SJS on patients. In one

study, the human leukocyte antigen (HLA) B1502

allele was found in 100% of SJS patients, placing

individuals with that particular HLA allele at a 900

times greater risk of developing SJS than the general

population (1). Given this genetic predisposition,

certain ethnic groups in Asia have been identified as

having an increased risk for SJS in comparison to the

general population (43). This genetic susceptibility

seems to have a strong association with specific

drugs such as carbamazepine (44). Although HLA-

B*1502 confers greater risk of SJS on patients, this

susceptibility is phenotype-specific. For instance,

Caucasian patients with the HLA-B*1502 allele do

not demonstrate the same susceptibility to SJS as

Asian patients with the same genotype (44,45).

Caucasian patients with the HLA-B*1502 genotype

tolerate carbamazepine relatively well while 100%

of the Han Chinese patients with the genotype

developed SJS following carbamazepine administra-

tion (44,45). The presence of the HLA-B*1501

allele also confers an increased risk of developing

SJS but in the presence of allopurinol, further

strengthening the genetic association of the disorder

(46). The increased frequency of HLA-B*1501 and

HLA-B*1502 alleles amongst certain Asian popula-

tions has prompted health care officials in endemic

regions to begin developing inexpensive tests to

identify at-risk individuals prior to prescribing them

allopurinol or carbamazepine (44). Furthermore, the

presence of the HLA-DQB1*0601 allele places

individuals at greater risk for the development of

SJS with ocular complications and strengthens the

notion of an underlying immunogenetic susceptibil-

ity to the development of SJS (46,47). These

findings may aid clinicians in assigning appropriate

therapy and yield improved benefit-to-harm ratios in

patients with SJS.

Diagnosis

Considering an appropriate differential diagnosis in

patients with mucocutaneous erosions can help

eliminate misdiagnoses associated with these condi-

tions (5,48). Among the most common disorders

mistaken for SJS are staphylococcal scalded skin

syndrome, toxic shock syndrome, exfoliative derma-

titis, erythema multiforme, autoimmune bullous

diseases, and chemical burns. Toxic shock syndrome

and scalded skin syndrome, which are bacterial in

nature, result in similar-appearing epidermolysis but

are readily distinguishable from SJS following biopsy

and immunofluorescence studies. Similarly, auto-

immune bullous disease can be distinguished from

SJS by the presence of IgA deposition in the former

conditions (48). The absence of IgA deposition is

characteristic of skin specimens of SJS patients

(48,49). Graft-versus-host disease (GVHD) is

another established cause of SJS independently of

drug administration (50,51). Like SJS, graft-versus-

host disease is mediated by cytotoxic T cells that

result in epidermal necrosis and keratinolysis (52–

54). Furthermore, the clinical and histological

appearance of GVHD can mimic SJS making

distinguishing the two disorders challenging (54).

For instance, the blister fluid of both conditions

demonstrate the presence of CD8+ T cells, further

complicating the ability of clinicians to distinguish

the two (55). Histologically, both GVHD and SJS

result in apoptosis of epidermal Langerhans cells

(LCs) and often show decreased numbers of such

cells in the dermis (56). Because of the difficulty in

distinguishing the two disorders clinically and

histologically, conducting a thorough history and

physical examination as well as early dermatologic

consultation remain the cornerstone of diagnosis in

instances where both SJS and GVHD are part of the

A review of Stevens-Johnson syndrome 131

differential diagnosis (6,54). Incidentally, Lyme

disease also presents with targetoid lesions.

However, unlike SJS, which is associated with

numerous targetoid lesions, Lyme disease typically

presents with a single or small number of targetoid

lesions that surround a central dusky area represent-

ing a tick bite site (57,58). Furthermore, mucosal

involvement is not present in Lyme disease, and

patients with SJS are generally ill and have a very

rapid onset of lesions as compared to patients with

erythema chronicum migrans.

The diagnosis of SJS is generally made on clinical

grounds based on the presence of classic mucocu-

taneous lesions. In most cases confirmation of

the diagnosis should be sought by skin biopsies,

which typically reveal vacuolization of basal layer

keratinocytes associated with lymphocytes along the

dermal-epidermal junction and necrotic spinous

layer keratinocytes (49,59–61). The typical histo-

pathological appearance of SJS is characterized by

apoptosis and necrosis of keratinocytes along with

dermoepidermal detachment and lymphocytic infil-

tration of perivascular regions (4,6). Intraepidermal

vesicles and papillary dermal edema may be noted

in more papular lesions. In severe cases, subepider-

mal blistering associated with full-thickness epider-

mal necrosis may be present, but this is generally

considered the hallmark of toxic epidermal necro-

lysis. To distinguish this condition from autoim-

mune blistering disorders, biopsies should be

submitted both for routine histopathology as well

as for direct immunofluorescence studies.

Etiology

Although a variety of etiologies, such as infections

and underlying malignancies, have been implicated

as potential causes of SJS, drugs remain the

predominant inciting agent (Table II). The most

commonly implicated drugs are sulfa derivatives,

nonsteroidal anti-inflammatory agents, penicillin-

related and cephalosporin antibiotics, antiepileptics,

allopurinol, and terbinafine. There also appears to

be an increased risk of developing SJS with higher

dosages of offending medications (62,63).

Although they have been implicated in rare cases,

overall, vaccine administration and chemical expo-

sure are rarely associated with SJS (64–66).

Cyclooxygenase-2 inhibitors have also been impli-

cated as potential underlying sources of the disorder

(67). Recreational drugs such as cocaine (68) as well

as over-the-counter and alternative medicines have

also recently been implicated as causes of SJS (69).

According to recent studies, as many as 64% of

individuals diagnosed with SJS have been exposed to

drugs suggesting that in up to one-third of cases no

specific etiology has been identified (70). Although

medications are the most common causative agents

in adults, similar trends do not apply in the pediatric

population (5). In fact, SJS in pediatric patients is

more commonly triggered by infectious organisms

than adverse drug reaction (5). An awareness of this

distinction is critical to arriving at an accurate

diagnosis and treatment of the condition.

Underlying infections are the second most com-

mon cause of SJS. The most commonly associated

infectious agents are listed in Table II. The most

common implicated organism is Mycoplasma pneu-

moniae which is oftentimes seen in children and may

be the reason for widespread cases of SJS during

Mycoplasma epidemics (71,72). Although other

infectious etiologies have been identified as causative

agents for the condition, most remain uncommon

with the exception of herpes simplex virus which has

been implicated in acute as well as recurrent bouts of

SJS in adults and children (71,73,74). Moreover, a

number of underlying malignancies, such as squa-

mous cell carcinoma of the lung, Hodgkin’s lym-

phoma, and certain forms of leukemia have been

associated with SJS (75–77).

Pathophysiology

The exact pathophysiologic mechanism of SJS

remains unknown. Various theories have implicated

Table II. Etiologies of Stevens-Johnson syndrome.

Etiologic agent Most frequently described

Viral AIDS, herpes simplex virus, Epstein-Barr, influenza, coxsackie, lymphogranuloma venereum, and variola

Bacterial Mycoplasma pneumoniae, typhoid, tularemia, diphtheria, and group A streptococci

Fungal Dermatophytosis, histoplasmosis, and coccidiomycosis

Protozoal Trichomoniasis, plasmodium

Drugs Sulfas, nonsteroidal anti-inflammatory drugs (NSAIDs), antiepileptics, barbiturates, allopurinol,

tetracyclines, antiparasiticsa

aSulfa drugs (96,107,120), antiepileptics (97,102,123,124,130), allopurinol (103,130), tetracyclines (104) are more common in the setting

of a compromised immune system (19,20,25,134), antiparasitic and antibacterial drugs (23,104,105), antiviral agents (48,119,120),

antifungal agents (24), NSAIDS (31,46,121,122), infectious etiologies (4,108,109,117,118).

132 R. Hazin et al.

both immunological and nonimmunological mecha-

nisms, with the prevailing evidence suggesting

primary involvement of the immunologic response

(78), in particular those mediated by memory

cytotoxic T cells (79). Although it was originally

classified as a type IV, delayed hypersensitivity

reaction, it now appears that the immunological

mechanisms governing the SJS reaction are initiated

by the Fas antigen, a cell surface molecule that can

mediate apoptosis (80,81). Activation of the Fas

signaling cascade leads to widespread keratinocyte

apoptosis and subsequent epithelial necrosis. Early

treatment of SJS via intravenous immunoglobulins

(IVIg) blocks the activation of the Fas pathway, thus

underscoring the potential effectiveness of IVIg in

treating the disorder (35,82,83). Recent studies have

also linked perforin, a pore-making monomeric

granule released from natural killer T-lymphocytes

in the development of SJS. Perforin is believed to

initiate the keratinolysis seen early in the develop-

ment of SJS (84). Some evidence also exists linking

IgE-mediated mechanisms and mast cell activation

contributing to SJS (85).

Genetic factors may play a role in the development

of SJS. It has been postulated that patients with slow

intrinsic acetylation rates and those taking medica-

tions such as azoles, protease inhibitors, serotonin-

specific reuptake inhibitors, and quinolones are at

increased risk of developing SJS (1,86–88). Slow

acetylation may indeed be a factor in the develop-

ment of a number of adverse cutaneous drug

reactions (89), as the reduced rate of acetylation

causes the accumulation of reactive metabolites that

induce cell-mediated cytotoxic reactions directed

against the epidermis, resulting in keratinocyte

apoptosis (90).

Treatment

SJS is a serious systemic disorder with the potential

for severe morbidity and mortality. In approximately

5%–15% of cases SJS is fatal (35,39). In order to

determine a patient’s risk of death with SJS, clinicians

are encouraged to use the SCORTEN (TEN-specific

severity of illness score) scale which employs impor-

tant prognostic indicators including heart rate, age,

and renal function (91,92) (Table III). Assessing the

SCORTEN score requires giving the patient one

point for each positive variable his condition fulfills.

The total points are tallied, with increased scores

correlated with poorer prognosis.

Effective management of SJS begins with prompt

recognition of the entity, combined with attention to

each of the major organs that may be affected, as

well as potential comorbidities. Since medications

are the most common cause of SJS, a thorough drug

history must be obtained, and all potential offending

agents must be immediately discontinued (32,39).

Indeed, immediate cessation of involved medica-

tions appears to improve the prognosis (93).

Comprehensive SJS treatment requires a skilled,

collaborative, multidisciplinary approach that

addresses the highly complex, systemic response to

the condition. A multispecialty team may also assist

in subsequent postdischarge management including

psychosocial issues that may arise from SJS-induced

disfigurations or scarring. The management of

milder cases of SJS may occur in an inpatient ward

with the same fundamental therapeutic protocol

used for burns: warming of the environment,

minimizing transepidermal water loss, treatment of

electrolyte imbalances, administration of high-cal-

orie nutrition and intravenous fluids to prevent

dehydration, and prevention of sepsis (38,39,94–

96). For patients with extensive cutaneous involve-

ment, prompt referral to a burns unit has been

shown to reduce the risk of infection, mortality, and

the length of hospitalization (94,96–101). This is

particularly true for SJS caused by drugs with short

half-lives, which represent a positive prognostic

factor for SJS (94). Patients must be counseled

regarding strict future avoidance of agents respon-

sible for the outbreak as well as chemically similar

compounds. Given the suspected hereditary associa-

tion with SJS, first-degree relatives should also be

encouraged to avoid similar chemical compounds.

Targeted nursing care including adequate main-

tenance of topical management reduces associated

morbidity and allows a more rapid reepithelialization

of skin lesions and the prevention of scarring,

synechia formation, and infection (39,100). Skin

erosions should be covered with moisture-retentive

ointments and/or topical antibiotics to improve

barrier function and to prevent bacterial infection.

Given the involvement of the lips and oral mucosa in

Table III. SCORTEN scale (91,92). One point is added for each

positive variable. A patient’s mortality can be predicted by the

total number of points according to the following breakdown: 0–1

points53.2% mortality; 2 points512.1% mortality; 3

points535.3% mortality; 4–5 points58.3% mortality; w5

points590% mortality.

Variable Value

Age w40 year

Malignancy Present

Heart rate w120 per minute

Body surface area involved at day 1 w10%

Serum blood urea nitrogen (BUN) w10 mg/dL

Serum bicarbonate v20 mg/dL

Serum glucose w14 mg/dL


many patients with SJS, adequate emphasis on

alleviating pain associated with lesions in the mouth

is an integral part of treating the disorder.

Application of petroleum jelly and sterile saline

compresses can promote rapid reepithelialization of

the lips. The use of viscous lidocaine on the oral

mucosa in combination with diphenhydramine or

sodium bicarbonate mouthwashes can dramatically

relieve pain associated with friable mucocutaneous

ulcerations and prevent the onset of odynophagia

(102–104).

For patients with ocular involvement, daily

erythromycin eye drops are recommended to prevent

bacterial infections, and corticosteroid eye drops are

administered to reduce inflammation (4). Continued

ophthalmologic care is recommended even after

recovery in order to monitor and minimize irrever-

sible ocular complications including visual loss.

Involvement of other organs is addressed with

appropriate supportive care as well as treatment of

any strictures, adhesions, or scarring that may

complicate the course of the disease. Respiratory

involvement may require prompt intubation and

ventilatory support (28,29).

The use of medications to treat SJS has met with

intense debate over the years. Treatment with

corticosteroids, while effective in most other acute

inflammatory disorders, is controversial (105–110).

Furthermore, numerous other anti-inflammatory,

immunosuppressive, and immunomodulatory agents,

such as cyclosporin, cyclophosphamide, thalido-

mide, and intravenous immunoglobulins (IVIg),

have been administered as possible means to arrest

underlying immunological mechanisms promoting

SJS (39,111,112). However, the efficacy of these

agents in the treatment of SJS has not been

demonstrated by any controlled clinical trial. In

the absence of strong evidence, none of these

regimens can be definitively proposed as a treat-

ment of choice. This notwithstanding, IVIg admi-

nistered early after the onset of mucocutaneous

lesions is thought to hold the most promise for

improvement in survival and a reduction in long-

term morbidity (82,83,113). The dose of IVIg

administered varies, but typically is 1–3 g/kg/day for

3–5 days, with a mean total dose of 2.7 g/kg

divided over 1–5 days (23,70,114,115). Studies

have demonstrated that IVIg arrests Fas-mediated

keratinolysis in vitro, which provides a pathophy-

siologic explanation of why it may improve SJS

through disruption of Fas-induced keratinocyte

apoptosis (83,109). Moreover, intravenous immu-

noglobulins have yielded promising results in

controlled studies involving children (111) as well

as adults (115). For example, a recent retrospective

analysis reported a 100% survival rate and com-

plete skin healing in 12 patients with SJS after

treatment with IVIg (115). However, the absence of

large or controlled trials raises questions regarding

the efficacy of IVIg, particularly given the high cost

of this treatment (116). In the absence of clear-cut

benefits, potential risks of IVIg should be reviewed

with the patient prior to treatment.

Sepsis is a major source of mortality in SJS

patients. However, prophylactic antibiotics are not

recommended in the treatment of acute SJS except

when the etiologic agent is identified as an infectious

agent. For example, although supportive therapy

was once considered treatment of choice for

Mycoplasma-induced SJS, antibiotic therapy is now

typically administered to treat the infection (72).

The presence of an opportunistic infection due to

HIV or immunosuppression represents a poor

prognosis in the evolution of SJS and toxic epidermal

necrolysis (TEN) (36,37,40).

Although prophylactic antibiotics are not recom-

mended, the use of skin cultures on the first day and

every 48 hours thereafter is recommended as a

means of monitoring possible bacterial growth.

Topical antibiotic treatment should begin if there

is an increased number of bacteria cultured from the

skin with selection of a single strain, a sudden drop

in temperature, and/or deterioration in the patient’s

condition.

Prompt and uninterrupted enteral nutrition

reduces the incidence of stress ulcers and bacterial

translocation, and allows earlier discontinuation of

intravenous lines (39). Finally, treating the patient’s

existing health concerns is paramount. For example,

regardless of whether SJS is suspected to be secondary

to a drug reaction, prophylactic use of anticoagulants

maybe indicated due to the risk of thromboembolism-

induced morbidity and mortality (1). Furthermore,

based on the severity of the disease, analgesics along

with supportive emotional and psychological care

should be provided as needed.

Conclusions

SJS is a rare but serious adverse cutaneous reaction

most commonly due to medications and infectious

agents. Prompt recognition is critical for the initia-

tion of appropriate care. The mainstay of treatment

remains addressing the causative agent as well as

supportive care for the mucocutaneous ulcerations.

This requires a multidisciplinary approach to all

organ systems that may be affected by this disease.

In severe cases, prompt transfer to a burns unit is

necessary in order to decrease both morbidity and

mortality. While systemic corticosteroids should be

134 R. Hazin et al.

avoided in the management of SJS, IVIg should be

considered early in the disease, even though its

efficacy has not been definitively established.

Patients at risk of or those previously afflicted by

SJS should receive counseling on the importance of

completely avoiding responsible agents or similar

compounds. Furthermore, physicians and health

care workers are encouraged to improve documenta-

tion of offending agents in patient charts in order to

minimize the risk of repeat outbreaks of the disease.

References

1. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC,

Ho HC, et al. Medical genetics: a marker for Stevens-

Johnson syndrome. Nature. 2004;428:486.

2. Ruiz-Maldonado R. Acute disseminated epidermal necrosis

types 1, 2, and 3: study of sixty cases. J Am Acad Dermatol.

1985;13:623–35.

3. Hussain W, Craven NM. Toxic epidermal necrolysis and

Stevens-Johnson syndrome. Clin Med. 2005;5:555–8.

4. Kumar G, Fadel HJ, Beckman TJ. 36-year-old man with

productive cough and diffuse rash. Mayo Clin Proc.

2006;81:945–8.

5. Leaute-Labreze C, Lamireau T, Chawki D, Maleville J,

Taieb A. Diagnosis, classification, and management of

erythema multiforme and Stevens-Johnson syndrome. Arch

Dis Child. 2000;83:347–52.

6. Paquet P, Pierard GE. Erythema multiforme and toxic

epidermal necrolysis: a comparative study. Am J Dermato-

pathol. 1997;19:127–32.

7. Kasper M. Stevens-Johnson syndrome. Clin J Oncol Nurs.

2001;5:25–6.

8. Wolf R, Davidovici B, Matz H, Mahlab K, Orion E,

Sthoeger ZM. Drug Rash with eosinophilia and systemic

symptoms versus Stevens-Johnson Syndrome—a case that

indicates a stumbling block in the current classification. Int

Arch Allergy Immunol. 2006;141:308–10.

9. Hansen RC. Blindness, anonychia, and oral mucosal

scarring as sequelae of the Stevens-Johnson syndrome.

Pediatr Dermatol. 1984;1:298–300.

10. Powell N, Munro JM, Rowbotham D. Colonic involvement

in Stevens-Johnson syndrome. Postgrad Med J. 2006;82:

e10.

11. Hart R, Minto C, Creighton S. Vaginal adhesions caused by

Stevens-Johnson syndrome. J Pediatr Adolesc Gynecol.

2002;15:151–2.

12. Ayangco L, Rogers RS 3rd. Oral manifestations of erythema

multiforme. Dermatol Clin. 2003;21:195–205.

13. Manders SM. Serious and life-threatening drug eruptions.

Am Fam Physician. 1995;51:1865–72.

14. Vanfleteren I, Van Gysel D, De Brandt C. Stevens-Johnson

syndrome: a diagnostic challenge in the absence of skin

lesions. Pediatr Dermatol. 2003;20:52–6.

15. Lowndes S, Darby A, Mead G, Lister A. Stevens-Johnson

syndrome after treatment with rituximab. Ann Oncol.

2002;13:1948–50.

16. Singla R, Brodell RT. Erythema multiforme due to herpes

simplex virus. Recurring target lesions are clue to diagnosis.

Postgrad med. 1999;106:151–4.

17. Dart J. PL3 Stevens Johnson syndrome and mucous

membrane pemphigoid: ocular manifestations and their

management. Oral Dis. 2006;12 Suppl 1:1.

18. Di Pascuale MA, Espana EM, Liu DT, Kawakita T, Li W,

Gao YY, et al. Correlation of corneal complications with

eyelid cicatricial pathologies in patients with Stevens-Johnson

syndrome and toxic epidermal necrolysis syndrome.

Ophthalmology. 2005;112:904–12.

19. Wall V, Yen MT, Yang MC, Huang AJ, Pflugfelder SC.

Management of the late ocular sequelae of Stevens-Johnson

syndrome. Ocul Surf. 2003;1:192–201.

20. Graham-Brown RA, Cochrane GW, Swinhoe JR, Sarkany I,

Epsztejn LJ. Vaginal stenosis due to bullous erythema

multiforme (Stevens-Johnson syndrome). Case report. Br J

Obstet Gynaecol. 1981;88:1156–7.

21. Wilson EE, Malinak LR. Vulvovaginal sequelae of Stevens-

Johnson syndrome and their management. Obstet Gynecol.

1988;71:478–80.

22. Murphy MI, Brant WE. Hematocolpos caused by genital

bullous lesions in a patient with Stevens-Johnson syndrome.

J Clin Ultrasound. 1998;26:52–4.

23. Noel JC, Buxant F, Fayt I, Bebusschere G, Parent D. Vulval

adenosis associated with toxic epidermal necrolysis. Br J

Dermatol. 2005;153:457–8.

24. Tan YM, Goh KL. Esophageal stricture as a late complica-

tion of Stevens-Johnson syndrome. Gastrointest Endosc.

1999;50:566–8.

25. Rottermann EM, Julia MV, Rovira J, Pari FJ, Morales L.

Esophageal stenosis following Stevens-Johnson syndrome.

Treatment with balloon dilation. Clin Pediatr (Phila).

1990;29:336–8.

26. Clayton NA, Kennedy PJ. Management of Dysphagia in

Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson

Syndrome (SJS). Dysphagia. 2007;22:187–92.

27. Zweiban B, Cohen H, Chandrasoma P. Gastrointestinal

involvement complicating Stevens-Johnson syndrome.

Gastroenterology. 1986;91:469–74.

28. Kamada N, Kinoshita K, Togawa Y, Kobayashi T,

Matsubara H, Kohno M, et al. Chronic pulmonary

complications associated with toxic epidermal necrolysis:

report of a severe case with anti-Ro/SS-A and a review of the

published work. J Dermatol. 2006;33:616–22.

29. Martin L, Hazouard E, Michalak-Provost S, Maurage C,

Machet L. [Fatal toxic respiratory epitheliolysis. Subacute

tracheo-bronchial desquamation in Stevens-Johnson syn-

drome]. Rev Pneumol Clin. 2001;57:297–301.

30. Shah AP, Xu H, Sime PJ, Trawick DR. Severe airflow

obstruction and eosinophilic lung disease after Stevens-

Johnson syndrome. Eur Respir J. 2006;28:1276–9.

31. Peters ME, Gourley G, Mann FA. Esophageal stricture and

web secondary to Stevens-Johnson syndrome. Pediatr

Radiol. 1983;13:290–1.

32. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to

drugs. N Engl J Med. 1994;331:1272–85.

33. Rzany B, Mockenhaupt M, Baur S, Schroder W, Stocker U,

Mueller J, et al. Epidemiology of erythema exsudativum

multiforme majus, Stevens-Johnson syndrome, and toxic

epidermal necrolysis in Germany (1990–1992): structure

and results of a population-based registry. J Clin Epidemiol.

1996;49:769–73.

34. Chan HL, Stern RS, Arndt KA, Langlois J, Jick SS, Jick H,

et al. The incidence of erythema multiforme, Stevens-

Johnson syndrome, and toxic epidermal necrolysis. A

population-based study with particular reference to reactions

caused by drugs among outpatients. Arch Dermatol.

1990;126:43–7.

35. Parrillo SJ, Parrillo CV, Stevens-Johnson Syndrome.

Emedicine website. Available at: http://www.emedicine.

com/emerg/topic555.htm (accessed December 17, 2006).


36. Shilad A, Predanic M, Perni SC, Houlihan C, Principe D.

Human immunodeficiency virus, pregnancy, and Stevens-

Johnson syndrome. Obstet Gynecol. 2005;105:1254–6.

37. Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous

disease and drug reactions in HIV infection. N Engl J Med.

1993;328:1670–4.

38. Gonzalez-Delgado P, Blanes M, Soriano V, Montoro D,

Loeda C, Niveiro E. Erythema multiforme to amoxicillin

with concurrent infection by Epstein-Barr virus. Allergol

Immunopathol (Madr). 2006;34:76–8.

39. Ghislain PD, Roujeau JC. Treatment of severe drug

reactions: Stevens-Johnson syndrome, toxic epidermal

necrolysis and hypersensitivity syndrome. Dermatol Online

J. 2002;8:5.

40. Sanwo M, Nwadiuko R, Beall G. Use of intravenous

immunoglobulin in the treatment of severe cutaneous drug

reactions in patients with AIDS. J Allergy Clin Immunol.

1996;98:1112–5.

41. Samimi SS, Siegfried E. Stevens-Johnson syndrome devel-

oping in a girl with systemic lupus erythematosus on high-

dose corticosteroid therapy. Pediatr Dermatol. 2002;19:

52–5.

42. Matsushita K, Ozaki A, Inoue H, Kaieda T, Akimoto M,

Satomura A, et al. Stevens-Johnson syndrome induced by

mizoribine in a patient with systemic lupus erythematosus.

Mod Rheumatol. 2006;16:113–6.

43. Lonjou C, Thomas L, Borot N, Ledger N, de Toma C,

LeLouet H, et al. A marker for Stevens-Johnson syndrome

…: ethnicity matters. Pharmacogenomics J. 2006;6:265–8.

44. Hung SI, Chung WH, Jee SH, Chen WC, Chang YT,

Lee WR, et al. Genetic susceptibility to carbamazepine-

induced cutaneous adverse drug reactions. Pharmacogenet

Genomics. 2006;16:297–306.

45. Alfirevic A, Jorgensen AL, Williamson PR, Chadwick DW,

Park BK, Pirmohamed M. HLA-B locus in Caucasian

patients with carbamazepine hypersensitivity. Pharmaco-

genomics. 2006;7:813–8.

46. Hung SI, Chung WH, Liou LB, Chu CC, Lin M,

Huang HP, et al. HLA-B*5801 allele as a genetic marker

for severe cutaneous adverse reactions caused by allopurinol.

Proc Natl Acad Sci U S A. 2005;102:4134–9.

47. Power WJ, Saidman SL, Zhang DS, Vamvakas EC, Merayo-

Lloves JM, Kaufman AH, et al. HLA typing in patients with

ocular manifestations of Stevens-Johnson syndrome.

Ophthalmology. 1996;103:1406–9.

48. Bachot N, Roujeau JC. Differential diagnosis of severe

cutaneous drug eruptions. Am J Clin Dermatol.

2003;4:561–72.

49. French LE. Toxic epidermal necrolysis and Stevens Johnson

syndrome: our current understanding. Allergol Int.

2006;55:9–16.

50. DiSesa VJ, Kirkman RL, Tilney NL, Mudge GH, Collins JJ

Jr, Cohn LH. Management of general surgical complications

following cardiac transplantation. Arch Surg. 1989;124:

539–41.

51. Ostlere LS, Harris D, Burroughs AK, Rolles K. Toxic

epidermal necrolysis after hepatic transplantation. Arch

Dermatol. 1992;128:1550–1.

52. Revuz JE, Roujeau JC. Advances in toxic epidermal

necrolysis. Semin Cutan Med Surg. 1996;15:258–66.

53. Mockenhaupt M, Norgauer J. Cutaneous Adverse Drug

Reactions. Stevens-Johnson syndrome and Toxic Epidermal

Necrolysis. Allergy Clin Immunol Int. 2002;14:143–50.

54. Schulz JT, Sheridan RL. Severe desquamating disorder after

liver transplant: toxic epidermal necrolysis or graft versus

host disease? J Burns Wounds. 2006;5:e1.

55. Correia O, Delgado L, Barbosa IL, Domingues JC,

Azevedo R, Vaz CP, et al. CD8+ lymphocytes in the blister

fluid of severe acute cutaneous graft-versus-host disease:

further similarities with toxic epidermal necrolysis.

Dermatology. 2001;203:212–6.

56. Asagoe K, Takahashi K, Yoshino T, Kondo E, Tanaka R,

Arata J, et al. Numerical, morphological and phenotypic

changes in Langerhans cells in the course of murine

graft-versus-host disease. Br J Dermatol. 2001;145:918–27.

57. Bennet L, Halling A, Berglund J. Increased incidence of

Lyme borreliosis in southern Sweden following mild winters

and during warm, humid summers. Eur J Clin Microbiol

Infect Dis. 2006;25:426–32.

58. Hubalek Z. North Atlantic weather oscillation and human

infectious diseases in the Czech Republic, 1951–2003. Eur J

Epidemiol. 2005;20:263–70.

59. Hilas O, Charneski L. Lamotrigine-induced Stevens-Johnson

syndrome. Am J Health Syst Pharm. 2007;64:273–275.

60. Caproni M, Torchia D, Schincaglia E, Volpi W,

Frezzolini A, Schena D, et al. The CD40/CD40 ligand

system is expressed in the cutaneous lesions of erythema

multiforme and Stevens-Johnson syndrome/toxic epidermal

necrolysis spectrum. Br J Dermatol. 2006;154:319–24.

61. Hockett KC. Stevens-Johnson syndrome and toxic epider-

mal necrolysis: oncologic considerations. Clin J Oncol Nurs.

2004;8:27–30, 55.

62. Severino G, Chillotti C, De Lisa R, Del Zompo M, Ardau R.

Adverse reactions during imatinib and lansoprazole treat-

ment in gastrointestinal stromal tumors. Ann Pharmacother.

2005;39:162–4.

63. Famularo G, De Simone C, Minisola G. Stevens-Johnson

syndrome associated with single high dose of lamotrigine in a

patient taking valproate. Dermatol Online J. 2005;11:25.

64. Vincenzi B, Santini D, Grilli C, La Cesa A, Dianzani C,

Tonini G. Complications of therapy in cancer patients: Case

3. Toxic epidermal necrolysis induced by oral phenobarbital

and whole-brain radiotherapy in a breast cancer patient. J

Clin Oncol. 2004;22:4649–51.

65. Ridgway HB, Miech DJ. Erythema multiforme (Stevens-

Johnson syndrome) following deep radiation therapy. Cutis.

1993;51:463–4.

66. Chopra A, Drage LA, Hanson EM, Touchet NL. Stevens-

Johnson syndrome after immunization with smallpox,

anthrax, and tetanus vaccines. Mayo Clin Proc. 2004;79:

1193–6.

67. Layton D, Marshall V, Boshier A, Friedmann P, Shakir SA.

Serious skin reactions and selective COX-2 inhibitors: a case

series from prescription-event monitoring in England. Drug

Saf. 2006;29:687–96.

68. Hofbauer GF, Burg G, Nestle FO. Cocaine-related Stevens-

Johnson syndrome. Dermatology. 2000;201:258–60.

69. Ventura MT, Viola M, Calogiuri G, Gaeta F, Pesole O,

Romano A. Hypersensitivity reactions to complementary

and alternative medicine products. Curr Pharm Des.

2006;12:3393–9.

70. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L,

Roujeau JC. Clinical classification of cases of toxic epider-

mal necrolysis, Stevens-Johnson syndrome, and erythema

multiforme. Arch Dermatol. 1993;129:92–6.

71. Levy M, Shear NH. Mycoplasma pneumoniae infections

and Stevens Johnson syndrome: report of eight cases and

review of the literature. Clin Pediatr. 1991;30:42–9.

72. Ravin KA, Rappaport LD, Zuckerbraun NS, Wadowsky RM,

Wald ER, Michaels MM. Mycoplasma pneumoniae and

atypical Stevens-Johnson syndrome: a case series. Pediatrics.

2007;119:e1002–5.

136 R. Hazin et al.

73. Detjen PF, Patterson R, Noskin GA, Phair JP,

Loyd SO. Herpes simplex virus associated with recurrent

Stevens-Johnson syndrome. A management strategy. Arch

Intern Med. 1992;152:1513–6.

74. Ng PP, Sun YJ, Tan HH, Tan SH. Detection of herpes

simplex virus genomic DNA in various subsets of Erythema

multiforme by polymerase chain reaction. Dermatology.

2003;207:349–53.

75. Hanno R, Bean SF. Hodgkin’s disease with specific bullous

lesions. Am J Dermatopathol. 1980;2:363–6.

76. Margolis RJ, Bhan A, Mihm MC Jr, Bernhardt M. Erythema

multiforme in a patient with T cell chronic lymphocytic

leukemia. J Am Acad Dermatol. 1986;14:618–27.

77. Klein PA, Stevens-Johnson Syndrome. Emedicine website.

Available at: http://www.emedicine.com/derm/topic405.htm

(accessed August 30, 2007).

78. Roychowdhury S, Svensson CK. Mechanisms of drug-

induced delayed-type hypersensitivity reactions in the skin.

AAPS J. 2005;7:E834–46.

79. Roujeau JC. Clinical heterogeneity of drug hypersensitivity.

Toxicology. 2005;209:123–9.

80. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S,

Sameshima M, et al. The polypeptide encoded by the cDNA

for human cell surface antigen Fas can mediate apoptosis.

Cell. 1991;66:233–43.

81. Iwai K, Miyawaki T, Takizawa T, Konno A, Ohta K,

Yachie A, et al. Differential expression of bcl-2 and

susceptibility to anti-Fas-mediated cell death in peripheral

blood lymphocytes, monocytes, and neutrophils. Blood.

1994;84:1201–8.

82. Khalili B, Bahna SL. Pathogenesis and recent therapeutic

trends in Stevens-Johnson syndrome and toxic epidermal

necrolysis. Ann Allergy Asthma Immunol. 2006;97:272–80.

83. French LE, Trent JT, Kerdel FA. Use of intravenous

immunoglobulin in toxic epidermal necrolysis and Stevens-

Johnson syndrome: our current understanding. Int

Immunopharmacol. 2006;6:543–9.

84. Inachi S, Mizutani H, Shimizu M. Epidermal apoptotic cell

death in erythema multiforme and Stevens-Johnson syn-

drome. Contribution of perforin-positive cell infiltration.

Arch Dermatol. 1997;133:845–9.

85. Greenberger PA. Drug allergy. J Allergy Clin Immunol.

2006;117:S464–70.

86. Nakajima T, Yamanoshita O, Kamijima M, Kishi R,

Ichihara G. Generalized skin reactions in relation to

trichloroethylene exposure: a review from the viewpoint of

drug-metabolizing enzymes. J Occup Health. 2003;45:8–14.

87. Liechty CA, Solberg P, Mwima G, Were W, Weidle PJ,

Mermin J. Nevirapine-induced Stevens-Johnson syndrome

in a mother and son. AIDS. 2005;19:993–4.

88. Pirmohamed M. Genetic factors in the predisposition to

drug-induced hypersensitivity reactions. AAPS J. 2006;8:

E20–6.

89. Evans DA. Survey of the human acetylator polymorphism in

spontaneous disorders. J Med Genet. 1984;21:243–53.

90. Nassif A, Bensussan A, Dorothee G, Mami-Chouaib F,

Bachot N, Bagot M, et al. Drug specific cytotoxic T-cells in

the skin lesions of a patient with toxic epidermal necrolysis. J

Invest Dermatol. 2002;118:728–33.

91. Guegan S, Bastuji-Garin S, Poszepczynska-Guigne E,

Roujeau JC, Revuz J. Performance of the SCORTEN during

the first five days of hospitalization to predict the pro-

gnosis of epidermal necrolysis. J Invest Dermatol.

2006;126:272–6.

92. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC,

Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness

score for toxic epidermal necrolysis. J Invest Dermatol.

2000;115:149–53.

93. Garcia-Doval I, LeCleach L, Bocquet H, Otero XL,

Roujeau JC. Toxic epidermal necrolysis and Stevens-

Johnson syndrome: does early withdrawal of causative drugs

decrease the risk of death? Arch Dermatol. 2000;136:323–7.

94. Becker DS. Toxic epidermal necrolysis. Lancet. 1998;351:

1417–20.

95. Prendiville JS, Hebert AA, Greenwald MJ, Esterly MB.

Management of Stevens-Johnson syndrome and toxic

epidermal necrolysis in children. J Pediatr. 1989;115:881–7.

96. Peng YZ, Yuan ZQ, Xiao GX. Effects of early enteral

feeding on the prevention of enterogenic infection in severely

burned patients. Burns. 2001;27:145–9.

97. Kelemen JJ 3rd, Cioffi WG, McManus WF. Burn center

care for patients with toxic epidermal necrolysis. J Am Coll

Surg. 1995;180:273–8.

98. Murphy JT, Purdue GF, Hunt JL. Toxic epidermal

necrolysis. J Burn Care Rehabil. 1997;18:417–20.

99. McGee T, Munster A. Toxic epidermal necrolysis syn-

drome: mortality rate reduced with early referral to regional

burn center. Plast Reconstr Surg. 1998;102:1018–22.

100. Paquet P, Jacob E, Quatresooz P, Jacquemin D, Pierard GE.

Delayed reepithelialization and scarring deregulation follow-

ing drug-induced toxic epidermal necrolysis. Burns. 2007;

33:100–4.

101. Sheridan RL, Weber JM, Schulz JT, Ryan CM, Low HM,

Tompkins RG. Management of severe toxic epidermal

necrolysis in children. J Burn Care Rehabil. 1999;20:

497–500.

102. Stoschus B, Allescher HD. Drug-induced dysphagia.

Dysphagia. 1993;8:154–159.

103. Hallgren J, Tengvall-Linder M, Persson M, Wahlgren CF.

Stevens-Johnson syndrome associated with ciprofloxacin: a

review of adverse cutaneous events reported in Sweden as

associated with this drug. J Am Acad Dermatol.

2003;49:S267–9.

104. Yusin JS, Crawford WW, Klaustermeyer WB. Facial edema,

oral ulcers, and a cutaneous eruption following a dental

procedure utilizing diflunisal and mepivacaine. Ann Allergy

Asthma Immunol. 1999;83:353–5.

105. Hynes AY, Kafkala C, Daoud YJ, Foster CS. Controversy in

the use of high-dose systemic steroids in the acute care of

patients with Stevens-Johnson syndrome. Int Ophthalmol

Clin. 2005;45:25–48.

106. Patterson R, Grammer LC, Greenberger PA, Lawrence ID,

Zeiss CR, Detjen PF, et al. Stevens-Johnson syndrome

(SJS): effectiveness of corticosteroids in management and

recurrent SJS. Allergy Proc. 1992;13:89–95.

107. Tripathi A, Ditto AM, Grammer LC, Greenberger PA,

McGrath KG, Zeiss CR, et al. Corticosteroid therapy in an

additional 13 cases of Stevens-Johnson syndrome: a total

series of 67 cases. Allergy Asthma Proc. 2000;21:101–5.

108. Roujeau JC. Treatment of severe drug eruptions. J

Dermatol. 1999;26:718–22.

109. Halebian PH, Corder VJ, Madden MR, Finklestein JL,

Shires GT. Improved burn center survival of patients with

toxic epidermal necrolysis managed without corticosteroids.

Ann Surg. 1986;204:503–12.

110. Engelhardt SL, Schurr MJ, Helgerson RB. Toxic epidermal

necrolysis: an analysis of referral patterns and steroid usage.

J Burn Care Rehabil. 1997;18:520–4.

111. Metry DW, Jung P, Levy ML. Use of intravenous

immunoglobulin in children with Stevens-Johnson syn-

drome and toxic epidermal necrolysis: seven cases and

review of the literature. Pediatrics. 2003;112:1430–6.


112. Viard I, Wehrli P, Bullani R, Schneider P, Holler N,

Salomon D, et al. Inhibition of toxic epidermal necrolysis by

blockade of CD95 with human intravenous immunoglobu-

lin. Science. 1998;282:490–3.

113. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ,

Ahmed AR, Foster CS. Stevens-Johnson syndrome and

toxic epidermal necrolysis: a review of the literature. Ann

Allergy Asthma Immunol. 2005;94:419–36.

114. Yeung CK, Lam LK, Chan HH. The timing of intravenous

immunoglobulin therapy in Stevens-Johnson syndrome and

toxic epidermal necrolysis. Clin ExpDermatol. 2005;30:

600–2.

115. Prins C, Vittorio C, Padilla RS, Hunziker T, Itin P, Forster J,

et al. Effect of high-dose intravenous immunoglobulin

therapy in Stevens-Johnson syndrome: a retrospective,

multicenter study. Dermatology. 2003;207:96–9.

116. Daoud YJ, Amin KG. Comparison of cost of immune

globulin intravenous therapy to conventional immunosup-

pressive therapy in treating patients with autoimmune

mucocutaneous blistering diseases. Int Immunopharmacol.

2006;6:600–6.

117. Tay YK, Huff JC, Weston WL. Mycoplasma pneumoniae

infection is associated with Stevens-Johnson syndrome, not

erythema multiforme. J Am Acad Dermatol. 1996;35:

757–60.

118. Pitche P, Padonou CS, Kombate K, Mouzou T, Tchangai-

Walla K. Stevens-Johnson syndrome and toxic epidermal

necrolysis in Lome (Togo). Evolutional and etiological

profiles of 40 cases. Ann Dermatol Venereol. 2005;132:

531–4.

119. Borras-Blasco J, Navarro-Ruiz A, Devesa P, Montesinos-

Ros A, Gonzalez-Delgado M. Photo-induced Stevens-

Johnson syndrome due to sulfasalazine therapy. Ann

Pharmacother. 2003;37:1241–3.

120. Gimnig JE, MacArthur JR, M’bang’ombe M, Kramer MH,

Chizani N, Stern RS, et al. Severe cutaneous reactions to

sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole

in Blantyre District, Malawi. Am J Trop Med Hyg. 2006;

74:738–43.

121. La Grenade L, Lee L, Weaver J, Bonnel R, Karwoski C,

Governale L, et al. Comparison of reporting of Stevens-

Johnson syndrome and toxic epidermal necrolysis in

association with selective COX-2 inhibitors. Drug Saf.

2005;28:917–24.

122. Goldberg D, Panigrahi D, Barazi M, Abelson M, Butrus S.

A case of rofecoxib-associated stevens-johnson syndrome

with corneal and conjunctival changes. Cornea. 2004;23:

736–7.

123. Sarris BM, Wong JG. Multisystem hypersensitivity reaction

to lamotrigine. Neurology. 1999;53:1367.

124. Chia FL, Leong KP. Severe cutaneous adverse reactions to

drugs. Curr Opin Allergy Clin Immunol. 2007;7:304–9.

125. Mockenhaupt M, Messenheimer J, Tennis P, Schlingmann J.

Risk of Stevens-Johnson syndrome and toxic epidermal

necrolysis in new users of antiepileptics. Neurology.

2005;64:1134–8.

126. Chen KT, Twu SJ, Chang HJ, Lin RS. Outbreak of Stevens-

Johnson syndrome/toxic epidermal necrolysis associated

with mebendazole and metronidazole use among Filipino

laborers in Taiwan. Am J Public Health. 2003;93:

489–92.

127. Narayan VS, Mamatha GP, Ashok L, Rajashekar N. Stevens

Johnson syndrome due to I.V Ceftriaxone—a case report.

Indian J Dent Res. 2003;14:220–3.

128. Liberopoulos EN, Liamis GL, Elisaf MS. Possible cefotaxime-

induced Stevens-Johnson syndrome. Ann Pharmacother.

2003;37:812–4.

129. Cac NN, Messingham MJ, Sniezek PJ, Walling HW.

Stevens-Johnson syndrome induced by doxycycline. Cutis.

2007;79:119–22.

130. Chang YS, Huang FC, Tseng SH, Hsu CK, Ho CL,

Sheu HM. Erythema multiforme, Stevens-Johnson syn-

drome, and toxic epidermal necrolysis: acute ocular mani-

festations, causes, and management. Cornea. 2007;26:

123–9.

131. Marazzi MC, Germano P, Liotta G, Guidotti G,

Loureiro S, da Gruz Gomes A, et al. Safety of nevirapine–

containing antiretroviral triple therapy regimens to

prevent vertical transmission in an African cohort of

HIV-1 infected pregnant women. HIV Med. 2006;7:

338–44.

132. Colebunders R, Vanwolleghem T, Meurrens P, Moerman F.

Efavirenz-associated Stevens-Johnson syndrome. Infection.

2004;32:306–7.

133. Terrab Z, El Ouazzani T, Zouhair K, El Kabli H,

Lakhdar H. Terbinafine-induced Stevens-Johnson syn-

drome and aggravation of systemic lupus erythematosus.

Ann Dermatol Venereol. 2006;133:463–6.

134. Davis MD, Rogers RS 3rd. Pittelkow MR. Recurrent

erythema multiforme/Stevens-Johnson syndrome: response

to mycophenolate mofetil. Arch Dermatol. 2002;138:

1547–50.

138 R. Hazin et al.

30024569.pdf

Documents

Transcript of 30024569.pdf