Stevens-Johnson Syndrome:

Pathogenesis, Diagnosis,
And Management
Masriana Mursaling
Nurrasty Liambana
A. Mufidah Darwis
Anugrah Pratama Putra
Rasiydah Helfiana
Irmawanti
Renaldy Rajab

Pembimbing:
dr. Alwi Mappiasse, Sp.KK, PhD

RIBHI HAZIN, OMAR A. IBRAHIMI, MOUSTAFA I. HAZIN & ARASH KIMYAI-ASADI

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
Introduction
• Stevens-Johnson Syndrome (SJS) is a life-threatening
inflammatory mucocutaneous drug reaction.
• SJS, also known as erythema multiforme major, lies on a
continuum between erythema multiforme minor and toxic
epidermal necrolysis
 Clinical manifestations
• Begins with vague upper respiratory tract symptoms lasting up
to 2 weeks (may complain fever, sore throat, chills, headaches,
and malaise).
• 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.
The characteristic skin lesions seen in SJS are diffuse
erythematous macules with purpuric, necrotic centers and
overlying blistering.
Affected portions of the skin slough, resulting in wide
spread superficial ulcers and loss of the epidermal barrier.

Cultures of oral mucosa are indicated to help differentiate

SJS from other causes of sore lesions in the oral mucosa.
For most patients, the most clinically significant elements
of SJS are the sequelae of mucosal ulceration followed by
scarring and stricture, resulting in significant deterioration
of function of the affected organ systems.
Incidence
SJS occurs at a rate of approximately 1–7 cases permillion people
per year. SJS is fatal in approximately 5%–15% of cases. 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 function.

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 function.
Diagnosis
• The diagnosis of SJS is generally made on clinical grounds
based on the presence of classic mucocutaneous 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 spinouslayer
keratinocytes.
• The typical histopathological appearance of SJS is
characterized by apoptosis and necrosis of keratinocytes along
with dermoepidermal detachment and lymphocytic infiltration
of perivascular regions.
Etiology
 Pathopysiology
• The exact pathophysiologic mechanism of SJS remains unknown.
• Various theories have implicated Various theories have implicated
prevailing evidence suggesting primary involvement of the
immunologic response, in particular those mediated by memory
cytotoxic T cells
• 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
• 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
• Some evidence also exists linking IgE-mediated mechanisms and mast
cell activation contributing to SJS.
Treatment
• 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.
• 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-calorie
nutrition and intravenous fluids to prevent dehydration, and
prevention of sepsis.
• Skin erosions should be covered with moisture-retentive ointments
and/or topical antibiotics to improve barrier function and to prevent
bacterial infection.
• For patients with ocular involvement, daily erythromycin eye drops
are recommended to prevent bacterial infections, and corticosteroid
eye drops are administered to reduce inflammation.
• Numerous other anti-inflammatory, immunosuppressive, and
immunomodulatory agents, such as cyclosporin, cyclophosphamide,
thalidomide, and intravenous immunoglobulins (IVIg), have been
administered as possible means to arrest underlying immunological
mechanisms promoting SJS. IVIg administered early after the onset
of mucocutaneous lesions is thought to hold the most promise for
improvement in survival and a reduction in longterm morbidity. 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.
• 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.
• Prompt and uninterrupted enteral nutrition reduces the incidence of
stress ulcers and bacterial translocation, and allows earlier
discontinuation of intravenous lines
Conclusions
• SJS is a rare but serious adverse cutaneous reaction most
commonly due to medications and infectious agents.
• The mainstay of treatment remains addressing the
causative agent as well as supportive care for the
mucocutaneous ulcerations.
• Patients at risk of or those previously afflicted by SJS
should receive counseling on the importance of
completely avoiding responsible agents or similar
compounds.