STEVEN JOHNSON Syndrome (SJS)

Definition

Stevens-Johnson syndrome (SJS) is a collection of symptoms characterized by a triad of clinical disorders of the skin, eyes and mucous orifice and can be accompanied by a severe general symptoms.  First introduced in 1922, SJS is a process of immune complex-mediated hypersensitivity that is a combination of symptoms of erythema multiforme is severe abnormalities of the skin form of erythema, vesicles / bull, can be accompanied by purpura.  SJS is a rare disease vesikobulous and has the characteristics of an acute cutaneous eruption, involving the skin and mucous membranes.

Etiology

Almost all patients with SJS is caused by the toxic reactions of medicines especially antibiotics  (eg group of sulfonamides and penicillin), anti-convulsive, anti-pain, and medications obtained without ressep from a doctor.

SJS etiology determined exactly difficult because the cause involves a variety of factors, although in general are often associated with immune response to the drug.  Several factors cause of SJS include: infection (viral, bacterial, fungal, parasitic), medicines (salicylates, sulfa, penicillin, Ethambutol, Tegretol, tetracyclines, digitalis, and contraceptive), food (chocolate), physical (cold air, sunlight  and X-rays), and others (collagen disease, malignancy and pregnancy).

Epidemiology

SJS occurs approximately 1-3 cases per one million residents each year SJS also reportedly common in Caucasians.  SJS can hit all ages.  But from some reports, SJS occurs more often in adults with a comparison of male and female 1:2.  For children while the ratio between boys and girls is 1:1.

Pathophysiology

Pathogenesis of SJS has not been clear, although often associated with hypersensitivity reaction type III and IV.

• Hypersensitivity Reaction Type III

This occurs when the complex antigens of circulating antibodies in the blood buildup in blood vessels, the antibodies are trapped in the capillary network.  In some cases, foreign antigens can be attached to the network causes the formation of antigen-antibody complex place.  Then type III hypersensitivity reaction occurs that activates complement and mast cell degranulation leading to tissue damage or capillary in place of the reaction.

Neutrophil are attracted to the area and will begin to accumulate and phagocytes damaged cells resulting in release of cellular enzymes and residual accumulation of cells.  This causes inflammation cycle continues.

• Hypersensitivity Reaction Type IV

This reaction is mediated by T cells, where there is activation of lymphokine-producing T cells or cytotoxic by an antigen that resulted in the destruction of the cells concerned.  Reactions mediated by these cells is slow (delayed) may take 14 hours to 27 hours for the formation.

Hypersensitivity process will cause damage to the skin are:

1.  Skin malfunction causing loss of fluid,

2.  Hormonal stress followed by increased insulin resistance, hyperglycemia and glucosuria,

3.  Failure of thermoregulation,

4.  Failure of immune function, and

5.  Infection.

Another theory associated with Stevens-Johnson Syndrome include:

• Theory Apoptosis of keratinocytes

Apoptosis of keratinocytes is a very rare occurrence in normal epidermis, but in this incident will increase SJS.  NK-cell and cytotoxic T-lymphocytes release porphyrin will then make a hole in the target cells so that the polymer changes shape and 3-dimensional tubular structure keratosit which makes it easy to experience apoptosis.

Many medicines, whether swallowed or used as eye drops, can trigger apoptosis of epidermal keratinocytes is widespread in individuals with SJS, causing the skin to blister and peel.  Several theories have been proposed for this condition.  

(A) Medicines may induce upregulation of FasL by keratinocytes constitutively express Fas, which leads to the point of death receptor-mediated apoptosis.  

(B) the medicines can also cause the production of peripheral mononuclear blood cells of sFasL, which moves receptor Fas on keratinocytes.  

(C) In another scenario, the drug can interact with MHC class I-expressing cells.  As a result, drug-specific cytotoxic CD8 + T cells to accumulate in the epidermal blisters and release perforin and granzyme B which kills keratinocytes.  

(D) provides evidence that these medicines can also trigger the activation of CD8 T cells, NK cells and NKT cells to secrete granulysin.  Consequently, keratinocytes die in a way that does not require cell contacts.

• The theory of metabolism associated with genetic defects.

Patients have metabolic functions that are not perfect the first level as a result of a genetic defect so that the work be imperfect biotransformation metabolism making it possible to produce a toxic metabolite.

Clinical manifestations

Prodromal symptoms ranges from 1-14 days of fever, lethargy, cough, runny nose, painful swallowing, chest pain, vomiting, muscle aches and atralgia which vary in degrees of weight and combination of symptoms.  After that will arise lesions in several areas namely:

a.  Skin

The lesions arise suddenly, beginning with the macula which develop into papules, vesicles, bull, urticaria or erythematous plaques accompanied by a comprehensive and systemic symptoms from internal organs.  These lesions can attack less than 10% body surface.  Specific lesions of atypical target lesions that are similar to the target lesion tipical on erythema multiforme.

   Skin Lesions In Stevens-Johnson Syndrome

b.  Mucosa (mouth, throat and genital)

Form of vesicles, bull, erosion, excoriation, bleeding and crusting red.  Bula to hemorrhagic and to the mucous membranes.  Oral mucosa and lips most often affected (100%), eyes (91%), genital (57%) and rectum (5%).  The initial symptoms are perceived is swelling, redness, and burning of the lips and oral mucosa, followed by the emergence of bull and shallow ulcers.

Bula easily broken, so leave erosion.  Covered with grayish white pseudomembranehypersalivation.  On a more serious condition of lesions can be on the gums, tongue, pharynx, nasal mucosa, larynx, esophagus or bronchus so that people with breathing difficulty.

In the genital area, the lesions cause pain and redness that can develop into vesicles, shallow ulcers and erosion.  Vulvovaginitis can occur in women who are very painful, whereas in men can occur at the external urethral meatus erosion of pain accompanied by the formation of purulent secretions.  Bleeding from the urethra or vagina can occur because of damage to the urethra.

  Mucosal Lesions In Stevens-Johnson Syndrome

c.  Eye

Catarrhalis form of conjunctivitis, blepharoconcjutivitis, iritis, iridocyclitis, eyelid edema and hard to open, in severe cases erosion and perforation of the cornea.  Lesions can occur on the conjunctiva that is characterized by symptoms of redness, swelling, and the bull or erosion causing a very painful feeling, photophobia and bilateral hyperlacrimation.

  Eye Lessions of Stevens-Johnson Syndrome

Diagnosis

Diagnosis of Stevens-Johnson Syndrome, 90% based on the clinical picture.  If caused by medication, there is a correlation between drug administration with the onset of symptoms.  Diagnosis directed against manifestations of the disorder according to the triad of skin, mucosa, eye, and its relationship with clinical factors that have shaped the target lesion, or eye sliced beef, abnormalities in the mucosa and fever.

Also supported by laboratory tests including peripheral blood examination, immunological examination, bacterial culture and resistance testing of blood and the lesion, and histopathological examination of skin biopsy.  Anemia can be found in severe cases with bleeding, leukocytes are usually normal or slightly elevated, there is an increase of eosinophils.  Levels of IgG and IgM can be high, C3 and C4 were normal or slightly decreased and can be detected circulating immune complexes.

Skin biopsy was planned if there is no classic lesions.  Histopathological and immunohistochemical examination to support the enforcement of the diagnosis.

Differential Diagnosis 

Differential diagnosis in the case of Stevens-Johnson Syndrome include:

1.  Toxic Epidermal Necrolisis.

Stevens-Johnson Syndrome is very close to TEN.  SJS with more than 30% bull called TEN.

2.  Staphylococcal Scalded Skin Syndrome (Ritter's disease).

In this disease is characterized by crusting skin lesions on the skin peeling.  Mucosa usually not affected.