STEVENS-JOHNSON SYNDROME (S.J.S)- TOXIC EPIDERMAL NECROLYSIS (TEN) ERYTHEMA MULTIFORME & STEVENS-JOHNSON SYNDROME (S.J.S)- TOXIC EPIDERMAL NECROLYSIS (TEN) DR MAHESH MATHUR MD,DVD,DCP (UK)

ERYTHEMA MULTIFORME DEFINITION Group of Diseases encompasses A number of acute self-limited exanthematic intolerance reaction that share at least two characteristic 1.skin lesion – Target lesions stable Circular erythemas or urticarial plaques with areas of blistering, necrosis and /or resolution in a concentric array 2.Histologically –satellite cells and widespread necrosis of epidermis

TYPES Erytema multiforme Common, mild relapsing eruption that is triggered by recurrent herpes Simplex infection Stevens-Johnson syndrome -Toxic Epidermal Necrolysis (SJS-TEN) An infrequent sever mucocutaneous intolerance most commonly triggered by drugs

Erythema Multiforme 1% of Dermatological out patient Infrequent age <3 years & > 50 years 75% of patients are under 40 years Equal incidence in M:F No predominance for any ethnic groups or geographical location Seasonal clustering of cases in Spring Recurrent U.V. light provocation of recurrent HSV infection

Etiology -HSV infection -Contact sensitization Sulphonamide, Anti histaminic, DNCB Rose wood, Primula, tea tree oil, Cinnamon -UV Light -Pregnancy

Pathogenesis Cell Mediated immune reaction leading to destruction of Keratinocytes expressing HSV antigens CD 8 + cells carry out the immunological attack on epidermal cells expressing viral DNA- leading to apoptosis of individual cells & necrosis CD 4+ T lymphocytes & monocytes cellular infiltration in Dermis causing wheal like erythema and microvasculature damage leads to epidermal necrosis and vesiculo-Bullous formation

Clinical Manifestations Mild Prodromal symptoms- Cough, Low-grade Fever Sudden appearance of Typical target skin lesions- Regular circular wheal-like Erythematous papules/plaques fixed and of variable size, Center of lesions become violaceous dark or vesicular bullus, Heals without scarring Mucosal Lesions 70% of cases- Lips Palate & gingiave in most of the cases

ERYTHEMA MULTIFORME

TARGET LESION

HISTOATHOLOGY SKIN SECTION H&E STAINING

SKIN SECTION H&E STAINING X100

TREATMENT Symptomatic Systemic Corticosteroid not Needed Recurrent EM Oral Acyclovir 200 mg 5 Times a Day for the treatment Low Dose Acyclovir- 400-800 mg oral per day for 6 Month may be indicated

STEVENS-JOHNSON SYNDROME (S.J.S) & TOXIC EPIDERMAL NECROLYSIS (TEN) DEFINITION Sever, episodic, acute mucocutaneous reaction most commonly elicited by drugs Characterized by rapidly spreading irreregular dusky erythematic maculs, necrosis of skin and detachment of skin resembling scalding of skin with involvement of more then one mucosal site Constitutional symptoms and internal organ involvement often occurs and may be sever Self-limited Significant morbidity scaring & mortality

Etiology 2 to 3 cases per million Occurs World wide M:F ratio is 2;1 Drugs * 3 fold increase in HIV infected Population Infections-Mycoplasma, Pneumoniae,Infectious mononucleosis, Histoplasmosis, Gram Negative septicemias Pathogenesis CD4+ & CD8+ cells & cytokines mediated injury to epidermal cells

DRUGS Sulphasalazine Co-Trimoxazole Hydantoins Carbamazepine Barbiturates Phenylbutazone Ibuprofen Piroxicam Allopurinol Aminopenicillens Fluroquinolones

Clinical Manifestations Non Specific sever prodormal Symptoms Macular morbiliform rash appears on face trunk. Positive Nikolsky’s sign Predominantly mucous membranes involvement- in 40% of cases Buccal mucosa, Hemorrhagic crusts at lips, bulbar conjunctiva Respiratory tract & G.I.T involvement Homodynamic instability & Shock

DUSKY ERYTHEMATOUS MACULES

SCALDING OF SKIN

SCALDING OF SKIN

SJ SYNDROME

Ocular Manifestations Mild-lid edema, Conjunctivitis, chemosis Moderate - conjunctival membranes, Corneal epithelial loss and corneal ulceration; Severe - perforation, Cicatricial changes. 9% of patients with EM-minor had ocular manifestations. ~ the SJS (69%) 27% of patients experiencing severe complications including, corneal melts and cicatricial changes. up to 50% of patients with severe cutaneous disease develop severe ocular manifestations.   

The acute phase of disease is characterized primarily by eyelid involvement. The lids are typically swollen and erythematous. Soon thereafter, or coincident with this, the conjunctiva is inflamed. The conjunctivitis frequently parallels the skin findings, with bullae formation and eruption. Membrane or pseudomembrane formation then occurs The healing process can result in cicatricial changes which include symblepharon, ankyloblepharon, eyelid margin rotation, severe dry eye and conjunctivilization of the corneal Recurrent ocular inflammation can occur in patients with resolved acute ocular and systemic disease in the absence of systemic recurrence

Conjunctival membranes & pseudomembrane

Cicatricial changes

conjunctivilization

MUCUS MEMBRAN LESION

CHILD WITH SJS-TEN SYNDROM

HISTOPATHOLOGY H&E SECTION X45

IMMUNO STAINING OF CORNEAL BIOPSIES

Treatment -Identification of causative agent & it’s elimination -Active therapy - Glucocorticoids - Immunoglobulin - Immunomodulator Cyclophosphamide Cyclosporine Thalidomide - Plasmapheresis -Supportive therapy- -Maintenance of Homodynamic status -Protein & electrolyte Homeostasis -Antimicrobial therapy

Prognosis INDICATOR OF POOR PROGNOSIS Age >40 years Malignancy Tachycardia BSA >10% Serum Urea level >10mmol/L Serum Glucose level 14mmol/L FATAL OUTCOME DUE TO – Septicemia GI bleeding Renal insufficiency & shock