Submitted by- SURABHI SHARMA

CONTENTS :y y y y y y y y y y y y y y y y

History Defination Alternative Names Frequency/ Prevalence Mortality/ Morbidity Prevalence Age predilection and Sex predilection Clinical Features Stevens-Johnson Syndrome Histopathology Differential Diagnosis Diagnosis Treatment/Management Prognosis Complications References

HISTORY
Erythema Multiforme (EM) was initially described in 1866 by Ferdinand von Hebra as an acute self-limited skin disease, symmetrically distributed on the extremities with typical and often recurrent concentric target lesions. The term EM minor was proposed later to differentiate the mild cutaneous syndrome from the more severe form,EM major, which involves several mucous membranes. Stevens-Johnson Syndrome(SJS) was considered as an extreme variant of EM for many years,while toxic epidermal necrolysis(TEN) was considered a different entity.Essentially SJS and TEN are considered severity variants of a single entity. The 2 spectrum are 1) EM consisting of erythema minor or major 2) SJS/TEN

DEFINITION:Erythema multiforme is a distinctive hypersensitivity syndrome characterised by skin and mucous membrane lesions and, in its more severe forms, mucosal lesions with constitutional symptoms and at time visceral involvement. It is usually considered acute and selflimiting,but recent observations indicate that it may also behave as a chronic recurrent disorder in many people.

ALTERNATIVE NAMES :Lyells syndrome,Stevens-Johnson Syndrome, EM Major, EM Minor, Herpes-induced EM Major, Herpes associated EM, Drug induced SJS.

Frequency :International- The true incidence of EM is unknown,but it has been estimated to be between 0.011%.Incidence of SJS and TEN are better charecterised and estimated at 0.4-1.2 and 1.2- 6 per million person years respectively.

Prevalence :The disorde may occur at any age,with its highest incidence in young adults 20-40 yrs of age; as many as 20% of cases are seen in children and adolescent.

Mortality/ Morbidity :EM not ususally associated with mortality. Most cases are self- limited and resolve without sequelae in 2-4 yrs. SJS- The mortality rate is 5% TEN- The mortality rate is 30%

Pathogenesis :The pathogenesis of erythema multiforme remains unknown. It appears to represent the end result of a hypersesitivity reaction to a number of infectious and other agents ; viral, bacteria, protozoal, fungal or mycoplasma , pneumonia(Eaton agent) infection;food or drugs; immunization;and a variety of other systemic diseases and physical agents, whereas drug reactions and malignancies are important causes of erythema multiforme in older persons,infectious diseases are most common preciptants in children and young adults, the most common cause of erythema multiforme appears to be the virus of herpes simplex a history of cold sores precedes the development of other lesions by about 314 days,recurrence are particularly common in this form of erythema multiforme.

The pathogenesis of EM include circulating immunereaction complexes binding to the vessel walls and liberation of lytic enzymes toxic to epithelial cells, resulting in skin and mucosal reaction ranging from mild erythema to widespread necrosis with sloughing of the epithelial layer.

Predisposing factor are :1- Infection, such as Herpes Simplex and Histoplasmosis. 2- Drug hypersensitivity, like pencillin, dilantin, barbiturates,iodine and salicylates. 3-Gastrointestinal conditions, most Crohn disease and ulcerative colitis. 4-Other,like malignancy, radiation therapy,behect syndrome,collagen vascular disease,dermatitis herpetiformis,ligunate erythema,lichen planus,pemphigoid,pemphigus vulgaris

Sex predilection :Male : Female ratio is 3:2 or 2:1 In case of SJS/TEN male:female ratio is 1:1

Age predilection :2nd and 4th decades of life 20% occur in children. Rare in children less then 3 yrs and adults more then 50 yrs of age.

Clinical Features :EM appears in 3 clinical forms :-

1- EM Minor :y Mostly affect the skin ,the oral cavity involved in 25% of cases. y There is a 3-7 days prodromic period before the lesions appear, y

y y y

such as severe headache, fever and malaise. Followed by classic skin lesion known as target lesion, bull eye or iris lesion. Which is characterized by a concentric erythematous patch with a peripheral thin zone of pallor followed by one or more additional thin erythematous ring. In the early stages the center of the ring develops a raised papule and small bulla that collapses, producing a transient central erosion that heal and return to normal, which then produces the center of the bulls eye. Each target lesion range from a few to many cms and mostly affect the flexors of the extremities, trunk and facial surface The disease can occur in any ages but mostly involves the young adult. The condition is self-limiting usually resolving in 2-3 weeks.

EM Minor

Mostly affect the flexor of extremities, trunk and facial surface.

TARGET LESION/BULLS EYE OR IRIS LESION

Characterized by a concentric erythematous patch with a peripheral thin zone of pallor followed by one or more additional thin erythematous ring. In early stages the center of ring develops a raised papule and small bulla that collapses, producing a transient central erosion that heals and return to normal, which then produces the center of the bulls eye

2- Chronic EM minor :y Is the mildest form of EM y Skin lesions are similar in size and of shorter duration and

distribution than in other forms. y The lesion may persist for 1 or more years.

3- EM Major :y Is an acute form of the disease, with severe involvement y y y

of both the skin and mucous membrane. In addition to the target lesion, large bulla of the mucous membrane and skin are characterized of this type. The bulla quickly rupture producing whitish psuedomembranes on the mucosa and dark red crusted lesions on dry skin surfaces mostly on lips. The oral mucous membrane lesions are not usually a significant feature of disease except for the pain and discomfort they cause the hyperemic, maculae, papules and vesicles may become eroded or ulcerated and bleed easily. The tongue, palate, buccal mucosa and gingiva are commonly diffusely involved.

Crusted lesions on the lips

Crusting bloody border of lips and target lesion on hand.

Hyperemic,macula e,papules and vesicles may become eroded or ulcerated.

Most commonly found on tongue,palate,bucc al mucosa and gingiva

Stevens-Johnson Syndrome:y A very severe bullous form of erythema multiforme with

widespread involvement typically including the skin, oral cavity, eyes and genitelia. y It commences with the abrupt occurrence of fever, malaise, photophobia and eruptions of oral mucosa, genitelia and skin. The cutaneous lesions in this muccocutaneous occular disease are similar to those of erythema multiforme, although they are hemorrhagic and are often vesicular or bullous. y Oral mucous membrane lesions may be extremely severe and also so painful that mastication is not possible. Mucosal vesicles or bullae occur which rupture and leave surfaces covered with a thick white and yellow exudate.Erosions of the pharynx are also common.The lips may exhibit ulcerations with bloody crusting and are painful.The oral lesions may be the chief complaint of the patient and undersatndably,have been mistaken for ANUG.The mucosal involvement in SJS is more severe and extensive than in EM major.

Lips may exhibit ulcerations with bloody crusting and are paiful.

StevensJohnson Syndrome

y Eye lesions :- consists of photophobia, a character of the disease referable to the conjuctivitis, corneal ulcerations and panophthamitis which may occur. y Keratoconjuctivitis sicca also has been decribed. y Blindness may result chiefly from recurrent bacterial infection. y Genital lesions:- are reported to consist of a nonspecific uretheritis, balanitis and/or vaginal ulcerations y Other reported complications are related to respiratory tract involvement such as tracheobronchial ulceration and pneumonia. y The patient usually recover unless they are secondarily infected.

Histopathology:y Histopathology are variable, reflecting the wide spectrum of clinical presentations. y In general the lesions show intercellular and intracellular edema of the epithelium with focal micro-vesicle formation in spinous layer. y Sometimes the edema results in pooling of an eosinophilic amorphous coagulum within the epithelium. y A generalized diffuse infiltration of both acute and chronic inflammatory cells are seen in the underlying connective tissue with vasodilation of blood vessels and connective tissue edema and sub-epithelial cleft. y Dilation of the superficial capillaries and lymphatic vessels in the uppermost layer of connective tissue is prominent.

Histopathologica l Diagram

Differential Diagnosis :y Viral lesion like primary herpetic gingivo-stomatitis-

They are small round, symmetrical and shallow but erythema multiforme lesions are large,irregular ,deeper ,often bleed. And also gingival enlagement is rare in erythema multiforme. y Phemphigus vulgaris less associated inflammation,progressive course,immunological auto antibodies against intracellular substance. y Mucous Membrane Phemphigoid- slow developing eyechanges,chronic course and frequent participant of gingiva. y Allergic reaction- target lesion are absent. y Erosive lichen planus- onset less acute,whitish lichen planus design on the border of erosion and skin changes. y Xerostomia- mucosa is dry. y Toxic epidermal necrolysis- very serious,often fatal ,bullous eruption,so severe that large sheets of skin peel off.

Diagnosis :The diagnosis is mainly based on the appearance of skin lesions1. Clinical Diagnosis- bulls eye lesion with hemorrhagic crusting of lip is typical of EM. 2. Lab Diagnosis- biopsy shows subcutaneous and intercellular vesiculisation.
y

Treatment :y    

Treatment goals include :Controlling the illness that is causing the condition. Preventing infection. Treating the syptoms. Stop taking any suspected medication,with your doctor approval.

y Treatment of mild case : Moist compresses applied on skin.  Over the- counter medication (such as acetaminophen) to reduce

fever and discomfort.

y Treatment of severe symptoms may include : Antibiotics to control any skin disease.  An initial dose of 30mg/day to 50 mg/day of   

   

prednisolone or methylprednisolone for several days,which is then tapered,is helpful in shortening the healing time of EM. Severe cases of recurrent EM have been treated with Dapsone 100150mg/day,azathioprine,levamisole or thiolidomide. EM triggered by progesterone, also referred to as autoimmune progesterone dermatitis and stomatitis has been treated successfully with tamoxifen. Antiherpes drugs such as acyclovir Adult- 600-800 mgm/day BD for 7-10 days Pediatric- 10mgm/kg or 500mgm/m2 i.v. Valacyclovir (valtrex,500-1,000 mgm/day) Famicyclovir (Famvir,125-250 mgm/day) Cyclosporine (4 mgm/kg/day for 1 week) Prophylactic use of antiherpes drug is effective in preventing frequent recurrent episodes of HSV associated EM.

Prognosis:y Mild form of EM usually get better in 2-6 weeks,but they may return. y More severe form of EM is difficult to treat. y SJS and TEN have high death rate.

Complications :y y y y

Body-wide infection Sepsis Loss of body fluids Shock

Occasionally, lesions on internal organs causing :y Heart inflammation (myocarditis) y Pneumonitis y Nephritis y Hepatitis y Cellulitis y Permanent skin damage and scarring

References :y Shafers Textbook of Oral Pathology- 6th Edition y Burkets Textbook of Oral Medicine 10th Edition y Crispian Scully-Oral and Maxillofacial Mediciney y y y y y y y

2nd

Edition Textbook of Oral Medicine- Anil Govindrao Ghom-2nd Edition Article by Sidney Hurwitz,MD,Clinical Professor,Pediatrics and Dermatology,Yale University,School of Medicine www.scribd.com www.google.com www.righthealth.com www.EDocFind.com www.icondata.com/health/pedbase/files/erythema.HTM www.hon.ch

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