Blistering Disorders

Blisters :- are accumulation of fluid within or under the epidermis. The appearance of blister is determined by the level at which it form. 1. Intra epidermal blisters :- appear within the prickle cell layer of the epidermis, & so have thin roof & rupture easily to leave an oozing denuded surface ; this tendency is even more marked with sub corneal blisters. 2. Sub epidermal blisters :- occur between the dermis & epidermis, their roof are relatively thick, & so they tend to be tense & intact.

Classification of bullous diseases according to location of blister in the skin :- the

Classification according to their location Subcorneal blister:- 1-bullous impetigo. 2-candidiasis. 3-miliria crystallina. 4-pemphigus folacieous. 5-SSSS. Intraepidermal blister:- 1-acute dermatitis. 2-viral vesicle. 3-pemphigus vulgaris. 4-Scabies. 5-friction blister.

Subepidermal blister:- 1-bullous pemphigoid. 2- dermatitis herpitiformis. 3-bullous LE. 4- bullous lichen planus. 5-TEN. 6- erythema multiforme.

Blistering Disorder Classification according to cause :- 1. Infection :- bullous impetigo, herpes simplex or zoster, SSSS, & candidiasis. 2. Auto immune :- pemphigus, pemphigoid, dermatitis herpetiformis, bullous LE, & bullous lichen planus. 3. Hereditary :- epidermolysis bullosa. 4. Unknown :- toxic epidermal necrolysis. 5. Miscellaneous :- dermatitis, erythema multiforme, friction blister.

Autoimmune Blistering Disorder These are disorders by which the damage is created by auto antibodies directed at molecules that normally bind the skin. These diseases tend to be chronic & many are associated with tissue bound or circulating Ab.. These include :- 1. Pemphigus. 2. Bullous pemphigoid. 3. Dermatitis herpetiformis. 4. Epidermolysis bullosa. 5. Bullous LE. 6. Bullous lichen planus.

Blistering Disorders Diagnosis of blistering disorder :- 1. History :- sometimes history helps to reach the diagnosis, as in cold or thermal injury, or in an acute contact dermatitis. 2. Examination :- the morphology or distribution of a bullous eruption gives the diagnosis away, as in herpes simplex or zoster. 3. Investigation :- when the cause is not obvious ( skin biopsy, direct immunoflouresence, indirect immunoflouresence ).

Pemphigus Pemphigus :- is a chronic lethal autoimmune intra epidermal blistering disease involving the skin & mucous membrane. Acantholysis :- loss of cohesion between epidermal cells caused by circulating IgG antibodies directed against the cell surface of keratinocytes, destroying the adhesion between epidermal cells producing blisters. Acantholysis :- loss of cohesion between epidermal cells caused by circulating IgG antibodies directed against the cell surface of keratinocytes, destroying the adhesion between epidermal cells producing blisters.

Pemphigus Classification of pemphigus :- 1. Pemphigus vulgaris (supra basal blister) pemphigus vegetans (localized). Drug induced pemphigus. 2. Pemphigus foliaceus (sub corneal blister) pemphigus erythematosus (localized). Drug induced. 3. Para neoplastic pemphigus.

Pemphigus Vulgaris The most common & severest form of pemphigus, charact. by thin walled flaccid, easily ruptured bullae that appear on either apparently normal skin & mucous membrane or on erythematous base.the bullae soon rupture to form erosions, covered with crusts that have little or no tendency to heal. The healed lesions often leave post inflammatory hyper- pigmentation. It may begin in many ways, but most commonly the lesions appear first in the mouth in up to 60%. It may begin in many ways, but most commonly the lesions appear first in the mouth in up to 60%. During the course of illness, oral mucosal involvement occur in 100% in the form of short lived bullae that quickly rupture in to painful erosions, lips are fissured & crusted. During the course of illness, oral mucosal involvement occur in 100% in the form of short lived bullae that quickly rupture in to painful erosions, lips are fissured & crusted.

Pemphigus Vulgaris Also there is involvement of the throat, esophagus, vagina, & penis. Also there is involvement of the throat, esophagus, vagina, & penis. The next most common sites are the groin, scalp, face, neck, axillae or genitalia. The next most common sites are the groin, scalp, face, neck, axillae or genitalia. Nikolsky sign is +ve (there is an absence of cohesion in the epidermis, so the upper layers are easily made to slip laterally by slight pressure or rubbing. Nikolsky sign is +ve (there is an absence of cohesion in the epidermis, so the upper layers are easily made to slip laterally by slight pressure or rubbing. male = female. male = female. 5 th – 6 th decades. 5 th – 6 th decades. Mediterraneous descent. Mediterraneous descent.

Pemphigus Vulgaris Differential diagnosis :- Cutaneous lesions :- bullous pemphigoid epidermolysis bullosa, bullous empitigo. Cutaneous lesions :- bullous pemphigoid epidermolysis bullosa, bullous empitigo. Oral lesions :- oral aphthosis, behcet disease, herpes simplex. Oral lesions :- oral aphthosis, behcet disease, herpes simplex. Course :- of all form of pemphigus is prolonged even with treatment & mortality rate of pemphigus is still at least 15%.

Pemphigus Vulgaris Diagnosis :- 1. Skin biopsy for light microscopy :- small, early vesicles or skin adjacent to a blister shows an intra- epidermal bulla, supra basal acantholysis, mild - moderate infiltrate of eosinophils. 2. Direct immunoflouresence :- shows deposition of IgG & in most instances C 3 in the intercellular space of the epidermis. 3. Indirect immunoflouresence :- detecting serum IgG which is present in all forms of pemphigus reflecting disease activity.

Pemphigus Vulgaris Complication :- 1. Due to high dose of systemic steroid & immunosuppressive drugs. 2. Infections of all types are common. The large areas of denuded skin may become infected. 3. Sever oral ulcers make eating painful. 4. Fluid & electrolyte imbalance (fluid loss & painful eating).

Pemphigus Vulgaris Treatment :- 1. Admission to hospital. 2. Very high dose of systemic steroid such as prednisolon mg\day, the dose is dropped only when new blister stop appearing & taper gradually to maintenance level. 3. Immunosuppresive agents as azathioprine, cyclophosphamide, & methotraxate are often used as steroid sparing agent. 4. Plasmapheresis & intravenous immunoglobulin.

Pemphigus Pemphigus Vegetance :- is a rare variant of pemphigus vulgaris with supra basal cleft & acantholysis, clinically there is vegetative growth in the flexure (excessive cowliflowered like granulation tissue & crusting. Drug induced pemphigus :- mostly due to pencillamine, captopril, pencilline, IL2, rifampicin. There is less mucosal involvement, most of the cases resolve after discontinuation of treatment.

Pemphigus Pemphigus foliaceus :- in this type there is sub corneal blister, this will lead to appearance of flaccid blister which is rapidly ruptured to form scaly crusted erosions. Mucous membrane is rarely involved. The disease may spread causing exfoliative dermatitis Pemphigus erythematosus :- a localized form of pemphigus folacieus with typical scaly crusted lesion on the malar area of the face & seborrheic area. Para neoplastic pemphigus :- rare type, associated with thymoma or underlying carcinoma, chara. By unusually sever mucosal lesion.

Bullous Pemphigoid Is a chronic sub epidermal autoimmune blistering disease usually occurring in elderly where auto antibodies are directed toward the epidermal basement membrane. Usually affect above 60 years. Usually affect above 60 years. No known racial or sexual predilection. No known racial or sexual predilection. Etiology :- it is auto immune where auto antibodies IgG class with C 3 are directed at the lamina lucida & hemidesmosome producing tense blister. Etiology :- it is auto immune where auto antibodies IgG class with C 3 are directed at the lamina lucida & hemidesmosome producing tense blister.

Bullous Pemphigoid Clinical manifestation :- Skin :- large, tense intact bullae arising on normal or erythematous base, or form large urticarial plaques, most commonly on lower abdomen, inner & anterior thighs, flexor forearms & may occur any where, usually associated with intense pruritus. Skin :- large, tense intact bullae arising on normal or erythematous base, or form large urticarial plaques, most commonly on lower abdomen, inner & anterior thighs, flexor forearms & may occur any where, usually associated with intense pruritus. Eroded lesions from ruptured blisters shows good tendency for spontaneous healing in contrast to pemphigus, on healing leaves post inflammatory hyper pigmentation. Eroded lesions from ruptured blisters shows good tendency for spontaneous healing in contrast to pemphigus, on healing leaves post inflammatory hyper pigmentation. -ve nikolysky sign. -ve nikolysky sign. Mucous membrane is involved in 25% of the cases with erosions & intact blister (less sever than pemphigus vulgaris). Mucous membrane is involved in 25% of the cases with erosions & intact blister (less sever than pemphigus vulgaris).

Bullous Pemphigoid Differential diagnosis :- Pemphigus, erythema multiforme, epidermolysis bullosa aquisita. Pemphigus, erythema multiforme, epidermolysis bullosa aquisita. Diagnosis :- 1. Skin biopsy :- sub epidermal bullae, heavy upper dermal infiltrate of eosinophils. 2. Direct immunoflouresence :- IgG & C 3 along basement membrane zone. 3. Indirect immunoflouresence :- circulating auto antibodies against basement membrane zone found in 70-80% of cases & does not correlate with disease activity.

Bullous Pemphigoid Treatment :- Usually self limiting, but may last for months or years. if localized disease could be treated with potent topical steroid. if localized disease could be treated with potent topical steroid. Extensive disease :- systemic steroid as oral prednisolon 40-60mg\day until control disease & then taper gradually. Sometime we add steroid sparing agent & dapson. Extensive disease :- systemic steroid as oral prednisolon 40-60mg\day until control disease & then taper gradually. Sometime we add steroid sparing agent & dapson.

Dermatitis Herpetiformis Is a chronic, relapsing, severely pruritic disease with grouped, symmetrical, polymorphous, erythematous-based lesions on the extensor surface with unique histologic, immunologic & GIT criteria. Clinical feature :- charac. clinically by papules, papulovesicular, vesiculobullous, bullous or urticarial lesions. On involution leaves post inflammatory hyper pigmentation charac. clinically by papules, papulovesicular, vesiculobullous, bullous or urticarial lesions. On involution leaves post inflammatory hyper pigmentation Intense itching & burning &their paroxysmal quality provokes scratching to the point of bleeding. Intense itching & burning &their paroxysmal quality provokes scratching to the point of bleeding. Site of predilection are scalp, nuchal area, posterior axillary folds,elbows, sacral region, buttocks, & knees. Site of predilection are scalp, nuchal area, posterior axillary folds,elbows, sacral region, buttocks, & knees. Symmetrically arranged lesions, in crops. Symmetrically arranged lesions, in crops.

Dermatitis Herpetiformis Mucous membrane involvement is rare. Mucous membrane involvement is rare. Course of disease is life long. Course of disease is life long. Slightly more common in men. Slightly more common in men. Any age could be affected mostly 2-5 decades. Any age could be affected mostly 2-5 decades. Most of the patients have an underlying gluten sensitive enteropathy. Although this may be asymptomatic. Most of the patients have an underlying gluten sensitive enteropathy. Although this may be asymptomatic. Strong association with HLA DR 3, HLA B 8. Strong association with HLA DR 3, HLA B 8. Differential diagnosis :- bullous pemphigoid, erythema muliforme, scabies, contact dermatits, atopic dermatitis, numular eczema, neurotic excoriation, insect bite. Differential diagnosis :- bullous pemphigoid, erythema muliforme, scabies, contact dermatits, atopic dermatitis, numular eczema, neurotic excoriation, insect bite.

Dermatitis Herpetiformis Diagnosis :- 1. Skin biopsy :- showed papillary micro abscess with neutrophils & eosinophilic infiltrate & sub epidermal bullae. 2. Direct immunoflouresence :- granular deposits of IgA at the dermal papillae of uninvolved skin. 3. Jejonal biopsy :- sub total vellous atrophy. Treatment :- Gluten free diet, dapson mg\day, sulphapyridine & sulphasalazine.

Erythema Multiforme acute often recurrent inflamm. Disease charac.by target shaped urticarial plaques which are arranged symmetrcally on the palms, back of the hand & feet. acute often recurrent inflamm. Disease charac.by target shaped urticarial plaques which are arranged symmetrcally on the palms, back of the hand & feet. Pathogenesis:- immune complex mediated in which IgM &C3 deposition around upper dermal blood vessel.

Etiology :- 50% idiopathic 1- viral infection:- herpes, hepatitisA,B,C, AIDs, ORF, polio, mycoplasma pneumonia. 2- bacterial infection:- TB, brucilla, typhoid. 3- fungal infection:- histoplasmosis. 4- Protozoal infection:- malaria, trichomoniasis. 5- Radiotherapy. 6- Drugs:- sulfonamide, pencilline, contraceptive, phenytoin phenothiazine. 7- polyarteritis nodosa, lupus erythematosus. 8- carcinoma, lymphoma, leukemia 9-Sarcoidos

Erythema Multiforme Charac. Clinically by dusky red maculopapular lesions or vesicular or bullous lesions, charactristic lesion is target lesion. Site back of hand and feet, palm, extensor of forearm & legs, but could be generalized. Mucus membrane could be affected. Not associated with prodromal symptoms. Treatment :- Self limited, sever systemic steroid 40-80mg 1-3 weeks. Oral acyclovir for recurrent EM

Stevens-johnson syndrome ● SJS is considered the most sever form of EM. ● characterized by widespread blisters and purpuric macules, is usually a sever drug-induced reaction with high morbidity and a poor prognosis with the mortality reaching 10%. ●Cutaneous eruption is preceded by fever and symptoms of an upper respiratory infection. ● Cutaneous lesions are flat atypical target or purpuric macules widespread. ● mucosal lesions: bullea appearing suddenly 1-14 days after prodromal symptoms, affecting conjunctivae, nose, mouth, anorectal junction, vulvovaginal, urethral.

Toxic epidermal necrolysis A life threatening full thickness loss of epidermis with a high mortality reaching 35-40%. Usually is a sever drug reaction. Chracterized by sever prodromal symptoms, the skin hot and red and painful, and slide laterally with slight pressure( nikolsky’s sign). With sever mucosal involvement.