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 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-chronic benign bullous disease of childhood.
7- erythema multiforme.
8-epidermolysis bullosa.

■ Classification according to cause :-

► Infection :- bullous impetigo , herpes simplex or zoster , SSSS , &
candidiasis .
► Auto immune :- pemphigus , pemphigoid , dermatitis herpetiformis , bullous
LE , & bullous lichen planus .

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► Hereditary :- epidermolysis bullosa , benign familial pemphigus , porphyria
► Unknown :- toxic epidermal necrolysis , sub corneal pustular dermatosis .
► 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-Herpes gestationis .
5-Chronic benign bullous disease of childhood .
6-Epidermolysis bullosa .
7-Bullous LE .
8. Bullous lichen planus .

■ Diagnosis of blistering disorder :-

● History :- sometimes history helps to reach the diagnosis , as in cold or

thermal injury , or in an acute contact dermatitis .
● Examination :- the morphology or distribution of a bullous eruption gives
the diagnosis away , as in herpes simplex or zoster .
● 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 .
■ Classification of pemphigus :-
1-Pemphigus vulgaris (supra basal blister)
pemphigus vegetans (localized) .
Drug induced pemphigus .
2-Pemphigus foliaceus (sub corneal blister)
pemphigus erythematosus (localized) .
Endemic Brazilian pemphigus .
Drug induced .
3-Para neoplastic pemphigus .

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■ 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% .
► 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 .
► Also there is involvement of the throat , esophagus , vagina , & penis .
► 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 .
► male = female .
► 5th – 6th decades .
► Mediterraneous descent .

● Differential diagnosis :-

1-Cutaneous lesions :- bullous pemphigoid epidermolysis bullosa , bullous

empitigo .
2-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% .

● 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
C3 in the intercellular space of the epidermis .
3-Indirect immunoflouresence :- detecting serum IgG which is present in all
forms of pemphigus reflecting disease activity .
● 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) .

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● Treatment :-

1-Admission to hospital .
2-Very high dose of systemic steroid such as prednisolon 80-320 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 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 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 .
► No known racial or sexual predilection .
► Etiology :- it is auto immune where auto antibodies IgG class with C3 are
directed at the lamina lucida & hemidesmosome producing tense blister .

● 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 .

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 ♪ 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 .
♪ Mucous membrane is involved in 25% of the cases with erosions & intact
blister (less sever than pemphigus vulgaris) .

● Differential diagnosis :-
Pemphigus , erythema multiforme , epidermolysis bullosa aquisita .

● Diagnosis :-

1-Skin biopsy :- sub epidermal bullae , heavy upper dermal infiltrate of

eosinophils .
2-Direct immunoflouresence :- IgG & C3 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 .

● Treatment :-
♣ Usually self limiting , but may last for months or years .
♣ 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 .

Chronic benign bullous disease

of childhood
► An acquired sub epidermal blistering disease of a young child , charac. By
auto antibodies of IgA class directed against basement membrane zone .
► Usually affect below 10 years , mean 4.5 years .
► Charac. clinically by large intact tense blister mainly on the lower abdomen
, perineum , lower extremities , & in the peri oral region , can be generalized .
► Charac. finding is the development of new blisters at the periphery of blister
or crust of old one (cluster of jewels) .
► Oral mucous membrane could be involved , usually pruritic .

● Treatment :-
ᴥ Most of the patients go into remission within 2 years & almost all will go
into remission at puberty .

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ᴥ Treatment is with sulphapyridine or dapson & sometime need systemic
steroid .

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
► Intense itching & burning &their paroxysmal quality provokes scratching to
the point of bleeding .
► Site of predilection are scalp , nuchal area , posterior axillary folds , sacral
region , buttocks , & knees .
► Symmetrically arranged lesions , in crops .
► Mucous membrane involvement is rare .
► Course of disease is life long .
► Slightly more common in men .
► Any age could be affected mostly 2-5 decades .
► Most of the patients have an underlying gluten sensitive enteropathy .
►Although this may be asymptomatic .
► Strong association with HLA DR3 , HLA B8 .

● Differential diagnosis :-

bullous pemphigoid , erythema muliforme , scabies , contact dermatits , atopic

dermatitis , numular eczema , neurotic excoriation , insect bite .

● 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 50 -300 mg\day , sulphapyridine & sulphasalazine .

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 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.
● 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

● 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

Anas Sa'adoon