Download MBBS Dermatology PPT 13 Imunobullous Disorder Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Dermatology PPT 13 Imunobullous Disorder Lecture Notes

Immunobul ous


? Blister: fluid filled cavity formed within or

beneath the epidermis

? Vesicle: blister < 0.5cm
? Bullae: >0.5cm

Mechanism of blister formation:

? 1. spongiosis: extracellular fluid in epidermis

Eg eczema, miliaria crystallina

? 2. Acantholysis: loss of keratinocyte cell to cell

contact........ Rounded keratinocytes......

condensed cytoplasm...large nuclei....

Peripheral condensation of chromatin and

prominent nucleoli

Eg: pemphigus, hailey hailey ds, darriers


Tzanck smear

? Reticular degeneration ? bal ooning degeneration

(intracel ular oedema)

? eg: viral infections

? Cytolysis- friction and heat

? Basement membrane zone destruction ?

? primary structural deficiency

? immunological y mediated damage- BP, linear

Ig A disease, DH

Based upon plane of separation

? Intraepidermal-

A. subcorneal- miliaria crystallina, SSSS, P.

foliaceous, Bullous impetigo, SCPD
B. Spinous- Eczema, Hailey Hailey, Miliaria

C. Suprabasal- Pemphigus vulgaris,

Paraneoplastic pemphigus, Darriers


? Subepidermal:
Bullous Pemphigoid
Linear Ig A disease
Porphyria cutanea tarda

Immunobullous disorders


? The immunobullous diseases are characterized by

pathogenic autoantibodies directed at target

antigens whose function is either cell-to-cell

adhesion within the epidermis or adhesion of

stratified squamous epithelium to dermis or


? These diseases are often associated with significant

morbidity and some can even cause mortality, if left


? Adhesion between keratinocytes:

Desmosomes (transmembrane glycoproteins)

? 1. desmogleins- 1,2,3
desmoglein 3 ? in basal and suprabasal

layers and mucosae

? 2. desmocollins

? Others: non glycosylated proteins

? Plakoglobin; desmoplakin 1 and 2; plakophilin

Intraepidermal immunobullous


Pemphigus vulgaris

? The term pemphigus stems from the Greek

`pemphix' meaning blister or bubble.

? Pemphigus is a group of autoimmune

blistering disease of skin & mucous

membranes characterized by:

? Histologically, intraepidermal blisters due to loss

of cell-cell adhesion of keratinocytes.

? Immunopathologically, the finding of in vivo

bound & circulating IgG autoantibodies directed

against the cell surface of the keratinocytes.

Pemphigus vulgaris

? Al patients develop painful oral erosions. More than

half of patients also have flaccid blisters and

widespread cutaneous erosions.

? Mucosa: painful erosions over buccal & palatine mucosa.

Intact blisters are rare. Esophagus, conjunctiva, & nasal

mucosa may develop these lesions.

? Skin lesions: primary lesions are flaccid, thin walled easily

ruptured blisters. Blisters are fragile and soon rupture to

form painful erosions.

? Erosions often become large and partially covered with crusts.

Some lesions on healing leave hyperpigmentation but no scarring.

Skin lesions

Oral mucosal lesions


? Nikolsky sign : positive

? Tzanck smear: Acantholytic cells

Pemphigus vegetans

? Rare vegetative variant of

pemphigus vulgaris.

? Flaccid blisters that become

erosions and then form


projections especially in

intertriginous areas and on

scalp or face.

? Two subtypes:

? Neumann type: severe

? Hal opeau type: mild

Figure: pemphigus vegetans. Extensive

vegetating papil omatous lesions

Pemphigus foliaceus

? Patients develop scaly, crusted cutaneous

erosions, often on an erythematous base.

? Lesions are wel demarcated and have a seborrhoeic

distribution, i.e. they favor the face, scalp and upper


? No clinical y apparent mucosal involvement.

? Patients are not severely il .

? Disease may remain localized for years or it may

rapidly progress, in some cases to erythrodermic

exfoliative dermatitis.

Early disease: Scaly crusted

Progressive disease: Lesions

erosions on the back

have become confluent


Pemphigus erythematosus (Senear

-Usher Syndrome)

? Localized variant of pemphigus foliaceus.

? Scaly and crusted lesions of pemphigus foliaceus appear in the

malar region of face and in other `seborrheic' areas.

? Immunologic features of both lupus erythematosus and


? In vivo IgG and C3 deposition on cell surface of keratinocytes as well as

basement membrane zone, in addition to circulating antinuclear


Paraneoplastic pemphigus

? Associated with underlying neoplasms, both malignant and


? Most commonly associated neoplasms are non-

Hodgkin lymphoma(40%), chronic lymphocytic

leukemia(30%), Castleman's disease , thymomas, sarcomas

? In children and adolescents, Castleman's disease is the most

commonly associated tumor.

? Most constant clinical feature is intractable stomatitis.

Cutaneous findings are pleomorphic and may present as

macules, flaccid/tense blisters, Erythema Multiforme like

lesions, lichenoid eruption.


Paraneoplastic pemphigus:

erythematosus: scaly

severe stomatitis extending

crusted erosions are

onto vermilion lip

seen on the nose and

malar area.
IgA Pemphigus = intercellular Ig A


? Intraepidermal antikeratinocyte IgA

? vesicopustular

1. Subcorneal pustular dermatosis (SCPD) type:

? Presents as flaccid vesicles or pustules on either

erythematous or normal skin.

? Pustules tend to coalesce to form an annular or

circinate pattern with crusts in the center of the


? Most commonly involved sites are axil a and groin.

? Mucus membrane involvement is rare.

? Pruritus is a significant symptom.

IgA Pemphigus

2. Intraepidermal neutrophilic (IEN) type:

? Presents as flaccid vesicles or pustules on either

erythematous or normal skin.

? Pustules tend to coalesce to form an annular or

circinate pattern with crusts in the center of the


? Sunflower -like configuration of pustules is a

characteristic sign of the IEN type.

? Most commonly involved sites are axilla and


Subcorneal pustular

Intraepithelial neutrophilic (IEN) type:

dermatosis(SCPD) type: pustules

characteristic sunflower-like

coalescing in annular or circinate

configuration of pustules is seen.

pattern with central crusting.


Induced Pemphigus

? Drugs: penicillamine


? Radiotherapy
? Thermal burns



? Bullous pemphigoid is an acquired non-scarring

autoimmune blistering disease of the elderly age

group characterized histological y by

subepidermal bullae and immunopathological y

by deposition of antibodies and complement

along the epidermal basement membrane zone


? The median age of onset ranges from 60 to 75


? tense blisters, hemorrhagic or fil ed with thick fibrinous

fluid, on normal appearing skin or on an erythematous


? The blisters range from vesicles to large bullae and may

be seen al over the body, the commonest sites of

involvement being the lower abdomen, inner thighs,

groin and the flexor aspects of the limbs.

? The flexural and intertriginous areas are often affected.
? Vesicles may also develop on the palms and soles.
? Nikolsky's sign is negative.

? For blisters that rupture, the resulting erosions and may

become covered with a crust.

? The erosions heals without scarring, but transient pigmentary

changes and milia formation can occur.

? Pruritus is generally present, but the degree is variable,

ranging from none to intense.

? Mucosal lesions have been reported in 10%? 40% of patients

? They are often mild and transient.



? Mucous membrane pemphigoid (MMP) is a group

of chronic inflammatory, autoimmune,

subepithelial blistering diseases predominantly

affecting mucous membranes and is

characterized by linear deposition of IgG, IgA, or

C3 along the epithelial basement membrane zone


? Scarring is the clinical hal mark, but is not always

obvious, particularly in the oral mucosa.
? Mucous membrane pemphigoid is a rare disease

that primarily affects the elderly (the peak

incidence is between the age of 60 and 80 years).

? It affects twice as many women as men.

? The onset is usual y insidious.

? The oral mucosa is most commonly involved

(approximately 85% of patients), fol owed by the

ocular, nasal, nasopharyngeal, anogenital, skin,

laryngeal, and esophageal mucosa in descending

order of involvement.

? In the oral cavity, the gingival and palatal mucosae and less

commonly the labial, glossal, and buccal mucosae are


? There may be swollen, bright, erythematous, focal or

generalized, mildly painful erosions on the gingiva (termed

`desquamative gingivitis')

? The presentation may also be as fluid- or sometimes blood-

filled blisters.

? The lips are rarely involved.

? The eyes are affected in about two-thirds of patients, most often by

a unilateral chronic cicatricial conjunctivitis with symptoms of

burning, irritation and excessive lacrimation.

? Genital involvement has been observed in about 20% of cases, as

blisters and erosions on the glans and prepuce or the labia.

? Skin lesions occur in 10%?30% of patients, and are of two types:

scarring and nonscarring.

? Flaccid blisters develop on erythematous plaques on the head, neck

and upper trunk, and heal with atrophic scars.

? This eruption tends to be localized and recurrent.


? Pemphigoid gestationis (PG), also known as herpes

gestationis, is a rare autoimmune pruritic

polymorphic dermatosis of pregnancy and


? pemphigoid gestationis is undoubtedly under

hormonal influence since it occurs only with

pregnancy, menstruation, oral contraceptive

ingestion, hydatidiform mole or choriocarcinoma.

? The PG antigen is the 180 kDa BP antigen (BP180 or

BPAG2),that is present in the hemidesmosomes of

the basement membrane.

? PG may occur in the first or any subsequent pregnancy.

? It usual y begins in the second or third trimester,

though it can begin at any time between the first

trimester and the immediate postpartum period.

? Intense pruritus usual y accompanies but occasional y

precedes a polymorphic eruption of erythematous

urticarial papules and plaques, vesicles or bul ae arising

on inflamed or normal skin.

? Classical y, there are erythematous urticarial plaques

rimmed by blisters, and crusts that enlarge peripheral y

to form annular or polycyclic patterns.

? The eruption usually begins on the abdomen,

especially around the umbilicus, or on the

extremities and then spreads to the rest of the trunk,

palms and soles.

? Facial and mucosal lesions are rare.


? Dermatitis herpetiformis is a rare chronic blistering

skin disease characterized clinically by intensely

pruritic grouped vesicles arising on an erythematous

base, by granular IgA deposits in the dermal papillae

on direct immunofluorescence, and associated with

gluten-sensitivity and a mostly asymptomatic


? It presents most often in the second or third

decades, but the disease can occasionally occur in

children also.

? A slight male predominance has been reported.
? Onset may be acute or gradual.

? The eruption is characteristical y polymorphous,

although at a given time any one type of lesion (e.g.

papular, urticarial, vesicular or bul ous) may


? The primary lesion is classical y, a smal vesicle on an

? erythematous, edematous base, or an erythematous

papule, or an urticarial plaque.

? The vesicles may be grouped in a herpetiform manner

on an erythematous plaque.

? Intense itching or a burning or stinging sensation is a


? If the rash is chronic, there are often lichenified

plaques at the sites of involvement.

? The areas of predilection are the elbows, knees,

buttocks, sacrum, shoulders, posterior hairline and


? The lesions are symmetrically distributed over the

extensor surfaces of the limbs.

? The face is occasionally affected, but the mucous

membranes, only rarely.


? Linear IgA disease can be clinical y categorized into two

disorders with two distinct presentations: CBDC, which

begins in childhood, and adult LAD, which begins in

adult life.

? In children, the disease usual y starts below the age of


? The onset is usual y abrupt, with large tense bul ae

fil ed with clear or hemorrhagic fluid on or near the


? They gradual y involve other areas such as the

buttocks, scalp and

? face, especial y the perioral and periocular areas.
? Blisters may also appear in a generalized but

asymmetric distribution.

? Typical features include herpetiform clustering of

blisters, formation of bizarre, irregularly shaped bul ae

as they enlarge and coalesce, and `rosettes' or `clusters

of jewels' which represent the annular arrangements

of new, smal , tense blisters around a crusted healing

erythematous plaque (the `string of pearls' sign) .

? Pruritus is variable in intensity.

? In adults, the onset may be insidious or abrupt, with

symptoms varying from mild pruritus to severe pruritus

and burning.

? There may be flexural and truncal involvement with

scattered vesicles and tense blisters similar to BP.

? The bullae may be somewhat linear, sausage- shaped

and hemorrhagic.

? A few patients of LAD may present with a DH like

itchy eruption with grouped papulovesicles involving

the extensor surfaces.

? Perineal and perioral involvement is less common

than in children.

? Approximately 80% of adults and children with LAD

have mucosal lesions

Treatment of Immunobul ous


? Management includes-
1. Investigations
2. Treatment


Full blood count and differential


Fasting blood sugar


Liver function tests


Renal function tests

? Chest x-ray
? Urinalysis

2-Specific ?for diagnosis
? Tzanck smear
? Histopathological examination
? I F
? Immunoblotting
? Immunoelectron microscopy

? The treatment of immunobul ous diseases consists of

three phases: control, consolidation, and maintenance.

? control phase- intense therapy is given to suppress

disease activity until no new lesions appear.

? consolidation phase during which drugs and doses are

maintained until complete clearance of lesions.

? Final y, medications can be gradual y tapered in the

maintenance phase, aiming for the lowest dose that

prevents new lesions from appearing .

? Aim of therapy is to prevent the appearance of new lesions &

produce healing of existing lesions.
? The choice of therapy
? Severity of the disease at presentation.

? Patient-related

? age

? general health

? associated medical illnesses

? Drug-related

? onset of action

? efficacy

? adverse effects

? cost


General measures

? It includes-

1. General nursing care-

? Proper and regular dressing of the raw area is done

until re-epithelization takes place.

? This is performed with sterile petroleum gauze or

gauge impregnated with topical antibiotics.

2.Adequate Nutrition ?

? Oral supplementation with protein and high calorie


? Soft easily chewable diet in case of oral lesions
3. control of secondary infection-antibiotics should be

given preferably following culture and sensitivity


4. restoring fluid and electrolyte equilibrium

Topical therapy

? Is indicated in more local oral lesion with less

aggressive behaviour.

? Skin lesions-
1. clobetasol propionate .05% may reduces the

requirement of oral steroid.

2. Potassium permanganate and antiseptics to reduce

the risk of secondary infection.
q Oral lesions-

? soft diets, soft toothbrushes help to minimize local trauma.

? Topical analgesics or anaesthetics - benzydamine

hydrochloride 0.15% (Oral Rinse) are useful in alleviating

oral pain, particularly prior to eating or tooth brushing.

? Tooth brushing should be encouraged and antiseptic

mouthwashes may be used such as

- chlorhexidine gluconate 0.2%

- hexetidine 0.1%

-01:4 hydrogen peroxide solutions.

? Patients are susceptible to oral candidiasis which

should be treated.

? Topical Corticostreoid therapy may help to reduce

the requirement for systemic agents.

? It include application of clobetasol gel .05%
? Clobetasol gel may be used with occlusive vehicle

mainly in desquamative gingivitis
? Soluble betamethasone sodium phosphate 0.5 mg

tablet dissolved in 10 mL water may be used up to four

times daily, holding the solution in the mouth for about

5 minutes.

? Isolated oral erosions could be treated with application

of triamcinolone acetonide 0.1% in adhesive paste

? 2.5 mg hydrocortisone lozenges or sprayed directly

with an asthma aerosol inhaler, for example

beclomethasone dipropionate 50-200 micrograms or

budesonide 50-200 micrograms.

? Topical ciclosporin (100 mg/mL) in oral pemphigus

has been described and may be of some benefit but

is expensive

? Tetracyclines are successful in pemphigus vulgaris

and cicatricial pemphigoid

? Tacrolimus is indicated in oral resistant cicatricial


? Corticosteroids:

? Oral

? Pulse IV

? Adjuvant drugs

? Azathioprine

? Oral cyclophosphamide

? Pulsed cyclophosphamide and dexamethasone


? Gold

? Methotrexate

? Ciclosporin

? Tetracyclin and nicotinamide

? Dapsone

? Chlorambucil

Newer treatment modalities
? Cholinomimetic drugs
? Plasma exchange
? Extracorporeal photophoresis
? Biologicals
? Immunoadsorption

This post was last modified on 07 April 2022