Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Dermatology PPT 13 Imunobullous Disorder Lecture Notes
Immunobul ous
disorders
? 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
dis
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
Rubra
C. Suprabasal- Pemphigus vulgaris,
Paraneoplastic pemphigus, Darriers
Disease
? Subepidermal:
Bullous Pemphigoid
DH
Linear Ig A disease
Porphyria cutanea tarda
Classification
Immunobullous disorders
Introduction
? 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
mesenchyme.
? These diseases are often associated with significant
morbidity and some can even cause mortality, if left
untreated.
? 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
disorders
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
PEMPHIGUS VULGARIS
? Nikolsky sign : positive
? Tzanck smear: Acantholytic cells
Pemphigus vegetans
? Rare vegetative variant of
pemphigus vulgaris.
? Flaccid blisters that become
erosions and then form
papillomatous
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
trunk
? 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 FOLIACEUS
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
pemphigus.
? In vivo IgG and C3 deposition on cell surface of keratinocytes as well as
basement membrane zone, in addition to circulating antinuclear
antibodies(ANA).
Paraneoplastic pemphigus
? Associated with underlying neoplasms, both malignant and
benign.
? 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.
Pemphigus
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
dermatosis
? 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
lesion.
? 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
lesion
? Sunflower -like configuration of pustules is a
characteristic sign of the IEN type.
? Most commonly involved sites are axilla and
groin
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.
IgA PEMPHIGUS
Induced Pemphigus
? Drugs: penicillamine
captopril
? Radiotherapy
? Thermal burns
SUBEPIDERMAL IMMUNOBULLOUS
DISEASES
BULLOUS PEMPHIGOID
? 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
(BMZ).
? The median age of onset ranges from 60 to 75
years.
? tense blisters, hemorrhagic or fil ed with thick fibrinous
fluid, on normal appearing skin or on an erythematous
base.
? 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
(SYN. CICATRICIAL PEMPHIGOID)
? 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
(BMZ).
? 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
affected.
? 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
? Pemphigoid gestationis (PG), also known as herpes
gestationis, is a rare autoimmune pruritic
polymorphic dermatosis of pregnancy and
puerperium.
? 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
? 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
enteropathy.
? 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
predominate.
? 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
common
? 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
scalp.
? 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
? 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
5.
? The onset is usual y abrupt, with large tense bul ae
fil ed with clear or hemorrhagic fluid on or near the
genitalia.
? 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
disorders
? Management includes-
1. Investigations
2. Treatment
INVESTIGATIONS
1-Routine
?
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
? DIF
? I F
? Immunoblotting
? Immunoelectron microscopy
? ELISA
TREATMENT
? 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
TREATMENT PHASES
? GENERAL THERAPY
? PHARMACOLOGICAL THERAPY-
A. TOPICAL
B. SYSTEMIC
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
fluids.
? Soft easily chewable diet in case of oral lesions
3. control of secondary infection-antibiotics should be
given preferably following culture and sensitivity
report.
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
pemphigoid
SYSTEMIC THERAPY
? Corticosteroids:
? Oral
? Pulse IV
? Adjuvant drugs
? Azathioprine
? Oral cyclophosphamide
? Pulsed cyclophosphamide and dexamethasone
? MMF
? Gold
? Methotrexate
? Ciclosporin
? Tetracyclin and nicotinamide
? Dapsone
? Chlorambucil
Newer treatment modalities
? IVIG
? Cholinomimetic drugs
? Plasma exchange
? Extracorporeal photophoresis
? Biologicals
? Immunoadsorption
THANKS
This post was last modified on 07 April 2022