Blistering disease Flashcards
What are the classifications of vesiculobullous disorders
1) - Congenital or acquired
2) Based on where the skin separates: subcorneal, intra-epidermal and subepidermal
What type of vesiculobullous disorder does not have oral mucous membrane involvement?
- Subcorneal as it separates below the stratum corneum
Where does intra-epidermal blistering originate?
Within the keratinocyte layer
Where does sub-epidermal blistering originate?
Between the dermis and epidermis
Describe the pathology of intraepidermal blistering
There is loss of cell to cell adhesion within the epithelium and the target antigens are within the desmosomes
Describe the pathology of subepithelial blistering
There is loss of adhesion between the epithelial layer and connective tissue layer, and the target antigens are in the hemidesmosome
What disease is associated with intraepidermal blistering
Pemphigus
What diseases are associated with subepithelial blistering
All variations of pemphigoid
Linerar IgA dermatosis
Epidermolysis bullosa acquisita
Dermatitis herpetiformis
How does the type of structural protein affected affect the severity and scarring potential?
The deeper the protein is, the more severe the phenoype and the greater the risk of scarring - e.g. sublamina densa type VII collagen
What is the most common target antigen in cutaneous blistering disorders?
Bp180
What is epidermolysis bullosa?
A group of rare inherited skin disorders due to mutations in genes encoding structural components of skin, resulting in skin or mucosal fragility
What does the severity of epidermolysis bullosa depend on?
- Recessive trait more severe than dominant
- The type of structural protein affected
- The specific mutation
- Penetrance
What are the three types of epidermolysis bullosa
EB simplex
EB junctional
EB dystrophic
Describe features of recessive dystophic epidermolysis bullosa
Stocking scarring (feet), curled fingers, oral and GIT scarring, short stature, life expectancy around 30 and tend to die due to squamous cell carcinoma
Describe EB simplex
Most common, usually autosomal dominant and causes localised blisters or grouped vesicles with limited mucosal involvement
Describe EB junctional
Most severe type, autosomal recessive type, chracterised by widespread blistering, scarring, granulation tissue, severe mucosal involvement, dental pitting, alopecia and nail dystophy
Describe EB dystrophic
Can be autosomal dominant or recessive, characterised by haemorrhagic blisters, scarring, severe mucosal involvement, physical and sexual retardation, and high mortality rates
What are the primary acquired blistering diseases
- Pemphigus
- Pemphigoid
- Linear IgA disease
- Epidermolysis bullosa acquisita
- Dermatitis herpetiformis
What are secondary acquired blistering diseases?
Trauma e.g. blisters from tight shoes Infections e.g. herpes Acute eczema Drug reactions Metabolic diseases - diabetes
History taking for blistering disease
- Age of onset
- Duration of lesions
- Any other lesions on the body
- Precipitating events e.g. drug history
- MH - systemic illness or coealic
- Family history of autoimmune disease
How to examine a blister
- Site (localised or generalised)
- Morphology and evidence of scarring/erosion
- Colour of background skin (normal or erythema)
- Nikolsky sign
IX for blisters
- Nikolsky sign
- FBC
- Antibody screen
- Biopsy
- Direct immunoflouresence
Management of blistering diseases
- Assess need fo admission to hospital - fluid balance, thermoregulation etx
- Topical tx for infection if present
- Systemic therapy
- Referral to opthal or ENT
What systemic therapy is used in blistering diseases
Prednisolone +/- steroid sparing agents
Antibiotics if required
List the types of intra-epithelial blisters
Pemphigus vulgaris/vegetans
Pemphigus foliaceous
Paraneoplastic pemphigus
What is pemphigus vulgaris?
An uncommon autoimmune disease characterised by vesicles or bullae on the skin and mucous membranes
Epidemiology of pemphigus vulgaris
Female
40-60
All races (except asian and jewish)
Describe the clinical appearance of pemphigus vulgaris
- Painful lesions on the mucous membranes and/or skin (2/3 have oral lesions)
- Fragile bullae and erosions on normal skin
- Positive nikolsky sign
What is a positive nikolsky sign?
- Gentle lateral pressure to the mucosa results in the formation of a vesicle of bulla
Results of direct immunoF for pemphigus vulgaris
Intercellular IgG and C3
Histological features of pemphigus vulgaris
Acantholysis due to antibody-antigen binding (separates and degrades desmosomal attachment and epithelium falls apart)
- Clefts form superficial to basal cells and may extend to form intraepithelial vesicles
What are the target antigens for pemphigus vulgaris
DSG 3 (130kd) and/or DSG1 (160kd)
What type of demoglein is dominant in the mucous membranes?
DSG3 (in comparison to dsg1 which is more dominant in the skin)
Describe the oral lesions in pemphigus vulgaris
- Site: BM, tongue and palate
- Initial erosions are superficial ulcers that are fragile (rare to see intact intraorally) but residual erosions have ragged edges and are painful/tender
- Serum exudate
- Desquamative gingivitis
- Scattered vegetations or haemorrhagic lesions on the lips
Why are intraoral bulla rare?
The keratin layer is not thick enough to form a strong roof for a blister
Describe skin lesions in pemphigus vulgaris
- Vesicles or bulla (mm or cms)
- Contain clear liquid initially, may become purulent or heamorrhagic
- Rupture results in painful erosions (can become secondarily infection)
Presentation of paraneoplastic pemphigus
Periocular and perioral erosions with haemorrhagic lesions around lips and eyes +/- flexural skin involvement
What does paraneoplastic pemphigus indicate
Underlying malignancy - commonly NHL or CLL
Describe the pathology of paraneoplastic pemphigus
Autoantibodies cross-react with the tumour and epidermal antigens, resulting in a t cell response
Describe the appearance of pemphigus foliaceous
Superficial red skin lesions, which may erode (BUT DO NOT BLISTER) on the face, neck, scalp and upper trunk
- NO INTRAORAL LESIONS !!!!!
What are the subepidermal blisters
- Bullous pemphigoid
- Mucous membrane pemphigoid
- Linear IgA disease
- Epidermolysis bullosa acquisita
Epidemiology of bullous pemphigoid
The most common immunobullous disease
Commonly affecting the elderly
Describe the presentation of bullous pemphigoid
Pruitic (but not painful), tense blisters with erythematous background
Located on the lower limbs (localised), or generalised
Oral involvement is rare (<30% and often transient)
What are the target proteins of bullous pemphigoid
BP180
BP230
NC16A
Tx of bullous pemphigoid
Topical corticosteroids Tetracycline Dapsone Prednisolone Azathioprine
Epidemiology of mucous membrane pemphigoid
Most common ORAL immunobullous disease (however it is still uncommon
Female predilection
Mean age of 60
Pathology of mucous membrane pemphigoid
Loss of attachment and separation of full thickness epithelium from connective tissue at the level of the basement membrane
Presentation of mucous membrane pemphigoid
- Site: mouth, eyes, nasopharynx, oesophagus, skin, genitals
- Oral lesions - attached gingiva or palate (keratinised mucosa) or on the tongue or BM - bulla often intact
- Bleeding of oral lesions gives the appearance of blood blisters
- Rupture results in raw ulcers with well defined marings and small tags of torn epithelium
- Desquamative gingivitis
- Skin involvement is minimal or absent
Target proteins in MMP
BP180
BP230
Alpha-6-b4
Laminin 5
Tx of MMP
- CHX, hydrogen peroxide of difflam mouthwash
- Topical corticosteroid (betamethasone)
- Systemic corticosteroids - dapsone, prednisolone, azathioprine
What is linear IgA disease
Rare, autoimmune blistering disease predominantly affecting the skin, but has some mucosal involvement
Describe oral lesions in linear IgA disease
Blisters, erosions and ulcers typically on the tongue
Direct IF for linear IgA disease
IgA visible along the membrane
Describe the features of epidermolysis bullosa acquisita
- Lesions affecting cutaneous areas prone to friction - elbows, knees and toes
- Scarring causes ankyloglossia, micostomia and oseophageal strictures
Epidemiology of dermatitis herpetiformis
- Dermatological complication of coealic
- 20-40 yo
Presentation of dermatitis herpetiformis
Intensely itchy rash found on extensor surfaces (elbows and buttocks)
RARELY affects oral mucosa
Pathology of dermatitis herpetiformis
Autoantibodies directed against skin and mucosal transglutaminase enzymes on the keratinocyte surface
Ix of dermatitis herpetiformis
Folate
Jejunal biopsy
Transglutaminase and anti-endomysial antibodies
Tx of dermatitis herpetiformis
Dapsone
Gluten free diet
Differential diagnosis of blistering diseases
- Erythema multiforme
- SJS/TENS
- Bullous lichen planus
- Angina bullosa
What is erythema multiforme?
Hypersensitivity reaction usually triggered by infections (HSV, mycoplasma, syphillis) or drugs (penicillin or phenytoin) resulting in self-limiting, episodic lesions on the skin and mucous membranes
Describe the presentation of erythema multiforme
- Target like lesions (centre is dusky or purpura with outer erythemaous ring - these may ulcerate) on the skin
- Ulcers on the lips and tongue
- Mild fever
Tx of erythema multiforme
Corticosteroids (symptomatic relief)
Tx of underlying infection if present
