Bullous diseases

Bullous diseases

1. Pemphigus

   • Paraneoplastic pemphigus
     • Variants
       • Lichenoid like
       • Pemphigus-like
       • Pemphigoid-like
       • Erythema-multiforme-like
     • = muco-cutaneous autoimmune disorder assoc. with neoplasia
       • Most common = lymphocytic malignancies
         • Non hodgkins lymphoma
         • Lymphocytic leukemia
         • Castleman's disease
     • Severe muco-cutaneous lesions with >1 disease pattern
       • Bilateral, widespread
       • unresponsive to treatment
     • Can cause RS failure
   • Pemphigus folaceus
     • No mucosal involvement
   • Pemphigus vulgaris
     • Treatment
       • Mild
         • Systemic steroids
           • No response -> + Mycophenolate mofetil
       • Moderate
         • Systemic steroids + Mycophenolate mofetil
           • No response -> Cyclophosphamide
       • Severe
         • Systemic steroids + Cyclophosphamide
           • Poor response/severe side effects
             • Rituximab
             • Photophoresis
             • IV antigens
     • Who gets it?
       • Men = women
       • 20-50yrs
       • Jewish
       • Mediterranean
     • Death rate
       • If treated with steroids
         • 10% die
       • If untreated
         • 75% die
     • Clinical features
       • Nikosky's sign positive
       • 1) Oral
         • Buccal mucosa, Palate, LIps
         • Blisters --> red erosions/ulcers
       • Extra-oral
         • 2) Skin
           • Flaccid blisters
           • Painful erosions
         • Ulceration
           • Conjunctiva
           • Nose
           • Pharynx & larynx
           • Genitals
     • Diagnosis
       • Biopsy uninvolved site
         • Because high level of circulating Abs
         • Histology
           • Intra-epithelial blister
           • Auto-Abs against keratinocytes
             • Target antigen
               • DSG 1, DSG 3 (desmoglein)
             • Causes acantholysis
         • Direct immunofluorescence
           • Intercellular IgG or C3 in a net like pattern

2. Pemphigoid

   • Mucous Membrane Pemphigoid
     • Diagnosis
       • Biopsy adjacent to lesion
         • Direct immunofluorescence
           • IgG, IgA & C3 at basement membrane
         • Histology
           • Subepithelial blister
             • Separation of basement membrane
           • Auto-abs against hemidesmosomes in BMZ
     • Clinical features
       • 1) Oral
         • 90% have oral involvement
         • Buccal mucosa, Palate, Gingiva, Tongue
           • NOT lips
         • Blisters -> erosions, red patches
         • Desquamative gingivitis
         • Nikolsky sign positive
       • 2) Eye
         • Sight-threatening
         • Conjunctivitis, symblepharon
       • 3) Genitals, nose, pharynx, larynx
     • Elderly (50-60s) women
     • Treatment
       • 1st line
         • Topical steroids
           • Clobetasol propionate in orobase
           • For gingiva -> give splint to put steroid in
           • + Anti-fungal
       • 2nd line
         • 1.Dapsone
           • Side effect = anaemia
         • 2. Mycophenolate Mofetil
           • Side effect = low WBC -> increased infection risk
       • 3rd line
         • Systemic steroids +/- Azathioprine
           • + alendronic acid & calcium tablets to reduce osteoporosis risk
           • Limit steroids to 5yrs
           • Azathioprine side effects = vomiting, no alcohol
     • More common
   • Angina bullosa haemorrhagica
   • Bullous pemphigoid
     • Rarely oral involvement

3. Diagnosing bullous disorders

   • Check these things in a patient with blistering
     • Nikolskys sign
     • Ocular lesion
     • Skin lesion
     • Ask if lesions anywhere else e.g. genital
   • Tests available
     • Histology
     • 1. Direct immunofluorescence
     • 2. Indirect immunofluorescence
       • Salt split skin
         • Better than normal IFF because more sensitive to Auto-Abs
     • 3. ELISA

4. Dermatitis Herpetiformis

   • Diagnosis
     • Direct immunofluorescence
       • IgA deposits
   • Men=women
   • Sub-epithelial blister