Pemphigus and pemphigoid Flashcards
Give two examples of vesiculobullous reactions in dermatology.
Autoimmune attack against the epidermis causing vesiculobullous disorders e.g.
- Pemphigoid
- Pemphigus
Which skin layers are affected in bullous pemphigoid vs pemphigus vulgaris?
Bullous pemphogoid = dermo-epidermal junctions
Pemphigus vulgaris = epiderma-epidermal junctions
Define bullous pemphigoid.
A chronic, acquired autoimmune blistering disease characterised by auto-antibodies against hemidesmosomal antigens, resulting in the formation of a sub-epidermal blister.
Describe the pathophysiology of bullous pemphigoid.
- Epidermal basement membrane is destroyed by autoantibodies - IgG and C3
- Eosinophils recruited to release elastase which damages anchoring proteins
- Direct immunofluorescence will show linear IgG (anti-hemi-hemidesmosomes)
- Fluid fills the gap between the BM and epithelium
How do the blisters appear in pemphigoid vs pemphigus? Where do lesions form?
Pemphigoid - tense, on flexor surfaces
Pemphigus - flaccid
Who is most affected by bullous pemphigoid?
- Elderly - age 60-90yrs
- MHC class II allele DQB10301
- Male > female
What are the clinical features of bullous pemphigoid?
Tense blisters on flexor surfaces
Pruritus - may precede tense blisters by 3-4 months
Other:
- Oral lesions - present in up to 30%
- Erythematous or urticarial plaques
How do you diagnose bullous pemphigoid?
Skin biopsy - for immunofluorescence, light microscopy. Immunofluorescence shows IgG and C3 at the dermoepidermal junction
Serum - for antibodies to bullous pemphigoid
What are some differentials for bullous pemphigoid?
Pemphigus vulgaris
Epidermolysis bullosa acquisita
Linear IgA bullous dermatosis
Dermatitis herpetiformis
Porphyria cutanea tarda
Erythema multiforme
Urticaria
What is the antibody target in bullous pemphigoid?
Hemidesmosomal proteins BP180 and BP230
What is shown?
Linear IgA bullous dermatosis
What is the management of bullous pemphigoid?
Localised lesions:
Topical corticosteroids e.g. clobetasol 0.05%
Topical tacrolimus
+/- sedating antihistamine e.g. diphenhydramine/hydroxizine
Widespread lesions:
Oral prednisolone - for shortest duration possible
+/- antibiotic e.g. tetracycline
+/- ciclosporin - steroid-sparing agent
No response:
Plasmapharesis or IVIG +/- rituximab
What are the complications and prognosis of bullous pemphigoid?
- Secondary infection
- x2-6 greater mortality compared to normal population
Prognosis - most go into remission with appropriate treatment but morality is high in older people
Define pemphigus.
A group of autoimmune blistering diseases that involve the epidermal surfaces of the skin, mucosa, or both.
What are the antibodies directed against in pemphigus?
- desmoglein 3 (Dsg3)
- desmoglein 1 (Dsg1)
What are the different types of pemphigus?
There are three broad categories:
- pemphigus vulgaris (PV) = deep form
- pemphigus foliaceus (PF) = superficial form
- paraneoplastic pemphigus (PNP)
What is the pathophysiology of pemphigus vulgaris
IgG attacjs between the keratin layers (epiderma-epidermal junctions) and cell connections between keratinocytes fall apart by acantholysis
Top epidermis sloughs off
Immunofluorescence shows intercellular deposists of IgG in a chicken wire pattern (IgG is surrounding individual keratinocytes)
What are the clinical features of pemphigus vulgaris?
- Flaccid blisters which rupture easily (Nikolsky sign positive)
- Predominantly on seborrhoeic areas e.g. chest, face, scalp, interscapular region, and extremities
- Affects mucous membranes - usually first; can affect oral, ocular, nasal, laryngeal, oesophageal and genital areas too.
- Antibodies to desmoglein 3 > 1
- Pain on eating
What are the clinical features of pemphigus foliaceus?
- Transient, flaccit blisters or crusty erosions in seborrhoeic skin areas
- NO mucosal involvement
- Antibodies to desmoglein 1 > 3
More extensive skin involvement in sporadit and endemic forms
Which malignancies is paraneoplastic pemphigus associated with?
- NHL
- CLL
- Thymoma
- Castleman’s disease
Often causes intractable mucositis with very painful lips
What are the risk factors for pemphigus?
- Age > 40yrs
- HLA DR4, DQ1
- Associated malignancy (PNP)
How do you diagnose pemphigus?
Skin biopsy - H&E staining and immunofluorescence
Serology - autoantibodies against epithelial cell surface by IIF and/or ELISA for Dsg1 and Dsg3.
What are the differentials for pemphigus vulgaris?
- Hailey-Hailey disease
- Bullous pemphigoid, linear IgA bullous dermatitis, epidermolysis bullosa
- Erythema multiforme
- Pityriasis rosea
- Apthous stomatitis
- Behcet’s
- Oral lichen planus
- SJS/TEN
What is the management of pemphigus?
Pemphigus vulgaris:
Supportive treatment - dental care, intralesionsal steroid injections, antiseptic baths, low adhesion dressings, emolliens, compresses, analgesia
Prednisolone PO +/- azathioprine OR MMF - taper steroids according to response
Rituximab +/- prednisolone PO - rituximab given IV on day 1 and 15 as single doses
Bone protection
If moderate: Rituximab infusions
If severe: IVIG or IV corticosteroid/immunosuppressioon
Pemphigus foliaceus:
Topical steroid e.g. betamethasone diproprionate 0.05%
+/- Dapsone 50mg OD - then adjusted to response
What are the complications and prognosis of pemphigus?
- Volume depletion
- Infection
- Pain
- Skin dyspigmentation - from post-inflammation
- Malignancy - from long term immunosuppression e.g. cutaneous, actinic keratosis
Prognosis - PV and PF is good if the disease is well controlled. Sometimes spontaneous remission occurs but often long-term immunosuppression is required. Rituximab works in 90%.
Compare and contrast bullous pemphigoid and pemphigus.
