Pemphigus

Pemphigus is a blistering disorder characterised by blistering within the epidermal layer.

Background

• Pemphigus can actually describe a group of blistering disorders
  • Pemphigus vulgaris is by far the most common (70%) and occurs in between 0.75-5/100000.  It is most commonly seen between the ages of 30 and 70 years old.
  • Other types include pemphigus foliaceus (which incorporates other types also e.g. pemphigus erythematosus and pemphigus herpetiformis; only affects the skin; no oral symptoms and is due to a mutation in the desmoglein 1 gene) and paraneoplastic pemphigus (due to an underlying tumour (usually B-cell lymphoproliferative disease)- which may or may not be diagnosed)

Pathophysiology

• Autoimmune condition mediated by circulating (IgG) antibodies directed against keratinocyte cell surface molecules, notably desmoglein 1 (Mucocutaneous form) and desmoglein 3 (mucosal form)
• This causes breakdown of skin adhesion within the epidermis, leading to the blistering
• There is some association with genetic factors, particularly MHC class 2: DR4 (HLA DRB1 0402)

Presentation

• Most patients first present with mucous membrane lesions e.g. mouth ulcers.  Skin lesions may develop weeks to months later.
  • Blisters are flaccid (not tense): most burst to form erosions early on
  • Most common area is the mouth, but other areas affected can be conjunctiva, oesophagus, genitals, anus.
  • Appear on normal or slightly erythematous skin
  • They are usually painful and may cause difficulty eating/swallowing and occasionally speaking (hoarseness)
  • Patients’ skin can be sore but is rarely rarely itchy

Investigations

• Diagnostic test (ideally from blister edge)
  • Skin biopsy with immunofluorescence
    • typical features include ’rounded up separated keratinocytes (acantholytic cells) within the blisters, just above the basal layer of the epidermis.
    • suprabasal clefting (gaps within the epidermis- above the basal layer) may also be seen
  • ELISA tests for DSG1 and DSG3 antibodies in the serum can also be used.

Management

• Most patients will receive high dose steroids to induce remission (e.g. 80+ mg of prednisolone/day)
  • This should be continued until >80% of the lesions have cleared (ideally all have cleared)
  • Then, a gradual reducing dose of steroid can be used to achieve the lowest maintenance dose required
• In severe cases, plasmapheresis can also be used to induce remission; steroid sparing agents e.g. azathioprine, cyclophosphamide etc can be used to lower maintenance doses; and, if the patient remains resistant to treatment, biological agents (rituximab) can be used