Monika Saha

Refractory epidermolysis bullosa acquisita: successful treatment with rituximab

A 54-year-old woman presented with oral erosions, skin fragility and recurrent blistering of the scalp, hands, feet, knees and elbows. On physical examination, multiple erosions and bullae were seen in a mechanobullous distribution, with milia formation, scarring alopecia and severe oral ulceration. Histological examination of a skin biopsy found a subepidermal blister containing neutrophils and few eosinophils. Indirect immunofluorescence revealed circulating IgG autoantibodies at a titre of 1 : 1600 mapping to the basement membrane zone (BMZ) on salt-split skin. Immunoblotting showed a band at 290 kDa, consistent with antibodies binding to type VII collagen. The clinical and immunopathological features were consistent with epidermolysis bullosa acquisita (EBA). The patient was treated with a succession of systemic agents over a period of 15 years including high-dose prednisolone (up to 40 mg), dapsone 100 mg, azathioprine 100 mg, ciclosporin A 2.5 mg ⁄ kg, oral cyclophosphamide 50 mg, seven intravenous pulses of cyclophosphamide and methylprednisolone, intravenous immunoglobulin (14 cycles of 2 g ⁄ kg ⁄ month) and mycophenolate mofetil 3 g daily; all had a minimal or a temporary therapeutic effect. Sixteen years after onset of disease, the patient was treated with rituximab (Mabthera; Roche, Basel, Switzerland) at a dose of 375 mg ⁄ m body surface area weekly for 4 weeks, which led to clear improvement of the cutaneous signs, but with little effect on the oral symptoms. A further two courses of rituximab were given 5 and 12 months later, leading to almost complete cutaneous clearance with improved oral intake and mobility. Throughout the treatment, the patient remained on mycophenolate mofetil 3 g ⁄ day but was able to stop the daily prednisolone. After the third course of rituximab, the IgG anti-BMZ antibodies had decreased impressively from a titre of 1 : 1600 to 1 : 100, paralleling the clinical improvement (Fig. 1). During treatment, the patient developed two episodes of skin sepsis; cellulitis in the leg and a methicillin-resistant Staphylococcal aureus leg ulcer, both of which responded to oral antibiotics. EBA is a rare chronic subepidermal blistering skin disease that is notoriously difficult to treat. It is characterized by IgG autoantibodies directed against type VII collagen, which is an integral structural constituent of the anchoring fibrils in the sublamina densa. Rituximab is a chimeric anti-CD20 monoclonal antibody that targets B cells, which express the B-cell differentiation antigen CD20, leading to B-cell depletion. Monitoring of peripheral B-cell levels in patients may be of value as a guide to treatment response. Rituximab was originally used in the treatment of B-cell tumours but has also been used successfully in several autoimmune diseases. There is a small but growing body of evidence for the use of rituximab in EBA. The commonest adverse effects of rituximab are mild to moderate infusion-related reactions; however, there is a considerable risk of sepsis, and fatal cases of pneumonia caused by Pneumocystis carinii and Pseudomonas species have been reported. Antimicrobial antibodies were not measured in our patient; however, rituximab has not been shown to reduce these antibodies significantly in patients with immunobullous disease. This case supports the concept that rituximab may be an effective treatment in EBA, although it may be slow to take effect and can be associated with an increased risk of infection.

Pulsed intravenous cyclophosphamide and methylprednisolone therapy in refractory pemphigus

Background  Pemphigus is a rare autoimmune blistering disorder. The mainstay of current treatment is high‐dose oral corticosteroid therapy in combination with a steroid‐sparing agent. Adjuvant therapy is important for disease control and to reduce the iatrogenic effects of oral prednisolone. Pulsed therapy with intravenous methylprednisolone and cyclophosphamide (PPC) has been shown to be an effective treatment but there are currently few data on its use in patients who have failed to respond to conventional immunosuppression.

Risk of herpes zoster infection in patients with pemphigus on mycophenolate mofetil

ficient for the delivery of dermatologic services. J Am Acad Dermatol 1999; 40:426–32. 3 Griffiths CEM, Taylor H, Collins SI et al. The impact of psoriasis guidelines on appropriateness of referral from primary to secondary care: a randomized controlled trial. Br J Dermatol 2006; 155:393– 400. 4 Herlufsen P, Olsen AG, Carlsen B et al. Study of peristomal skin disorders in patients with permanent stomas. Br J Nurs 2006; 15:854– 62. 5 Nybæk H, Olsen AG, Karlsmark T, Jemec GBE. Topical treatment of parastomal pyoderma gangrenosum. J Cutan Med Surg 2004; 8:220–3. 6 Hughes AP, Jackson JM, Callen JP. Clinical features and treatment of peristomal pyoderma gangrenosum. JAMA 2000; 284:1546–8.

Is the incidence of pemphigoid really increasing

We found the data reported by Langan et al on the apparent increasing incidence of pemphigoid striking.1 It might reasonably be expected that a fivefold increase in incidence of pemphigoid would be apparent to physicians caring for patients with the disorder. Blistering disorders are perhaps unusual among skin conditions in that they are nearly always reported to dermatologists, and specialised testing is required …

Sporadic pemphigus foliaceus and class II human leucocyte antigen allele associations in the white British and Indo-Asian populations in the UK

Pemphigus foliaceus (PF) has both genetic and environmental susceptibility factors. Current data on human leucocyte antigen (HLA) in patients with sporadic PF are limited.