K. E. Harman

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus

Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies.

A successful therapeutic trial of rituximab in the treatment of a patient with recalcitrant, high-titre epidermolysis bullosa acquisita

hands of manual workers. Discrimination between occupational dermatitis and MH is difficult; however, lesions appear well demarcated with interface dermatitis in the latter. Therefore, the diagnosis of MH should be considered in patients especially when they present with general signs, interstitial lung disease and/or inflammatory muscle disease and/or polyarthritis requiring a search for anti-Jo-1 antibodies. A close association has been shown between MH and anti-Jo-1 antibodies, but MH has also been reported in polymyositis, dermatomyositis, childhood sclerodermatomyositis and mixed connective disease. In two of seven patients, MH occurred in the course of known idiopathic inflammatory myopathy in whom the skin was not involved initially. In these cases, systemic involvement developed concomitantly or soon after. A skin flare was therefore always associated with deep tissue flare; such an event in patients with antisynthetase syndrome implies deep organ assessment. The patients with MH became clear of their lesions together with clearance of the deep tissue disease. When MH was associated with idiopathic inflammatory myopathy in our series, it never appeared as an isolated skin sign. This suggests that when MH is present in a patient free of systemic signs, the diagnosis cannot be antisynthetase syndrome; the hand lesions belong rather to a classical occupational dermatitis and a search for anti-Jo-1 antibodies need not be done in this situation. Prognosis of the antisynthetase syndrome is poor as its mortality rate is 40%, with 62% in patients with interstitial lung disease, but could be improved by an early diagnosis. Therefore, in view of the frequent occurrence of this sign in antisynthetase syndrome, and the importance of early management, careful examination of the hands is mandatory in patients with systemic signs such as interstitial lung disease, myositis and arthritis.

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial

Summary Background Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3–9, 10–30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1–3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3–5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. Findings Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1–26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9–30·1), p=0·001. Interpretation Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. Funding NIHR Health Technology Assessment Programme.

Acute generalized exanthematous pustulosis associated with azathioprine hypersensitivity.

Acute generalized exanthematous pustulosis (AGEP) is identified by several characteristic features. We present a patient showing AGEP associated with azathioprine hypersensitivity. To our knowledge, this is the first reported case of this association.

Pyoderma gangrenosum complicating pegylated granulocyte colony‐stimulating factor in Hodgkin lymphoma

Pegylated granulocyte colony-stimulating factor (GCSF) (Pegfilgrastim/Neulasta, Amgen, Thousand Oaks, CA, USA) is a covalent conjugate of recombinant human GCSF and monomethoxypolyethyene glycol. Its advantage over regular GCSF is its reduced renal clearance and consequent prolonged persistence in vivo, allowing it to be administered in a single subcutaneous injection, once per cycle of chemotherapy. Pegylated GCSF does not routinely result in marked neutrophilia because serum clearance is directly related to the number of neutrophils. It is being used increasingly in oncology as a simple and cost-effective means of maintaining adequate neutrophil levels during intensive combination chemotherapy. We report here the occurrence of pyoderma gangrenosum following pegylated GCSF in a patient being treated for advanced Hodgkin lymphoma, who had previously received regular GCSF without incident. A previously fit 21-year-old female presented with clinical stage IIIB nodular sclerosing Hodgkin lymphoma. She was treated with combination chemotherapy according to the Adriamycin, Bleomycin, Vinblastine and Doxorubicin (ABVD) protocol. She was admitted to hospital following cycles 1A and 1B of chemotherapy with constipation and a urinary tract

Confluent and reticulated papillomatosis successfully treated with amoxicillin

SIR, Further to the recently published experience of the Mayo Clinic in the treatment of confluent and reticulated papillomatosis (CRP), we report a case of CRP treated successfully with amoxicillin. Confluent and reticulated papillomatosis is an unusual skin disorder originally described by Gougerot and Carteaud. It consists of a scaly, macular and papular eruption typically affecting the seborrhoeic areas of young adults. As the name suggests, lesions become confluent in the centre, coalescing to form a reticulated pattern at the periphery of affected areas. We describe a 29-year-old female who initially presented in 2004 with a 4-year history of an asymptomatic eruption affecting the axillae, mons pubis, submammary (Fig. 1) and inguinal folds. She had been treated unsuccessfully with topical steroids and antifungal agents. Differential diagnoses included a fungal eruption, pityriasis versicolor, Darier’s disease and Dowling–Degos disease (reticulate pigmented

Erythema annulare centrifugum associated with chronic lymphocytic leukaemia

SIR, Many conditions have been described as causing or being associated with erythema annulare centrifugum (EAC). We describe a patient in whom the simultaneous diagnoses of EAC and chronic lymphocytic leukaemia (CLL) were made, an association not previously reported. A 74-year-old woman presented to the Department of Dermatology with a 3-week history of pruritic skin lesions affecting her upper back, upper arms, buttocks and thighs. On examination, there were several annular and arcuate erythematous plaques with central clearing and no scales (Fig. 1), consistent with an annular erythema. She was concurrently referred with a lymphocytosis and diagnosed as having stage A(0) CLL, which did not require active treatment. The white cell count was 16Æ2 · 10 L (normal 4Æ0–11Æ0 · 10) with a lymphocytosis of 7Æ5 · 10 L (normal 1Æ0–4Æ0 · 10). The leukaemic cells expressed an immunophenotype consistent with CLL (CD19+ ⁄CD5+, CD23+ and weak surface immunoglobulin) but unexpectedly expressed CD20 and FMC7 strongly. Interphase fluorescent in situ hybridization studies showed trisomy 12 as the sole abnormality in 24% of cells. The concurrent presentation of an annular erythema and CLL in this patient prompted suspicion that they might be linked. Cutaneous lesions in patients with leukaemia can be nonleukaemic (or ‘nonspecific’) such as caused by infections, drug reactions, vasculitis or secondary to a haemorrhagic

Case 1. Sarcoidosis presenting as a scarring alopecia resembling necrosis lipoidica.

A 56-year-old woman gave a 4-year history of a progressively enlarging patch of hair loss on her scalp. She had a 26-year-history of insulin-controlled diabetes and a 14-year-history of Grave’s disease. Figure 1a shows the clinical appearances 2 years ago. Despite treatment, the plaque enlarged (Fig. 1b) and a second 5 · 4 cm lesion developed above the left ear. Three skin biopsies showed similar findings, as shown in Fig. 2a and b).

Positron emission tomography features of hidradenitis suppurativa

A 35-year-old male with classical Hodgkins lymphoma (nodular sclerosing, grade 1 histology, clinical stage 2A) underwent a positron emission tomography (PET) scan to assess response to treatment. Half body CT PET imaging was obtained using a Siemens Biograph scanner from eyes to thighs. 405 MBq of 18-fluorodeoxyglucose (FDG) was injected with acquisition starting at 60 min. There was unexpected intense focal uptake in the superficial subcutaneous tissues of the abdomen, pelvis and lateral chest wall with overlying skin thickening seen on the CT component. This was initially of concern, but the patient was known to have a history of hidradenitis suppurativa (HS). On further examination, the radiological abnormalities corresponded to the clinical sites of involvement. To the best of our knowledge, this is the first documentation of the appearance of HS on PET scan.

Blistering skin disorders: an evidence‐based update. Conference report

Evidence‐based update meetings are held annually by the Centre of Evidence Based Dermatology, University of Nottingham. Past topics have included important themes such as eczema, psoriasis, hair disorders and skin cancers. This year, the seventh Evidence Based Update meeting focused on blistering disorders and took place in Loughborough University on 5 June 2008. The latest data on incidence and mortality, therapeutic trials and management of bullous pemphigoid, pemphigus and epidermolysis bullosa (EB) were presented by an international panel of renowned speakers. The highlights of the meeting included an informal atmosphere, an international perspective, a practical question and answer session and hearing first‐hand a patient and carer’s perspective of living with EB.