Emma Benton

A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome

BACKGROUND There is no prognostic index for primary cutaneous T-cell lymphomas such as mycosis fungoides (MF) and Sezary syndrome (SS). METHOD Two prognostic indices were developed for early (IA-IIA) and late stage (IIB-IVB) disease based on multivariate data from 1502 patients. End-points included overall survival (OS) and progression free survival (PFS). External validation included 1221 patients. FINDINGS Significant adverse prognostic factors at diagnosis consisted of male gender, age >60, plaques, folliculotropic disease and stage N1/Nx for early stage, and male gender, age >60, stages B1/B2, N2/3 and visceral involvement for late stage disease. Using these variables we constructed two separate models each defined using 3 distinct groups for early and late stage patients: 0-1 (low risk), 2 (intermediate risk), and 3-5 factors (high risk). 10 year OS in the early stage model was 90.3% (low), 76.2% (intermediate) and 48.9% (high) and for the late stage model 53.2% (low), 19.8% (intermediate) and 15.0% (high). For the validation set significant differences in OS and PFS in early stage patients (both p<0.001) were also noted. In late stage patients, only OS differed between the groups (p=0.002). INTERPRETATION This proposed cutaneous lymphoma prognostic index provides a model for prediction of OS in early and late stage MF/SS enabling rational therapeutic choices and patient stratification in clinical trials.

An unusual case of granulomatous slack skin disease with necrobiosis.

Granulomatous slack skin disease (GSS) is a very rare form of T-cell lymphoma, with only 52 cases reported in the literature. In the recent World Health Organization-European Organization for Research and Treatment of Cancer consensus classification GSS is considered to be a variant of mycosis fungoides. We describe a patient with GSS and histologic evidence of necrobiosis, which has not been previously reported.

Crescendo response to rituximab in oral pemphigus vulgaris: a case with 7-year follow-up.

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and mucous membranes. Rituximab, a CD20 chimeric monoclonal antibody, has efficacy in PV management. We report a case of severe oral PV that showed a progressive response to repeated courses of rituximab, culminating in a rapid response within 4 weeks following severe relapse 4 years after initial therapy. It demonstrates the progressively shorter time to achieve partial or complete remission following rituximab infusions, combined with minimal adjuvant therapy over a 7‐year follow‐up period.

Painful ulceration of the lower legs in a young woman.

A 35-year-old woman presented with a 8-year history of painful ulceration on both lower legs, which had appeared gradually. She was otherwise well and had been on no medication prior to the onset of symptoms. On physical examination, multiple punched-out ulcers were seen on the patient’s legs with surrounding erythema and subcutaneous nodules affecting her calves and the dorsa of both feet. In addition, there were areas of postinflammatory hyperpigmentation over the lower legs (Fig. 1a ). The rest of the skin examination was unremarkable.

Beware the blistering patient with dysphonia

A 34-year-old man presented with a 6-month history of recurrent blistering and erosions affecting the dorsa of his hands and the extensor surfaces of his elbows and feet. In addition, he described skin fragility and intermittent buccal mucosal ulceration. On physical examination, there was evidence of widespread scarring, with erosions and bullae present in a mechanobullous distribution, together with ulceration of the buccal mucosa and soft palate. On histological examination of a skin biopsy, a subepidermal blister was seen, which contained neutrophils and a few eosinophils. Indirect immunofluorescence identified circulating IgG autoantibodies at a titre of 1 : 800, mapping to the dermal side of the basement membrane zone (BMZ) of salt-split skin (Fig. 1). Immunoblotting highlighted 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). Over the next 3 years, the patient was treated with a succession of systemic immunosuppressive agents, including high-dose oral and intravenous steroids, ciclosporin, azathioprine, mycophenolate mofetil, intravenous immunoglobulin (IVIg) and rituximab. Treatment improved his cutaneous disease, but had only a minimal or temporary effect on mucosal involvement. The patient then presented with dysphagia, frequent epistaxis and a hoarse voice. He was noticeably dysphonic with obvious stridor at rest. On clinical assessment of the upper airway, extensive crusting was noted throughout the nose, and the larynx was grossly scarred with distortion of the epiglottis. Owing to a combination of supraglottic oedema and an arytenoid mucosal web, the airway was only a narrow slit. An attempt to assess the airway under general anaesthesia was abandoned, as the rigid laryngoscope caused formation of haemorrhagic bulla on minimal mucosal contact. Successful ventilation was managed postoperatively perorally with an I-gel airway device, after which the patient required monitoring in the intensive care unit. Once the patient recovered, further aggressive medical management with a combined treatment of low-dose prednisolone, mycophenolate mofetil 1 g daily, monthly IVIg and two infusions of rituximab 1 g was carried out, and the airway managed with supportive care by nocturnal continuous positive airway pressure. This led to an improvement in his stridor and a patent airway, although the posterior glottic web persists. EBA is a rare autoimmune blistering mechanobullous disease characterized by the presence of IgG autoantibodies directed against type VII collagen. Cutaneous disease is most commonly reported, with mucosal involvement being rarer. Laryngeal involvement is uncommon. The diagnostic clinical criteria for EBA are traumainduced blisters that heal with milia and scarring, in the absence of a family history. There are several different clinical presentations. The classic presentation is characterized by a noninflammatory mechanobulllous disease primarily involving sites predisposed to trauma such as the hands, elbows, knees and feet, and in some cases the oral mucosa. Treatment includes supportive care, such as wound management and education of the patient regarding trauma prevention. Systemic treatments include systemic corticosteroids and immunosuppressive agents including azathioprine, methotrexate and cyclophosphamide. Dapsone and colchicine may be useful in some patients. IVIg and rituximab have also been effective. Mucosal involvement in immunobullous disease can lead to significant morbidity because of bridging scars, strictures, wound contraction and tissue loss. Pharyngolaryngeal involvement has been infrequently reported in the literature in association with EBA. Many patients PD

A pigmented lesion in a 30-year-old man

A 30-year-old man presented with a long-standing pigmented lesion on the left lower leg, which he reported had recently changed in appearance, becoming larger and more pigmented. On physical examination, an asymmetrical red brown papular lesion measuring 8 mm in diameter was seen, with several surrounding smaller papules on the left leg (Fig. 1). Full skin examination did not reveal any further suspicious lesions. An excisional biopsy of the lesion was obtained (Figs 2a,b).

A solitary nodule in a paediatric patient.

A 14-year-old boy presented with a 10-year history of a lesion on the right thigh. It had gradually increased in size over the years. There was no family history of similar lesions, and the boy was otherwise well. On physical examination, a firm solitary nodule was seen on the right anterior thigh, which was tender to touch and measured 20 mm in diameter (Fig. 1a). The nodule was well circumscribed, and was red-brown in colour with an obvious blue vascular component seen superficially. The full skin examination was otherwise unremarkable.