Methotrexate for papuloerythroderma of Ofuji

Abstract

Papuloerythroderma of Ofuji (PEO) is a rare and underrecognized skin disease, which was first described by Ofuji in 1984 with four detailed cases. The disease mostly affects elderly men, and is characterized by intensely pruritic papules that later progress to plaques and may evolve into erythroderma. Diagnosis is based on the typical presentation of erythroderma featuring flat-topped papules that spare the cutaneous folds and mucous membranes, known as the ‘deck-chair sign’. Other minor characteristics of the disease are: age > 55 years, raised serum IgE, peripheral lymphopenia and peripheral eosinophilia. It is necessary to exclude cutaneous T-cell lymphoma before a diagnosis can be made. In 2010, based on a meta-analysis involving 170 cases, Torchia et al. divided forms of the disease into four categories: (i) primary, (ii) secondary, (ii) papuloerythroderma imitating lymphoma and (vi) other diseases with similar symptoms to papuloerythroderma. Previous studies have shown that PEO can result in patients with pre-existing neoplasm such as lymphomas, hepatocellular carcinoma and gastrointestinal malignancy. Pathogenic infection, or medical agents such as ranitidine, aspirin and furosemide, have been reported to precede the development of PEO. The pathogenesis of PEO is unclear; however, the presence of increased numbers of dermal Langerhans cells and presence of vascular occlusion have been proposed as possible mechanisms. Treatment options include topical corticosteroids and oral antihistamines. Psoralen and ultraviolet A has also been demonstrated to be efficacious. A 90-year-old white man presented with a 2-year history of an evolving pruritic eruption with no associated weight loss, fever or night sweats. Physical examination revealed coalescing, flat-topped, red–brown papules (Fig. 1a). The patient soon became suberythrodermic. The eruption continued to evolve with marked hyperpigmentation and thickened plaques over the trunk and limbs, with sparing noted around the skin folds with the deck-chair sign (Fig. 1b). Laboratory investigations found a raised eosinophil count (2.1 9 10/L; normal range 0–0.5 9 10/L) but an otherwise normal full blood count. Immunoglobulin levels were normal, except for IgE, which was raised (208 kU/L; 0–41 kU/L). Serum electrophoresis was normal and serology for human T-cell lymphotropic virus 1/2. Computed tomography of the chest, abdomen and pelvis revealed visible bilateral axillary and inguinal lymph nodes. Histological examination of skin biopsies showed mild hyperkeratosis and mild psoriasiform epidermal hyperplasia. There was a moderately dense upper dermal lymphohistiocytic infiltrate with prominent numbers of eosinophils. There were no features to suggest mycosis fungoides and T-cell receptor gene rearrangement was not detected. Lymph node biopsy showed dermatopathic lymphadenitis. A diagnosis of PEO was made. The patient was initiated on a course of prednisolone and topical steroids with limited effect. He was subsequently initiated on methotrexate (MTX) once weekly reaching up to 17.5 mg. Within 4 months, there was an improvement in the pruritus with complete resolution of the eruption by 1 year (Fig. 2). MTX was tapered off, but itching recurred at doses below 2.5 mg/week. The patient has continued taking MTX 2.5 mg/week without any adverse effects. There is one other case reported in the literature of the use of MTX to treat PEO. Allegue et al. reported a patient in 2018 with PEO; MTX 15 mg/week was administered, and the rash, eosinophilia and pruritus rapidly cleared after 2 months of treatment. The hypothesized mechanism of action of MTX is through suppression of activated T cells or induction Correspondence: Dr Aaron Hughes, Department of Dermatology, Kingston Hospital NHS Foundation Trust, Galsworthy Road, London, KT2 7QB, UK E-mail: [email protected]