Muscle cramps and weakness secondary to graft versus host disease fasciitis.

Sir, Uncommon manifestations of chronic graft versus host disease (GvHD) include a variety of neurological presentations (Bolger et al., 1986; Urbano-Marquez et al., 1986; Nelson and McQuillen, 1988; Tse et al., 1999; Takahashi et al., 2000; Ma et al., 2002; Nagashima et al., 2002) and sclerodermatous skin changes (Shulman et al., 1978; Chosidow et al., 1992; Janin et al., 1994; Penas et al., 2002). Here we report a case of chronic GvHD fasciitis presenting with progressive muscular cramps and weakness, not previously reported. The patient was diagnosed with Hodgkin’s disease in 1983 at the age of 19 years, suffering two relapses in 1987 and 1997. In 1999, he developed a plasmacytoma and severe auto-immune haemolytic anaemia which were treated with chemotherapy and cyclosporin, respectively, followed by a reduced intensity allogeneic bone marrow transplant. Two months later, he developed mild GvHD with skin and liver involvement, treated with oral steroids. Over the following year, he developed chronic skin changes requiring intravenous methylprednisolone followed by maintenance prednisolone and cyclo sporin A. In 2001, he was referred to neurology with a 1-year history of painful muscular cramps particularly around his mouth and neck, across his stomach and in his legs and hands, as well as muscular stiffness and proximal weakness. Examination revealed mild wasting of the left interossei and mild bilateral hip flexion weakness. Tone and power were otherwise normal. Reflexes were absent apart from knee jerks. Plantars were flexor. There was mild reduction of pain and temperature sensation in the hands. Creatine kinase was normal. By January 2002, his skin had become thickened and sclerodermatous, requiring PUVA therapy, which resulted in some improvement. He had no other features of GvHD and his steroid dose was reduced. However, the severe muscle cramps continued, failing to respond to baclofen or dantrolene. He also developed more proximal limb weakness. A vastus medialis muscle biopsy was performed. The biopsy showed a moderate inflammatory cell infiltrate within a thickened perimysium, consisting predominantly of T lymphocytes and macrophages (Fig. 1a). There was perifascicular atrophy with occasional necrotic fibres at the periphery of fascicles. Following immunocytochemistry increased sarcolemmal expression of class 1 major histocompatibility antigen was noted in perifascicular fibres (Fig. 1b). The cramps continued to progress in association with worsening, primarily proximal weakness, distal wasting and joint pains and stiffness, resulting in reduction in mobility and requiring increasing doses of opiates for pain control. Treatment with steroids, mycophenolate, intravenous immunoglobulin, methotrexate, clofazimine or infliximab failed to halt his progression. Symptomatic trials of phenytoin and gabapentin were unsuccessful. Sclerodermatous chronic GvHD is a rare but well recognized form of GvHD (Van den Bergh et al., 1987; Chosidow et al., 1992; Penas et al., 2002). Muscular presentations are more rarely reported