Long-term follow-up in a patient with the dermato-neuro syndrome treated with high-dose melphalan, thalidomide, and intravenous immunoglobulins for more than 7 years

Abstract

Dear Editor, Scleromyxedema (SME), a subtype of lichen myxedematosus, is characterized by a generalized sclerodermoid eruption and a monoclonal gammopathy in the absence of thyroid disease. Mucin deposition, fibroblast proliferation, and fibrosis are seen at skin biopsy [1]. The “dermato-neuro syndrome” (DNS) is a rare manifestation of scleromyxedema and only a few cases have been described. It is characterized by a flu-like prodrome, followed by high fever, tonic-clonic convulsions, and coma in the setting of scleromyxedema [2, 3]. We report a case of DNS successfully treated with high-dose melphalan and autologous stem cell transplantation, followed by thalidomide during 1 year and ongoing monthly administration of intravenous immunoglobulins (IVIg). In December 2005, a 39-year-old Caucasian man was referred to our institute after developing a subacute neurological deterioration (increased confusion, agitation, and visual hallucinations) while being treated for pneumonia. Prior to transfer, he developed generalized tonic-clonic seizures. During the 9-month period, before, the patient had two similar episodes of subacute encephalopathy progressing to status epilepticus and coma. Both were preceded by a flu-like prodrome. Upon admission, the patient was disoriented, agitated, and had fever. Due to progressive loss of consciousness, urgent sedation and mechanical ventilation were mandatory. Serum protein electrophoresis revealed an IgG kappa monoclonal protein (15.9 g/L). The bone marrow plasmocytosis was low (3, 7 %). Electrophoresis of CSF showed a monoclonal protein [4]. High-dose dexamethasone and plasmapheresis were started and neurological, hemodynamic, and respiratory improvement occurred. After 8 weeks, the patient was able to leave the hospital with mild residual cognitive impairment and an Mprotein level of 7 g/L. Ten days after discharge, he again developed a flu-like prodrome followed by high fever, confusion, and tonic-clonic convulsions. The M-protein value peaked to 26 g/L in a few days. As a consequence, a relation between the epileptic insult and the rapid increase of paraprotein was suspected. At that time, an erythematous skin induration with longitudinal furrowing of the glabella (leonine facies) was observed (Fig. 1a). The skin biopsy of the glabella showed typical dermal mucin deposition, fibroblast proliferation, and fibrosis, confirming the histological diagnosis of scleromyxedema (Fig. 1c, d). The combination of the dermatologic manifestations, the presence of a monoclonal gammopathy, and the neurologic manifestations led to the diagnosis of DNS [5, 6]. Dexamethasone was resumed in association with IVIg [7]. In February 2006, CAD mobilization chemotherapy (cyclophosphamide 1,000 mg/m2 on day 1; adriamycine 15 mg/m2 on day 1–4; dexamethasone 40 mg on day 1–4) was administered. Three weeks later, high-dose melphalan (200 mg/m) was administrated followed by autologous T. Devos (*) :M. Delforge Department of Hematology, University Hospitals Leuven, Leuven, Belgium e-mail: Timothy.Devos@uzleuven.be