Small fiber neuropathy associated with multiple myeloma and IgA monoclonal gammopathy

Abstract

Dear Editor,Monoclonal gammopathy (MG) is frequent in patients withperipheral neuropathy of otherwise undetermined etiology[1]. Clinically, MG-associated neuropathy usually manifestsas a slowly progressive sensorimotor polyneuropathy withnumbness and ataxia, with rare involvement of small nervefibers [1–4].Case reportA 33-year-old Caucasian woman with stage IA multiplemyeloma [5] presented with a 4-year history of painfulneuropathy. She was diagnosed with myeloma 18 months agoand treated with thalidomide and later fludarabine at anoutside hospital. Neuropathic pain continued to worsen afterchemotherapy and was described as a severe deep achegraded 10/10 that worsened with activity, restricting her to theuse of a motorized wheelchair. Laboratory testing showedmonoclonal IgA λ protein at 1.91 g/dl, with elevated freelight chains in the serum at 84.9 mg/l (normal 5.7 –26.3 mg/l).There were no skin or endocrine abnormalities. Bone marrowbiopsy and fat pad biopsy were negative for amyloid, butshowed 20% myeloma cell infiltration rate in the marrow.There was no history of diabetes. Current medicationsincluded transdermal fentanyl patch, pregabalin, sertraline,and hydrocodone. Examination showed normal sensation tovibration and proprioception, with mildly decreased sensationto pinprick and cold temperature below ankles. Cranialnerves, muscle strength, deep tendon reflexes, proprioception,and coordination were normal. Nerve conduction studies andelectromyography were normal. Semithin plastic and paraffinsections of sural nerve biopsy were suggestive of small nervefiber dropout, without evidence of inflammation or amyloid-osis. Quantitative sensory testing (QST) using CASE IV (WRElectronics, Stillwater, MN, USA) showed decreasedsensory thresholds to vibration (>95th percentile in the leftfoot and >99th percentile in the left hand and right foot;normal 99th percentile inboth feet and the left hand). Neuropathic symptoms did notimprove after plasmapheresis. Subsequent MRI of the spineshowed diffusely abnormal bone marrow signal in cervical,thoracic, and lumbar regions, and serum electrophoresisshowed rise of β-2-microglobulin. Subsequently, patientunderwent chemotherapy with cyclophosphamide and mel-phalan, followed by autologous peripheral blood stem celltransplantation. At 1 year after transplantation, there wasno significant change in her neuropathic pain.DiscussionSmall fiber neuropathy has been defined as a peripheralneuropathy manifest by paresthesias with findings of small-fiber dysfunction on examination, specialized testing (e.g.,