Abstract
ObjectiveGraft-versus-host disease (GVHD) is an immune-mediated multisystemic disorder and the leading cause of morbidity after allogeneic hematopoietic stem cell transplantation. Peripheral nervous system manifestations of GVHD are rare but often disabling. Whereas immune-mediated neuropathies are an established feature of GVHD, muscle cramps are not well characterized.MethodsIn a single-centre retrospective cohort we studied 27 patients (age 23 to 69 years) with GVHD (acute n = 6, chronic n = 21) who complained of symptoms suggestive of peripheral nervous system complications. Clinical, laboratory and neurophysiological findings were evaluated by descriptive statistics and regression analysis to detect factors associated with muscle cramps. Patient’s sera were examined for anti-neuronal antibodies.ResultsNine patients had polyneuropathy, 4 had muscle cramps, and 14 had both. Median onset of polyneuropathy and muscle cramps was 6 and 9 months after allogeneic hematopoietic stem cell transplantation, respectively. Neurophysiology revealed a predominantly axonal polyneuropathy in 20 of 26 patients. In 4 of 19 patients electromyography showed signs of myopathy or myositis. Muscle cramps were more frequent during chronic than acute GVHD and affected muscles other than calves in 15 of 18 patients. They typically occurred daily, lasted 1 to 10 minutes with medium to severe pain intensity, compromised daily activity or sleep in 12, and were refractory to therapy in 4 patients. Muscle cramps were less likely with tacrolimus treatment and signs of severe polyneuropathy, but more likely with myopathic changes in electromyography and with incipient demyelinating polyneuropathy, shown by increased high frequency attenuation of the tibial nerve. Serological studies revealed antinuclear or antimitochondrial antibodies in a subset of patients. Two of 16 patients had a serum reactivity against peripheral nervous tissue.ConclusionMuscle cramps are associated with chronic GVHD, often compromise daily activity, and correlate negatively with axonal polyneuropathy and positively with myopathy and incipient demyelination.
Highlights
Graft-versus-host disease (GVHD) is a frequent complication and the leading cause of morbidity after allogeneic hematopoietic stem cell transplantation [1,2]
We found that muscle cramps occurred in the context of chronic GVHD and were less frequent in patients with axonal neuropathy and tacrolimus treatment
Patients and Clinical Outcome Measures In this single-centre, retrospective cohort study all consecutive patients presenting to our tertiary referral centre between March 2008 and August 2010 were included if they had a history of alloHSCT, acute or chronic GVHD, and complained of muscle cramps or other symptoms suggestive of a nervous system disorder
Summary
Graft-versus-host disease (GVHD) is a frequent complication and the leading cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [1,2]. It is characterized by immune-mediated multisystemic inflammation. The pathogenesis of GVHD involves proliferation and activation of allo- and autoreactive T and B lymphocytes, inappropriate generation of central and peripheral tolerance and various unspecific mechanisms of chronic inflammation [3]. The classical targets of acute GVHD are skin, intestinal tract, and liver. Chronic GVHD may involve additional organs (eye, oral mucosa, lung, fascia, and genital tract) and mimic autoimmune diseases like myasthenia gravis or autoimmune cytopenias
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