Case Report
Rituximab treatment of stiff-person syndrome in a patient with thymoma, diabetes mellitus and autoimmune thyroiditis

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Abstract

Stiff-person syndrome (SPS) is an autoimmune neurological disorder characterized by stiffness of the skeletal muscle with superimposed spasms and production of autoantibodies to glutamic acid decarboxylase (GAD) and amphiphysin. The disorder results from B cell-mediated clonal production of autoantibodies, requiring treatment with immunosuppressors; however, treatment results have been somewhat inconsistent. We report the results of rituximab treatment in a patient with SPS associated with a thymoma, diabetes mellitus, autoimmune thyroiditis and the presence of anti-GAD and anti-amphiphysin autoantibodies. The patient experienced a partial improvement following a thymectomy and the administration of prednisone, intravenous immunoglobulins and mycophenolate mofetil. Treatment with rituximab was followed by a complete sustained remission and the disappearance of serum anti-amphiphysin antibodies.

Introduction

Stiff-person syndrome (SPS) is a rare neurological disorder characterized by progressive muscle rigidity with superimposed painful muscle spasms and gait impairment, owing to continuous motor activity. SPS is an autoimmune, predominantly encephalomyelopathic disorder resulting from B cell-mediated clonal production of autoantibodies against presynaptic inhibitory epitopes on the glutamic acid decarboxylase (GAD) enzyme and the synaptic membrane protein amphiphysin.1 Three variants of SPS have been recognized: (i) a purely autoimmune variant that is linked to anti-GAD antibodies and commonly associated with other autoimmune diseases, mainly Type I diabetes mellitus and autoimmune thyroid disease; (ii) a less common paraneoplastic variant related to breast cancer and small-cell lung cancer that is characterized by anti-amphiphysin autoantibodies; and (iii) an idiopathic variant that has no detectable autoantibodies. While the pathogenic role of anti-GAD antibodies is uncertain,2 a convincing role of anti-amphiphysin antibodies has been established through the passive transfer of SPS to rats.3 These data taken together have prompted clinicians to treat SPS with plasmapheresis, intravenous (i.v.) immunoglobulins (Ig) or immunosuppressive agents. Treatment generally slows the course of the disease or, at best, improves muscle rigidity, but rarely achieves a total remission.4 Rituximab, by contrast, has shown promising results. Baker et al. first reported its efficacy in 2005;5 however, no subsequent publication has confirmed the findings.

We demonstrate the efficacy of rituximab in a patient with paraneoplastic SPS associated with a thymoma, who secondarily developed Type I diabetes mellitus and autoimmune thyroiditis, and who produced both anti-GAD and anti-amphiphysin autoantibodies. The patient’s condition initially showed a marked improvement after a thymectomy followed by treatment with i.v. Ig, prednisone, and mycophenolate mofetil (MM) but the disease relapsed and the patient produced a persistent high titre of anti-GAD and anti-amphiphysin antibodies. Following treatment with rituximab, the patient achieved a complete remission with suppression of anti-amphiphysin autoantibodies.

Section snippets

Case report

A 53-year-old caucasian man was admitted to our unit for painful muscle spasms affecting the neck, back, arms and legs and a stiffness of the spinal column, and muscles of the abdomen and legs. The patient was bed-bound. His muscle tone was markedly increased in all muscle groups, predominantly in the axial and proximal limb muscles, and his leg spasms were precipitated by movement, startle, and light touch. The spinal column was hyperlordotic, and the patient was unable to walk. In a standing

Discussion

SPS is an autoimmune disorder, resulting from B cell-mediated clonal production of autoantibodies against presynaptic inhibitory epitopes on the GAD enzyme and the synaptic membrane protein amphiphysin.1 Two variants have been categorized according to autoantibody types: (i) a purely autoimmune variant, characterized by anti-GAD antibodies and involvement of the DQ B1 0201 allele, and commonly associated with autoimmune diseases such as diabetes mellitus and autoimmune thyroiditis, as well as

Conclusion

Rituximab has demonstrated efficacy in the treatment of numerous autoimmune disorders, and it also has promising applications for patients with SPS. The positive correlation between the clinical improvement of the patient and the elimination of anti-amphiphysin antibodies provides additional evidence for the inhibitory role of this antibody on GABAergic neurons.

References (7)

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