Sustained remission of CIDP associated with celiac disease after immunotherapy and gluten-free diet

Letter to Editor

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by symmetric proximal and distal weakness, large fiber sensory loss, and areflexia. It is thought to involve immune-mediated insult to the myelin sheath and may be associated with autoimmunity, including celiac disease (CD).¹ CIDP may respond to immunotherapy but is often progressive or relapsing. Some evidence suggests that CD-associated neuropathic symptoms can improve with a gluten-free diet.^2–4 We present a 77 year-old man, with history of undifferentiated connective tissue disease/clinical dermatomyositis in remission and two years of Parkinson disease, who was diagnosed with CIDP at age 69, was found to have celiac disease and achieved sustained remission after intravenous immune globulin (IVIG) therapy and strict gluten-free diet.

At age 69 he developed bilateral leg weakness and pain and was found to have proximal leg weakness and elevated creatine phosphokinase (370 U/L). After transient improvement with prednisone, he developed further weakness and leg parasthesias with steroid taper. Subsequent exams showed distal leg weakness, sensory loss and areflexia. Workup revealed elevated CSF protein (117 mg/dL); nerve conduction studies showed conduction block, prolonged distal latencies and temporal dispersion, consistent with multifocal demyelinating sensorimotor polyneuropathy; IgG and IgA gliadin and IgA tissue transglutaminase antibodies and duodenal biopsy confirmed celiac disease. Gastrointestinal symptoms were limited to decreased appetite and chronic constipation. Additional workup for nutritional deficiency, autoimmune and infectious etiologies was otherwise negative. IVIG resulted in symptomatic improvement. Subsequent strict gluten-free diet (but not IVIG) normalized his celiac antibody levels, and he remains in remission (mild distal numbness) seven years after tapering off IVIG and continuing a gluten-free diet. His Parkinson symptoms have continued to mildly progress.

Prior case series of neuropathies associated with CD have reported varied response to gluten-free diet. In a study of two patients with motor-predominant neuropathy associated with biopsy-proven CD, both showed significant improvement in strength, nerve conduction studies and intestinal pathology after gluten-free diet, including in one for whom IVIG did not provide benefit.² In 17 patients with sensory ganglionopathy and gluten sensitivity (diagnosed via serologic markers), 11 who adhered to strict gluten-free diet had stable symptoms, while six who either did not strictly adhere or did not participate in the diet had progressive symptoms.³ A single patient with multifocal acquired motor axonopathy found to have CD did not show clinical benefit with gluten-free diet despite normalization of antibodies.⁴ The case reported here highlights the importance of testing for CD in patients with CIDP even without gastrointestinal symptoms, and suggests that gluten-free diet along with immunotherapy may enable patients with CD-related CIDP to achieve sustained remission.

This case also raises questions about autoimmunity in Parkinson disease. One genome-wide association study reported common genetic pathways in Parkinson disease and several autoimmune diseases including CD.⁵ CIDP-like syndromes are also reported in Parkinson patients, with some evidence of peripheral nerve alpha-synuclein deposition.⁶ Research into the role of autoimmunity in both neuropathies and neurodegenerative diseases will better elucidate both their pathogenesis and novel therapeutic targets.