Can ulcerative colitis (UC) cause neuropathy?

Can Ulcerative Colitis Cause Neuropathy?

Yes, ulcerative colitis can cause neuropathy, but it is uncommon, occurring in approximately 0.7% of patients after 10-20 years and 2.4% after 30 years of disease. 1

Epidemiology and Risk

• Neuropathy is an established but rare extraintestinal manifestation of UC, with a cumulative incidence of 0.7% after 10 and 20 years, and 2.4% after 30 years in a large population-based cohort of 772 IBD patients 1
• The overall prevalence of peripheral neuropathy in IBD patients ranges from 12.4% for small-fiber neuropathy to 19.8% for large-fiber neuropathy when actively screened, though many cases may be subclinical 2
• There is no significant increased risk of other neurological conditions like multiple sclerosis, myasthenia, or amyotrophic lateral sclerosis in UC patients, except for a possible increased risk of multiple sclerosis in middle-aged men with UC (risk ratio 1.90) 1

Types of Neuropathy Associated with UC

Direct UC-related neuropathy:

• Motor axonal polyneuropathy affecting primarily lower extremities, occurring during active colitis and likely autoimmune-mediated 3
• Acute motor and sensory neuropathy (AMSAN) with axonal sensorimotor involvement, predominantly affecting lower limbs, associated with positive anti-ganglioside antibodies (anti-GM1) 4
• Chronic polyneuropathy with sensory impairment, muscular atrophy, and weakness in distal extremities, with evidence of myelin degeneration on nerve biopsy 5
• Cranial nerve involvement including isolated unilateral hypoglossal nerve palsy presenting as mononeuritis 6

Phenotypic characteristics:

• Small-fiber neuropathy affects 6-12.4% of UC patients 2
• Large-fiber predominantly axonal sensory neuropathy is most common, with sural and median sensory nerves most frequently affected 2
• Sensory and motor amplitudes are more sensitive markers than conduction velocities for detecting neuropathy in IBD 2
• Carpal tunnel syndrome is more common in UC compared to Crohn's disease 2

Mechanisms and Contributing Factors

Primary mechanisms include: 1

• Autoimmune inflammation (likely the primary mechanism for UC-related neuropathy)
• Malnutrition and malabsorption with vitamin and micronutrient deficiencies
• Intercurrent infections (zoster viruses, EBV, CMV, HIV)
• Iatrogenic causes from medications or surgical trauma

Critical medication-related causes to exclude: 1

• Metronidazole: 21-39% prevalence of peripheral neuropathy
• Sulfasalazine: Associated with folate deficiency-related neuropathy
• Anti-TNF agents: Can cause peripheral neuropathy and central demyelination
• Thalidomide: 25% of users develop peripheral neuropathy
• Ciclosporin A: 25% risk of neurological symptoms including peripheral neuropathy

Clinical Approach

When neuropathy occurs during active UC:

• Neurological symptoms typically correlate with intestinal disease activity in autoimmune-mediated cases 3, 4
• Treatment of the underlying UC flare with corticosteroids often improves neurological symptoms 3, 4, 6
• High-dose intravenous methylprednisolone (500 mg/day) has been effective for acute presentations 6

Important caveat: Since peripheral neuropathy is usually unrelated to IBD activity in chronic cases, treatment of the underlying bowel disease does not necessarily improve established neuropathy 1

Management Recommendations

Initial evaluation must include: 1

• Immediate discontinuation of any implicated medications (especially metronidazole, thalidomide)
• Assessment and correction of vitamin deficiencies and nutritional status
• Exclusion of infectious causes (CMV, EBV, HIV, zoster)
• Evaluation for metabolic complications that may modify phenotype 2

Treatment options based on limited evidence: 1

• Intravenous immunoglobulin has been successful in case series 4
• Plasmapheresis has shown benefit in case series
• Immunosuppressants may be recommended for immune-mediated lesions
• Azathioprine combined with corticosteroids has demonstrated efficacy 4

Critical contraindication: Demyelinating neuropathy is an absolute contraindication to anti-TNF agents, which have been associated with causing demyelination with 'possible' or 'probable' causality 1

Key Clinical Pitfalls

• Do not assume all neuropathy in UC patients is disease-related; medication adverse effects are likely the most frequent neurological manifestation 1
• Recognize that neuropathy may occur during mildly active or even quiescent UC, not just severe flares 6
• Be aware that sensory symptoms may precede motor involvement, and small-fiber neuropathy may be present without abnormal nerve conduction studies 2
• Remember there are no controlled trials to guide therapeutic recommendations, so treatment decisions rely on case series and clinical judgment 1