Tripping in the dark, pigmented in the light: a case of insidious myelopathy unmasked by an antifolate in a patient with rheumatoid arthritis

Abstract

Introduction: We report an unusual case in which prominent cutaneous hyperpigmentation preceded a progressive myelopathy in a non-vegetarian patient with rheumatoid arthritis (RA) receiving long-term methotrexate (MTX) therapy—a combination that conspired to produce overt cobalamin deficiency through a shared disruption of one-carbon metabolism, despite concurrent folic acid supplementation.

Main symptoms and findings: A 64-year-old male presented with a one-year history of ascending paraesthesia and sensory ataxia, notably preceded by facial and acral hyperpigmentation. Examination revealed posterior column dysfunction and pyramidal signs, with bilateral mild hip flexor weakness. Macrocytic anemia and severely subnormal serum vitamin B12 (114 pg/mL) were confirmed. Serological screening (Venereal Disease Research Laboratory test [VDRL], HIV enzyme-linked immunosorbent assay [ELISA], hepatitis B surface antigen [HBsAg], and anti-hepatitis C virus [anti-HCV]) was negative. Spinal magnetic resonance imaging (MRI) demonstrated posterior column T2 hyperintensity from C6 to D7 with the characteristic inverted V sign on axial imaging.

Diagnosis, intervention, and outcome: Subacute combined degeneration (SCD) secondary to vitamin B12 deficiency was diagnosed. Parenteral hydroxocobalamin was commenced with significant neurological, hematological, and cutaneous improvement within 6 weeks.

Conclusion: Cutaneous hyperpigmentation is a clinically accessible early warning sign of cobalamin deficiency that predates neurological involvement and deserves active recognition. Folic acid supplementation does not prevent neurological injury from cobalamin deficiency. Routine B12 surveillance is essential in all patients on chronic MTX therapy.