Interferon-α-related microscopic polyangiitis in a patient with chronic hepatitis C infection

To the Editor: A 38-year-old man with genotype 1b chronic hepatitis C infection had been treated with 48 weeks of pegylated interferon (IFN)-α and ribavirin. Autoimmune serology performed just before treatment showed positive perinuclear antineutrophil cytoplasmic antibodies (ANCA) accompanied by an elevated antimyeloperoxidase antibody level (22 U/mL; reference range [RR], < 5 U/mL). Notably, the patient was ANCA-negative 12 months previously. The treatment course was uneventful.

Autoimmune disease is a well recognised complication of IFN-α therapy in chronic hepatitis C infection. The clinical manifestations of IFN-α-related autoimmune disease can be either organ-specific (thyroiditis, psoriasis) or, less commonly, systemic (rheumatoid arthritis, lupus-like disease, sarcoidosis).1 IFN-α-based treatment in chronic hepatitis C infection unmasks silent autoimmune processes, or induces de novo autoimmune diseases or autoantibodies.2 A predisposition to autoimmunity, together with the presence of baseline auto-antibodies, has been demonstrated in most instances of IFN-α-mediated autoimmune diseases,1 as observed in our case.

Although rare, the diagnosis of microscopic polyangiitis needs to be considered in patients treated with IFN-α-based therapy for chronic hepatitis C infection presenting with skin rash, fevers, arthritis, an active urine sediment, renal failure or pulmonary haemorrhage. One could consider reducing the duration of therapy in patients who achieve negative RNA polymerase chain reaction at Week 4 of treatment. There is emerging evidence that 24 weeks of response-guided therapy in genotype 1b chronic hepatitis C infection is as effective as the standard-of-care treatment for 48 weeks in rapid responders.3 We also suggest that, in the presence of a positive ANCA at baseline screening, a chest x-ray and urinalysis be performed before initiating IFN-α-based treatment, and that patients be monitored clinically and with urinalysis during treatment. A chest x-ray should also be performed at the completion of treatment. The presence of auto-antibodies alone is not a contraindication to IFN-α therapy, but it does mandate careful monitoring and a high index of suspicion of an immune diathesis.

A: High-resolution computed tomography scan of the patient’s chest showing patchy foci of ground glass opacification and nodules bilaterally.

B: Renal biopsy showing focal crescentic necrotising glomerulonephritis (haematoxylin-eosin stain; original magnification x 400).