Vasculitis Recurrence? Or An Infection?

Venna N, Niles JL, Lev MH, Frosch MP. Case 21-2014 - A 68-Year-Old Man with a Sudden Onset of Diplopia. N Engl J Med (2014) 371:162-173 doi: 10.1056/NEJMcpc1403308

This intriguing case study describes a patient successfully treated for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consistent with granulomatosis with polyangiitis who returned several months later with neurological symptoms. It seemed to be a recurrence of the vasculitis, but an infection had to be excluded.

A radiologist and a neurologist discuss the progress of the disease through the patient’s brain, and a pathologist resolves some questions with the autopsy.

A 68-year old man was diagnosed with ANCA-associated vasculitis consistent with granulomatosis with polyangiitis (GPA), characterized by sinus pain and renal insufficiency due to rapidly progressive glomerulonephritis with crescentic glomerulonephritis and creatinine 5.4 mg/dL. He was treated aggressively to preserve renal function, with plasma exchange, methylprednisonlone, and cyclophosphamide (for six months), and finally rituximab and prednisone, with a final creatinine level of 6.0 mg/dL. The active ANCA-associated vasculitis disappeared.

Twenty-one months after that diagnosis, he presented with diplopia, fatigue, weakness and nausea. Magnetic resonance imaging (MRI) of the head showed findings consistent with chronic microangiopathic disease: mild, scattered white-matter changes in the periventricular, subcortical and midbrain region. The foci progressed as a multifocal intraaxial process of the midbrain, pons and medulla. On day 5, during hemodialysis, the patient became unresponsive, and temperature rose to 39°C, without confirmatory evidence of infection.

Was this a recurrence of vasculitis, or an infection? Meningeal involvement and peripheral-nerve involvement are recognized features of ANCA-associated vasculitis, but central nervous system involvement is unusual. So infection was a possibility, but no infection was found.

The pattern of cerebral infarctions combined with the normal appearance of large and medium-sized arteries on magnetic resonance angiography, along with suggestions of fluid leakage through the blood-brain barrier, suggest widespread small-vessel vasculopathy. The final diagnosis was cerebral vasculitis due to GPA.

The patient died on day 16, and an autopsy confirmed and clarified the diagnosis.

An editorial aside: Up to now, GPA has carried the parenthetical note, “formerly Wegener’s granulomatosis.” This article no longer mentions Wegener, whose name has fallen out of favor in view of his affiliation with the Nazi party.