ANCA-negative Granulomatosis with Polyangiitis: A Difficult Diagnosis

Granulomatosis with polyangitiis (GPA) is a systemic small and medium vessel vasculitis, commonly associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Presenting signs and symptoms in GPA are varied and patients may present with constitutional, non-specific symptoms, which can delay the diagnosis. Tissue biopsy of the site of active disease can confirm the diagnosis of GPA, in which necrotising granulomatous inflammation is seen. However, surrogate markers may be used for diagnosis without a tissue biopsy. They include upper and lower airway symptoms, signs of glomerulonephritis and a positive ANCA. However, approximately 10-20% of patients with GPA are ANCA negative, allowing for the diagnosis to be overlooked, particularly in those patients with non-specific findings. The reason for the absence of ANCAs is unclear.

A case of granulomatosis with polyangitiis presenting with non-specific findings is described.Some 10% of cases are ANCA negative.When a vasculitis is suspected, a negative ANCA does not exclude the diagnosis of GPA, so further investigations (i.e. tissue biopsy) should be considered.