E032 A reminder that a positive PR3-ANCA does not always mean vasculitis

Antibodies to proteinase 3 (PR3) are an important diagnostic marker in the diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, most notably granulomatosis with polyangiitis (GPA). However, PR3 antibodies may also be found in other autoimmune conditions including ulcerative colitis (UC) and primary sclerosing cholangitis. We present the case of a 23-year-old male in whom PR3 antibodies were strongly positive who ultimately was diagnosed with inflammatory bowel disease.

The patient was admitted to hospital with severe oral ulceration such that he was unable to eat and drink. He had a history of weight loss and intermittent bloody diarrhoea, and there was evidence of right eye conjunctival inflammation. There were no symptoms of arthritis, genital ulceration or rashes. Admission blood tests showed Hb 125 g/L, CRP 23 mg/L, ESR 31 mm/h and normal renal function. A CT scan revealed patchy ground-glass changes within the right lower lobe. He had no respiratory symptoms but was found to be Covid positive on the ward, which was thought to be the cause of these findings. A colonoscopy with biopsies showed evidence of colitis in the caecum, sigmoid and rectum with lamina propria inflammation, crypt abscess formation and absence of granulomas. A small bowel MRI and capsule endoscopy were normal. Further investigations revealed a strongly positive PR3-ANCA at 338 CU (reference range 0-19) with normal complement C3 and C4. Antinuclear antibody was negative. Infection screening including HIV, hepatitis, syphilis, CMV and EBV were negative. He had no significant sinonasal symptoms and flexible nasoendoscopy showed normal nasal mucosa with no evidence of ulceration or subglottic stenosis.

The initial suspicion was ANCA-associated vasculitis and the patient was treated with intravenous methylprednisolone followed by oral prednisolone. This led to significant improvement in his symptoms, however he developed recurrence of oral ulceration and diarrhoea on steroid tapering. He was unable to tolerate azathioprine and was commenced on methotrexate. A repeat colonoscopy showed active proctitis and a repeat CT chest was normal. He was commenced on infliximab by gastroenterology for suspected ulcerative colitis. There was suboptimal control of his bowel symptoms and he was then switched to vedolizumab with good clinical response. His PR3 level also improved with treatment to 89 CU.

PR3 antibodies may be found in 30-60% of patients with UC and may be used to help differentiate UC from Crohn’s disease. There is also evidence that PR3 levels may reflect disease activity in UC and that high levels may predict failure of steroid therapy and primary non-response to anti-TNF agents. Our case is an important reminder that PR3 antibodies can be present in other conditions and is not necessarily indicative of vasculitis. It also highlights the importance of a multidisciplinary approach to complex patients.

J. Carroll: None. M. Malik: None.