P0637 - Cough, Cough: A Rare Case of Co-Existing Granulomatosis with Polyangiitis and Autoimmune Hepatitis in a Pediatric Patient

Case Description:
A 15-year-old female presented with two weeks of worsening abdominal pain and a non-productive cough. Prior to presentation, she had a low-grade fever, sore throat, conjunctivitis and an erythematous pruritic rash over her extremities that resolved. She was transferred from an outside hospital with elevated transaminases, positive liver-kidney microsome-1 antibody and elevated immunoglobulin G, overall concerning for autoimmune hepatitis. Her past medical history was significant for mild intermittent asthma, seasonal allergies and GERD. Her family history was significant for hereditary angioedema in her sister. Vital signs were 39C, pulse 119, respiratory rate 31, blood pressure 109/65 and oxygen saturation 93% on room air. She was toxic-appearing with persistent hemoptysis, diffusely diminished breath sounds and mild epigastric tenderness to palpation. Eyes, skin and musculoskeletal exam were normal. Liver function tests were consistent with a hepatocellular inflammation pattern. Creatinine was 0.71 mg/dL, urinalysis revealed microscopic hematuria and urine protein creatine ratio was 0.27. Diffuse bilateral multifocal airspace opacities were seen on chest x-ray and bronchoscopy confirmed diffuse alveolar hemorrhage. A liver biopsy revealed diffuse marked periportal lymphoplasmacytic hepatitis with interface activity and portal fibrosis, consistent with autoimmune hepatitis. Her autoantibody profile had antineutrophil cytoplasmic autoantibodies with a cytoplasmic pattern (c-ANCA) and highly positive proteinase 3 antibody (PR3) levels, confirming a co-existing diagnosis of granulomatosis with polyangiitis (GPA). The work-up for other autoimmune and infectious etiologies was negative, except for a non-specific antinuclear antibody titer of 1:640. Treatment was initiated with high-dose corticosteroids, plasmapheresis and rituximab. Her hospitalization course was complicated by respiratory failure due to diffuse alveolar hemorrhage requiring mechanical intubation and worsening proteinuria leading to renal biopsy, which revealed crescentic glomerulonephritis without immune deposition. Following her extended hospitalization, she was discharged home to continue treatment for GPA and autoimmune hepatitis with corticosteroids, rituximab and azathioprine.

Discussion:
GPA is an ANCA-associated vasculitis primarily affecting the small and medium-sized arteries that classically involves the upper and lower respiratory tract and kidneys. GPA is more common in adults than in children; however, children are more likely to have a delay in diagnosis and a severe, relapsing course. The prognosis of GPA in children and adults has significantly improved with more precise classification criteria and targeted treatment with monoclonal antibodies. This case demonstrates the co-existence of ANCA-associated vasculitis and autoimmune hepatitis, which has rarely been reported in the pediatric and adult literature. The nature of the relationship between autoimmune hepatitis and GPA is unknown, but likely involves a complex interplay between loss of self-tolerance and environmental triggers that remains an area of ongoing research .

Conclusion:
While GPA and overlapping autoimmune disease in pediatric patients is extremely rare, failure to recognize their co-existence can result in severe, multiorgan damage.