HERMANSKY-PUDLAK SYNDROME-ASSOCIATED INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW ON CLINICAL MANIFESTATIONS AND INVESTIGATIONS INTO OPTIMAL MANAGEMENT

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal condition resulting from a mutation in 1 of at least 7 different genes leading to the triad of tyrosine-positive oculocutaneous albinism, platelet dysfunction leading to prolonged bleeding time, and ceroid lipofuscin within the reticuloendothelial system. The latter of these can result in systemic derangements including renal failure, pulmonary fibrosis, cardiomyopathy, and a disabling granulomatous colitis. This colitis is a unique type of inflammatory bowel disease (IBD) with complications such as intestinal fistulization, ileitis, enterocolitis and perianal disease. There is data to suggest that HPS colitis is due to the development of classical IBD. However, optimal management remains undetermined. Our systematic review aims to analyze the clinical presentation behind HPS colitis, endoscopic versus histopathological findings, and ultimate treatment plans required for optimal management of this disease among HPS genotypes. A comprehensive literature review was conducted on patients with HPS and its associated colitis manifestations from inception to August 2023. Analyses on patient demographics, clinical presentation, HPS genotype, endoscopic versus histopathological findings, medical versus surgical interventions were thoroughly performed. Six cohort studies on HPS patients with coexisting colitis were identified. A total of 84 patients comprised these studies with mean age 32 +/- 9.65. Racial breakdowns were 68% Puerto Rican, 23% white, 4% Indian, 2% Mexican, 1% Honduran, and 1% African American. 59 patients had the HPS-1 genotype, 8 with HPS-3, 3 with HPS-4, and 1 with HPS-6. The most common presenting symptoms were hematochezia (37%), diarrhea (23%), abdominal pain (16%), and constipation (10%). Endoscopic evaluation showed normal gross findings in 65% of cases and abnormalities in only 35%. However, IBD-associated histopathological positivity was more prevalent with the most common findings being granulomas (33%), macrophages without colitis (19%), macrophages with colitis (15%), and lymphoid aggregates (10%). Medical therapy was initiated in 48 cases with the most common medications being steroids (46%), followed by anti-TNFa agents (40%), and immunomodulators (35%). 28 cases required surgical intervention with the most common operation performed being a (subtotal) colectomy and ileostomy. There were scattered cases of laparoscopic loop ileostomies, total colectomies, and proctocolectomies too. I