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P360 Aggressive Inflammatory Bowel Disease is associated to Hermansky-Pudlak Syndrome: Characterization of a Puerto Rican Cohort

Marrero Torres, R.(1);Coste-Sibilia, S.(1);Nieves-Jimenez, H.(1);Torres, G.(1);Rivera, E.(2);Torres, E.A.(1);

(1)University of Puerto Rico - School of Medicine, Department of Medicine - Gastroenterology, San Juan, Puerto Rico;(2) University of Puerto Rico - School of Medicine, Department of Hematology - Pediatric Hem-Onc Section, San Juan, Puerto Rico

Background

Hermansky-Pudlak Syndrome (HPS), a rare autosomal recessive disorder, is the most common single-gene disorder in Puerto Rico. It is characterized by an aberrant biogenesis of lysosome-related organelles inducing oculocutaneous albinism, bleeding diathesis, and damage to other organs. Around 30% of patients with HPS develop granulomatous enterocolitis, a Crohn’s-like inflammatory bowel disease (IBD). The mutant HPS1 gene is associated with a more severe Early Onset IBD (EO-IBD). We wish to describe a group of patients with HPS-associated IBD.

Methods

Puerto Ricans with HPS and concomitant IBD were recruited in our IBD clinic for a prospective cohort study. After informed consent, demographic and medical data were collected from the patient and the medical record. Variables included sex, HPS genotype, age at the time of IBD diagnosis, IBD location and behavior according to Montreal and Paris Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM).  Descriptive analysis was performed calculating mean and standard deviations. This study is approved by the MSC IRB.

Results

13 patients with HPS and IBD, 9 with confirmed genotype 1, were identified:  8 males and 5 females. The mean age at the time of IBD diagnosis was 22 ± 11 years. 6 were diagnosed at ≤ 16 y/o (A1), 6  were diagnosed between 17-40 years (A2) and 1 patient was in the range of EO-IBD (7 y/o). 9 patients had advanced penetrating behavior (B3) of which 7 had concomitant perianal involvement. Most patients (9) had a surgical intervention; 8 have an ostomy. The majority (10) are using biologics (4 with concurrent immunomodulators). The most frequent EIM was peripheral arthropathy seen in 45%.

     Table 1. Surgery for IBD (n=13)

None4
Strictureplasty1
Diversion Colostomy3
Segmental Resection with Colostomy2
TAC + End Ileostomy
   
     Table 2. Medications

Category Previous UseCurrently Using
Aminosalicylates9-
Corticosteroids9-
Immunomodulators36
Biologics    
   TNF α blocker    
   Integrin  blocker    
   a-IL12/a-IL 23 antagonist
5
5
0
0
10
6
2

Conclusion

HPS patients had a severe course of IBD, as shown by age at diagnosis, phenotype, the prevalence of perianal disease, surgery and use of biologics. In comparison to a database of 836 Puerto Ricans with non HPS Crohn’s Disease, those with HPS were more likely to have surgeries (69% vs 55%, P=.303) and use biologics (77% vs 43%, P=.015). Gastrointestinal symptoms including bleeding may be overlooked by the primary physician. Proactive vigilance in patients with HPS to make an early diagnosis of IBD and aggressive medical treatment may result in better outcomes for these patients.

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