Inflammatory bowel disease in Hermansky–Pudlak syndrome: a retrospective single-centre cohort study

K. J. O’Brien; X. Parisi; N. R. Shelman; M. A. Merideth; W. J. Introne; T. Heller; W. A. Gahl; M. C.V. Malicdan; B. R. Gochuico

doi:10.1111/joim.13224

Inflammatory bowel disease in Hermansky–Pudlak syndrome: a retrospective single-centre cohort study

K. J. O’Brien
, X. Parisi
, N. R. Shelman
, M. A. Merideth
, W. J. Introne
, T. Heller
, W. A. Gahl
, M. C.V. Malicdan
, B. R. Gochuico

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Background: Knowledge about inflammatory bowel disease (IBD) in patients with Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, could provide insights into IBD in general. Objective: To expand the understanding of IBD in patients with HPS. Methods: Retrospective review of records from patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2019 was conducted. Clinical features of IBD, genotyping results and histologic findings of colectomy specimens were analysed. Results: IBD affected 37 (14.2%; 12 male, 25 female) of 261 patients with HPS. Median age of onset was 17 years; range was 1 to 52 years. The most common symptoms of HPS IBD were hematochezia, abdominal pain and loose stools. Fistulae or extra-intestinal manifestations developed in 30% or 22%, respectively. Genotyping showed that patients with biallelic variants in HPS1, HPS3, HPS4 or HPS6 were diagnosed with IBD. Six children had very early-onset IBD. Patients with HPS-3 had mild manifestations of IBD. Medical therapy and bowel resection were utilized to treat 73% and 35% of patients with HPS IBD, respectively; 7 of 13 patients receiving anti-tumor necrosis factor alpha therapy had prolonged clinical responses. Active cryptitis, chronic inflammatory changes, granulomas and ceroid lipofuscinosis were histopathologic findings in three colectomy specimens. Conclusions: IBD resembling Crohn’s disease affects some patients with HPS; genetic heterogeneity is a feature of HPS IBD. HPS3 is a new gene associated with human IBD. Very early-onset IBD can develop in HPS.

Original language	English
Pages (from-to)	129-140
Number of pages	12
Journal	Journal of Internal Medicine
Volume	290
Issue number	1
DOIs	https://doi.org/10.1111/joim.13224
State	Published - Jul 2021

Bibliographical note

Publisher Copyright:
© Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

Funding

The authors thank our patients who participated in our studies. This study was supported in part by the Intramural Research Programs of the National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of the Director, National Institutes of Health, Bethesda, Maryland. An HPS colon tissue sample was provided by the Cooperative Human Tissue Network, which is funded by the National Cancer Institute; other investigators may have received specimens from the same subject. Colon tissue samples were also provided by the Histopathology & Tissue Shared Resource, which is partially supported by NIH/NCI grant P30-CA051008. The funding sources had no role in the design or conduct of the study, reporting or interpretation of the data, or manuscript preparation. The authors thank our patients who participated in our studies. This study was supported in part by the Intramural Research Programs of the National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of the Director, National Institutes of Health, Bethesda, Maryland. An HPS colon tissue sample was provided by the Cooperative Human Tissue Network, which is funded by the National Cancer Institute; other investigators may have received specimens from the same subject. Colon tissue samples were also provided by the Histopathology & Tissue Shared Resource, which is partially supported by NIH/NCI grant P30‐CA051008. The funding sources had no role in the design or conduct of the study, reporting or interpretation of the data, or manuscript preparation.

Funders	Funder number
NCI/NIH	P30‐CA051008
National Institutes of Health (NIH)
National Human Genome Research Institute	ZIAHG000215
National Childhood Cancer Registry – National Cancer Institute	P30-CA051008
National Institute of Diabetes and Digestive and Kidney Diseases
Office of the Director

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Hermansky–Pudlak syndrome
colitis
inflammatory bowel disease
infliximab
tumor necrosis factor alpha

ASJC Scopus subject areas

Internal Medicine

Access to Document

10.1111/joim.13224

Cite this

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title = "Inflammatory bowel disease in Hermansky–Pudlak syndrome: a retrospective single-centre cohort study",

abstract = "Background: Knowledge about inflammatory bowel disease (IBD) in patients with Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, could provide insights into IBD in general. Objective: To expand the understanding of IBD in patients with HPS. Methods: Retrospective review of records from patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2019 was conducted. Clinical features of IBD, genotyping results and histologic findings of colectomy specimens were analysed. Results: IBD affected 37 (14.2\%; 12 male, 25 female) of 261 patients with HPS. Median age of onset was 17 years; range was 1 to 52 years. The most common symptoms of HPS IBD were hematochezia, abdominal pain and loose stools. Fistulae or extra-intestinal manifestations developed in 30\% or 22\%, respectively. Genotyping showed that patients with biallelic variants in HPS1, HPS3, HPS4 or HPS6 were diagnosed with IBD. Six children had very early-onset IBD. Patients with HPS-3 had mild manifestations of IBD. Medical therapy and bowel resection were utilized to treat 73\% and 35\% of patients with HPS IBD, respectively; 7 of 13 patients receiving anti-tumor necrosis factor alpha therapy had prolonged clinical responses. Active cryptitis, chronic inflammatory changes, granulomas and ceroid lipofuscinosis were histopathologic findings in three colectomy specimens. Conclusions: IBD resembling Crohn{\textquoteright}s disease affects some patients with HPS; genetic heterogeneity is a feature of HPS IBD. HPS3 is a new gene associated with human IBD. Very early-onset IBD can develop in HPS.",

keywords = "Hermansky–Pudlak syndrome, colitis, inflammatory bowel disease, infliximab, tumor necrosis factor alpha",

author = "O{\textquoteright}Brien, \{K. J.\} and X. Parisi and Shelman, \{N. R.\} and Merideth, \{M. A.\} and Introne, \{W. J.\} and T. Heller and Gahl, \{W. A.\} and Malicdan, \{M. C.V.\} and Gochuico, \{B. R.\}",

note = "Publisher Copyright: {\textcopyright} Published 2021. This article is a U.S. Government work and is in the public domain in the USA.",

year = "2021",

month = jul,

doi = "10.1111/joim.13224",

language = "English",

volume = "290",

pages = "129--140",

number = "1",

}

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T1 - Inflammatory bowel disease in Hermansky–Pudlak syndrome

T2 - a retrospective single-centre cohort study

AU - O’Brien, K. J.

AU - Parisi, X.

AU - Shelman, N. R.

AU - Merideth, M. A.

AU - Introne, W. J.

AU - Heller, T.

AU - Gahl, W. A.

AU - Malicdan, M. C.V.

AU - Gochuico, B. R.

N1 - Publisher Copyright: © Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

PY - 2021/7

Y1 - 2021/7

N2 - Background: Knowledge about inflammatory bowel disease (IBD) in patients with Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, could provide insights into IBD in general. Objective: To expand the understanding of IBD in patients with HPS. Methods: Retrospective review of records from patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2019 was conducted. Clinical features of IBD, genotyping results and histologic findings of colectomy specimens were analysed. Results: IBD affected 37 (14.2%; 12 male, 25 female) of 261 patients with HPS. Median age of onset was 17 years; range was 1 to 52 years. The most common symptoms of HPS IBD were hematochezia, abdominal pain and loose stools. Fistulae or extra-intestinal manifestations developed in 30% or 22%, respectively. Genotyping showed that patients with biallelic variants in HPS1, HPS3, HPS4 or HPS6 were diagnosed with IBD. Six children had very early-onset IBD. Patients with HPS-3 had mild manifestations of IBD. Medical therapy and bowel resection were utilized to treat 73% and 35% of patients with HPS IBD, respectively; 7 of 13 patients receiving anti-tumor necrosis factor alpha therapy had prolonged clinical responses. Active cryptitis, chronic inflammatory changes, granulomas and ceroid lipofuscinosis were histopathologic findings in three colectomy specimens. Conclusions: IBD resembling Crohn’s disease affects some patients with HPS; genetic heterogeneity is a feature of HPS IBD. HPS3 is a new gene associated with human IBD. Very early-onset IBD can develop in HPS.

AB - Background: Knowledge about inflammatory bowel disease (IBD) in patients with Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, could provide insights into IBD in general. Objective: To expand the understanding of IBD in patients with HPS. Methods: Retrospective review of records from patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2019 was conducted. Clinical features of IBD, genotyping results and histologic findings of colectomy specimens were analysed. Results: IBD affected 37 (14.2%; 12 male, 25 female) of 261 patients with HPS. Median age of onset was 17 years; range was 1 to 52 years. The most common symptoms of HPS IBD were hematochezia, abdominal pain and loose stools. Fistulae or extra-intestinal manifestations developed in 30% or 22%, respectively. Genotyping showed that patients with biallelic variants in HPS1, HPS3, HPS4 or HPS6 were diagnosed with IBD. Six children had very early-onset IBD. Patients with HPS-3 had mild manifestations of IBD. Medical therapy and bowel resection were utilized to treat 73% and 35% of patients with HPS IBD, respectively; 7 of 13 patients receiving anti-tumor necrosis factor alpha therapy had prolonged clinical responses. Active cryptitis, chronic inflammatory changes, granulomas and ceroid lipofuscinosis were histopathologic findings in three colectomy specimens. Conclusions: IBD resembling Crohn’s disease affects some patients with HPS; genetic heterogeneity is a feature of HPS IBD. HPS3 is a new gene associated with human IBD. Very early-onset IBD can develop in HPS.

KW - Hermansky–Pudlak syndrome

KW - colitis

KW - inflammatory bowel disease

KW - infliximab

KW - tumor necrosis factor alpha

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U2 - 10.1111/joim.13224

DO - 10.1111/joim.13224

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C2 - 33423334

AN - SCOPUS:85099018374

SN - 0954-6820

VL - 290

SP - 129

EP - 140

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

IS - 1

ER -

Inflammatory bowel disease in Hermansky–Pudlak syndrome: a retrospective single-centre cohort study

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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