Gastrointestinal Disorders Associated with Primary Immunodeficiency Diseases

Abstract

There are now 354 inborn errors of immunity (primary immunodeficiency diseases (PIDDs)) with 344 distinct molecular etiologies reported according to the International Union of Immunological Sciences (IUIS) (Clin Gastroenterol Hepatol 11: p. 1050-63, 2013, Semin Gastrointest Dis 8: p. 22-32, 1997, J Clin Immunol 38: p. 96-128, 2018). Using the IUIS document as a reference and cross-checking PubMed ( www.ncbi.nlm.nih.pubmed.gov ), we found that approximately one third of the 354 diseases of impaired immunity have a gastrointestinal component [J Clin Immunol 38: p. 96-128, 2018]. Often, the gastrointestinal symptomatology and pathology is the heralding sign of a PIDD; therefore, it is important to recognize patterns of disease which may manifest along the gastrointestinal tract as a more global derangement of immune function. As such, holistic consideration of immunity is warranted in patients with clinically significant gastrointestinal disease. Here, we discuss the manifold presentations and GI-specific complications of PIDDs which could lead patients to seek advice from a variety of clinician specialists. Often, patients with these medical problems will engage general pediatricians, surgeons, gastroenterologists, rheumatologists, and clinical immunologists among others. Following delineation of the presenting concern, accurate and often molecular diagnosis is imperative and a multi-disciplinary approach warranted for optimal management. In this review, we will summarize the current state of understanding of PIDD gastrointestinal disease involvement. We will do so by focusing upon gastrointestinal disease categories (i.e., inflammatory, diarrhea, nodular lymphoid hyperplasia, liver/biliary tract, structural disease, and oncologic disease) with an intent to aid the healthcare provider who may encounter a patient with an as-yet undiagnosed PIDD who presents initially with a gastrointestinal symptom, sign, or problem.

Calculation of a Primary Immunodeficiency “Risk Vital Sign” via Population-Wide Analysis of Claims Data to Aid in Clinical Decision Support

“…We hypothesized that weighted diagnosis codes and pharmacy records may inform individual risk for PI across a population and could therefore be utilized as a clinical decision aid during routine patient care. This is important because the presentation of PI is variable and recognition of the disease entity can be challenging (19). Also, among patients with immune deficiency, annual disease-related care exceeds $100,000 and post-diagnosis cost savings are calculated to be $78,166 (USD) even when cost of therapy is accounted for (15, 16, 20).…”

Primary Humoral Immune Deficiencies: Overlooked Mimickers of Chronic Immune-Mediated Gastrointestinal Diseases in Adults

“…According to Malamut et al, villous atrophy was observed in over 50% of CVID patients [ 156 ], while Luizi et al indicated it to be 31.2% [ 221 ]. A literature review performed by Hartono et al reported the presence of villus atrophy in CVID patients within the range of 24% to 50% [ 222 ]. However, Karaca et al showed a lower incidence of celiac-resembling enteropathy in CVID, as it affected only 10% of the study participants [ 92 ].…”

“…Histological findings in coexistent SIgAD and UC or CD are consistent with those concerning UC or CD separately, which are described above [ 8 , 287 ]. Despite this, many authors underline the need of ruling out PID in patients with IBD and a consistent history of recurrent infection, failure to respond to therapy, or a particularly severe course of disease [ 14 , 15 , 222 ].…”

“…In many reviews, the prevalence of 2–13% of IBD among CVID patients repeats [ 13 , 174 , 222 ]. Hermaszewski and Webster reported the prevalence of IBD in CVID as 4% [ 288 ].…”

“…Hartono et al summarized that histopathology assessment of colon specimens from CVID patients shows endoscopic and histopathological features that overlap considerably with CD or UC [ 157 , 222 , 303 , 304 ]. One difference that can help distinguish idiopathic IBD from CVID enteropathy/colitis remains the paucity of plasma cells in their biopsy (observed in 68% of the patients) [ 222 , 305 ]. Additionally, Tegtmeyer et al indicated that both symptoms and histologic findings are indistinguishable in idiopathic IBD and IBD related to PID [ 15 ].…”