Recognizing Gastrointestinal and Hepatic Manifestations of Primary Immunodeficiency Diseases

Abstract

Given the complex immune function of the gastrointestinal (GI) tract, it is not surprising that many children with primary immunodeficiencies present with GI tract manifestations. Although many immunodeficiency disorders present with overt evidence of immune dysregulation, a few can present in older children with more subtle signs and symptoms. Such children may present first to a gastroenterologist with common symptoms, including malabsorption, diarrhea, hepatomegaly, or inflammatory bowel disease, which may actually be a manifestation of their underlying immune disorder. A thorough clinical history in combination with a careful review of histology from biopsies may reveal clues that one is dealing with a disease entity outside the norm and may prompt additional laboratory studies beyond the usual set of screening laboratory tests. Once the true underlying diagnosis is revealed, more appropriate therapy can be initiated. Additionally, more appropriate anticipatory guidance regarding the expected disease course, response to medications, and any additional risks that therapy may entail can be provided to the family.

Gastrointestinal Manifestations in Children with Primary Immunodeficiencies: Single Center: 12 Years Experience

“…In our cohort, colitis was found in 42.8% of the patients with CVID, and 1 out of 7 patients with CVID presented with Crohn-like clinical and histopathological features except for the absence of plasma cells in the lamina propria of the colon biopsies. IBD-like manifestations have been reported in nearly 4-6% of patients with CVID [7,22,23]. In our study population, 12 patients with different PID had presented with clinical features of enteropathy and/or colitis, and histopathological findings of the colonic and/or intestinal biopsies were similar to the patients with IBD as well.…”

“…The prevalence of celiac disease in IgA-deficient people has been reported to be between 10 and 30% [7]. Since IgG-based serological tests are not sufficiently reliable, and IgA-based tests are usually negative in these patients, serologic screening of celiac disease would be misleading in patients with PID.…”

“…Flattening of the intestinal villi, resembling classical celiac disease is a common histopathological finding in PID [17,19]. Previously, intraepithelial lymphocytosis with villous atrophy had been demonstrated in 31-60% of patients with CVID [7,17]. However, celiac disease-specific IgA and IgG antibodies are usually absent in those patients [20].…”

“…However, clinical manifestations may be more subtle and surreptitious, and can present later in life, even during adulthood. Children with PID are prone to developing infectious, inflammatory, autoimmune diseases, and malignancies [7][8][9][10][11]. GI manifestations have been reported in approximately 5-50% of patients with PID [2,12,13].…”

Decoding inflammatory bowel disease through the lens of immunodeficiency

“…Intestinal granulomas are found in nearly 50% of patients with chronic granulomatous disease (CGD), and up to 17% of CGD patients develop colitis. 6 Patients with mutations in interleukin-10 receptor (IL-10R) and IL-10 genes can develop early-onset enterocolitis. 7,8 Gastrointestinal inflammation can also be seen in patients with Wiskott-Aldrich syndrome (WAS), immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and NFκB essential modulator defects.…”