Enteropathy - IBD
IPEX - Patients develop intractable chronic diarrhea secondary to autoimmune small bowel inflammation (the colon can also be affected). The diarrhea may be watery, bloody or mucoid. Biopsy of the bowel reveals villous atrophy and lymphocytic infiltrates in the mucosa. Additional features of this disease include atopic dermatitis, endocrinopathies (Type I diabetes and thyroid disease), and autoimmune cytopenias.
STAT1 Gain of Function Mutations
Gain of Function STAT1 Mutations - Patients can develop an IPEX-like phenotype with polyendocrinopathy, enteropathy and dermatitis. Patients have normal frequency and function of Treg cells
Chronic Granulomatous Disease - Patients may develop chronic inflammatory bowel disease similar to Crohn's. Formation of granulomas causing gastric outlet obstruction can also occur. Inflammatory bowel disease has been treated with immunosuppressive therapies. Resolution of refractory inflammatory bowel disease following stem cell transplantation has been reported.
Leukocyte adhesion deficiency - Patients initially presenting with colitis have been reported. Colitis in LAD differs histologically from Crohns due to the absence of neutrophilic inflammation (due to impaired neutrophil migration). Instead, lesions are characterized by lymphocyte, plasma cell, and eosinophil infiltration and lack of granuloma formation.
CVID - Patients are at risk for developing a number of GI tract pathologies including lymphoid nodular hyperplasia and inflammatory bowel disease. An enteropathy with villous blunting (resembling celiac disease) may be present but does not respond to dietary gluten removal. The risk of developing GI tract malignancies (lymphoma, adenocarcinoma) is increased 50 fold.
Wiskott-Aldrich syndrome -Autoimmune disorders have been reported in 40% of patients. These include inflammatory bowel disease, hemolytic anemia, autoimmune neutropenia, skin and cerebral vasculitis, arthritis, renal disease, and Henoch-Shonlein purpura.
Dyskeratosis congenita - The severe infant-onset form of disease (Hoyeraal-Hreidarsson syndrome) presents with enteropathy, IUGR, failure to thrive, cerebellar hypoplasia, and combined immunodeficiency. The enteropathy results from the premature apoptosis of rapidly dividing gut epithelial cells as telomeres reach critically short lengths (this allows for microbial translocation and triggers inflammation). GI biopsies may reveal the presence of epithelial cell apoptosis identical to gut GVHD.
X-linked Hyper IgM - Patients commonly develop infectious diarrhea from Cryptosporidium or Giardia. However, inflammatory bowel disease and nodular lymphoid hyperplasia have also been described in patients.
NEMO deficiency - Inflammatory bowel disease has been described in this disease.
AID deficiency - Inflammatory bowel disease has been described in this disease. Autoimmunity (thrombocytopenia, hemolytic anemia, autoimmune hepatitis) affects approximately 25% of patients with AID deficiency.
Intestinal Lymphangiectasia
Intestinal lymphangiectasia - This condition is characterized by abnormal dilation of gut lymphatics leading to chronic diarrhea and protein-losing enteropathy. Immune abnormalities include hypogammaglobulinemia and lymphopenia. Naïve (CD45RA) T cell numbers are decreased to a greater extent than memory (CD45RO) T cell numbers.
Omenn syndrome - Patients may develop diarrhea and protein-losing enteropathy. Other key clinical features include erythroderma with desquamation, splenomegaly, and lymphadenopathy. Immunologic features include a normal absolute lymphocyte count and normal total T cell numbers (due to oligoclonal T cell expansion), low or normal mitogen proliferation, low IgG and specific antibody response, elevated IgE, and eosinophilia.
Cartilage Hair Hypoplasia - Patients can develop autoimmune enteropathy and Hirschsprung disease. Other autoimmune manifestations include ITP, hemolytic anemia, juvenile idiopathic arthritis, and autoimmune enteropathy.
XIAP Deficiency - Patients can develop chronic hemorrhagic colitis. This clinical
feature has not been observed in patients with SAP Deficiency.
IL-10 and IL-10 Receptor Deficiency
IL-10 and IL10 Receptor Deficiency - Patients present early in life with severe inflammatory bowel disease resulting in formation of anal fissues and fistulae as well as abscesses. Patients commonly require surgical interventions including partial or total colectomy. Patients are typically unresponsive to immunosuppressive therapies (corticosteroids, methotrexate, anti-TNFalpha).