Gastrointestinal Diseases in Primary Immunodeficiencies

literature performed by Odineal and Gershwin . In the aforementioned Ludvigsson cohort study, the prevalence of UC in SIgAD patients was 1.7% in contrast to 0.46% in the control group. In the same study, the prevalence of CD in SIgAD individuals was 2.4%, compared to 0.42% among controls. Both results were statistically significant, suggesting an association between SIgAD and UC, as well as between SIgAD and CD . date, indicates no significant differences IBD SIgAD IBD in of histological features, treatment. Histological findings in coexistent SIgAD concerning or CD separately


Celiac Disease in Common Variable Immunodeficiency
The prevalence of enteropathy in CVID patients varies depending on the author (10 up to 60%) . These values concern the incidence of non-infectious enteropathy, which is not synonymous with CeD. The true prevalence of the latter is very difficult to estimate, as it is not fully established whether we are facing CeD or only celiac-like enteropathy in CVID patients. Regardless of the way we classify this entity, CeD-resembling findings, including villus atrophy and increased intraepithelial lymphocytes, are common among CVID patients (8-50%) .
Enteropathy accompanied by malabsorption is a common clinical presentation of CVID; however, villus atrophy remains a challenging finding in this group. Serological diagnostics is insufficient in individuals with CVID . In the vast majority of cases, CVID enteropathy differs from CeD not only the results of the serological assays, so it is debated whether it can be classified as true CeD or rather should be called celiac like . Histological assessment of a duodenal biopsy shows a paucity or absence of plasma cells . Besides, villous atrophy is usually less severe and the IEL count is often lower than in CeD, excessive neutrophil infiltration can be observed, as well as graft versus host- up to 80% . GFD is recommended only in HLA-DQ2 or HLA-DQ8 carriers as an attempt of a 6-to 12-month trial with follow-up histologic assessment . Patients without HLA-DQ2 or HLA-DQ8 or unresponsive to GFD should be treated as a distinct disorder. In this case, short-term steroids or immunomodulators, including azathioprine and 6mercaptopurine, can be used . There is also evidence for the efficacy of an elemental diet, while in the case of severe malabsorption, limited use of total parenteral nutrition might be required .
A graphical summary concerning CeD in the discussed PIDs is presented in Figure 1.

Inflammatory Bowel Disease in Selective IgA Deficiency
Various authors seem to agree that the prevalence of IBD in SIgAD patients is increased in contrast to non-SIgAD patients. Ludvigsson et al., in a large population-based matched cohort study, reported a prevalence of 3.9% among SIgAD individuals to 0.81% among controls . In research conducted by Azizi et al., the prevalence of IBD in SIgAD patients was 3.3% . Both results were statistically significant. When concerning the coexistence of SIgAD and UC or SIgAD and CD separately, the prevalence was reported as 0.63% to 7.9% (weighted average of 1.73%) and between 1.21% and 15.8% (weighted average of 2.49%), respectively, in a comprehensive review of the literature performed by Odineal and Gershwin . In the aforementioned Ludvigsson cohort study, the prevalence of UC in SIgAD patients was 1.7% in contrast to 0.46% in the control group. In the same study, the prevalence of CD in SIgAD individuals was 2.4%, compared to 0.42% among controls. Both results were statistically significant, suggesting an association between SIgAD and UC, as well as between SIgAD and CD .
To date, the literature indicates no significant differences between IBD in SIgAD and only IBD in terms of histological features, symptoms, and treatment. Histological findings in coexistent SIgAD and UC or CD are consistent with those concerning UC or CD separately .

Inflammatory Bowel Disease in Common Variable Immunodeficiency
Enteropathy is a common manifestation of CVID . It is difficult to determine the actual prevalence of IBD among CVID patients. Not many studies on this topic are available and authors usually limit themselves to stating that concomitant CVID and IBD occurrence exceeds this in the general population. In many reviews, the prevalence of 2-13% of IBD among CVID patients repeats . Most authors agree on that the clinical signs in IBD or IBD-like within CVID patients show no significant differences with those without CVID and include weight loss, chronic diarrhoea, rectal bleeding, abdominal pain, and malabsorption . The main difference concerns the possibility of co-occurring severe infections in immunocompromised patients . Histopathology assessment of colon specimens from CVID patients shows endoscopic and histopathological features that overlap considerably with CD or UC . 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) . Many authors are in favour of the theory that CVID enteropathy/colitis is a distinct independent disorder, separate from classic IBD, as there is an aforementioned lack of plasma cells in the mucosa . This approach highlights that CVID can mimic lymphocytic colitis, collagenous colitis, and colitis associated with graft-versus-host disease . All the abovedescribed observations suggest that some cases of gut inflammation in CVID patients can be diagnosed as true IBD, while others should be referred to as IBD-like. There is an ongoing discussion on this topic and no consensus has been reached yet.
The clinical approach in managing IBD in primary antibody deficiencies remains a challenge. Regardless of the doubts of whether IBD in CVID should be referred to as IBD, or rather IBD-like disease, or CVID enteropathy/colitis, most authors recommend using therapy schemes for IBD, with increased caution concerning immunosuppressive drugs . However, there is little data about the therapeutical approach in this case. Gut inflammation in CVID is usually difficult to control and often resistant to standard IBD therapy . Treatment of non-infectious GI disease in CVID includes corticosteroids, elimination of bacterial overgrowth with antibiotics, 5-aminosalicylic acid, 6-mercaptopurine, and azathioprine . Besides, several groups reported substantial efficacy of targeted biological therapies, including anti-TNF-α drugs (infliximab and adalimumab), and the anti-IL−12/IL−23 monoclonal antibody ustekinumab . Vedolizumab, an inhibitor of α4β7integrin, was also used in CVID-enteropathy, although with different results . Furthermore, CVID patients with substantial T-cell defects require careful monitoring for fungal infections when on biological treatment. Immunoglobulin replacement therapy lowers the frequency of recurrent or severe infections and reduces the rate of hospitalization, but it was found to be ineffective in IBD-like disease in CVID .
A graphical summary concerning IBD and CVID is presented in Figure 2.