Gastrointestinal lesions associated with spondyloarthropathies

Abstract

Subclinical gut inflammation has been described in up to two-thirds of patients with spondyloarthropathies (S pA). Ar t hr i t is represents an extra-intestinal manifestation of several gastrointestinal diseases, including inflammatory bowel disease (IBD), Whipple's disease, Behcet's disease, celiac disease, intestinal bypass surgery, parasitic infections of the gut and pseudomembranous colitis. Moreover about twothirds of nonsteroidal anti-inflammatory drug users demonstrate intestinal inflammation. Arthritis may manifest as a peripheral or axial arthritis. The spondyloarthropathy family consists of the following entities: ankylosing spondylitis, undifferentiated s p o n d y l o a r t h r i t i s , r e a c t i ve a r t h r i t i s , p s o r i a t i c arthritis, spondyloarthritis associated with IBD, juvenile onset spondyloarthritis. This topic reviews the major gastrointestinal manifestations that can occur in patients with SpA and in nonsteroidal antiinflammatory drugs users.

Different effects of anti-TNF-alpha biologic drugs on the small bowel macroscopic inflammation in patients with ankylosing spondylitis

“…This complicated our investigation but offered a chance to look into the impact of anti-TNF alpha agents on NSAID use and their intestinal side effects. Supporting the role of NSAIDs in fueling the smoldering inflammatory intestinal activity in AS is the association with inflammatory changes, such as erythema, erosions, ulcers, and also strictures and perforations [14,20] reported in healthy controls. In fact, up to two thirds of NSAID users present inflammatory small bowel mucosal changes or an increase in intestinal permeability [11,16], and, surprisingly, up to the same two thirds of AS patients are previously described to harbor intestinal inflammatory lesions [2,18,20,21].…”

“…Supporting the role of NSAIDs in fueling the smoldering inflammatory intestinal activity in AS is the association with inflammatory changes, such as erythema, erosions, ulcers, and also strictures and perforations [14,20] reported in healthy controls. In fact, up to two thirds of NSAID users present inflammatory small bowel mucosal changes or an increase in intestinal permeability [11,16], and, surprisingly, up to the same two thirds of AS patients are previously described to harbor intestinal inflammatory lesions [2,18,20,21]. Thus, the issue of intestinal inflammation in spondyloarthritides is very complex, and no one proved so far what is the real contribution of NSAIDs to its development and maintenance Because NSAID therapy is currently considered to be the first-line therapy of AS [34], it has been difficult to isolate their effect on intestinal inflammation in this setting [35][36][37].…”

“…Appleyard et al proved in an experimental study that TNF alpha plays a pivotal role in the pathogenesis of intestinal injuries induced by NSAIDs [17]. Knowing that NSAID treatment has the potential to enhance the bowel inflammation in AS patients [11,14,16,20], we speculated that these patients could benefit from anti-TNF alpha therapy both for lowering ASrelated intestinal injuries as well as for the NSAIDinduced lesions. Similar to our findings, recent studies have shown that rheumatoid arthritis patients who received anti-TNF agents had less severe NSAID-induced enteropathy in comparison to those who did not receive such therapy, supporting the protective effect of anti-TNF alpha agents against NSAID-induced gut lesions [12].…”

“…Studies have shown that up to two thirds of AS patients harbor intestinal inflammatory lesions [2,18,20,21] and that these chronic inflammatory bowel involvements are histopathologically similar to Crohn's disease (CD) -mucosal glandular structure is disorganized due to crypts destruction, irregular and fused villi, and lamina propria includes a mononuclear infiltrate. As such, current data (clinical, genetic, histopathologic and immunologic) suggests that AS and CD should be acknowledged as two different phenotypes of a common underlying immune-mediated inflammatory disease pathway [22], especially seeing that 5-13% of AS patients go on to develop IBD [23,24].…”

New aspects of spondyloarthritis pathogenesis. Part II – environmental factors, microbiome disturbances, extra-articular symptoms

“…W zmianach przetrwałych, stwierdzanych przede wszystkim u chorych na ZZSK i niezróżnicowane SpA, jelito naciekają różne rodzaje komórek, a struktura błony śluzowej jest zaburzona, co przypomina chorobę Leśniowskiego i Crohna (ChL-C). U 1/3 chorych rozpoznaje się wczesną postać tej choroby [9,35,39]. Ryzyko rozwoju NZJ w SpA zwiększają uwarunkowania genetyczne, które mogą zaburzać homeostazę w jelicie -polimorficzne odmiany genów upośledzających wrodzoną odpowiedź immunologiczną na bakteryjne zakażenia jelit (geny NOD2 i ATG16L1), wpływające na integralność bariery nabłonkowej i procesy naprawcze (gen PTPRS), a także geny kodujące cytokiny lub ich receptory (geny IL-10 i IL-23R) oraz geny związane z prezentacją antygenów (geny ERAP) [35].…”