Chronic granulomatous disease mimicking early-onset Crohn’s disease with cutaneous manifestations

Abstract

BackgroundChronic granulomatous disease is a rare inherited disorder of the innate immune system. In patients with a clinical history of recurrent or persistent infections, especially infections caused by uncommon species, chronic granulomatous disease should be considered.Case presentationWe report the case of a 5-year-old boy with a presumptive diagnosis of Crohn’s disease with extraintestinal manifestations. Chronic granulomatous disease was suspected in this case after Serratia marcescens was isolated from a skin ulcer culture. Granulomas were confirmed on histology and chronic granulomatous disease was diagnosed.ConclusionThis case emphasizes the importance of high clinical suspicion of an alternative diagnosis of immune deficiency in patients with presumed inflammatory bowel disease and opportunistic infections, especially when disease occurs in early life.

ROS in gastrointestinal inflammation: Rescue Or Sabotage?

“…CGD patients may present with perirectal abscesses, GI tract obstruction and recurrent diarrhoea. Colon endoscopy often reveals colonic narrowing, a thickened bowel wall, pancolitis and pseudopolyps, whereas the histology shows submucosal oedema, crypt abscesses, inflammatory cell infiltration, cryptitis, epithelioid granulomas (usually in the muscularis ) and large pigment‐laden histiocytes in the LP (Agarwal and Mayer, ; Barbato et al , ). Decreased NOX2 activity, above the threshold leading to CGD, has also recently been linked to very early onset (VEO)IBD (defined as IBD in children <6 years of age according to the modified Paris classification) (Eszter Muller et al , ).…”

Genetic disorders coupled to ROS deficiency

“…The 35–40% prevalence of IBD with CD-like features in CGD patients places impairment of the Nox2 complex prominently as a risk factor for intestinal disease. Histologically this disease can be distinguished from CD by the presence of multiple granulomas in the lamina propria and large pigment-laden histiocytes [119–121] . The susceptibility for developing CGD-CD is associated with inactivating CYBB variants rather than with NCF1 variants or with the remaining ROS output in stimulated neutrophils [55,119] .…”

The NET, the trap and the pathogen: neutrophil extracellular traps in cutaneous immunity

“…In humans, only few studies have linked NETosis to cutaneous host defense. The in vivo role of NETs in this regard might possibly be suggested by the fact that neutrophils isolated from patients with chronic granulomatous disease (CGD), which are prone to infections including skin , were severely defective in NETosis . Moreover, in biopsies of human cutaneous leishmaniasis, complexes of DNA and elastase were observed , indicating the in vivo presence of NETs in leishmania infection.…”