Among physicians who take care of patients with inflammatory bowel disease (IBD), there is an understanding that the labels “Crohn’s disease” (CD) and “ulcerative colitis” (UC) are imprecise labels. There may be many subtypes of IBD that are classified as CD or UC. This is becoming even more clear with advances in genetics which have shown specific genetic defects that predispose to an IBD phenotype. In fact, more than 100 genetic loci have been uncovered that contribute to IBD, more than any other complex disease (according to editorial in same issue as reference below, pgs 285-87).
Immunodeficiency disorders, like chronic granulomatous disease, are well-recognized as potential mimics for IBD. More recently, IL-10 and IL-10 recpetor genetic mutations have been associated with early-onset IBD phenotypes (Gastroenterol 2012; 143: 347-55.)
In this study, 66 patients whose IBD started before age 5 were investigated for mutatons in the genes encoding IL-10, IL10R1, and IL-10R2. IL-10R deficiency was confirmed with functional assays of patients’ mononuclear cells. “Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency.” In all 16 patients, the phenotype included refractory colitis with perianal disease; symptoms developed in the first three months of life in these 16 patients. Five of these patients improved after hematopoietic stem cell transplantation with a median followup of 2 years.
Test patients with infantile IBD for IL-10 and IL-10 receptor deficiency
Contact for IL-10 testing (free):
Karoline Fiedler, Clinical Research Coordinator, IBD Program, Toronto
Crohn’s disease Differential Diagnosis:
- C. diff
- Klebsiella oxytoca
- Vasculitis (dermatomyositis, Wegener’s, SLE)
- Allergic colitis
- Autoimmune enteropathy
- Chronic granulomatous disease
- Glycogen storage dz, 1B
- Hermansky-Pudlak syndrome
- Wiskott Aldrich syndrome
- NEMO (NF-kB essential modifier) deficiency
- Leukocyte adhesion deficiency
- FELS/hemophagocytic lymphohistiocytosis
- Solitary rectal ulcer syndrome
- Early-onset: IL10/IL10R deficiency, XIAP, ADAM17, NCF2 gene variant
- -Gastroenterol 2012; 143: 347-55. IL-10 signaling defects and IBD.
- -Gut 2012; 61: 1028-35. NCF2 gene variant and IBD.
- -NEJM 2011; 365: 1502-408. ADAM17 deletion and IBD.
- -NEJM 2009; 361: 2033-45. IL-10 receptor and IBD.
- -JPGN 2010; 51: 690. Discusses sarcoid (check angiotensin converting enzyme, CGD, Hermansky Pudlak)
- -JPGN 2010; 50: 99. Perianal dz in young children may be due to autoimmune neutropenia. -IBD 2008; 14: 1443. phagocyte dysfunction. Also, discusses Hermansky-Pudlak, GSD 1B, chronic granulomatous disease, Chediak-Higashi, leukocyte adhesion deficiency, cylic neutropenia, congenital neutropenia
- -Clin Gastro & Hep 2009; 7: 1037. MRI best study for perianal fistulas.
- -JPGN 2006; 42: 405. Vasculitis mimicking IBD.
- -Pediatr 2008; 121: 447. Consider chronic granulomatous disease -particularly if recurrent. 15-18% of CGD pts with perianal abscess. Immunocompromised hosts at increased risk along with Crohn’s patients. However, “vast majority” do not have underlying disease. Can treat perianal abscess medicaly in otherwise healthy infants. (Peds 2007; 120: e548). www.pediatrics.org/cgi/content/full/120/3/e548
- -NEJM 2005; 352: 489-94.
- -Gold B et al. NEJM 2003; 349 (26): 2541, Table 2
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