IL-10 and IL-10 Receptor Deficiency — Pediatric Gastroenterology Review

Pathophysiology

Role of IL‑10 signaling: IL‑10/IL‑10 receptor signaling restrains hyperinflammatory responses in innate and adaptive immune cells and is critical for maintaining intestinal mucosal homeostasis and tolerance.

Genetic defects: Loss‑of‑function mutations in IL10, IL10RA, or IL10RB impair this anti‑inflammatory pathway and precipitate severe intestinal inflammation.

Clinical presentation

Age at onset: Typically presents in infancy, often within the first 3–6 months of life.
Intestinal disease: Severe, treatment‑refractory colitis with fulminant features including bloody diarrhea, failure to thrive, and diffuse mucosal inflammation.
Perianal and fistulizing disease: Marked propensity for perianal abscesses, complex perianal fistulae, and enterocutaneous fistulas.
Extraintestinal features: Chronic folliculitis, recurrent skin inflammation, and occasional arthritis or systemic inflammatory manifestations.
Oncologic risk: Increased lifetime risk of B‑cell lymphoma reported in affected cohorts.

Diagnosis

Clinical suspicion: Consider in infants with very early‑onset, severe, treatment‑resistant IBD, especially with perianal disease or severe skin inflammation.
Laboratory and pathology: Basic immune testing may be unrevealing; histology shows severe colitis and may include profound immune activation. Genetic testing confirms pathogenic variants in IL10, IL10RA, or IL10RB.
Family history and consanguinity: Positive family history or consanguineous background increases pretest probability and supports genetic evaluation.

Treatment and prognosis

Medical therapy: Intestinal inflammation is typically refractory to conventional immunosuppressive and biologic therapies used for IBD.
Curative therapy: Allogeneic hematopoietic stem cell transplantation corrects the underlying immune defect and is the definitive therapy; outcomes are substantially improved when performed early.
Supportive management: Aggressive nutritional support, control of sepsis and perianal sepsis, and multidisciplinary care involving gastroenterology, immunology, surgery, and transplant teams.

Clinical pearls

Think IL‑10 pathway defects in infants with onset of severe colitis and perianal disease in the first months of life that do not respond to standard IBD therapy.
Pursue genetic testing early because prompt diagnosis enables timely referral for HSCT and avoids prolonged ineffective immunosuppression.
Coordinate care with immunology and transplant centers; prioritize infection control and nutritional optimization prior to transplant.