Hematopoietic Stem Cell Transplantation From Unrelated Donors in 2 Cases of Interleukin-10 Receptor Deficiency: Is Surgery Not a Requirement?

Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, and enterocutaneous fistulas. Patients with infantile IBD often require several surgical interventions, including complete colectomy, and hematopoietic stem cell transplantation is currently the only known medical therapy. Traditionally, operative management has been preferred before stem cell transplantation because of the latter's increased susceptibility to procedural complications; however, surgical intervention could be delayed, and possibly reconsidered, because our 2 patients with infantile IBD demonstrated a rapid response to treatment via engraftment.

Immune Reconstitution Inflammatory Syndrome After DLI in a SCID Patient After Hematopoetic Stem Cell Transplantation.

Immune reconstitution inflammatory syndrome (IRIS) is a clinical condition emerging after immune recovery of an immunocompromised status, mostly in human immunodeficiency virus infected patients but also in several other settings, such as the recovery from the severe combined immunodeficiency status after hematopoietic stem cell transplantation. Herein, we report a patient transplanted for severe combined immunodeficiency who developed IRIS for 2 times, namely shortly after transplantation and after donor lymphocyte infusion. Pediatric transplant teams need to be aware of the previous IRIS phenomenon of BCG-adenitis while making the decision of donor lymphocyte infusions.

Cutaneous leukocytoclastic vasculitis due to Salmonella enteritidis in a child with interleukin-12 receptor beta-1 deficiency.

Defects in the interleukin 12 (IL-12)/interferon gamma (IFN-γ) pathway result in Mendelian susceptibility to mycobacterial disease (MSMD). IL-12 receptor beta 1 (IL-12Rß1) deficiency, the most common form of MSMD, is associated with weakly virulent mycobacteria and salmonella. Infections in patients with this deficiency are extraintestinal, or septicemic, recurrent infections with nontyphoid salmonellae. Here we report a case of an IL-12Rß1 deficiency with cutaneous leukocytoclastic vasculitis due to Salmonella enteritidis.

Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation.

BACKGROUND: Inherited deficiencies of IL-10 or IL-10 receptor (IL-10R) lead to immune dysregulation with life-threatening early-onset enterocolitis. OBJECTIVES: We sought to gather clinical data of IL-10/IL-10R-deficient patients and devise guidelines for diagnosis and management, including hematopoietic stem cell transplantation (HSCT). METHODS: We enrolled 40 patients with early-onset enterocolitis and screened for mutations in IL10/IL10R using genetic studies, functional studies, or both of the IL-10 signaling pathway. Medical records of IL-10/IL-10R-deficient patients were reviewed and compiled. RESULTS: Of 40 patients, we identified 7 with novel mutations, predominantly in consanguineous families with more than 1 affected member. IL-10/IL-10R-deficient patients had intractable enterocolitis, perianal disease, and fistula formation. HSCT was carried out in 2 patients with IL-10 deficiency and 1 patient with IL-10R α chain deficiency and proved to be an effective therapy, leading to rapid improvement of clinical symptoms and quality of life. CONCLUSION: Because the defect in patients with IL-10/IL-10R deficiency resides in hematopoietic lineage cells and their colitis is resistant to standard immunosuppressive therapy, HSCT should be considered early as a potentially curative therapeutic option.