A rare immunological disease, caspase 8 deficiency: case report and literature review

Abstract

Background Caspase-8 is a molecule in the FAS pathway that initiates apoptosis. One of the rarest autoimmune lymphoproliferative syndromes is caspase-8 deficiency. Immunodeficiency, splenomegaly, and lymphadenopathy are the common symptoms of this condition. Case Presentation A two-year-old boy entered this study with a fever of unknown origin (FUO) and dysentery. Moreover, he suffered from failure to thrive and was allergic to the cow's milk protein. His fever and dysentery did not respond to antibiotic therapy. The colonoscopy revealed diffuse ulcerations regions in the sigmoid along with skipped areas, mimicking Crohn's disease aphthous lesions. He represented very early-onset inflammatory bowel disease (IBD) and was diagnosed with the caspase-8 deficiency. Conclusion There can be diarrhea or dysentery as the first or main symptoms of inborn errors of immunity (IEIs). The cause of diarrhea and dysentery in this case was early-onset IBD. One of the symptoms of IEIs such as caspase-8 deficiency is early-onset of IBD. Patients with early-onset had normal T cell count and low or normal immunoglobulin levels with insufficient immune response.

Infections in Disorders of Immune Regulation

“…Following activation of FAS, procaspase-8 is recruited by the death-effector domain (DED) heterodimer, and caspase-8 is ultimately activated [ 14 ]. Thus, deficiency of caspase-8 leads to a range of clinical manifestations like ALPS [ 14 , 15 , 16 ]. Caspase-8 is essential for T cell activation (specifically TCR-induced NF-kB activation), in addition to death receptor-mediated apoptosis.…”

“…Caspase-8 also regulates necroptosis and pyroptosis, which are inflammatory lytic cell death pathways [ 17 ]. Therefore, apart from lymphoproliferation, CEDS is associated with profound immunodeficiency and manifests as recurrent infections, inflammation, and autoimmunity [ 14 , 15 , 16 , 18 ].…”

“…Very-early-onset inflammatory bowel disease with fistulating perineal disease presenting with chronic diarrhea and mimicking cow milk protein has been described. Other autoimmune manifestations like hemolytic anemia and interstitial lung disease have also been described [ 14 , 15 , 16 , 18 , 19 ]. Recurrent mucocutaneous herpetic infection was reported as a cardinal infection in patients with CEDS [ 19 ].…”

“…Recurrent mucocutaneous herpetic infection was reported as a cardinal infection in patients with CEDS [ 19 ]. Recurrent sinopulmonary bacterial infections and viral infections like herpes, EBV, and molluscum contagiosum are also described [ 15 , 16 , 18 , 19 , 20 ] ( Table 2 ). Fatal Nocardia meningoencephalitis has also been reported in a patient [ 16 ].…”