CARMIL2‐related immunodeficiency manifesting with photosensitivity

Abstract

We report a case of a newly recognized primary immunodeficiency due to biallelic mutations in CARMIL2 manifesting as an actinic prurigo-like photodermatitis, allergic diathesis and recurrent infections in a child. We present this case to highlight a rare phenotype seen in this T-cell immunodeficiency and provide an overview of other dermatologic manifestations among published reports of this condition.

Evolution and long‐term outcomes of combined immunodeficiency due to CARMIL2 deficiency

“…All the described mutations were deleterious as they led to undetectable or reduced protein expression (P5) in CD4 + and CD8 + T cells, as measured by flow cytometry (Figure 2B). The current and previously reported mutations were located mostly in the LRR and HD domains, followed by the PH domain, 1,2,[11][12][13][14][15][16][17][18][19][20] and only one mutation in the CBR domain, 28 while mutations in PRR domain have not been identified. Despite undetectable CARMIL2 expression (regardless of mutation location), the clinical presentation varied in severity even between members of the same family.…”

“…Topical corticosteroids and calcineurin inhibitors are effective in managing eczema and psoriatic lesions, and sun protection helped in cases with photosensitive dermatitis. 16 More commonly used options are mesalazine, sulfasalazine, steroids, azathioprine, and infliximab for IBD. Abatacept was received by one patient 12 and provided partial response, which can be promising, since lower CTLA4 expression was found in our tested patients.…”

“…So far, fewer than 40 cases of CARMIL2 deficiency have been reported worldwide. Patients with CARMIL2 deficiency present with a broad range of symptoms, including cutaneous and respiratory allergies mainly characterized by eczematous lesions, early‐onset inflammatory bowel disease (EO‐IBD), recurrent bacterial, fungal, and viral infections, mucocutaneous candidiasis, skin abscesses, mycobacterial infections, EBV‐related smooth muscle tumors (SMT), and growth retardation 1,2,11–20 . Immunologically, affected individuals have elevated naive CD4 + T cells and decreased proportions of circulating T follicular helper cells (cT FH ), mucosal‐associated invariant T‐cell, T H 1, T H 17, and regulatory Foxp3 + T cells concomitant with impaired T‐cell activation, proliferation, and cytokine responses due to the defective CD28 engagement 1,2 .…”

“…inflammatory bowel disease (EO-IBD), recurrent bacterial, fungal, and viral infections, mucocutaneous candidiasis, skin abscesses, mycobacterial infections, EBV-related smooth muscle tumors (SMT), and growth retardation. 1,2,[11][12][13][14][15][16][17][18][19][20] Immunologically, affected individuals have elevated naive CD4 + T cells and decreased proportions of circulating T follicular helper cells (cT FH ), mucosal-associated invariant T-cell, T H 1, T H 17, and regulatory Foxp3 + T cells concomitant with impaired T-cell activation, proliferation, and cytokine responses due to the defective CD28 engagement. 1,2 Defective memory B-cell formation with poor specific antibody responses was also described in some patients, although this cellular defect is not as prominent as those observed in T cells.…”

Epstein–Barr Virus in Inborn Immunodeficiency—More Than Infection

“…Patients present with low-level EBV-viremia. Interestingly, EBV-LPD or lymphoma has never been observed, instead 20% of the patients (8/44) developed EBV-associated smooth muscle tumors (SMT) [ 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. The mechanisms are still unknown.…”