Cutaneous Granulomas with Predominantly CD8⁺ Lymphocytic Infiltrate in a Child with Severe Combined Immunodeficiency

Abstract

Disseminated granulomatous lesions in children with a history of frequent infections should prompt the clinician to initiate detailed immunocompetence evaluation as they might prove to be the first manifestation of immunologic impairment.

Granulomatous inflammation: The overlap of immune deficiency and inflammation

“…In addition to increased susceptibility to infections, these patients can present a broad range of symptoms such as autoimmunity, granulomatous inflammation, lymphoproliferation, and increased risk of malignancy [66,67]. Granulomatous inflammation has been reported in patients with various genetic defects (Table 5), mainly hypomorphic recombination-activating gene (RAG) mutations [68], hypomorphic Artemis deficiency [69], hypomorphic JAK3 deficiency [70], CD40L deficiency [71], ataxia telangiectasia [72], Nijmegen breakage syndrome [73], cartilage hair hypoplasia [74], and lipopolysaccharideresponsive beige-like anchor (LRBA) deficiency [75]. It has also been reported in a patient as a complication of low immune reconstitution after a haploidentical hematopoietic stem cell transplantation (HSCT) for an X-linked SCID [76].…”

Cutaneous Granulomas in Ataxia Telangiectasia and Other Primary Immunodeficiencies: Reflection of Inappropriate Immune Regulation?

“…Included were all primary publications published in English, German and French. Ten primary reports were found describing cutaneous granulomas in A-T [4,5,6,7,8,9,10,11,12,13] and a series of articles reporting skin granulomas in other PIDs [14,15,16,17,18,19,20,21,22,23,24,25,26]. For common variable immunodeficiency (CVID), often associated with granulomas in various organs, only the recently published article of Ardeniz and Cunningham-Rundles [23] dealing with skin granulomas was included.…”

“…Skin granulomas have been reported also in severe combined immunodeficiency caused by RAG deficiency [16] (2 patients), Artemis deficiency [17] (1 patient) or JAK3 deficiency [18] (1 patient). In Griscelli syndrome, characterized by partial pigmentary dilution or albinism, frequent infections and neurological abnormalities, defective NK- and T-cell cytotoxicity and uncontrolled lymphocyte and macrophage activation, 1 patient has been described [22].…”

“…Our literature search on the occurrence of skin granulomas in other PIDs revealed description of cutaneous granulomas in Nijmegen breakage syndrome (NBS) [14,15], severe combined immunodeficiency caused by deficiency of recombinant activating gene (RAG) [16], Artemis [17] and JAK3 [18], TAP deficiency syndrome [19,20,21], Griscelli syndrome [22] and CVID [23] (table 3). Three studies on skin granulomas were cancelled: 2 studies describing lesions in a patient with X-linked hyper-IgM [24] and IgA deficiency [25], because from the decription the lesions appeared sarcoid-like not resembling the skin granulomas in A-T, and 1 study on a man with X-linked agammaglobulinaemia [26] because the paper was published in 1991 before the btk gene analysis became available and the description of the patient did not fit to what is now known for X-linked agammaglobulinaemia.…”

Chronic active Epstein–Barr virus infection as the initial symptom in a Janus kinase 3 deficiency child

“…Some patients came from families with a medical history of PID and consanguineous marriage. [ 4 – 17 ] Other atypical symptoms such as skin warts [ 8 ] and extensive granuloma [ 15 ] have been found. Some patients are almost normal.…”