Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report

Abstract

Ataxia-telangiectasia (A-T) is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM) gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children.We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively with extensive cutaneous granulomatosis and severe combined immunodeficiency, without neurological abnormalities, at the time of diagnosis. This case clearly emphasizes the variable presentation of A-T syndrome and highlights the difficulties in the early diagnosis of A-T.A-T should be considered in children with evidence of combined humoral and cellular immunodeficiency associated with unexplained skin granulomatous lesions, even in the absence of the classic features of this syndrome.

B Cell-Specific Expression of Ataxia-Telangiectasia Mutated Protein Kinase Promotes Chronic Gammaherpesvirus Infection

“…ATMdeficient hosts, whether humans or mice, are selectively susceptible to severe chronic, but not acute, viral infections. Specifically, A-T patients display elevated EBV and HHV-6 loads, have prolonged and exacerbated primary varicella-zoster virus infection, and display more robust and persistent skin lesions associated with human papillomavirus (HPV) infection (11)(12)(13)(14)(15)(16)(17). These observations contradict the well-established proviral phenotypes in tissue culture systems, where ATM facilitates infection and replication of diverse herpesviruses and HPV.…”

“…Intriguingly, in contrast to the proviral activity of ATM manifested in tissue culture, A-T patients are selectively susceptible to severe herpesvirus infections, including frequent complications of primary varicella-zoster virus infection (11)(12)(13)(14)(15)(16)(17). Further, EBV (and human herpesvirus 6 [HHV-6], when present) loads are significantly elevated in A-T patients, and abnormal EBV-driven lymphoproliferation observed early in life has been suggested as a possible diagnostic trigger for A-T (12).…”

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.…”

Testing for Herpesvirus Infection Is Essential in Children with Chromosomal-Instability Syndromes

“…Thus, we would like to call attention to the existence of more literature on the investigation of herpesvirus infection in children with chromosomal instability syndromes (e.g., Masucci et al [2], Okano [3], Okano and Gross [4], and Reyes et al [5]) than just the one case report by Folgori et al (6) which was cited by the authors.…”