Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease.

Laura Dotta, Omar Scomodon, Rita Padoan, Silviana Timpano, Alessandro Plebani, Annarosa Soresina, Vassilios Lougaris, Daniela Concolino, Angela Nicoletti, Giuliana Giardino, Amelia Licari, Gianluigi Marseglia, Claudio Pignata, Nicola Tamassia, Fabio Facchetti, Donatella Vairo, Raffaele Badolato

Journal: Clinical immunology (Orlando, Fla.) 2016;164():1-9

PMID: 26732859

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Abstract

In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis.

Address: Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy. Electronic address: [email protected].; Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy.; Unit of Paediatric Pneumonology, Spedali Civili of Brescia, Brescia, Italy.; Department of Paediatrics, University of Catanzaro, Catanzaro, Italy.; Department of Translational Medical Sciences, Federico II University, Naples, Italy.; Department of Paediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.; Department of Medicine, General Pathology Unit, University of Verona, Verona, Italy.; Department of Molecular and Translational Medicine, Pathology Unit, University of Brescia, Brescia, Italy.; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

DOI: 10.1016/j.clim.2015.12.010

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MeSH Terms: Adolescent, Adult, Antifungal Agents, Autoimmunity, Azoles, Bacterial Infections, Candidiasis, Chronic Mucocutaneous, Child, Chronic Disease, Cryptococcosis, Cryptococcus neoformans, Drug Resistance, Female, Humans, Leishmaniasis, Visceral, Lung Diseases, Lymphopenia, Male, Middle Aged, Mutation, Phosphorylation, STAT1 Transcription Factor, Virus Diseases, Young Adult