1. Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease.
- Author
-
Dotta L, Scomodon O, Padoan R, Timpano S, Plebani A, Soresina A, Lougaris V, Concolino D, Nicoletti A, Giardino G, Licari A, Marseglia G, Pignata C, Tamassia N, Facchetti F, Vairo D, and Badolato R
- Subjects
- Adolescent, Adult, Antifungal Agents therapeutic use, Autoimmunity, Azoles therapeutic use, Bacterial Infections complications, Candidiasis, Chronic Mucocutaneous complications, Candidiasis, Chronic Mucocutaneous drug therapy, Child, Chronic Disease, Cryptococcosis complications, Cryptococcus neoformans, Drug Resistance, Female, Humans, Leishmaniasis, Visceral complications, Lung Diseases complications, Lung Diseases drug therapy, Lung Diseases genetics, Lymphopenia complications, Male, Middle Aged, Mutation, Phosphorylation, STAT1 Transcription Factor metabolism, Virus Diseases complications, Young Adult, Candidiasis, Chronic Mucocutaneous genetics, STAT1 Transcription Factor genetics
- 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF