Challenges toward management of CARD9-deficient patients with phaeohyphomycosis: a case report and case series study

Abstract

Here, we studied the genetic and immunological mechanisms underlying recalcitrant phaeohyphomycosis and shared our clinical experiences regarding its treatment. We followed-up and analyzed 10 patients with phaeohyphomycosis with CARD9 deficiency admitted to our department in the past two decades; one of them was a novel case of recalcitrant phaeohyphomycosis harboring CARD9 mutations. Consequently, we identified a total of seven CARD9 mutations in the analyzed patients. Moreover, patient-derived cells exhibited a significant impairment of innate and adaptive immune responses upon fungus-specific stimulation. All the patients experienced recurrence and exacerbation; among them four died, two exhibited continued disease progress with unsatisfactory therapeutic efficacy, three showed obvious improvement under maintenance therapy, and only one achieved clinical cure. Our study highlighted that otherwise healthy patients diagnosed with early-onset, unexplained, and recalcitrant phaeohyphomycosis should be analyzed for CARD9 mutations and immune deficiency. Thereafter, the length and choice of management remain challengeable, and must be adjusted based on the clinical presentation and response of patients over their lifetimes. Although continued posaconazole treatment may be the promising first-line therapy at present, novel strategies are worth exploring.

Post-translational changes in Phialophora verrucosa via lysine lactylation during prolonged presence in a patient with a CARD9-related immune disorder

“…Their relatively high prevalence in patients with CARD9 -related immune disorders ( 3 ) is as yet unexplained. Particularly members of the Phialophora verrucosa complex are overrepresented ( 3 , 30 ). All CARD9 -related infections have a chronic character and are poorly controlled by antifungal treatment ( 31 ), even if the respective antifungals are in vitro effective ( 32 ).…”