RESUMO
The use of voriconazole, a trifluorinated antifungal, has been associated with the development of fluoride excess and periostitis/exostoses. We evaluated a cohort of patients on long-term triazole therapy and found that other fluorinated triazoles (fluconazole and posaconazole) conferred no risk for the development of hyperfluorosis and its complications in our cohort.
Assuntos
Antifúngicos/efeitos adversos , Coccidioidomicose/tratamento farmacológico , Fluconazol/administração & dosagem , Pirimidinas/efeitos adversos , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Adolescente , Adulto , Antifúngicos/administração & dosagem , Coccidioides/efeitos dos fármacos , Coccidioides/crescimento & desenvolvimento , Coccidioidomicose/microbiologia , Estudos de Coortes , Exostose/induzido quimicamente , Feminino , Fluoretos/metabolismo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Periostite/induzido quimicamente , Pirimidinas/administração & dosagem , Estados Unidos , VoriconazolRESUMO
BACKGROUND: We have observed a number of patients who fail to develop coccidioidal complement fixing (CF) antibody (immunoglobulin [IgG]) after the initiation of early antifungal therapy. Although this is the first description of this phenomenon in mycology, a precedent for the abrogation of the immune response has been observed in other conditions, including primary syphilis and primary Lyme disease. METHODS: We conducted a retrospective case-control study to determine any patient-specific risk factors associated with this observation. Additionally, in vitro analysis of the coccidioidal CF (IgG) antigen (Cts1) was performed after Coccidioides was grown under escalating fluconazole concentrations. RESULTS: Seventeen patients persistently positive for coccidioidal IgM antibodies without developing an IgG response (cases) were compared with 64 consecutive patients who did develop coccidioidal CF (IgG) antibodies (controls). Early treatment with antifungals (within 2 weeks of symptom onset) was associated with an abrogation of IgG antibody production (P < .001). With immunodiffusion testing, control serum demonstrated a lack of IgG seroreactivity when Coccidioides posadasii grown in the presence of escalating fluconazole doses (0.5-128 µg/mL) was used as the antigen; however, control serum remained seroreactive for the presence of IgM. The coccidioidal IgG antigen (Cts1) was shown to be diminished when cultures were grown in the presence of fluconazole, lending further in vitro plausibility to our findings. CONCLUSIONS: The abrogation of an IgG response in patients treated early in the course of coccidioidal infection may complicate serodiagnosis and epidemiologic studies, and further study to determine the potential clinical implications should be performed.