Eficácia e segurança da oxigenoterapia hiperbárica como terapia adjuvante no tratamento da esporotricose humana

Abstract

Sporotrichosis is a subcutaneous mycosis caused by Sporothrix species, acquired mainly through traumatic inoculation of fungal spores from soil, plants, or through scratches and bites from infected cats. The lymphocutaneous form is the most common and may take several months to up to one year for complete healing, requiring prolonged use of antifungals such as itraconazole. There are challenges in conventional treatment, including slow clinical response, recurrence, and drug toxicity. Hyperbaric oxygen therapy (HBOT) has demonstrated antimicrobial properties, improvement in tissue oxygenation, and immunomodulatory effects, potentially capable of accelerating wound healing and improving therapeutic outcomes. The main objective of this study was to evaluate whether the addition of HBOT to standard itraconazole treatment safely reduces the time to cure in patients with cutaneous/lymphocutaneous sporotrichosis, compared to itraconazole monotherapy. This was a prospective, non-randomized, non-placebo-controlled study, conducted between May 2021 and December 2024, involving patients with clinical and/or microbiological diagnosis of cutaneous or lymphocutaneous sporotrichosis, clinically stable, with tolerance to antifungal treatment and adherence to the protocol. Participants were allocated into two groups: (1) itraconazole alone (200 or 400 mg/day) and (2) itraconazole (200 mg/day) combined with HBOT, until clinical cure of lesions. HBOT was administered in a monoplace chamber at 2.4 ATA for 90 minutes, three times per week, until evidence of healing. The primary endpoint was the time to clinical cure of the lesion. Clinical evaluations and photographic records were performed weekly in the HBOT group and monthly in the control group. Fungal cultures were obtained using Mycosel and Sabouraud media at 30 °C for up to 30 days. Statistical analyses included Chi-square, Fisher’s exact, Mann-Whitney tests, and survival analysis (Log-Rank and multivariate Cox model). A total of 74 patients were included, with 61 in the itraconazole-only group and 13 in the HBOT group. Demographic and clinical characteristics were balanced between the groups, except for geographic and racial distribution (p < 0.001). The lymphocutaneous form was predominant (≈70%), with most lesions located on the upper limbs. The mean time to cure was significantly shorter in the HBOT group (57.54 days) compared to the control group (208.53 days; p < 0.0001), equivalent to a 3.6-fold faster recovery. The mean number of HBOT sessions was 18.23. In the multivariate Cox analysis, the addition of HBOT increased the likelihood of earlier cure by 65-fold (HR = 65.97; p < 0.0001). Male sex showed a trend toward faster healing (HR = 1.62; p = 0.0632), and each additional year of age reduced the probability of rapid cure by 2% (HR = 0.98; p = 0.0771). No significant differences were observed in clinical or laboratory adverse effects between groups. The HBOT group required fewer additional antimicrobials. Hyperbaric oxygen therapy as an adjuvant to itraconazole significantly and safely reduced the time to cure of cutaneous/lymphocutaneous sporotrichosis, decreasing the need for prolonged antifungal therapy. Larger randomized, placebo-controlled, double-blind trials as well as cost-effectiveness analyses are needed to validate the routine inclusion of hyperbaric oxygen therapy in treatment protocols.