The Japanese Society of Medical Mycoses (JSMM) has issued guidelines regarding the diagnosis and management of candidiasis, aspergillosis, and cryptococcosis in 2013, 2015, and 2019, respectively, and published the updated guidelines for the management and diagnosis of candidiasis in 2021. JSMM is presently preparing new guidelines for the diagnosis and management of rare fungal infections, including mucormycosis, trichosporonosis, fusariosis, scedosporonosis, imported mycoses (histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis, and penicilliosis), candidiasis caused by Candida auris, and endogenous endophthalmitis resulting from mold infections. To obtain new evidence, a working group has attempted to conduct a systematic literature review pertaining to six clinical questions (CQs).

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　Invasive fungal infections are usually observed in severely immunosuppressed patients. The underlying diseases of mucormycosis include diabetes mellitus and hematological malignancies. Rhino-orbital disease is frequent among patients with diabetes, whereas patients with hematological malignancies often develop pulmonary mucormycosis. The prognosis of mucormycosis is extremely poor, and thus early diagnosis and early treatment start are important. However, diagnosis is difficult as its clinical manifestation is similar with that of aspergillosis. There has been no specific serological test for mucormycosis, and biopsy of the involved lesion should be considered. High-dose (5 mg/kg/day) liposomal amphotericin-B is the first line treatment, while azole antifungals with activity against mucormycosis, such as posaconazole or isavuconazole, can be used for refractory or intolerant cases and when switching to oral treatment. Surgical resection or debridement should be considered, if possible, especially for rhino-orbital disease, soft tissue lesion, and single pulmonary lesion, concomitant with antifungal treatment. In addition, reversal of immune function should be tried, as far as possible.

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　Guidelines have provided for early diagnosis and treatment of candidiasis and management of central venous catheter placement, and endophthalmitis is now rare. When appropriate systemic antifungal therapy is administered in the early stages of ocular candidiasis, visual prognosis is relatively good. The early onset of ocular candidiasis following intravenously inoculation of Candida albicans spores in rabbits has been reported to occur on the third day after fungal administration, making early identification of ocular candidiasis the most important step in the “management of fungal eye infections”. The sensitivity of fundus examination for detecting ocular candidiasis is comparable to that of observing histological changes and is superior to that of subjective symptoms. Therefore, fundus examination with pupil dilation by ophthalmologists is necessary to manage ocular candidiasis. Recently, however, the American Academy of Ophthalmology published a report questioning the necessity of fundus examination in patients with candidemia. In view of the report, I would like to discuss the proper timing of ophthalmologic consultation for ocular candidiasis.

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　There is limited evidence available for the diagnosis and management of rare fungal infections including mucormycosis, fusariosis, trichosporonosis, and scedosporiosis. To prepare the JSMM guidelines for the diagnosis and management of rare fungal infections, JSMM organized a Systematic Review Working Group (WG) consisting of eight members (the launching meeting was held on July 20, 2021). WG members came up with ideas on clinical questions (CQs) for systematic review. From among those ideas, a total of six CQs were selected. They include two CQs regarding mucormycosis (optimal duration of treatment, usefulness of combination antifungal therapy), and one each regarding fusariosis (monotherapy or combination therapy as initial therapy), trichosporonosis (azole or polyene antifungal agent as initial therapy), scedosporonosis (optimal initial therapy), and endogenous endophthalmitis due to mold infection (optimal initial therapy). Using a search formula, the WG conducted systematic literature review for each CQ. The progress of the systematic review was reported by the WG in the 66th Annual Meeting of JSMM held in October 2022. In March 2023, a preliminary draft on the recommendations for CQs based on the results of the systematic review was proposed and is now being discussed in the WG. This article provides a report on the progress of the Systematic Review WG activities, from the setting of CQs to the systematic review.

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