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Background: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. Methods: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). Results: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] − 5.4–27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI − 15.5–10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI − 1.5–8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. Conclusion: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required. [ABSTRACT FROM AUTHOR]

Disseminated cryptococcosis primarily affects immunosuppressed patients and has a poor outcome if diagnosis and treatment are delayed. Skin lesions are rarely manifest causing misdiagnosis. We present a case of cryptococcal cellulitis with severe pain in a kidney transplant recipient on long-term immunosuppressive therapy. Multiple organs were involved, and there was cutaneous dissemination of the lesions. Histopathology revealed abundant yeast-like cells with wide capsular halos in subcutaneous tissue, suggesting Cryptococcus spp. infection. Laser capture microdissection (LCM)-PCR on skin biopsies confirmed Cryptococcus neoformans var. grubii. A literature review of 17 cases of disseminated cryptococcosis with cutaneous cellulitis or panniculitis in HIV-negative individuals found that over half the patients (52.9%, 9/17) had a history of glucocorticoid therapy, and that the most common site was the legs (76.5%, 13/17). C. neoformans was the main pathogenic species, accounting for 88.2% (15/17) of cases. Fungal cellulitis should be included in the differential diagnosis of cellulitis that fails to respond to antimicrobial therapy in HIV-negative immunosuppressed individuals. Non-culture-based molecular techniques aid in rapid pathogen identification in histologically positive, unculturable specimens. [ABSTRACT FROM AUTHOR]