Adriany Lucas dos Santos

“Unusual sporotrichosis”, a concept proposed in this review, refers to severe, extracutaneous, or anatomically atypical manifestations of sporotrichosis occurring in immunocompetent hosts and represents an underrecognized clinical subset associated with important diagnostic and therapeutic challenges. This systematic review aimed to characterize unusual sporotrichosis worldwide and to clarify its epidemiological, clinical, diagnostic, and therapeutic patterns. Following a registered protocol and PRISMA guidelines, PubMed, Scopus, and BVS/LILACS were searched up to November 2025 using a PICO-based strategy. Eligible studies included peer-reviewed case reports and case series with laboratory-confirmed sporotrichosis in patients without immunosuppression, diabetes mellitus, alcoholism, or other confounding comorbidities; classical lymphocutaneous and fixed cutaneous forms were excluded. From 922 records, 39 studies were included (13 case series and 26 case reports), yielding 55 cases reported between 1957 and 2024 across five world regions, mainly from the United States of America and Brazil. Adults aged 40–59 years (41.8%) and males (74.5%) predominated. Sapronotic transmission was most frequent (69.0%), although zoonotic transmission increased over time. Sporothrix schenckii/Sporothrix schenckii sensu stricto was the predominant species (87.3%). Osteoarticular (30.9%) and systemic (27.2%) forms were the most common presentations. Although cure was achieved in most cases (58.1%), sequelae were frequent (21.8%), and the worst prognosis—including most deaths—was observed in osteoarticular sporotrichosis. Unusual sporotrichosis is globally distributed and clinically distinct; therefore, early recognition and multimodal diagnostic and therapeutic strategies are essential to improve outcome.