Atypical Patients With Severe Fever With Thrombocytopenia Syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. The clinical diagnosis criteria mainly rely on white blood cell (WBC) and platelet (PLT), which, however, are of limited usage in identifying atypical SFTS. A multicenter study was performed in two hospitals from 2011 to 2023. SFTS patients were categorized as atypical or typical based on the clinical diagnosis criteria. Clinical progress and outcomes were compared between the two groups. A total of 2876 laboratory-confirmed SFTS patients were included in this study, 90.54% (2604/2876) of whom exhibited both thrombocytopenia and leukopenia and were defined as typical SFTS patients, while 9.46% (272/2876) were defined as atypical SFTS patients. Patients with typical SFTS were more likely to develop complications (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]:1.48-2.92, p < 0.001) and fatal outcomes (adjusted OR = 2.24, 95% CI: 1.37-3.89, p = 0.002) compared to patients with atypical SFTS. Among atypical patients, those with decreased PLT and normal WBC levels (PLT down arrow and WBC ->) experienced increased complication rates (adjusted OR = 2.76, 95% CI: 1.30-6.05, p < 0.001) compared to those with decreased WBC and normal PLT (WBC down arrow and PLT ->). In the typical group, 238 patients developed thrombocytopenia earlier than leukocytopenia (defined as the TL group), while 311 subjects developed leukocytopenia earlier than thrombocytopenia (defined as the LT group). Compared to the LT group, patients in the TL group were more likely to develop fatal outcomes (HR = 1.91, 95% CI: 1.04-3.50). These findings highlight the presence of atypical SFTS cases that did not meet the clinical diagnosis criteria. Clinical profiles and outcomes differed between typical and atypical SFTS patients. A less stringent diagnostic criterion than combined thrombocytopenia and leukopenia is suggested for making clinical diagnoses within 7 days of disease onset.