Fatal case of TAFRO syndrome associated with over-immunosuppression: a case report and review of the literature.

TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman's disease. A 58-year-old man was diagnosed as TAFRO syndrome by clinical and histopathological findings. After receiving intensive immunosuppressive therapy, his thrombocytopenia and anasarca had not improved. He developed complications such as methicillin-resistant Staphylococcus aureus sepsis, gastrointestinal bleeding, peritonitis caused by Stenotrophomonas maltophilia, gastrointestinal perforation, and disseminated candidiasis resulting in death. Autopsy revealed disseminated candidiasis and hemophagocytic lymphohistiocytosis, with no evidence of TAFRO syndrome. During treatment, we regarded his lasting thrombocytopenia and anasarca as insufficient control of TAFRO syndrome. However, the autopsy revealed that thrombocytopenia was caused by secondary hemophagocytic lymphohistiocytosis caused by over-immunosuppression. We reviewed the published literature to identify indicators of adequate treatment, which suggested improvement of platelet count and anasarca several weeks after initial therapy. This indicated that we could not depend on the platelet count and anasarca in acute medical care after initial treatment. We should treat TAFRO syndrome based on patients' clinical status and obviate the risk of treatment-related complications caused by over-immunosuppression.

Phosphorylated signal transducer and activator of transcription 3 in the epidermis in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is characterized by multiple systemic inflammation of unknown etiology. Although the typical eruption of AOSD is salmon-pink rheumatoid rash on the trunk and extremities, persistent pruritic papules and plaques have also been reported. Correlations between serum cytokines, including interleukin-6 and -18, and disease activity in AOSD have been reported. Activated signal transducer and activator of transcription 3 (STAT3) is transported into the nucleus, where it functions as a transcription factor that regulates genes involved in cell survival and inflammation. To assess whether STAT3 was phosphorylated in skin samples from AOSD patients, we conducted immunohistochemical analysis of affected and unaffected lesions from four AOSD patients in comparison with 10 normal controls. Quantitative analysis was conducted by measuring the ratio of epidermal keratinocytes with phosphorylated STAT3 (p-STAT3)-positive nuclei to total epidermal keratinocytes. p-STAT3 was found to be more strongly expressed in the nuclei in the epidermis of AOSD than in normal controls. Quantification of the data revealed significant differences in staining for p-STAT3 between AOSD and normal skin. Our findings suggest that phosphorylation of STAT3 may be a potential therapeutic target for AOSD.