Case Presentation: A 36-years old man presented with five weeks history of intractable diarrhea. Colonoscopy was normal, but abdominal computed tomography (CT) scan revealed mural thickening at duodenojejunal junction, and subsequent jejunofiberoscopy showed a circumferential ulceration at the jejunum. Histo-immunopathology confirmed the diagnosis of enteropathyassociated T-cell lymphoma (EATL) type II. His disease course proved to be aggressive and refractory to standard front-line chemotherapy, and eventually progressed through second-line salvage regimen with CNS and intracranial involvement. He died nine months after the initial diagnosis.
Conclusion: EATL with brain metastasis is a very rare occurrence with dismal prognosis.
METHODS: We report the establishment of an immunocompetent wild type strain 129 (wt-129) mouse model, which can be cross-species infected with human EV-A71 clinical isolates via an intraperitoneal route.
RESULTS: One intriguing disease phenotype of this new model is the development of characteristic "White-Jade" patches in the muscle, which lost sporadically the normal pink color of uninfected muscle. Viral VP1 protein and massive leukocyte infiltration were detected in muscles with or without white-jades. We demonstrated further that hypoxia is a general phenomenon associated with white-jades in both immunocompetent and immunodeficient mouse models. Therefore, hypoxia appears to be a feature intrinsic to EV-A71 infection, irrespective of its host's immunogenetic background. To date, no effective treatment for EV-A71 is available. Here, using this new wt-129 mouse model, we showed that timely treatment with compound R837 (a TLR7 immune modulator) via oral or intraperitoneal routes, rescued the hypoxia, limb paralysis, and death at a high therapeutic efficacy.
CONCLUSIONS: In this new immunocompetent mouse 129 model, we observed an unexpected white-jade phenotype and its associated hypoxia. The successful treatment with TLR7 immune modulators via an oral route, provide us a new research direction for EV-A71 basic science and translational research. It remains an open issue whether R837 or its related compounds, will be a promising drug candidate in clinical trials in EV-A71 endemic or epidemic areas in the future.