Cases of TMA triggered by PVB19 infection in both healthy and immunocompromised patients in the absence of an alternative cause have previously been reported [6C8]. HSV stomatitis. HLH was diagnosed based on clinical criteria and qPCR revealed an acute parvovirus B19 infection as potential underlying infectious trigger. Treatment was started with both IVIG and dexamethasone. Subsequently, kidney biopsy demonstrated TMA. Conclusions In rare cases both HLH and aHUS can occur simultaneously in a patient as a consequence of viral infections. Insights from this unusual case might help physicians understand this complex symptom constellation. strong class=”kwd-title” Keywords: Hemophagocytic Lymphohistiocytosis (HLH), Atypical hemorrhagic uremic syndrome (aHUS), Evobrutinib Parvovirus B19, Case report Background Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical condition (1/800000 adults per year, 1C10/Million children per year) with excessive immune activation and inflammation, eventually leading to multi organ failure. It can be divided into primary (genetic) forms which mostly affect children and secondary forms which are subclassified as viral, autoimmune, or paraneoplastic [1, 2]. Thrombotic microangiopathies (TMA) are a group of disorders characterized by microthrombi causing microangiopathic hemolytic anemia, thrombocytopenia and ischemic tissue injury [3]. TMAs encompass primary forms which occur spontaneously and secondary forms which develop in the context of pregnancy, autoimmune disease, malignancy, infection, malignant hypertension, bone marrow transplantation or the use of certain medications [4]. Here we report a case of simultaneous HLH and TMA after acute infection with parvovirus B19 (PVB19) in a kidney transplant recipient. Evobrutinib Case presentation In September 2020, a 50-year-old female was admitted to our hospital with PCR-diagnosed HSV-1 stomatitis and refractory anemia. The patient had received a cadaveric donor kidney transplantation for kidney failure due to IgA vasculitis in 2007 and was on triple immunosuppressive therapy including prednisolone (2.5?mg Rabbit Polyclonal to TUBGCP6 daily), mycophenolate mofetil (1500?mg daily) and cyclosporine A (100?mg daily). Laboratory testing on admission showed chronic allograft dysfunction (creatinine 3.1?mg/dl), anemia (Hb 5.9?g/dl) with low reticulocytes (32/nl) and Evobrutinib low markers of systemic inflammation (CRP 1.9?mg/l, ferritin 324?g/l). Transferrin saturation, vitamin B12 and folic acid levels, cyclosporine A through concentrations (48?ng/ml) as well as haptoglobin were within the normal range. There was no clinical sign of blood loss. Serum PCR-testing was negative for HSV-1/2, varicella zoster, CMV, EBV, HIV and parvovirus B19 (PVB19) respectively. A nasopharyngeal swab for SARS-CoV-2 was negative. The patient was initially treated with intravenous acyclovir for 14?days, and immunosuppression was reduced by pausing mycophenolate mofetil and reducing cyclosporine A. Reticulocytes and hemoglobin levels recovered consequently and stomatitis resolved. Eleven days after admission the patient suddenly developed fever up to 40?C, low oxygen saturation (92%) and a cough. The lab results indicated acute on chronic allograft dysfunction (creatinine 4.1?mg/dl), acute hepatitis (ASAT 249?U/l, ALAT 300?U/l, bilirubin 4.1?mg/dl), moderately elevated CRP (29?mg/l) and an extremely high ferritin level (20,659?g/l). Additionally, the patient showed thrombocytopenia (92/l), elevated LDH (1170?U/l) and reduced haptoglobin ( ?0.1?g/l), elevated d-dimer (8.8?mg/l), elevated soluble IL-2 receptor (12,458?IU/ml), elevated triglycerides (255?mg/dl) and low fibrinogen (1.0?g/l), reduced C3 and C4 (620 and 140?mg/l respectively). Coombs test was negative and a blood smear was negative for schistocytes. A chest CT scan ruled out pneumonia and pulmonary embolism. Abdominal ultrasound revealed ascites and moderate splenomegaly. Multiple urine and blood cultures did not show bacterial infection. A second PCR for SARS-CoV-2 was negative. The diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made based on the patients extremely high ferritin levels, presence of 6 out of 8 HLH diagnostic criteria and an HScore of 269 indicating a 99% probability of HLH. Treatment with dexamethasone 20?mg daily was started on day 13. Bone marrow aspiration and biopsy were conducted on day 14 and revealed no pathological findings (no evidence of HLH). Fever subsided 1 day after starting dexamethasone, kidney function improved, and the levels of ferritin, transaminases and bilirubin decreased. PCR for hepatitis B, C, D and E as well as for EBV and CMV were negative. Repeated PCR testing for PVB19 revealed ?10 million copies/ml. Treatment with intravenous immunoglobulins (100?g cumulative) was started over a course of 3 days to address the PVB19 infection. Dexamethasone dose was tapered to 8?mg on the day of discharge. PCR testing of the bone marrow sample revealed ?9 million copies/ml of PVB19. Serologic testing of blood samples was positive for IgM and negative IgG suggesting primary infection with PVB19. In the following days the patients condition further improved, the viral load fell to 16,400 copies/ml at the time of discharge and.