European Study of Cerebral Aspergillosis treated with Isavuconazole (ESCAI): A study by the ESCMID Fungal Infection Study Group.

BACKGROUND: Cerebral aspergillosis (CA) is associated with high mortality. According to the European Conference on Infections in Leukemia and the European Society of Clinical Microbiology and Infectious Diseases guidelines, the recommended first-line treatment for all forms of aspergillosis is voriconazole or isavuconazole. However, little is known about the efficacy and safety of isavuconazole in CA. METHODS: We conducted a European multicenter retrospective study of patients treated with isavuconazole for proven or probable CA between 2014 and 2022 and compared the outcomes with those of weighted control groups from the previously published French national cohort of CA, the Cerebral Aspergillosis Lesional Study (CEREALS). RESULTS: Forty patients from 10 countries were included. The main underlying conditions were hematological malignancies (53%) and solid-organ transplantation (20%). Isavuconazole was administered as a first-line treatment to 10 patients, primarily in combination therapy, resulting in control of CA in 70% of these cases. Thirty patients received isavuconazole after a median of 65 days on another therapy, mostly because of side effects (50%) or therapeutic failure (23%) of the previous treatment. Predominantly given as monotherapy, it achieved control of CA in 73% of the patients. Seventeen patients (43%) underwent neurosurgery. When measured, isavuconazole levels were low in cerebrospinal fluid but adequate in serum and brain tissue. Isavuconazole toxicity led to treatment interruption in 7.5% of the patients. Twelve-week mortality was 18%. Comparison with the CEREALS cohort showed comparable survival in patients receiving isavuconazole or voriconazole as a first-line treatment. CONCLUSIONS: Isavuconazole appears to be a well-tolerated treatment. Mortality of CA treated with isavuconazole is similar to that reported with voriconazole.

Hemophagocytic lymphohistiocytosis following an acute HIV infection, in a known immunosuppressed patient: A case report.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition with a wide range of causes, being frequently associated with infections in adults. The association between HLH and acute HIV infection has been rarely described. Case presentation: A 62-year-old male, with a past medical history of Henoch-Schönlein purpura under immunosuppressive treatment, presented with a two-week history of fever, asthenia, anorexia, cough and purpuric rash. Initial blood tests showed pancytopenia, elevated C-reactive protein and renal failure. Microbiological investigations were negative, but persistent fever and pancytopenia led to HLH suspicion. This diagnosis was supported by hyperferritinemia, hypertriglyceridemia, high soluble-interleukin-2 receptor levels and hepatosplenomegaly, fulfilling 5/8 diagnostic criteria of the Histiocyte Society-2004. Further investigation revealed a positive HIV-1 antibody and the patient reported recent sexual risks, with TCD4 + lymphocytes below 100/mL and HIV-1 viremia above 10 million copies/mL, confirming an acute HIV infection. Antiretroviral therapy (ART) and glucocorticoids were started with full clinical recovery. Conclusion: HLH occurrence can be obscured by the features of a primary disease and can mimic other clinic conditions. In this patient, the prompt identification of an acute HIV infection as the cause of HLH allowed the early initiation of antiretroviral treatment and corticosteroids, with an efficient control of the viral replication and inflammatory response, preventing a potentially fatal evolution.

Investigating Febrile Polyserositis: An Unusual Case of Idiopathic Hypereosinophilic Syndrome.

Hypereosinophilic syndrome (HES) is a heterogenous group of diseases characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues. It can affect all organs and therefore clinical manifestations are highly variable. We describe the case of a 38-year-old man admitted for febrile polyserositis. He developed cardiac tamponade requiring pericardiocentesis complicated by left ventricle perforation which was successfully repaired. He presented mild peripheral eosinophilia. Bronchoalveolar lavage evidenced eosinophilic alveolitis, and pleural and pericardium histopathology revealed the presence of abundant eosinophils. All other causes of tissue eosinophilia were excluded and the diagnosis of idiopathic HES was made. The patient was started on glucocorticoids with resolution of symptoms. This case report describes a rare but potentially fatal presentation of HES and demonstrates the difficulty and delay in diagnosis when peripheral hypereosinophilia is absent. LEARNING POINTS: Hypereosinophilic syndrome (HES) is characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues.The clinical manifestations of HES are highly variable.It may be difficult to diagnose HES when peripheral hypereosinophilia is absent.