PD-1 blockader-associated atypical hemophagocytic lymphohistiocytosis: A cautionary case report

Hemophagocytic lymphohistiocytosis (HLH) is a fatal immune hyperactivity syndrome with high mortality. It seriously endangers human health. HLH associated with immune checkpoint inhibitors is rare, and no particular diagnostic guidelines or treatment regimens exist. A 36-year-old patient with metastatic right atrial angiosarcoma was treated with programmed cell death-1 (PD-1) blockader toripalimab and pazopanib, a vascular endothelial growth factor receptor blockader. However, the patient presented to our center with HLH, and he accepted combination therapy of therapeutic plasma exchange (TPE) and immunotherapy. The patient improved quickly, after only one TPE procedure. Finally, he was discharged after completing two TPE procedures. We summarize a case of PD-1 blocker associated atypical HLH that was successfully treated with TPE. Further evidence is needed to elucidate whether TPE has therapeutic potential for immunotherapy associated HLH.     

Acute hepatitis A infection‐associated hemophagocytic lymphohistiocytosis in adult presenting as impending acute liver failure: A case report and literature review

Hemophagocytic lymphohistiocytosis has been reported as a severe complication of various viral infections but unusual for the hepatitis A virus. We report a case of 25‐year‐old man with hepatitis A infection‐associated hemophagocytic lymphohistiocytosis and impending acute liver failure to emphasize the importance of early diagnosis and treatment of this condition.     

Aggressive natural killer cell leukemia with skin manifestation associated with hemophagocytic lymphohistiocytosis: A case report

BACKGROUNDAggressive natural killer cell leukemia (ANKL) is a rare natural killer cell neoplasm characterized by systemic infiltration of Epstein–Barr virus and rapidly progressive clinical course. ANKL can be accompanied with hemophagocytic lymphohistiocytosis (HLH). Here, we report a case of ANKL with rare skin lesions as an earlier manifestation, accompanied with HLH, and review the literature in terms of etiology, clinical manifestation, diagnosis and treatment.CASE SUMMARYA 30-year-old woman from Northwest China presented with the clinical characteristics of jaundice, fever, erythema, splenomegaly, progressive hemocytopenia, liver failure, quantities of abnormal cells in bone marrow, and associated HLH. The immunophenotypes of abnormal cells were positive for CD2, cCD3, CD7, CD56, CD38 and negative for sCD3, CD8 and CD117. The diagnosis of ANKL complicated with HLH was confirmed. Following the initial diagnosis and supplementary treatment, the patient received chemotherapy with VDLP regimen (vincristine, daunorubicin, L-asparaginase and prednisone). However, the patient had severe adverse reactions and complication such as severe hematochezia, neutropenia, and multiple organ dysfunction syndrome, and died a few days later. CONCLUSIONThis is the first reported case of ANKL with rare skin lesions as an earlier manifestation and associated with HLH.     

Secondary hemophagocytic lymphohistiocytosis due to nivolumab/ipilimumab in a renal cell cancer patient—A case report

Secondary immune‐related hemophagocytic lymphohistiocytosis is a rare but life‐threatening complication of immune checkpoint inhibitors. HLH‐2004 and HLH‐1994 guidelines originally developed for primary HLH are the only available guidelines. It has proven to have a good prognosis if diagnosed promptly with discontinuation of immunotherapy and treated with corticosteroid monotherapy.     

Congenital nephrogenic diabetes insipidus due to the mutation in AVPR2 (c.541C>T) in a neonate: A case report

BACKGROUNDCongenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary renal disorder that is caused by mutations in AVPR2 or aquaporin 2 (AQP2). Up to now, there are few reports about CNDI in neonates. Early clinical manifestations of CNDI in neonates are atypical. A lack of understanding of the disease by clinicians causes frequent misdiagnoses or missed diagnoses, which may result in failure to administer treatments in time and ultimately leads to severe complications. In this study, clinical data of a case of AVPR2 gene mutation-induced CNDI, which was confirmed by genetic testing, were retrospectively analyzed to improve our understanding of this disease.CASE SUMMARYOn February 1, 2020, a male neonate was hospitalized 17 d after birth due to a 7 d period of pyrexia. The patient’s symptoms included recurrent pyrexia, hypernatremia and hyperchloremia, which were difficult to treat. The patient was fed on demand, and water was additionally provided between milk intakes. A combination treatment of hydrochlorothiazide and amiloride was administered. After the treatment, body temperature and electrolyte levels returned to normal, the volume of urine was significantly reduced and the patient was subsequently discharged. Genetic tests confirmed that the patient carried the AVPR2 gene missense mutation c.541C>T (P.R181C), and the patient’s mother carried a heterozygous mutation at the same locus. After clinical treatment with a combination of hydrochlorothiazide and amiloride, the body temperature and electrolyte levels returned to normal. Up until the most recent follow-up examination, normal body temperature, electrolyte levels and growth and development were observed.CONCLUSIONCNDI in the neonatal period is rare, and its clinical manifestations are unspecific with some patients merely showing recurrent fever and electrolyte disturbance. Genetic testing of AVPR2 and AQP2 can be used for screening and genetic diagnosis of CNDI.     

Multiple neurofibromas plus fibrosarcoma with familial NF1 pathogenicity: A case report

BACKGROUND Neurofibromatosis(NF)is a genetic disease consisting of seven types,of which types 1 to 4 are caused by a dominant autosomal gene mutation;such disease sometimes arises in patients with NF type 1.However,it remains unclear whether the origin of neurofibrosarcoma is directly linked to the incidence of NF type 1,as no reports have been published on this issue.Here,we report a case of NF1-positive multiple neurofibromas with malignant fibrosarcomatous transformation in the pleural cavity.CASE SUMMARY A 51-year-old male was admitted to our hospital due to fever accompanied by coughing,chest tightness and asthma for more than one month.The preliminary diagnosis was NF type 1,which was pathologically confirmed by a subsequent thoracoabdominal subcutaneous biopsy.The definitive diagnosis was neurofibrosarcoma with a pathogenic NF1 gene.The patient refused surgery and chemoradiotherapy,and died two months later.NF is a genetic disease consisting of seven types,of which types 1 to 4 are caused by a dominant autosomal gene mutation.The case reported belongs to the class of NF1-positive dominant inheritance.Neurofibrosarcoma is a malignant tumor derived from cells surrounding the peripheral nerves.However,due to the lack of previous reports,it remains unclear whether the origin of neurofibrosarcoma is directly linked to the incidence of NF type 1.CONCLUSION We report the first case of NF1-positive multiple neurofibromas with malignant fibrosarcomatous transformation in the pleural cavity.     

Progressive ataxia of cerebrotendinous xanthomatosis with a rare c.255+1G>T splice site mutation: A case report

BACKGROUNDCerebrotendinous xanthomatosis is an autosomal recessive disorder of lipid metabolism caused by the mutation of the CYP27A1 gene encoding sterol 27-hydroxylase, an essential enzyme for the conversion of cholesterol to chenodeoxycholic and cholic acids. Cerebrotendinous xanthomatosis is a rare neurological disease with a wide range of clinical symptoms that are easily misdiagnosed.CASE SUMMARYHere we report the clinical, biochemical, and molecular characterization of a 33-year-old female patient with cerebrotendinous xanthomatosis. The patient developed ataxia and had the typical symptoms of juvenile cataracts, tendon xanthomata, and progressive nervous system dysfunction. Magnetic resonance imaging of the brain revealed bilateral dentate nucleus lesions and white matter abnormalities. This patient was misdiagnosed for 2 years resulting in severe neurological complications. After 2 years of chenodeoxycholic acid treatment, she still presented with ataxia and dysarthria. The pathogenic sites of CYP27A1 were identified as c.255+1G>T and c.1263+1G>T, which were both caused by shear denaturation.CONCLUSIONCerebrotendinous xanthomatosis requires a multidisciplinary diagnosis that must be made early to avoid progressive neurological degeneration. c.1263+1G>T is a known mutation, but c.255+1G>T is a rare mutation site.