{"title":"Epstein-Barr Virus encephalitis associated hemophagocytic lymphohistiocytosis in childhood-onset systemic lupus erythematosus: a case-based review.","authors":"Krit Cheawcharnpraparn, Thiraporn Kanjanaphan, Oranooj Lertkovit, Napaporn Puripat, Chutima Chavanisakun, Ornatcha Sirimongkolchaiyakul, Sirikarn Tangcheewinsirikul","doi":"10.1186/s12969-024-01025-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation that results in an uncontrolled hyperinflammatory state. HLH is classified into two main categories: primary (familial) HLH and secondary (acquired) HLH. Secondary HLH can result from various underlying, including infection-associated hemophagocytic syndrome (IAHS) and macrophage activation syndrome (MAS) associated with rheumatologic disorders, among others. Epstein-Barr virus (EBV) often causes IAHS, but central nervous system (CNS) involvement is rare among systemic lupus erythematosus (SLE) patients. We report a case of EBV encephalitis associated with HLH in a patient with childhood-onset SLE.</p><p><strong>Case presentation: </strong>A 12-year-old girl had received a diagnosis of SLE 2 months before presentation. After a period of inactive disease on treatment, fever and seizures, with altered mental status and hallucinations, developed over several weeks. A complete blood cell count (CBC) revealed pancytopenia, accompanied by elevated levels of inflammatory markers: 86 mm/hr erythrocyte sedimentation rate, 8.9 mg/dl c-reactive protein, and 3,966 ng/mL of ferritin. The differential diagnosis included active neuropsychiatric SLE, CNS infection and neurological manifestations in secondary HLH, which could have represented either IAHS or MAS. Meropenem and acyclovir were initially administered for clinical acute encephalitis, followed by pulse methylprednisolone; however, the fever persisted, and another CBC revealed progressive cytopenia. A bone marrow study showed hypocellularity and active hemophagocytic activity, and intravenous immunoglobulin was additionally given due to the diagnosis of HLH. Cerebrospinal fluid (CSF) analysis showed 60/mm<sup>3</sup> white blood cells (N 55%, L 45%), 141 mg/dL glucose (0.7 blood-CSF glucose ratio), < 4 mg/dL protein; results of Gram stain and bacterial culture were negative. The viral encephalitis panel from the CSF confirmed EBV infection. Bone marrow immunohistochemistry examination revealed increasing levels of CD8 + T-cell and equivocal positive results for EBV-encoded RNA in situ hybridization; therefore, HLH potentially associated with EBV was diagnosed. After treatment with IVIg, cyclosporin A, and prednisolone, the patient's symptoms gradually improved and she was eventually able to return to school.</p><p><strong>Conclusions: </strong>Our case highlights the importance of a thorough differential diagnosis, including EBV encephalitis associated with HLH, in patients with childhood SLE, particularly in cases of clinical deterioration occurs after initial treatment.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529320/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12969-024-01025-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation that results in an uncontrolled hyperinflammatory state. HLH is classified into two main categories: primary (familial) HLH and secondary (acquired) HLH. Secondary HLH can result from various underlying, including infection-associated hemophagocytic syndrome (IAHS) and macrophage activation syndrome (MAS) associated with rheumatologic disorders, among others. Epstein-Barr virus (EBV) often causes IAHS, but central nervous system (CNS) involvement is rare among systemic lupus erythematosus (SLE) patients. We report a case of EBV encephalitis associated with HLH in a patient with childhood-onset SLE.
Case presentation: A 12-year-old girl had received a diagnosis of SLE 2 months before presentation. After a period of inactive disease on treatment, fever and seizures, with altered mental status and hallucinations, developed over several weeks. A complete blood cell count (CBC) revealed pancytopenia, accompanied by elevated levels of inflammatory markers: 86 mm/hr erythrocyte sedimentation rate, 8.9 mg/dl c-reactive protein, and 3,966 ng/mL of ferritin. The differential diagnosis included active neuropsychiatric SLE, CNS infection and neurological manifestations in secondary HLH, which could have represented either IAHS or MAS. Meropenem and acyclovir were initially administered for clinical acute encephalitis, followed by pulse methylprednisolone; however, the fever persisted, and another CBC revealed progressive cytopenia. A bone marrow study showed hypocellularity and active hemophagocytic activity, and intravenous immunoglobulin was additionally given due to the diagnosis of HLH. Cerebrospinal fluid (CSF) analysis showed 60/mm3 white blood cells (N 55%, L 45%), 141 mg/dL glucose (0.7 blood-CSF glucose ratio), < 4 mg/dL protein; results of Gram stain and bacterial culture were negative. The viral encephalitis panel from the CSF confirmed EBV infection. Bone marrow immunohistochemistry examination revealed increasing levels of CD8 + T-cell and equivocal positive results for EBV-encoded RNA in situ hybridization; therefore, HLH potentially associated with EBV was diagnosed. After treatment with IVIg, cyclosporin A, and prednisolone, the patient's symptoms gradually improved and she was eventually able to return to school.
Conclusions: Our case highlights the importance of a thorough differential diagnosis, including EBV encephalitis associated with HLH, in patients with childhood SLE, particularly in cases of clinical deterioration occurs after initial treatment.
期刊介绍:
Pediatric Rheumatology is an open access, peer-reviewed, online journal encompassing all aspects of clinical and basic research related to pediatric rheumatology and allied subjects.
The journal’s scope of diseases and syndromes include musculoskeletal pain syndromes, rheumatic fever and post-streptococcal syndromes, juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, local and systemic scleroderma, Kawasaki disease, Henoch-Schonlein purpura and other vasculitides, sarcoidosis, inherited musculoskeletal syndromes, autoinflammatory syndromes, and others.