Epstein–Barr Virus-Associated Lymphoproliferative Disorders/Lymphoma with Skin Manifestations as the Primary Symptom: A Systematic Review

Abstract

Background. Epstein–Barr virus (EBV) associated skin lesions have been mentioned in case report studies under multiple kinds of lymphoproliferative disorders/lymphoma diagnoses. However, due to the rarity and scattered reporting of cases, it is still unclear whether the related skin symptoms and their pathological findings can guide the clinical diagnosis and treatment of EBV-associated lymphoproliferative disease/lymphoma. Methods. In this review, we summarized the skin symptoms and clinicopathological features mentioned by previously reported cases of EBV-associated lymphoproliferative disorders/lymphoma to assist future clinical diagnosis. The inclusion criteria were based on the population, intervention, comparator, outcomes, and study designs. An electronic search was conducted by September 2023, and the following databases were used: PubMed, EMBASE, Cochrane Library, and Web of Science. Search keywords included “Epstein-Barr Virus Infections,” “Herpesvirus 4, Human,” “Lymphoma,” “Lymphoproliferative Disorders,” and “skin.” Results. The primary outcome was the clinical skin features and pathological findings of EBV-associated lymphoproliferative disease/lymphoma patients. Although it seems unrealistic to differentiate between patients with EBV-related lymphoproliferative disorders/lymphomas with different diagnoses on the basis of cutaneous symptoms and pathological findings alone, based on the evidence summarized in previous case reports, the clinical importance of EBV detection and identification in the differential diagnosis of lymphomas and lymphoproliferative disorders should be recognized. Conclusion. Given the homogeneity of risk factors associated with disease progression found in EBV-associated lymphoproliferative disease/lymphoma patients during the review, future studies can focus on summarizing skin symptoms and pathological outcomes based on possible risk factors for further deterioration in these patients.