https://orcid.org/0000-0001-7238-0389
![A 23-month-old boy presented with a 5-day history of fever, rash, and lymphadenopathy. Complete blood count revealed a white blood cell count of 69.4 K/µL, with lymphocytes of 88%. Peripheral blood smear showed a spectrum of mature, reactive, and plasmacytoid lymphocytes (panel A; Wright-Giemsa stain [WG], original magnification ×50; panel B; an immunoblast [solid arrow] and reactive lymphocyte [broken arrow], WG, original magnification ×100). Peripheral blood flow cytometry showed no evidence of malignancy. Bone marrow aspirate showed hemophagocytosis (panel C; WG, original magnification ×100). There was coagulopathy, hypofibrinogenemia, and hyperferritinemia, ferritin 1855 ng/mL (5-100 ng/mL). Epstein-Barr virus (EBV) serology showed evidence of recent EBV infection. EBV antibody to viral capsid antigen immunoglobulin M was >160.0 units/mL (0.0-43.9 units/mL), and EBV quantitative polymerase chain reaction was 96 800 copies per mL (<390 copies per mL). There was elevation of sCD25 4295 pg/mL (175-858 pg/mL) and sCD163 8257 ng/mL (range, 399-1968 ng/mL), decreased natural killer cell function by functional assay, and increased granzyme B expression, confirming hemophagocytic lymphohistiocytosis (HLH) diagnosis. Signaling lymphocytic activation molecule-associated protein (SAP) expression was abnormally absent, and SH2D1A gene mutation was detected leading to the diagnosis of X-linked lymphoproliferative disease (XLP1).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/139/18/10.1182_blood.2022015531/4/m_bloodbld2022015531f1.png?Expires=1767939030&Signature=OsoxeKm0EomXONMwWL4RSigCpMiII3NNjA5TttVuwG-TKy5san43yVs01IF2ZHXQIcmfIvfH7Y~QKz~rb1Jc8exObsvxhVoREjGlQ3U4HdlwzR-IY7FuvPyVL~QCrpV32cHIibVmPfEYEdK4nJlegwztLIJjfOai-FPaZZ-n-trQr6H8TwmR2H3IoQQ7xCSckfkfarKbVfsZ9-p6JfAO7pF90FQQ4JjaB2xf-FP8FkxKH5G3QPCEW0DUbaQt6MzhzOINhtDxlkZtV5EbkVWJ5h7deQYMMkloGgufG8h5y59C6pArvTOCbE7jEv3qFzsOarENQ6eQF8g~5~Ln3L90FA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
A 23-month-old boy presented with a 5-day history of fever, rash, and lymphadenopathy. Complete blood count revealed a white blood cell count of 69.4 K/µL, with lymphocytes of 88%. Peripheral blood smear showed a spectrum of mature, reactive, and plasmacytoid lymphocytes (panel A; Wright-Giemsa stain [WG], original magnification ×50; panel B; an immunoblast [solid arrow] and reactive lymphocyte [broken arrow], WG, original magnification ×100). Peripheral blood flow cytometry showed no evidence of malignancy. Bone marrow aspirate showed hemophagocytosis (panel C; WG, original magnification ×100). There was coagulopathy, hypofibrinogenemia, and hyperferritinemia, ferritin 1855 ng/mL (5-100 ng/mL). Epstein-Barr virus (EBV) serology showed evidence of recent EBV infection. EBV antibody to viral capsid antigen immunoglobulin M was >160.0 units/mL (0.0-43.9 units/mL), and EBV quantitative polymerase chain reaction was 96 800 copies per mL (<390 copies per mL). There was elevation of sCD25 4295 pg/mL (175-858 pg/mL) and sCD163 8257 ng/mL (range, 399-1968 ng/mL), decreased natural killer cell function by functional assay, and increased granzyme B expression, confirming hemophagocytic lymphohistiocytosis (HLH) diagnosis. Signaling lymphocytic activation molecule-associated protein (SAP) expression was abnormally absent, and SH2D1A gene mutation was detected leading to the diagnosis of X-linked lymphoproliferative disease (XLP1).
This is a rare, inherited immunodeficiency, characterized by immune dysregulation resulting in increased risk of HLH, lymphomas, and extreme vulnerability to EBV infection. XLP1 should be suspected if fulminant EBV infection occurs in a male.
A 23-month-old boy presented with a 5-day history of fever, rash, and lymphadenopathy. Complete blood count revealed a white blood cell count of 69.4 K/µL, with lymphocytes of 88%. Peripheral blood smear showed a spectrum of mature, reactive, and plasmacytoid lymphocytes (panel A; Wright-Giemsa stain [WG], original magnification ×50; panel B; an immunoblast [solid arrow] and reactive lymphocyte [broken arrow], WG, original magnification ×100). Peripheral blood flow cytometry showed no evidence of malignancy. Bone marrow aspirate showed hemophagocytosis (panel C; WG, original magnification ×100). There was coagulopathy, hypofibrinogenemia, and hyperferritinemia, ferritin 1855 ng/mL (5-100 ng/mL). Epstein-Barr virus (EBV) serology showed evidence of recent EBV infection. EBV antibody to viral capsid antigen immunoglobulin M was >160.0 units/mL (0.0-43.9 units/mL), and EBV quantitative polymerase chain reaction was 96 800 copies per mL (<390 copies per mL). There was elevation of sCD25 4295 pg/mL (175-858 pg/mL) and sCD163 8257 ng/mL (range, 399-1968 ng/mL), decreased natural killer cell function by functional assay, and increased granzyme B expression, confirming hemophagocytic lymphohistiocytosis (HLH) diagnosis. Signaling lymphocytic activation molecule-associated protein (SAP) expression was abnormally absent, and SH2D1A gene mutation was detected leading to the diagnosis of X-linked lymphoproliferative disease (XLP1).
This is a rare, inherited immunodeficiency, characterized by immune dysregulation resulting in increased risk of HLH, lymphomas, and extreme vulnerability to EBV infection. XLP1 should be suspected if fulminant EBV infection occurs in a male.
For additional images, visit the ASH Image Bank, a reference and teaching tool that is continually updated with new atlas and case study images. For more information, visit http://imagebank.hematology.org.
