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Malar rash with pancytopenia

      Keywords

      1. Case description

      A 35-year-old Japanese man presented with a four-month history of persistent flushing and persistent high fever (≥38 °C) for the past several weeks.
      Erythema was observed on both cheeks (malar rash: Fig. 1), not including the nasolabial fold. Contrarily, he had no rash on his trunk or limbs and no enanthema. Physical examination revealed enlarged non-tender cervical, supraclavicular, and axillary lymph nodes. Blood tests revealed pancytopenia (white blood cell count, 520 cells/μL; neutrophils, 59%; lymphocytes, 25%; atypical lymphocytes, 3%; hemoglobin, 8.5 g/dL; platelet count, 15,000/μL). Lactate dehydrogenase blood level increased to 778 U/L and the soluble interleukin-2 receptor was 29,200 U/mL. The antinuclear antibody test was negative (40 times or less). The HTLV-1 antibody was negative, and the EBV-VCA IgG antibody (fluorescent antibody method) titer was 2560 times the normal level. Computed tomography revealed marked splenomegaly. Bone marrow examination revealed phagocytic cells.
      Fig. 1
      Fig. 1Malar rash as seen on physical examination Both cheeks show erythema and swelling with unclear borders and dilation of the capillaries in some areas.
      What is the diagnosis?

      2. Discussion

      Peripheral blood EBV-DNA levels were 3.6 × 105 copies/μg. Axillary lymph node biopsy confirmed paracortical proliferation of large atypical lymphoid cells, identified as CD3+CD8+CD20 T cells by immunostaining. EBV-encoded small nuclear RNA in-situ hybridization was positive (Fig. 2). Flow cytometry confirmed EBV infection of CD8+ T-cells. The patient was diagnosed with chronic active EBV infection (CAEBV).
      CAEBV is a lymphoid neoplasm where EBV-infected T- or natural killer (NK) cells proliferate clonally. Its prognosis is poor; therefore, early diagnosis is important .
      Fig. 2
      Fig. 2Histology of the axillary lymph node Hematoxylin and eosin (HE) staining and immunostaining of the axillary lymph node show proliferation of large atypical lymphoid cells in the paracortical region (top left, arrowheads). These cells are CD3-positive (bottom left), CD8-positive (bottom right) T cells on immunostaining, and positive for Epstein-Bar virus-encoded small nuclear RNA (EBER) on in-situ hybridization (top right). Scale on the bottom right: 50 µm. EBER, Epstein-Bar virus-encoded small nuclear RNA; HE, hematoxylin and eosin.
      The two types of eruptions common in infectious mononucleosis caused by EBV infection are faint erythematous macropapular eruption in 5–15% of cases and maculopapular rash after antibiotic administration. Many of these symptoms persist for a few weeks and improve spontaneously. Contrarily, in CAEBV, a skin rash is seen in 21%–26% of cases [
      • Kimura H.
      • Cohen J.I.
      Chronic active epstein-barr virus disease.
      ]. Hypersensitivity to mosquito bites and hydroa vacciniforme are characteristic, but a malar rash is rare. The differential diagnosis of a malar rash includes systemic lupus erythematosus (SLE), cellulitis, erysipelas, rosacea, dermatomyositis, and pellagra. In EBV infection, skin damage by ultraviolet stimulation is mediated by T- and NK cells [
      • Ciccarese G.
      • Trave I.
      • Herzum A.
      • Parodi A.
      • Drago F.
      Dermatological manifestations of Epstein-Barr virus systemic infection: a case report and literature review.
      ]. EBV reactivation may trigger SLE. SLE and EBV infection have similar symptoms, including fever, rash, and arthralgia [
      • Draborg A.H.
      • Duus K.
      • Houen G.
      Epstein-Barr virus and systemic lupus erythematosus.
      ] and pancytopenia is also a common finding in both. When examining a malar rash, it is important to consider EBV infection in addition to SLE.

      Informed consent

      We have obtained written informed consent for publication from the patient.

      Funding statement

      None.

      Declaration of Competing interest

      All authors declare no conflicts of interest.

      Acknowledgments

      The authors would like to thank Editage (https://www.editage.jp/) for English language editing.

      References

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        • Cohen J.I.
        Chronic active epstein-barr virus disease.
        Front Immunol. 2017; 8: 1867https://doi.org/10.3389/fimmu.2017.01867
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        • Trave I.
        • Herzum A.
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        • Drago F.
        Dermatological manifestations of Epstein-Barr virus systemic infection: a case report and literature review.
        Int J Dermatol. 2020; 59: 1202-1209https://doi.org/10.1111/ijd.14887
        • Draborg A.H.
        • Duus K.
        • Houen G.
        Epstein-Barr virus and systemic lupus erythematosus.
        Clin Dev Immunol. 2012; 2012370516https://doi.org/10.1155/2012/370516