A case of coexistence of hydroa vacciniforme-like lymphoproliferative disorder and Epstein-Barr virus pneumonia

Introduction

As a member of the herpes virus family, Epstein-Barr virus (EBV) is a human carcinogenic virus associated with a variety of diseases and malignancies.¹ More than 90% of adults are infected with EBV at some point in their lives.² The primary infection is usually asymptomatic, and the onset age is younger in developing countries and later in countries with a higher degree of industrialization.³ Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare form of cutaneous disease associated with chronic active EBV infection. It is characterized by monoclonal proliferation of natural killer cells or T lymphocytes (T cells) that can progress to an extremely rare systemic lymphoma.⁴ In China, HVLPD is concentrated in children, but it also occurs in adults.^5,6 EBV pneumonia is another rare complication of EBV infection that can be life-threatening. This occurs when EBV infects lung tissue and causes inflammation and respiratory system damage. Therefore, it is very rare for EBV infection to lead to the coexistence of HVLPD and EBV pneumonia.

Case report

This is a 52-year-old Chinese Han female presenting with blisters, ulcers, and crusts covering her body, accompanied by pain for 3 months and cough for over 1 month. She had no history of food or drug allergies and no family history of similar disorders. Examination revealed facial redness and swelling, as well as ulcers, crusts, depressed scars, and hyperpigmented patches on the head, face, trunk, perineum, and extremities (Fig 1, A-C).

Fig 1.

A, Based on the patient's red and swollen face, black crusts are visible. B, Pigmentation and black crusts are observed scattered on the trunk and upper limbs. C, Scattered erythema, pigmentation, and black crusts are observed on the back and upper limbs. D, (Hematoxylin-eosin staining) Low power. E, (Hematoxylin-eosin staining) Medium power microscopy. A significant number of eosinophils (as shown by red arrows) and moderate lymphocytic infiltrates (as shown by black arrows) are observed around blood vessels, as well as between collagen fibers throughout the dermis and subcutaneous tissue. No atypical lymphocytes were found.

Laboratory examination

The blood routine revealed an elevated eosinophils count of 7.92 × 109 (normal range: 0.02-0.52 × 109). The patient declined to undergo bone bone puncture. C-reactive protein levels were slightly elevated at 10.98 mg/L (normal range: 0-10 mg/L), and serum IgE was significantly elevated at 1493IU/ml (normal range: 0-100IU/ml). Stool was negative for parasites. EBV DNA was slightly elevated at 9.11 × 102 (<5 × 102). The deoxynucleotide determination of varicella zoster virus and herpes simplex virus (types I and II) were within the reference range.

Histology revealed prominent vesiculation in the epidermis, accompanied by a significant number of eosinophils and moderate lymphocyte infiltration, primarily T lymphocytes. Additionally, scattered Epstein-Barr encoding region–positive lymphocytes were observed throughout the dermis and subcutaneous fat (Fig 1, D and E). Immunohistochemical demonstrated positive cluster of differentiation (CD)4 (partially positive), CD8 (partially positive), CD3, CD2, CD20, CD30 (scattered positive), CD5, granzyme B, and EBERpb (7-20 cells/high power field), and negative for CD56, with a nuclear-associated antigen ki-67 proliferation index of 8%. Furthermore, immunofluorescence analysis indicated no deposits of IgA, IgG, IgM, or C3 present.

The chest computed tomography scan (Fig 2) indicated inflammation in the middle lobe of the right lung, soft tissue density shadow in the lower lobe of the left lung, multiple lymph nodes in the mediastinum and bilateral axilla, as well as localized thickening of the pleura on both sides. Pulmonary function tests showed mild obstructive pulmonary ventilation dysfunction, reduced small airway function, normal pulmonary diffusion function, and normal residual volume or total lung volume ratio. Tracheoscopy revealed a moderate amount of white viscous secretion in the tracheal lumen and bronchial lumens with yellow-white necrosis leading to luminal stenosis in certain areas. Alveolar lavage fluid culture showed normal bacterial growth without haemophilus, mycoplasma pneumoniae, acid-fast bacilli, or fungi. Genetic testing of alveolar lavage fluid revealed the presence of EBV (sequence number 11799) and human coronavirus 229E (sequence number 2414). Histopathological findings of the distal orifice of the right middle lobe bronchus showed extensive necrosis, focal mucosal lymphocyte infiltration, and a small number of eosinophils. Immunohistochemistry showed CD2 (T+), CD3 (T+), CD5 (−), CD5 (T+), CD4 (T+), CD8 (small amount +), CD20 (B+), paired box protein 5 (B+), T-cell intracellular antigen-1 (small amount +), granzyme B (small amount +), EBERpb (small amount +), and nuclear-associated antigen ki-67 (about 25%+).

Fig 2.

Chest computed tomography scan. The patchy shadow is observed in the right lung, while a mass shadow is present in the left hilum.

We believe that the patient was infected with EBV, leading to HVLPD. Additionally, coinfection of EBV and Human Coronavirus 229E resulted in pneumonia. During hospitalization, she received methylprednisolone 20 mg intravenous guttae (intravenous infusion) quaque die, interferon a-2b 30 ug intrahypodermic injection (intradermal or hypodermic injection) quaque die, thymalfasin 1.6 mg intrahypodermic injection twice a week, and human interferon a-2b gel for external use. She also received supplementation with potassium, calcium, and acid suppression to protect the gastric mucosa. After nearly 10 days of treatment, the facial redness and swelling resolution, most of the crust fell off, and the patient was discharged. After discharge, she continued antiviral and low-dose glucocorticoid treatment for 1 month which led to complete subsidence of skin lesions but left depressed scars. However, the patient still complained of coughing. She is currently seeking traditional Chinese medicine treatment.

Discussion

The uniqueness of this patient lies in the simultaneous involvement of the skin and lungs due to infection with EBV. Similar to the case reported by Hoshino et al,⁷ our final diagnosis was established based on the identification of infiltrating T cells that were positive for EBV-encoded RNA in both the skin and lungs, as well as the detection of EBV DNA in peripheral blood. Skin biopsy showed prominent eosinophilic infiltrates. Although the specific mechanism is unknown, HVLPD can lead to eosinophil infiltration in oral mucosa.⁸ Based on very small amounts of human coronavirus 229E were detected in alveolar lavage fluid, the pathological results about lung biopsy and skin biopsy were very similar, considering that lung inflammation is primarily caused by EBV infection. EBV pneumonia is common in individuals with weakened immune function,⁹ but it rarely occurs in other healthy individuals.¹⁰ This patient has no evidence of immune dysfunction and is not a patient with HIV/AIDS, undergoing chemotherapy, or an organ transplant recipient. After 1 month of antiviral and low-dose glucocorticoid therapy, the patient's eosinophil count in blood significantly decreased and EBV value returned to reference range values. Although the skin lesions completely resolved, her cough did not fully dissipate. Lung involvement due to EBV infection is a seldom reported complication, with limited evidence of complete recovery after treatment. The absence of antiviral therapy for EBV remains a therapeutic challenge.

Conclusion

It is extremely rare for EBV to cause the coexistence of HVLPD and EBV pneumonia. Low-dose corticosteroids in combination with antiviral drugs have been found to be effective for HVLPD; however, their effectiveness for EBV pneumonia is not ideal.

Conflicts of interest

None disclosed.