Foot Note

HSV: Herpes simplex virus
BAL: Bronchoalveolar lavage
HIV: Human Immunodeficiency Virus

Case Report

A 42 year-old African American man presented to the emergency department (ED) with complaints of fever, cough and progressive dyspnea in the past several days. One month before presentation, he was diagnosed with Human Immunodeficiency Virus (HIV) infection, the origin of which was thought to be as a result of unprotected homosexual intercourse. His CD4 lymphocyte count was 34 /ml at that time. Highly Active Anti-Retroviral Therapy (HAART) and prophylactic Bactrim was offered to him, but he declined. One week before presentation, he was seen at ED for fever and cough. Chest radiograph revealed bilateral interstitial infiltrates (Figure 1). Pneumocystis jiroveci (Pneumocystis carinii) pneumonia was suspected and he was treated and discharged on oral Bactrim.

Figure 1

Figure 1: Chest radiograph one week before presentation showing interstitial infiltrates.

On the admission physical examination his temperature was 38.5ºC, heart rate was 140 beats/min, respiratory rate was 40 breaths/min, and oxygen saturation was 70% on room air. Skin and mucosal surfaces were free of any lesions. Chest auscultation revealed diffuse bilateral crackles. The cardiac and abdominal exams were unremarkable. The neurological examination was normal. White blood cell count was 19,800 /ml³. Blood chemistry and hemoglobin level were normal. The patient was intubated for hypoxia and transferred to intensive care unit. Repeat chest radiograph showed worsening of bilateral infiltrates (Figure 2).>

Figure 2

Figure 2: Chest radiograph on admission showing progression of bilateral infiltrates.

A fluoroquinolone and a macrolide were empirically started to treat presumed severe community acquired pneumonia. Patient also received Bactrim along with corticosteroids for possible Pneumocystis jiroveci pneumonia. Several blood cultures were negative. An echocardiogram showed normal left ventricular systolic function. Bronchoscopy with bronchoalveolar lavage (BAL) was done. BAL cytological evaluation revealed no evidence of Pneumocystis jiroveci infection. BAL cultures were negative for bacteria, mycobacteria, and legionella. BAL viral culture grew Herpes Simplex Virus (HSV) type 2. This positive result for HSV was though to be due to contamination or colonization of respiratory tract. Unfortunately the patient developed multiple pulmonary emboli and died. An autopsy was performed. The pathologic examination of lung tissue showed lymphocytic interstitial infiltrates. Viral inclusions were noticed in endothelial cells and macrophages. HSV type 2 was isolated from lung tissue (cell culture by ELVIS® method). These findings strongly suggest a diagnosis of HSV type 2 pneumonia in an HIV infected patient.

Discussion

Herpes simplex virus (HSV) is a widespread pathogen that is capable of causing a lower respiratory tract infection in a susceptible host, the most common form of which is tracheobronchitis. Although rare, HSV also can cause pneumonia. HSV type 2 pneumonia is extremely rare₁. HSV lower tract infection is most likely the result of the reactivation of endogenous herpes virus. In recipients of liver and heart-lung transplants, HSV pneumonia was diagnosed only in patients that were Anti-HSV-IgG seropositive preoperatively₂, ₃. Although few cases of HSV pneumonia have been reported in immunocompetent hosts, it seems that suppression of cell-mediated immunity is the most important risk factor for development of HSV pneumonia. Conditions that are associated with HSV pneumonia includes HIV infection₄, aplastic anemia, acute myeloblastic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, Hodgkin's disease, bone marrow transplantation, solid organ transplantation, alcoholism₅, burns₆, postthoracotomy₇ and cardiac surgery₈. In one report, all three patients that developed HSV pneumonia after thoracotomy were immunosuppressed, had a recent history of chemotherapy, malnutrition, and severe postoperative complications₇. Depressed cell-mediated immunity after cardiopulmonary bypass has been described as an important risk factor in the development of HSV pneumonia after cardiac surgery₈. Pulmonary HSV infection has also has been associated with intubation and mechanical ventilation in patients with chronic disease. Since HSV usually infects squamous epithelial cells, squamous metaplasia of tracheobronchial tree as a result of intubation may explain the association between intubation and HSV lower respiratory tract infection. Infection and colonization of squamous metaplasia of trachea could lead to an extension of the infection to the lower respiratory tract and eventually could cause pneumonia in a susceptible patient₁.

Two patterns of HSV pneumonia have been identified. The first pattern is a focal or multifocal necrotizing pneumonia caused by the direct spread of the virus from lesions in the upper respiratory tract or through the extension of herpetic tracheobronchitis. The second pattern is a diffuse pneumonia secondary to the hematogenous dissemination of HSV, most likely from oral or genital mucocutaneous lesions₁, ₉. In one study, all bone marrow transplant recipients developed HSV pneumonia within 28 days after transplantation. Interestingly, at the time diagnosis of pneumonia most of these patients were neutopenic₅. In another observation in recipients of heart-lung transplants, all cases of HSV pneumonia were diagnosed within 2 months after transplant ₂. Oral and genital herpetic lesions, tracheitis, and esophagitis are commonly reported in patients with HSV pneumonia. Clinical manifestations of HSV pneumonia include fever, cough, dyspnea, and respiratory failure₅. Diffuse infiltrates, lobar consolidation, multifocal infiltrates, unilateral and bilateral pleural effusions can be seen on chest imaging₁₀. Detection of HSV in sputum, BAL, lung tissue by culture, polymerase chain reaction (PCR), and immunochemical staining has been utilized to establish the diagnosis of HSV pneumonia₃, ₅, ₇. HSV pneumonia is a potentially fatal condition₅. Successful treatment with Acyclovir and supportive care has been reported in the literature₁,₈. The acyclovir-resistant HSV strains causing pneumonia have been described. These strains of HSV are also resistant to Gancyclovir. Foscarnet is an alternative agent for treatment of these patients₁₁.

HSV type 2 pneumonia is extremely rare. HSV pneumonia should be considered in susceptible patients with pneumonia and respiratory failure who do not respond to antibiotics. When no bacterial or fungal pathogenic agent can be identified, empiric Acyclovir could be considered. Herpetic oral, genital, and tracheal lesions should alert the physicians to the possibility of HSV pneumonia.

Acknowledgement

Correspondence to

Bobbak Vahid, MD Thomas Jefferson University 1015 Chestnut Street, Suite M-100 Philadelphia, PA 19107 Tel: 215 955-6591 Fax: 215 955-0830 Bobbak.vahid@mail.tju.edu