Introduction

Although more prevalent in transplanted patients, cytomegalic lung disease also occurs in patients with autoimmune diseases under immunosuppressive therapy [1, 2]. We recently saw a patient with systemic lupus erythematosus (SLE), who presented with a recidivant interstitial lung disease mimicking lupus lung activity, which, on follow-up, was shown to be a cytomegalic viral infection (CMV). Treatment with conventional doses of ganciclovir, a first-line antiviral medication for this condition, was shown to be ineffective. Introduction of foscarnet, a second-line antiviral treatment for this disease, was associated with full recovery.

Case report

VNS is a 47-year-old woman who came to our service in 2001 because of thrombocytopenia followed by arthritis and, later in 2003, positive antinuclear antibodies (ANA) and serum hypocomplementemia which established the diagnosis of SLE. Her disease was successfully controlled with systemic steroids, azathioprine, and intravenous gamma-globulin. In September 2005, the disease relapsed with low platelet counts, and the patient was treated with Rituximab as previously described [3], going into clinical remission. Nine weeks after her discharge, with her disease under control with mycophenolate mofetil (1 g twice a day) and prednisone (20 mg per day), she started complaining of blindness of the left eye and dysphagia. Eye examination revealed macular lesions compatible with CMV and biopsy of the esophageal mucosa revealed esophagitis by the same agent. She was immediately started on intravenous ganciclovir (250 mg twice a day) with improvement of symptoms and discharged on a maintenance regimen of ganciclovir (300 mg per day, five times a week).

Soon after, the patient was readmitted with an acute episode of respiratory failure (pO2 = 65 mmHg with nasal O2 5 l/min) and high fever (39°C). Chest tomography revealed an interstitial infiltrate. To differentiate between infection and lupus lung activity, CMV antigenemia and viral load were collected, and the patient was submitted to an analysis of bronchoalveolar cellular lavage as previously described [4, 5]. This analysis showed a pleomorphic cellular population with large and small mononuclear cells and absence of cytopathic inclusions. Since she was already on ganciclovir and with the results of the bronchoalveolar lavage, this new episode was initially attributed to lupus disease activity, and tests for lupus activity were performed. Simultaneously, immunosuppressive therapy with prednisone was increased to 60 mg per day.

After 3 days of immunosuppressive therapy, all tests for lupus activity returned normal, and measurements of viral load and antigenemia for CMV returned positive. The hypothesis of a ganciclovir-resistant CMV pneumonitis was considered, and ganciclovir was replaced with intravenous foscarnet (90 mg/kg twice a day). After the introduction of this medication, the patient’s clinical status improved significantly, the hypoxia, fever, and lung images resolved, and she was discharged with foscarnet (90 mg/kg per day).

Discussion

The development of CMV lung disease in immunocompromised patients has been extensively reported, especially in AIDS and transplantation, being characterized by increased respiratory rate, hypoxemia, and pulmonary infiltrates [6, 7]. There are several laboratory procedures to confirm the diagnosis of recurrent CMV infection including serum enzyme immune assay, antigenemia, cytomegalic inclusion bodies in bronchoalveolar lavage, transbronchial biopsy, and viral load [8]. In our case, three of these assays came positive.

Lupus lung disease is very polymorphic. The immune complex-mediated inflammatory process can cause interstitial pulmonary disease, lupus pneumonitis, pleural effusions, and, rarely, pulmonary hemorrhage. A clue to pulmonary involvement is the presence of cough and chest pain on breathing; however, neither one has a good predictive value. Ground glass opacity and reticular shadows are typical X-ray findings, but when pulmonary infiltrates are associated with fever cough and dyspnea, infection has to be ruled out [9]. The treatment of acute lupus lung disease includes high-dose steroids and, in its chronic stages, immunosuppressive drugs.

The classical CMV pneumonitis treatment includes ganciclovir and hyperimmune specific gammaglobulin, with some reports showing similar efficacy between the oral and intravenous treatment with ganciclovir [10–12]. Ganciclovir resistance is rare but has been reported in solid organ transplant patients [13]. To our knowledge, this is the first case reported in a patient with SLE. CMV strains with known ganciclovir resistance mutations have been described although this was not tested in our case.

Although previously reported, association of CMV and SLE is uncommon [2, 14], but even more rare is the development of CMV pneumonitis in lupus patients. An extensive review of the literature was able to find a single case reported by Alonso et al. [15].

New strategies for the treatment of CMV disease include the use of the oral agent valganciclovir and the combination of ganciclovir and foscarnet [16]. Currently available drugs can achieve control of CMV infection but, in a small number of cases, resistance develops. Our case is somewhat atypical because it developed after a successful treatment of retinitis and a falling CMV viral load [13, 17]. Finally, as illustrated in our case, in patients with SLE interstitial lung disease, it is essential to consider CMV lung infection early and, in case of poor response to proper treatment or lack of response to ganciclovir, to raise the suspicion of resistance to specific antiviral therapy [18].