Mystery lung mass in a kidney transplant recipient

A 64-year-old female with end-stage kidney disease due to hypertension received a deceased donor kidney transplant with alemtuzumab and methylprednisolone induction. Maintenance immunosuppression included tacrolimus, mycophenolate, and prednisone, with no episodes of rejection. She received trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis but developed recurrent hyperkalemia and thus switched to pentamidine completing 6 months of prophylaxis. She presented 1-year post-transplant with a 1-month weight loss, fever, and productive cough. On presentation, the temperature was 102.6°F and she was hypoxic. Blood work revealed a serum creatinine of 1.67 mg/dL (at baseline), and a leukocytosis of 14.4 × 103/mcL. Chest X-ray showed an extensive consolidation in the right middle and lower lobes (Figure 1). Subsequent chest computed tomography (CT) scan revealed a large right lower lobe mass with mediastinal invasion and encasement of vasculature accompanied by extensive consolidations with internal locules of gas (Figure 2A–C). An extensive serologic work-up including fungal testing was sent and was negative. The acid-fast bacilli stain was negative. Expectorated sputum and bronchoalveolar lavage cultures returned positive for Nocardia nova on hospital day 4. On day 5, she underwent a bronchoscopy with transbronchial needle aspiration of the mass that was negative for malignancy. Brain magnetic resonance imaging did not show any lesions. She was initially treated with imipenem-cilastatin and oral trimethoprim-sulfamethoxazole then transitioned to ceftriaxone and oral trimethoprim-sulfamethoxazole once susceptibilities resulted, with the regimen continued for 3 months. Follow-up imaging at 3 months showed marked improvement in her radiologic findings (Figure 2D). She was then transitioned to amoxicillin/clavulanate and oral trimethoprim-sulfamethoxazole to complete a 6-month treatment course followed by suppression with oral trimethoprim-sulfamethoxazole. She remained on tacrolimus and prednisone for maintenance immunosuppression while holding mycophenolate. Nocardia species are branched gram-positive, variably acid-fast, low-virulence bacteria found ubiquitously in soil and water. Nocardiosis is a rare and life-threatening opportunistic infection that often affects the lungs, brain, and skin. The usual host response is T-lymphocyte-mediated recognition and killing of Nocardia.1 Thus, clinically significant disease occurs in immunocompromised hosts including solid organ transplant recipients, and presents 1–2 years post-transplant. The risk of infection after kidney transplant is associated with age >65 years, history of transplant failure or rejection, receipt of deceased donor transplant, and treatment with basiliximab, cyclosporine, tacrolimus, or thymoglobulin.2 Trimethoprim-sulfamethoxazole prophylaxes against both Pneumocystis and Nocardia, although breakthrough infections can occur. Among alternative prophylactic agents, pentamidine, which was utilized in this case, and atovaquone do not have activity against Nocardia while dapsone does. Clinical presentation is usually nonspecific, and symptoms are dependent on organ involvement. Pulmonary infection can mimic diseases that can cause cavitary lung lesions such as primary and metastatic lung, pulmonary abscess, mycobacterial infections, infections with endemic mycoses, and infective endocarditis with septic emboli resulting in a delay in appropriate therapy.3 A chest radiograph alone lacks adequate sensitivity and specificity for diagnosing pulmonary opacifications in general and nocardiosis in immunocompromised hosts in particular.1, 2 Therefore, practitioners should have a low threshold to obtain a CT scan that shows cavitary lesions in 33% of patients or a mass in 24%–58% of patients with multifocal lung consolidations being the predominant finding on CT.4, 5 Pulmonary nodules that are intraparenchymal, pleural-based, or extending into the chest wall can also be present as seen in our patient, although mediastinal and hilar adenopathy is not a usual feature of pulmonary nocardiosis.6 Ground glass opacities if present usually surround as a halo around pulmonary nodules or mass. CT may also reveal involvement of the chest wall and pleural space resulting in abscess formations and pleural effusions; chronic infections may lead to pleural thickening and loss of chest wall fat.7 Suspicion should be raised for nocardiosis based on imaging characteristics as listed above, however, other fungal and mycobacterial infections such as Actinomycosis and tuberculosis may have similar CT findings. Thus, definitive diagnosis requires isolation of the organism from the suspected site, which often requires tissue biopsy.8 Nocardia may take about two to several weeks to grow in culture, thus empiric treatment should be initiated if suspicion is high. Antibiotics remain the mainstay of therapy with trimethoprim-sulfamethoxazole being used as first-line therapy for stable patients with pneumonia, and at least two agents, including imipenem with amikacin or trimethoprim-sulfamethoxazole used for severe pulmonary infection, CNS involvement, or disseminated disease. Upon completion of therapy, monitoring for relapse is recommended for an additional 1 year as relapse rates have been reported at ∼5% among solid organ transplant recipients.9. Our case demonstrates the importance of having a low threshold to obtain CT imaging whenever plain films are non-specific, particularly in immunocompromised hosts presenting with symptoms atypical of bacterial pneumonia. In our patient's case, she had symptoms for 1-month prior to presentation. The cavitary pulmonary mass was initially not evident on chest X-ray but became clear on CT imaging. prompted an extensive yet expeditious work-up that allowed timely diagnosis and initiation of treatment of pulmonary nocardiosis. The data that support the findings of this study are available from the corresponding author upon reasonable request.