Concurrent pulmonary Aspergillosis and Nocardiosis in an old tubercular cavity masquerading as malignancy in an immunocompetent individual
Article Outline
- Summary
- Educational Aims:
- Introduction
- Case report
- Discussion
- Conflicts of interest statement
- References
- Copyright
Summary
Pulmonary Nocardiosis and Aspergillosis closely mimic malignancy both clinically and radiologically. An aggressive workup is important since these infections are curable but potentially fatal. We present an immunocompetent person in whom malignancy was strongly suspected but actually had mixed infection with Nocardia and Aspergillus that responded to medical therapy.
Keywords: Aspergillus, Nocardia, Tuberculosis, Malignant
Educational Aims:
Introduction
Nocardia and Aspergillus species are well established opportunistic pathogens in immunocompromised persons. Pulmonary disease is the predominant clinical presentation in infection by both organisms, and can be fatal if untreated. They are usually considered in the differential diagnosis of indolent pulmonary disease in persons with immune compromise, along with other actinomycetes (mycobacteria), and eumycetes (Cryptococcus neoformans, etc). However, they are uncommon in immunocompetent persons, and concomitant infection with both even rarer. In these situations, the clinician may be misled towards a malignant disorder. We report one such rare occurrence of simultaneous infection with Nocardia and Aspergillus species in an immunocompetent host.
Case report
A 54 year old male, security guard by occupation, presented to the medicine outpatient with multiple episodes of hemoptysis since the last 20 years, which became more frequent since 2 years. Each episode lasted for 7 to 10 days with streaky blood tinged sputum interspersed with bouts of significant hemoptysis of approximately 0.4–0.8
L of blood loss. He also complained of left sided burning chest pain. He gave no history of bleeding from any other site, cough with expectoration, dyspnea, fever, loss of appetite or weight. He denied any history of trauma to chest or history suggestive of connective tissue disorder.
The patient was treated for pulmonary tuberculosis in 1984 for 18 months with good compliance. He left smoking 20 years back, never consumed alcohol or any other addictives. He denies any history of hypertension or diabetes in the past. He has no history of exposure to organic or inorganic dust or other noxious substances.
On initial evaluation, he was well preserved with mild pallor and no other abnormalities on systemic examination. Blood investigations revealed normal hemogram, hepatic and renal profile, erythrocyte sedimentation rate, blood sugar, and coagulation profile. Antinuclear antibodies, anti-cytoplasmic antibodies, and HIV tests were negative. CD 4 and Immunoglobulins A, M, and G were within normal limits. Sputum smear was negative for acid-fast bacilli or malignant cells and culture did not reveal any bacteria or fungi. The chest skiagram had bilateral scattered fibro-calcific lesions, left upper lobe bronchiectasis, and a right mid zone non-homogenous opacity. The contrast enhanced computed tomogram of the chest done previously revealed a soft tissue density mass with speculated margins and satellite nodular specks in the right lower lobe suspicious of a malignant lesion (Fig. 1A). Fiberoptic bronchoscopy revealed normal airways and no intrabronchial growth. Bronchoalveolar lavage fluid grew Pseudomonas species; no acid-fast bacilli or malignant cells were seen.
Figure 1
(A and B) Contrast enhanced CT scan of chest showing a spiculated mass-like lesion with satellite nodules in the right lower lobe (A) and a crescent sign in the same lesion after one month (B).
A CT guided fine needle aspiration was performed from the right lung lesion which revealed masses of fungal hyphae admixed with fine filaments. Fungal hyphae showed acute angled branching and septation (Fig. 2A). These features were consistent with Aspergillus. The fine, beaded, and branching filaments stained with silver stain and were weakly acid-fast (Fig. 2B) suggestive of Nocardia. The background showed dead fungal hypae with negligible inflammation. The cytological diagnosis of Aspergilloma with colonization by Nocardia species was made. A CT scan done after one month showed a crescent sign in the nodular lesion in the right upper lobe (Fig. 1B). The patient was offered surgery to resect this lesion, but declined.
Figure 2
(A) Mass of fungal hyphae and fine branching filaments (Papanicolaou 400×). (B) Acid-fast filamentous bacteria (Ziehl-Neelsen 1000×).
Ketoconazole 400mg solution was instilled intrabronchially into the right upper lobe, and the patient was started on oral itraconazole 200mg twice daily for two months and cotrimoxazole (double strength) tablet for six months. After one month of starting treatment, the hemoptysis stopped and the patient has remained asymptomatic after one year of follow-up. However, repeat CT scan of the chest did not show any significant reduction in the lung lesion.
Discussion
Pulmonary Nocardiosis is an uncommon but potentially serious infection usually found in immunosuppressed patients. Nocardia species are aerobic branching, filamentous gram positive, weakly acid-fast bacteria that exist as soil saprophytes. N. asteroides are the most frequent cause of pulmonary infection in humans (85%).1 Aerosol route is the major portal of entry and lung is the commonest site of infection. The crucial role of cell mediated immunity has been proven in experimental in vitro studies, hence explaining the increased occurrence in immunocompromised persons, such as HIV infection, alcoholism, chronic obstructive pulmonary disease, malignancy, or prolonged corticosteroid therapy.2, 3, 4 Patients present with fever, chills, cough, sputum, weight loss, progressive dyspnea, and occasionally hemoptysis. Radiological manifestations include consolidation with/without cavitation, single or multiple abscesses, nodules, or pleural involvement.5 Since the clinic-radiological findings are relatively non-specific, differential diagnosis includes several other bacterial, fungal, and tubercular infections of the lung, as well as malignancy. The diagnosis is based on the isolation or demonstration of Nocardia in respiratory secretions such as sputum, bronchoalveolar lavage, or percutaneous lung aspirates. Nocardia is a slow growing organism that requires prolonged incubation for at least 4–6 weeks. Antimicrobial testing is a useful guide to therapy and is performed using broth microdilution or BACTEC radiometric method.6, 7
Most Nocardia isolates are sensitive to sulfonamides and trimethoprim-sulfamethoxazole (TMP-SMX). The recommended dose of TMP-SMX is 5–10mg/kg (trimethoprim) and 25–50mg/kg (sulfamethoxazole) in two or four divided doses. Therapy must be given for at least six months in immunocompetent patients with pulmonary Nocardiosis, and for twelve months in patients with cerebral involvement, HIV or other immunodeficient states. Other parenteral drugs having activity against Nocardia include Amikacin, Carbepenems and third generation cephalosporins. Resolution of the disease is defined as eradication of the Nocardia species along with clinical and radiological improvement. However, some patients achieve predominantly clinical improvement, while radiological resolution may be partial and delayed.
Pulmonary Aspergilloma is the commonest invasive fungal infection in immunocompromised persons. A significant percentage of patients with residual inactive tubercular cavities may develop aspergillomas, commonest being A. flavus.8 The spectrum of Aspergillosis ranges from simple colonization (eg. Aspergilloma) to life threatening invasive infection. Factors predisposing to infection include local causes (COPD, pneumonia, pulmonary infarction, post-influenza) as well as systemic causes (diabetes, bone marrow and solid organ transplant recipients, HIV/AIDS, chronic steroid therapy, chronic granulomatous diseases). However, immunocompetent persons are not immune from Aspergillosis and a similar spectrum of infection may occur in these individuals, although at a much lesser frequency.
The clinical manifestation and severity depends on the immunologic state of the patient and are similar to pulmonary Nocardiosis. Patients may be asymptomatic or present with varying degree of hemoptysis (upto 30%). Radiological findings include nodules ranging from 1 to 3cm which cavitate in 50% of patients. Cavitation usually occurs after 10–14 days and produces a ‘crescent sign’ on computed tomography. The ‘halo sign’ and the ‘air crescent sign’ are relatively specific but poorly sensitive.9, 10 Although serological methods such as detection of the antigen galactomannan (cell wall glycoprotein) by ELISA, EIA or immunoblot test (sensitivity and specificity >90%); and the polymerase chain reaction (PCR) for detection of DNA and RNA copies are being increasingly used,11 the cytological/histopathological demonstration of typical septate hyphae or growth of Aspergillus in tissue specimens remains the gold standard for a definitive diagnosis. Symptomatic Aspergillomas may be treated by surgical resection; however, the benefits should out weigh the risk of surgery for patient at high risk of severe hemoptysis.
Although the long duration of hemoptysis in this patient may be explained by the presence of old tubercular cavity with Aspergilloma, the background history of smoking, and a spiculated lung lesion initially seen on the CT scan strongly suggested a possible malignant disorder. However, fine needle aspiration cytology yielded multiple infections with Aspergillus and Nocardia. The presence of such concurrent pulmonary infection was reported once previously in an immunosuppressed patient due to long-term steroid therapy; however, the current patient is probably the first such report in an immunocompetent individual. This clinical presentation emphasizes the importance of keeping a broad differential diagnosis with rare non-malignant disorders in mind even in persons with lung lesions highly suspicious for malignancy.
Conflicts of interest statement
The authors have no conflict of interest.
References
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PII: S1755-0017(08)00052-3
doi:10.1016/j.rmedc.2008.07.011
© 2008 Elsevier Ltd. All rights reserved.
