S K Verma, MD Professor of Pulmonary Medicine
Chhatrapati Sahuji Maharaj Medical University(erstwhile King George’s Medical University),Lucknow, Uttar Pradesh, India
[emedpub – International Infectious Diseases :   Vol 1:2]                  [Date of Publication: 03.25.2011]
ISSN 2231-6019

March 25, 2011 at 1:04 AM

Abstract :

A case of chronic necrotising pulmonary aspergillosis (CNPA) in a female, who was treated initially as a case of pulmonary tuberculosis is presented. Patient was treated successfully with oral antifungal drug.

Introduction :

Aspergillus is a ubiquitous fungus that causes a variety of clinical syndromes in the lung, ranging from aspergilloma in patients with lung cavities, to chronic necrotizing aspergillosis in those who are mildly immune-compromised or have chronic lung disease. Chronic necrotizing pulmonary aspergillosis (CNPA) is a sub acute infection that is most commonly seen in patients with altered local defense from pre-existing pulmonary disease or in patients with risk factors that alter systemic immune status.1 Delays in diagnosis are common. Although initial reports advocated intravenous amphotericin B, itraconazole has emerged as a better initial therapy because of its documented efficacy and minimal toxicity. The dose and duration of therapy should be based on clinical response.

Case Report :

A 30 year old female, was admitted to the department of pulmonary medicine with chief complaints of, off and on low grade fever, cough with minimal expectoration since the past 14 months. She had anorexia and significant weight loss and severe breathlessness (grade IV MMRC) since the last 2 months, prior to presentation. She gave no history of hemoptysis. There was no significant family history or addictions. Her menstrual history was normal. Past history revealed that she had been hospitalised for left side consolidation 14 months ago, when she was treated with broad spectrum antibiotics which was met with poor response. Following this, she was put on CAT-1 of the Revised National Tuberculosis Control Programme (RNTCP), and her sputum smear for AFB was negative. Sputum status at completion of treatment was also negative.

As patients did not improve she was hospitalized after a gap of 2 months, for complaints of fever, cough and chest pain. At second admission, the Chest X- ray showed bilateral consolidation and cavity formation. (Fig 1). Sputum repeatedly turned out to be negative and broncho-alveolar lavage revealed inflammatory cells only. A CT scan of the thorax was performed at that time which showed extensive nodules bilaterally, more on the right side with cavitating collapse/consolidation in left upper lobe with thick walled cavity in the left upper lobe. (Fig 2). There were multiple significant mediastinal lymph nodes. She was then put on CAT-II of the RNTCP following this, after ruling out HIV seropositivity and diabetes mellitus. But her sputum was still negative for AFB.

Six months post treatment; the patient defaulted because of breathlessness. Her X-ray at third admission is presented (Fig 3). Examination revealed an emaciated female. There was no cyanosis, and clubbing of grade II was present. Pulse was 126/min, BP from right arm was 110/70 mm Hg and her respiratory rate was 34/min. Respiratory examination revealed amphoric bronchial breathing in the left interscapular and mammary area. Bilateral coarse crepitations were also present in all areas, predominantly on the right side. No rhonchi were audible. Rest of the systemic examinations were normal. Investigations showed Hb 10.6g%, TLC-9200/mm3, P 78 L 16, E 6, absolute eosinophil count was 406/mm3. Renal and liver function tests were normal. Fasting and Postprandial blood sugar were within normal limits. Sputum for AFB was persistently negative on six occasions. Culture by BACTEC was also negative. Sputum for nocardia was also negative. Sputum for fungal elements was positive in KOH mounted smears showing classical branching septate hyphae. Culture on Sabouraud’s dextrose agar media revealed aspergillus growth with Candida (later probably due to contamination). Chest X-ray showed bilateral extensive consolidation with a thick walled cavity in the left lower zone. She was started on tab Itraconazole 200mg twice daily. She was started on oral steroids initially because of severe dyspnoea which were then tapered off in a month. Patient clinically improved following this and is currently on follow up.

Fig 1. Chest X-ray at second admission showing left lower zone cavity and consolidation. There was extensive consolidation and nodularity on the right side.

Fig 2. CT thorax at second admission showed extensive nodulations on the right side and thick walled cavities on left side.

Fig 3. Chest X-ray at third admission showed left lower zone cavity and consolidation. There was extensive consolidation and nodular infiltrates on the right side.

Discussion :

Aspergillus is a ubiquitous soil-dwelling organism found in organic debris, dust, compost, foods, spices, and rotted plants. There are approximately 200 species of Aspergillus; however, only a few are known to be pathogenic for humans. Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger are the most commonly encountered species. Aspergillus manifestations include Aspergilloma, allergic broncho-pulmonary Aspergillosis, CNPA and Invasive Aspergillosis. Chronic necrotizing Pulmonary Aspergillosis (CNPA) also called semi-invasive aspergillosis, was first described in two reports in 1981 and 1982.2,3 CNPA is usually seen in middle-aged and elderly patients with documented or suspected underlying lung diseases like COPD, inactive tuberculosis, previous lung resection, radiation therapy, pneumoconiosis, cystic fibrosis, lung infarction, or, rarely, sarcoidosis. It also has been described in patients with mild immune-suppression, including those with diabetes mellitus, those with poor nutrition, those on low-dose corticosteroid therapy, and those with connective tissue diseases such as rheumatoid arthritis and ankylosing spondylitis.2

Patient with CNPA usually presents with fever, cough, sputum production, and weight loss of 1 to 6 months’ duration. A minority of the patients may be asymptomatic. The chest radiograph usually shows an infiltrative process in the upper lobes or the superior segments of the lower lobes and cavity formation. Cavity formation is often accompanied by the development of a mycetoma, which  may be seen in nearly one half of the cases.2 Adjacent pleural thickening is a characteristic finding and may be an early indication of a locally invasive process.3 This entity is different from aspergilloma in that there is local invasion of the lung tissue, and a preexisting cavity is not needed, although a cavity with a fungal ball may develop in the lung as a secondary phenomenon due to destruction by the fungus. On occasion, an aspergilloma may invade the cavity wall, causing local parenchyma destruction, as seen in patients with CNA3 . CNA is also different from invasive aspergillosis. The former, in contrast to the latter, is a chronic process that progresses slowly over months to years, and there is no vascular invasion or dissemination to other organs2. The diagnosis is suggested by the clinical course and the isolation of the fungus from pulmonary secretions; negative cultures for other pathogens and failure to respond to antibacterial or antimycobacterial therapy are characteristic. In clinical practice, the diagnosis of semi invasive aspergillosis is usually based on the presence of multiple cultures positive for Aspergillus organisms, chest radiographs with abnormal findings and bronchoscopy biopsy specimens consistent with tissue invasion. Sputum culture for fungus gave positive yield for Aspergillus species on 6 occasions. However, the yield of transbronchial biopsy specimens or percutaneous aspirates is relatively poor, and a thoracoscopic or open-lung biopsy is rarely performed in these patients. The diagnosis can also be confirmed by a response to specific antifungal therapy. The symptomatic response to antifungal chemotherapy, at times combined with surgical drainage or resection, is favorable. However, roentgenographic resolution is not uniform, and many patients have residual cavitatory disease. The long-term prognosis is uncertain2,4,5. Other helpful but non-diagnostic tests include serum IgG antibodies to Aspergillus (positive results in > 90% of the patients) and immediate skin reactivity for Aspergillus antigens. Treatment with antifungal is indicated once the diagnosis is made. The response to therapy with amphotericin B IV is generally favourable.2,3 However, therapy with itraconazole has emerged as an effective alternative to the relatively toxic amphotericin B.5 Itraconazole seems to be effective in CNPA when used in a suppressive (rather than curative) role in patients with limited life expectancy.6 We opted for oral itraconazole taking into account the patients poor socioeconomic status and fear of adverse effects with amphotericin B, as the patients general condition was below par. Surgical resection is generally reserved for healthy young patients with focal disease and good pulmonary reserves, patients not tolerating antifungal therapy, and patients with residual localized but active disease despite adequate antifungal treatment.

In the initial series by Binder et al, 90% of patients who underwent surgical resections had good responses. However, there were significant postoperative complications, and one patient died2. The long-term prognosis for patients with CNPA is not well-documented. In the original series, 73% of the patients were alive for 1-2 years following therapy, and the majority of deaths were due to other causes2. This patient is in our follow up and has symptomatically improved with therapy with a weight gain of 5 kg. .

In conclusion, since the incidence of fungal diseases is currently increasing worldwide especially in developing countries and it may present with different clinico-radiological manifestations, they should always be recalled in cases not responding to appropriate antibiotics or antituberculous chemotherapy after ruling out bacterial etiology.

References :

1.      Joseph L, Saraceno D O, Douglas T, Phelps T J, Ferro R F,  Douglas B S. Chronic Necrotizing pulmonary aspergillosis: Approach to management Chest 1997;112:541-548.

2.      Binder RE, Faling LJ, Pugatch RD.  Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine 1982,61(2),109-124.

3.      Gefter WB, Weingrad TR, Epstein, DM.  ”Semi-invasive” pulmonary aspergillosis: a new look at the spectrum of Aspergillus infections of the lung. Radiology 1981; 140:313-321.

4.      Yu VL, Muder RR, Porsattar A. Significance of isolation of Aspergillus from the respiratory tract in diagnosis of invasive pulmonary aspergillosis: results from a three-year prospective study. Am J Med 1986;81:249-254.

5.      Treger TR, Visscher DW, Bartlett MS, Smith JW. Diagnosis of pulmonary infection caused by Aspergillus: usefulness of respiratory cultures. J Infect Dis 1985;152:572-576

6.      Caras WE, Pluss JL. Chronic necrotizing pulmonary aspergillosis: pathologic outcome after itraconazole therapy. Mayo Clin Proc 1996; 71:25-30.

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