Please wait. Loading...
 
Αποστολή σε φίλο
 
Salvage therapy in invasive pulmonary aspergillosis in an immunocompetent host
treatment outcome, immunocompetence, aspergillosis
The majority of cases of invasive pulmonary aspergillosis (IPA) are seen in immunocompromised patients but IPA has been rarely reported in immunocompetent patients. The case is described of invasive pulmonary aspergillosis in an immunocompetent 17 year-old male, who was successfully treated with salvage therapy, including Itraconazole and Amphotericin B. Pneumon 2008; 21(1):77–80

INTRODUCTION

Invasive aspergillosis remains the most invasive fungal infection world wide, in spite of improvements in medical therapy.1,2

The majority of cases of invasive pulmonary aspergillosis (IPA) are seen in immunocompromised patients.3-5 IPA has rarely been reported in immunocompetent patients1,6,7, but from a review of a large case series of patients with IPA, it appears that no underlying risk factors (prolonged neutropenia, transplantation, corticosteroid therapy, AIDS, malignancy, cytotoxic therapy) were identified in 2% of patients.8 Salvage therapy in invasive fungal infection refers to the treatment cases resistant or intolerant to initial therapy administered for at least 7 days. A number of agents have been used in treatment of invasive aspergillosis in a salvage setting, including amphotericin B, caspofungin, itraconazol, voriconazol, posconazol and micofungin. However, the unavailability or high cost of these drugs may create a problem.9 A case is reported of invasive aspergillosis caused by Aspergillus fumigatus in an apparently immunocompetent host, which was successfully treated with Itraconazole.

CASE REPORT

A 17 year-old Afghani male worker presented with a 1-month history of fever, dyspnoea, cough with purulent and bloody sputum, and constitutional symptoms compatible with community acquired pneumonia (CAP). He had been previously healthy, with no history of tuberculosis or other medical illnesses. He had no risk factors for human immunodeficiency virus (HIV) and neither drank alcohol nor used opium, but had started to smoke cigarettes (5 cigarettes/day) one month earlier. On examination, the patient was febrile and his body temperature was 39°C with a pulse rate of 108/min, blood pressure 110/70 mmHg and respiration rate of 36 breaths per minute. Supraclavicular retraction was noted. Crackles were audible over the whole lung field. His laboratory investigations were: Hb 10.6 g/dl, WBC 22,300/mm3, ESR 104 mm/hr, CRP was elevated, serum Na 128mmol/l), liver function tests were abnormal (albumin 2.5gr/dl, alkaline phosphate 631 IU/L, ALT 240 IU/L, AST 257 IU/L), serum ferritin was increased (683 μg/dl), and blood culture after 48 hours was negative. Chest X-ray revealed bilateral infiltrations and cavities. On the basis of the clinical and radiological findings, a diagnosis of tuberculosis was made and antituberculosis therapy was started, plus ceftazidim, clindamycin and ciprofloxacin. On the eighth hospital day, despite antituberculosis therapy, the patient was still febrile and ill. A thorax computed tomography (CT) showed bilateral multiple and severe pulmonary patchy consolidations and multiple cavities with fluid levels within some spaces, compatible with abscess formation (Figure 1). Sputum smears were negative for Bacterium - Koch (BK) on three occasions. Echocardiography revealed a little pericardial effusion and no vegetation on the heart valves. These findings raised the suspicion of vasculitis, Wegener's Granulomatosis (WG), so, methylprednisolone pulse therapy (500mg/IV) and cyclophosphamide (500mg orally twice daily) were started and antituberculosis therapy was stopped. On the fourteenth hospital day, rigid bronchoscopy and video-assisted thoracoscopic lung biopsy were performed. A specimen from the lung biopsy showed extensive bronchiolar destruction, obstruction and cavity formation, and granulomatous inflammation surrounded by fungal hyphae, compatible with fungal lung infection. Both bronchial washings and sputum grew Aspergillosis fumigatus on Sabouraud dextrose agar. Treatment with prednisolone and cyclophosphamide was ceased and antifungal therapy with itraconazole (300mg/twice/daily) was started. The patient showed clinical improvement after a few days, and further investigations were performed. Flow cytometry of peripheral blood immunoelectrophoresis were within normal limits (Table I). Human immunodeficiency virus (HIV) antibody, antinuclear antibody (ANA), P.A.N.C.A. and C.A.N.C.A. were negative, and NBT test was 100%. The patient was ultimately discharged after 40 days in good condition and he received oral itraconazole (200mg twice daily) maintenance therapy. During the first 8 months after discharge, he was hospitalized twice because of to haemoptisis and after one month of treatment with itraconazole alone, treatment with amphotericin B was administered in addition; response to this treatment was excellent, and he was discharged on oral itraconazole (200mg twice daily) for two months. At the present time, 4 months after the last discharge, he has no problems, without any further treatment.

DISCUSSION

IPA usually occurs in an immunocompromised host, such as patients with marked neutropenia, acute leukaemia and other malignancies, immunodeficiency either congenital or acquired, diabetes, CGD, CMV infection or alcoholism, and in patients on parenteral antibiotic therapy.9 The number of reported cases of invasive pulmonary aspergillosis in immunocompetent hosts is small. Clancy et al,11 discussed about nine patients with IPA with a previous healthy history whose most important manifestations were fever, productive cough, dyspnoea, chest pain, and haemoptisis. In that study, the diagnosis was delayed in all patients because no patients was in an immunocompromised state or had underlying pulmonary disease, so all the patients had advanced infection at the time of diagnosis and died a short time after hospitalization. The patient presented here revealed no evidence of immunosuppression or neutropenia, and had no underlying pulmonary disease. The common clinical features of fever, cough, malaise, weight-loss, and dyspnoea are nonspecific and consistent with bronchopneumonia. In this case, cavernous infiltration in the lung field was at first suggestive of lung tuberculosis, so antituberculosis therapy was started, and as there was neither evidence of underlying pulmonary disease nor the predisposing factors of immunosuppression, IPA was not considered. Despite antituberculosis therapy, he remained febrile and ill. For further evaluation, he underwent rigid bronchoscopy and video-assisted thoracoscopic lung biopsy. His lung biopsy revealed extensive bronchiolar destruction, obstruction and cavity formation granulomatous inflamation surrounded by fungal hyphae. Both bronchial washing and sputum grew Aspergillosis fumigatus on Sabouraud dextrose agar. These findings were suggestive of lung fungal infection with A. fumigatus, so antifungal therapy with itraconazole (300mg twice daily) was started and after a few days, the patient showed clinical improvement. The diagnosis of invasive aspergillosis remains difficult even today and there is no single test available to establish definitive diagnosis of aspergillosis regardless histopathologic evidence of disease. Detection of aspergillose antigen in serum and positive aspergillose culture are the most important diagnostic tools.12,13 Bronchoalveolar lavage (BAL) for fungal smear and culture is usually helpful in invasive aspergillosis diagnosis in patients with diffuse lung involvement.14,15 The pathologic findings of granulomatous inflammation and necrosis is mostly seen in a mildly immunocompromised patient with rare vascular invasion by fungal hyphae,16-18 but these pictures are also seen in immunocompetent hosts.6,17 Primary invasive aspergillosis manifests as bilateral diffuse infiltration or localized infiltration that progresses to diffuse infiltration, but infiltration with cavitary lesion and nodules are rather characteristic findings in secondary invasive aspergillosis19. Here a patient is described with radiologic findings of patchy consolidation and cavitary lesions that mimic TB or WG, which are rare in the immunocomponent host, Infiltration and cavitary lesions of the lung can be easily attributed to tuberculosis. As a rule, the above radiologic findings can be demonstrated in diseases such as malignancies as well as fungal infections, septic emboli, lymphoma and WG. As illustrated by this case, pulmonary aspergillosis can be concealed in unexpected ways, especially in immunocompetent patients.

In summary, IPA may occur in apparently immunocompetent patients but is rare, so the absence of an immunocompromised state results in late diagnosis and its side effects. The differential diagnosis of aspergillosis should be considered in patients not responding to antimicrobial therapy or antituberculous therapy; early diagnosis aggressive antifungal therapy and increases the chance of a favourable outcome. The outcome in invasive aspergillosis is directly linked to early diagnosis and treatment.20

REFERENCES

  1. Raja NS, Singh NN. Disseminated invasive aspergillosis in an apparently immunocompetent host. J Microbiol Immunol Infect 2006; 39:73-77
  2. Groll AH, Shah PM, Mentzel C, Schneider M, Just-Nuebling G, Huebner K. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 1996; 33: 23-32.
  3. Polat G, άrpek G, Yilmaz U, et al. Successful treatment of invasive pulmonay aspergillosis in an immunocompetent host. Respirology 2005; 10: 393-395.
  4. Minamoto GY, Barlam TF, Vander Els NJ. Invasive aspergillosis in patients with AIDS. Clin Infect Dis 1992; 14: 66-74.
  5. Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest 2002; 121: 1988-99.
  6. Chong S, Kim TS, Koh WJ, Cho EY, Kim K. Invasive pulmonary aspergillosis complicated by pulmonary artery occlusion in an immunocompetent patient. Clinical Radiology 2006; 61:287- 290
  7. Kang EY, Kim DH, Woo OH, Choi JA, Oh YW, Kim CH. Pulmonary aspergillosis in immunocompetent hosts without underlying lesions of the lung: radiologic and pathologic findings. AJR Am J Roentgenol 2002; 178: 1395-9.
  8. Patterson TF, Kirkpatrick WR, White M et al. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group. Medicine (Baltimore) 2000; 79: 250-60.
  9. Garcia RJ, Troya P, Edwads C. Invasive Aspergillosis with Central Nervous System Dissemination in a Presumably Immunocompetent, Non-neutropenic Patient. Southern Medical Journal 2006 Jun; 99(6): 607-10
  10. Dockrell DH. Salvage therapy for invasive aspergillosis. J Antimicrob Chemother 2008 61 Suppl 1:141-4
  11. Clancy CJ, Nguyen MH. Actue community-acquired pneumonia due to Aspergillous in presumably immunocompetent hosts: clues for recognition of a rare but fatal disease. Chest 1998; 114: 629-34.
  12. Kontoyiannis DP, Bodey GP. Invasive aspergillosis in 2002: an update. Eur J Clin Microbiol Infect Dis 2002; 21: 161-72. 12. Denning DW. Early diagnosis of invasive aspergillosis. Lancet 2000; 355:423-4
  13. Treger TR, Visscher DW, Bartlett MS, Smith JW. Diagnosis of pulmonary infection caused by Aspergillosis: usefulness of respiratory cultures. J Infect Dis 1985; 152:572-6.
  14. Kahn FW, Jones JM, England DM. The role of bronchoalveolar lavage in the diagnosis of invasive pulmonary aspergillosis. Am J Clin Pathol 1986; 86:518-23.
  15. Horvath JA, Dummer S. The use of respiratory tract cultures in the diagnosis of invasive pulmonary aspergillosis. Am J Med 1996; 100:171-8.
  16. Hayashi H, Takagi R, Onda M, Kumazaki T. Invasive pulmonary aspergillosis occluding the descending aorta and left pulmonary artery: CT features. J Comput Assist Tomogr 1994; 18:492-4
  17. Katz JF, Yassa NA, Bhan I, Bankoff MS. Invasive aspergillosis involving the thoracic aorta: CT appearance. Am J Roentgenol 1994; 163:817-9.
  18. Hashino S, Imamura M, Tanaka J, et al. Invasive pulmonary aspergillosis complicated by subclavian artery occlusion following allogeneic stem cell transplantation. Acta Haematol 1997; 98: 167-9.
  19. Choi YW, Kang E-Y, Choi J-A. Isit a new pattern of pulmonary aspergillosis. Am J Roentgenol February 1 2003;180(2):539- 540
  20. Horger M, Einsele H, Schumacher U, et al. Invasive pulmonary aspergillosis: frequency and meaning of the "hypodense sign" on unenhanced CT. Br J Radiol, 2005; 78(932):697-703.

© 2011 PNEUMON Magazine, Hellenic Bronchologic Society.
Developed by LogicONE Logo LogicONE