Invasive Pulmonary Aspergillosis after Renal Transplantation Treated by Surgery

Introduction

Opportunistic mycoses, such as candidiasis and aspergillosis, seldom affect healthy individuals and usually occur in immunocompromised subjects. As polymorphonuclear cells play an important role in damaging Aspergillus hyphae and in the phagocytosis of yeasts, the degree and duration of neutropenia contribute to the risk of developing invasive aspergillosis, which is pulmonary in up to 90% of cases. ^1,2 Although invasive pulmonary aspergillosis (IPA) with angioinvasion and tissue destruction usually occurs in immunocompromised patients suffering from prolonged granulocytopenia (due to chemotherapy, total body irradiation, bone marrow or solid organ transplantation, prolonged high-dose steroid treatment, or hematological malignancies), neutropenia was not detected by Weiland and colleagues ³ in 25 renal transplants complicated by IPA. The diagnosis of aspergillosis is based on the clinical picture as well as direct microscopic examination, isolation, and cultivation of a specimen collected usually from the respiratory tract. When IPA is suspected, total body computed tomography is mandatory because it can provide a quick evaluation of the extent of infection. We report a case of IPA after renal transplantation, which was treated with complementary lung resection.

Case Report

A 48-year-old woman weighing 71 kg underwent renal transplantation for chronic renal failure and was discharged after an uneventful course with immunosuppressive therapy based on cyclosporine A, mycophenolate mofetil, and steroids. Two months later, she was admitted to a local hospital with high fever and a productive cough. A chest radiograph showed consolidation of the upper lobe, suggestive of pneumonia. She was treated with wide-spectrum antibiotics while awaiting the results of the sputum examination. After a week of treatment with no response, she was transferred to our hospital. A computed tomography scan of the chest (Figure 1) showed a lung parenchymal consolidation with fluid in the right upper lobe. Tracheobronchoscopy showed ulcerative tracheobronchial lesions of the epithelium, mainly at the level of the right main stem bronchus and in the right upper lobe bronchus, which were biopsied (bronchocentric granulomatosis); bronchial brushings, washing, and biopsies supported the diagnosis of IPA. Examination of sputum allowed isolation of Aspergillus flavus, and the same fungus was detected in cutaneous eczematous lesions (a rare finding). Head and abdominal computed tomography scans showed no extrapulmonary localization, while a fundus oculi examination for reduced vision showed bilateral lesions suggestive of fungal colonization. The neutrophil count was within the normal range. A diagnosis of systemic invasive aspergillosis was made. Due to this widespread infection, immunosuppressive treatment was reduced to low-dose steroids only, and antimycotic treatment was started using a liposomal formulation of amphotericin B. A low dosage (< 3 mg·kg⁻¹ daily) had to be given in order to preserve renal function, but this proved ineffective with continuing enlargement of the IPA mass. It was decided to surgically remove the right upper lobe and, marginally, the apical segment of the inferior lobe, the most important source of infection.

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Figure 1.

Chest computed tomography demonstrating multiple cavitations of the right upper lobe and involvement of the apical segment of the right lower lobe.

A right upper lobectomy and an atypical pulmonary resection of the apical segment of the lower lobe was performed using a posterolateral muscle-sparing thoracotomy. We preferred not to cut muscles because of the impaired healing due to chronic use of steroids. The right upper lobe bronchus was stapled and covered with a pedicled pericardial fat pad. Two chest tube drains were placed in the pleural space and a closed suction drain was positioned subcutaneously. Macroscopic examination of the specimen showed a 7 cm cavity filled with a pultaceous material. Histopathology revealed a pulmonary localization of aspergillosis, associated with colliquation and necrosis. The postoperative course was uneventful and the patient was able to continue antimycotic therapy based on amphotericin B, which was discontinued after 2 weeks when the dermatological, ocular, and tracheobronchial lesions had disappeared; it was replaced with itraconazole 400 mg per day. She was discharged 18 days postoperatively on steroids, mycophenolate mofetil, and itraconazole.

Discussion

A mortality rate as high as 100% was reported by Wingard and colleagues ⁴ with medical treatment alone of IPA in their bone marrow transplant patients. For solid organ transplant patients, the mortality rate was similar in cases of IPA complicating liver transplantation. ⁵ According to Weiland and colleagues, ³ mortality was only 38% in renal transplant patients, although 60% of survivors lost their allograft kidney due to rejection which occurred when antirejection treatment was withheld because of antifungal therapy. More recently, Reichenberger and colleagues ⁶ reported a mortality rate ranging from 55% to 80% in immunocompromised patients with IPA treated by medical therapy alone. Due to the dismal results of medical therapy for IPA, the Infectious Diseases Society of America stated that “adjunctive therapy (particularly surgery) may be useful in certain situations”. ⁷ Although there is some fear of performing surgery in immunocompromised patients due to the risk of infection, and in those taking steroids because of impairment of the healing process, surgery with removal of the pulmonary source of infection was advocated by some investigators who realized that the patients surviving IPA were those who had undergone lung resection. ^3,4 Recently Habicht and colleagues ⁸ reported 30- and 90-day mortality rates of 7.1% and 25%, respectively, in 28 immunocompromised patients with IPA complicating hematological diseases who also underwent pulmonary resection. Enough surgical series have now accumulated to suggest that resection of IPA is indicated in this highly fatal disease.

Complete resection of the fungal lesion along with excision of sufficient normal lung tissue to prevent contamination of the noninfected lung should be performed as soon as clinical and radiological examinations confirm the diagnosis. For surgery to be beneficial, the pulmonary lesion should be localized and preferably there should be no extrapulmonary localization. In our case, although there were extrapulmonary localizations, the removal of the source of infection was followed by complete recovery. Moreover, the allograft function was not lost, in spite of antifungal drug toxicity and suboptimal antirejection treatment. This experience shows that aggressive treatment of IPA can be lifesaving in properly selected immunocompromised patients. The timing of resection is of paramount importance both to try to save allograft function by reducing the duration of graft exposure to the toxicity of antifungal therapy, and to avoid contralateral lung infection and systemic spread of the disease.