Disseminated zygomycosis with renal involvement simulating malignancy in a diabetic patient.

Zygomycosis or mucormycosis refers to a group of uncommon but frequently fatal mycoses caused by fungi of the class Zygomycetes. The disease is usually an opportunistic infection in patients with diabetes, immunosuppression, trauma, burn wounds and other chronic debilitating diseases. Isolated renal involvement is rare although involvement of kidneys in disseminated mucormycosis is not uncommon. Clinical awareness and thorough appropriate investigations are required for an early diagnosis and successful treatment. We herein report a case of disseminated zygomycosis presenting as renal mass with pulmonary lesions, which was initially suspected to be disseminated renal cell carcinoma before a tissue diagnosis was obtained.

INTRODUCTION

Zygomycosis or mucormycosis is a rare opportunistic infection caused by fungi of the order Mucorales and the genera Rhizopus, Absidia and Mucor. Isolated renal mucormycosis is extremely rare, however, renal involvement in disseminated mucormycosis ranges from 14–19% of patients.[1] We herein report a case of renal mass which was referred to our institute as suspected renal cell carcinoma but on histopathology proved to be zygomycosis. Clinical presentation and management of zygomycosis, is also discussed briefly.

CASE REPORT

A 59-year-old diabetic and hypertensive male presented with two months’ history of dry cough, shortness of breath, bilateral pleuritic chest pain and hiccoughs. Investigations done at another hospital two weeks after onset of symptoms had revealed fasting blood glucose - 246 mg/ dL, blood urea - 28 mg/dL and serum creatinine-2.28 mg/dL. Urine examination revealed glucosuria, red blood cells 1-2/high-power field (HPF), leucocytes full/HPF and negative ketones. He was treated with antibiotics and was shifted to insulin therapy from oral hypoglycemics. However, his symptoms continued to worsen and repeat urine examination two weeks later showed persistent leucocyturia with serum creatinine of 1.4 mg/dL. Imaging of the chest (radiograph and computed tomography (CT) scan) revealed bilateral multiple ill-defined nodules, few of them showing cavitation [Figure 1a,b]. CT scan of abdomen showed normal left kidney and enlarged right kidney with heterogeneous enhancement without any retroperitoneal adenopathy or renal vein thrombosis [Figure 2]. Based on imaging he was suspected to have renal cell carcinoma with dissemination and was referred to us. By this time his respiratory symptoms and hiccoughs had worsened. He also developed marked generalized weakness and was home-bound for the last three weeks. He had significant anorexia and lost seven kilograms of weight. There was no history of fever, pain abdomen, dysuria, hematuria or bony pains, alcohol consumption, intravenous drug abuse or sexual promiscuity.

Figure 1

Chest radiograph (a) and CECT (b) reveal multiple ill-defined bilateral pulmonary nodules. Few of the lesions showed cavitation (arrow in b). Also note presence of right pleural effusion (arrow in a)

Figure 2

Axial CECT abdomen images demonstrate enlarged right kidney showing heterogeneous enhancement (arrow). No retroperitoneal adenopathy seen. Contralateral kidney and right renal vein were normal

On examination his body mass index (BMI) was 21.8 kg/m.[2] He had marked pallor and tachypnea and his blood pressure was 160/76 mm Hg. Respiratory system examination revealed bilateral extensive coarse crepitations, more marked in infrascapular and infraaxillary areas. Blood investigations showed hemoglobin of 6.1 mg/dL, total leucocyte count 6500/mm[3] with a differential count of 65% neutrophils and 35% lymphocytes. Peripheral smear showed normocytic normochromic erythrocytes and serum iron studies showed low serum iron and transferrin saturation. Renal and liver function tests were normal. Urine examination showed 30-35 leucocytes/HPF, proteinuria, negative Gram stain and acid-fast bacilli (AFB) stain and negative malignant cytology. Stool tested thrice for occult blood was negative. Both urine and blood bacterial and fungal cultures were negative repeatedly and tuberculin test was non-reactive. HIV serology was non-reactive and serum immunoglobulin levels were within normal limits.. Patient could not undergo bronchoscopy due to poor general condition. Renal dynamic scan was performed as nephrectomy was being planned. It showed poorly functioning right kidney (15% fractional function) with delayed clearance. A trucut biopsy from right renal mass showed evidence of fungal hyphae consistent with zygomycetes. A final diagnosis of disseminated zygomycosis was made and patient was started on Amphotericin B for about a week. Due to worsening renal functions he was switched to liposomal formulation which was given at a rate of 3-4 mg/kg/ day for a total dose of 5 g. Due to financial constraints further treatment with liposomal Amphotericin B could not be given. Insulin and antihypertensive therapy was optimized along with appropriate nutritional care and blood transfusion. With antifungal treatment patient had symptomatic relief, subjective feeling of wellbeing and regained 5 kg weight. Repeat imaging done showed improvement in bilateral lung lesions but no change in the size of renal mass. Patient underwent right nephrectomy and its histopathology revealed extensive fungal involvement. Patient was discharged on oral Itraconazole as Posaconazole was not available. About six weeks later patient was readmitted with left hemiparesis due to extensive right-sided cerebral parenchymal hemorrhage and died within a day of admission.

DISCUSSION

Zygomycosis and mucormycosis are often interchangeably used terms to describe a group of frequently lethal infections caused by pathogenic moulds belonging to the class Zygomycetes. Infections occur equally in both sexes irrespective of age. Classically described predisposing factors include poorly controlled diabetes, corticosteroid use, immunosuppression therapy, neutropenia, deferoxamine therapy, HIV/AIDS, and renal failure.[2] Besides, there are numerous reports showing occurrence of disease in immunocompetent hosts. Based on clinical presentation and anatomic predilection, invasive zygomycosis can be classified as one of six forms: (1) rhinocerebral syndrome and (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated, and (6) uncommon presentations.[3]

Disseminated zygomycosis is often clinically unapparent ante mortem. Its symptoms vary widely and may pertain to the organs involved and the severity of involvement. Isolated renal involvement is rare although involvement of kidneys in disseminated mucormycosis is not uncommon. Major clinical features of renal zygomycosis are fever, flank pain and tenderness, gross hematuria and pyuria.[4] Confirmation of the diagnosis of zygomycosis depends on obtaining tissues for microscopic examination and culture. Successful treatment of zygomycosis largely depends on timely diagnosis, reversal of the underlying predisposing factors, early broad surgical debridement, and rapid initiation of effective systemic antifungal therapy. Historically, the agent of choice was conventional amphotericin B. However, the availability of the less toxic lipid formulations, backed by clinical data to support their use in zygomycosis, has led them to become drugs of first choice.[5] Posaconazole is now the alternative agent of choice based on individual case reports of successful treatment in patients with different underlying conditions. Itraconazole is the only marketed azole drug that has in vitro activity against Mucorales. There are case reports of successful therapy with itraconazole alone.[6] The duration of antifungal therapy is not clearly defined. In the absence of comparative data, the total duration of therapy for mucormycosis should be individualized for each patient. In general, antifungal therapy should be continued until there is resolution of clinical signs and symptoms of infection and there is resolution or stabilization of residual radiographic signs of disease on serial imaging. Surgical debridement should always be considered as an option early in management as the evidence indicates that this intervention improves survival.