Invasive mucormycosis in chronic granulomatous disease

Case 1

A 2-year-old girl with sickle cell anemia was transferred to King Fahad Medical City in Riyadh, Saudi Arabia with pneumonia and pleural effusion that failed to respond to prolonged courses of broad spectrum antibiotics and pleural drainage. Her past medical history was negative for recurrent infections, exposure to blood transfusions or immunosuppressive drugs. Examination revealed a febrile, malnourished child with enlarged liver and spleen. Chest examination showed a firm mass extending from the axial to the posterior aspect of the right chest wall. Initial laboratory results were: hemoglobin (77 g/L; normal range: 105-140 g/L), white blood cell count (29 x 10⁹/L; normal range: 5-14.5 x 10⁹/L), erythrocyte sedimentation rate (80 mm/hour; normal range: 0-10 mm/hour), C-reactive protein (320 mg/L; normal range: 0-8 mg/L). Computed tomography scan showed consolidation involving right lower lobe, middle lobe, and posterior segment of the right upper lobe with pleural effusion. A right chest wall lesion with intraspinal extension was also noted. Magnetic resonance imaging of chest and spine showed an extradural extramedullary intensely enhancing mass extending from T2 through T7 and in continuity with a heterogeneously enhancing, necrotic, right sided chest wall mass. There were also destructive bony changes involving the costovertebral junction. Cultures of tissue obtained from surgical biopsy of the chest wall mass grew Rhizopus spp. (Figure 1).

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Figure 1

Rhizopus spp. grown from intraoperatively obtained lung tissue specimen.

Histopathology revealed acute and chronic necrotizing granulomatous inflammation with eosinophils. Fungal hyphae with pauciseptations were also evident on Gomori methenamine silver (GMS) stain. She was subsequently diagnosed to have CGD based on oxidative burst test result. Treatment with liposomal amphotericin B was initiated at a dose of 5 mg/kg/day then increased to 7 mg/kg/day. Caspofungin and interferon γ (IFN-γ) were added to treatment. She underwent surgical debulking of the chest wall mass and near-total pneumonectomy. Since she had no neurological symptoms from the intraspinal extension of the infection, conservative management with antifungal treatment and close follow up were planned. The intraspinal lesion continued to regress on further MRI studies. While on treatment, she developed a gaping wound at the surgical site due to poor healing and osteomyelitis of the ribs. Surgical debridement followed by excision of 2 ribs and primary closure of the wound were performed. She showed gradual improvement, but did not show complete recovery. She was then referred to a specialized center for hematopoietic stem cell transplantation (HSCT).

Case 2

A 22-year-old male known to have CGD was referred to King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia for surgical management of a large right lung abscess. He was diagnosed to have CGD at the age of 17 years and maintained solely on trimethoprim/sulfamethoxazole prophylaxis. His current illness started as fever and cough for 3 weeks for which he was admitted to a local hospital and started on broad spectrum antibiotics. Chest imaging with CT scan revealed a large abscess in the middle and lower lobes of the right lung and pleural effusion. Thoracotomy and drainage was performed at the referring hospital; however, he failed to show clinical improvement and no microbial etiology was identified. At KFSHRC, initial investigations were: white blood cell count (16 x 10⁹/L; normal range: 4-11 x10⁹/L), hemoglobin (85 g/L; normal range: 125-180 g/L), and procalcitonin (4.78 mcg/L; normal range: <0.5 mcg/L). Computed tomography scan of the chest and abdomen showed a right hemothorax mass lesion measuring 11 x 10 cm with invasion to the mediastinum, superior vena cava, right atrium, part of the inferior vena cava, diaphragm, part of the liver, and anterior chest wall. Computed tomography guided biopsy showed inflammatory cells with fungal elements. He was treated initially with voricaonazole and caspofungin in addition to antibacterial therapy. Tissue from open lung biopsy showed necrotizing granulomatous inflammation and cultures grew Rhizopus spp. Voricaonazole was changed to liposomal amphoterecin B and caspofungin continued. He underwent sternotomy with attempted mass resection. The procedure was aborted after identifying that the mass was unresectable and adherent to the right atrium and ventricle. Echocardiography showed a low ejection fraction of 35% with severely reduced right ventricular function. Unfortunately, he died several days later due to severe hypotension with bradycardia and pulseless electrical activity.