- Department of Surgery, Section of Neurosurgery, The Aga Khan University Hospital Karachi, Pakistan
- Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital Karachi, Pakistan
Muhammed E. Bari
Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital Karachi, Pakistan
DOI:10.4103/2152-7806.183166Copyright: © 2016 Surgical Neurology International This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Waqas M, Zafar S, Rehman T, Riyaz M, Bari ME, Idrees R. Cerebral aspergillosis and pulmonary tuberculosis in a child with chronic granulomatous disease. Surg Neurol Int 30-May-2016;7:62
How to cite this URL: Waqas M, Zafar S, Rehman T, Riyaz M, Bari ME, Idrees R. Cerebral aspergillosis and pulmonary tuberculosis in a child with chronic granulomatous disease. Surg Neurol Int 30-May-2016;7:62. Available from: http://surgicalneurologyint.com/surgicalint_articles/cerebral-aspergillosis-and-pulmonary-tuberculosis-in-a-child-with-chronic-granulomatous-disease/
Background:Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians.
Case Description:We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed tomography scan revealed multiple cerebral abscesses. These abscesses were excised. The microbiological specimen was determined to be positive for Aspergillus fumigatus. His tracheal aspirate was positive for Mycobacterium tuberculosis polymerase chain reaction assay. Further work-up confirmed the diagnosis of CGD in the child.
Conclusion:This report describes the course of the patient's illness in order to highlight the challenges associated with the management of these infections. We also aim to stress on the importance of pathological diagnosis before starting a therapy.
Keywords: Cerebral abscess, chronic granulomatous disease, tuberculosis
Chronic granulomatous disease (CGD) is a rare, primary immunodeficiency disorder of phagocytes.[
Although these patients have an increased susceptibility to tuberculosis (TB), reports of TB in CGD are rare.[
A 4-year-old boy was brought to the Emergency Department (ED) from a rural area with complaints of fever, headache, and weight loss. He was suffering from these symptoms for the past 4 months, which had worsened in the past week. His brother informed that the child had been unwell since infancy with several episodes of respiratory infection and has had several hospital admissions. Recently, he had started complaining of severe persistent diffuse headaches along with nausea, vomiting, and anorexia. He also suffered from low grade fever intermittently over this period of time. Physicians in his locality who had treated him with antibiotic courses for chest infections started him on antituberculosis (ATT) drugs 2 months back after an MRI, which suggested meningeal enhancement and small ring enhancing lesions. He had no history of seizures or loss of consciousness. One of his brother had passed away at the age of 8 years who was considered to suffer from disseminated tuberculosis. On examination, the child was listless, emaciated, and extremely irritable. He had left-sided weakness in both the upper and lower extremities.
An urgent computed tomography (CT) scan of the head showed multiple rings enhancing the left parietooccipital region, with significant surrounding edema and mass effect [
Intravenous (IV) voriconazole was commenced at 6 mg/kg/dose every 12 h for 2–3 days, which was later switched to 6 mg/kg/day orally. Five-drug ATT treatment was restarted for the management of pulmonary TB. He was also given broad-spectrum antibiotics. Pneumococcal and meningococcal vaccines were administered as prophylaxis, and co-trimoxazole was included in the regimen for the prevention of pneumocystis carinii pneumonia.
The child showed slow improvement, however, the treatment course was complicated by fever, seizures, and hyponatremia. Repeat CT scans did not show residual or recurrent abscesses [
CGD is a congenital disorder of the immune system, which is characterized by impaired NADPH oxidase activity of the phagocytes. This results in defective intracellular killing of catalase-positive microorganisms, and clinically presents as recurrent, severe infections usually in early infancy.[
The child in our case presented with brain abscess caused by Aspergillus fumigatus with pulmonary TB. Aspergillus is a common pathogen in CGD patients, and most commonly manifests as pulmonary complications or as infections of the chest wall and bones. Neurological complications, especially abscesses of the brain, are uncommon and are rarely documented.[
Kolb et al. reported the case of a child suffering from CGD along with pulmonary TB where Aspergillus brain abscess was highly suspected, but was not proven on microscopy or fungal culture. Another case was discussed by Frank et al. where Aspergillus growth was proven in culture and the child was successfully treated with itraconazole and interferon.[
Alsultan et al. reviewed literature on intracranial abscesses in CGD and found four cases of intracranial aspergillosis.[
This case highlights several issues of medical and surgical importance. In endemic areas, where incidence of TB is very high, it is a common practice among physicians to start patients on ATT drugs on the basis of history, examination, and nonspecific blood tests such as ESR. This child had several key features in history to suggest the possibility of an underlying immune disorder. Important hints were not recognized and the diagnosis had a significant delay. Another important point to note from this case is the need for a close clinical and radiological follow-up because of the high risk of acute hydrocephalus that warrants urgent surgical intervention.
Coexisting cerbral aspergillosis and pulmonary TB in CGD is rare. Surgical excision of abscesses is essential to reduce the mass effect as well as to establish a diagnosis. However, these patients need prolonged antifungal drugs and a close follow-up because they are at a high risk for the development of hydrocephalus and recurrence of abscesses. This case also stresses on the fact that no treatment should be offered to such patients without a definite pathological diagnosis in the form of biopsy or culture.
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1. Alsultan A, Williams MS, Lubner S, Goldman FD. Chronic granulomatous disease presenting with disseminated intracranial aspergillosis. Pediatr Blood Cancer. 2006. 47: 107-10
2. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002. 347: 408-15
3. Johnston RB. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001. 8: 17-22
4. Kloss S, Schuster A, Schroten H, Lamprecht J, Wahn V. Control of proven pulmonary and suspected CNS aspergillus infection with itraconazole in a patient with chronic granulomatous disease. Eur J Pediatr. 1991. 150: 483-5
5. Lee E, Oh SH, Kwon JW, Kim BJ, Yu J, Park CJ. A case report of chronic granulomatous disease presenting with aspergillus pneumonia in a 2-month old girl. Korean J Pediatr. 2010. 53: 722-6
6. Pollack IF, Pang D, Schuit KE. Chronic granulomatous disease with cranial fungal osteomyelitis and epidural abscess: Case report. J Neurosurg. 1987. 67: 132-6
7. Saulsbury FT. Successful treatment of Aspergillus brain abscess with itraconazole and interferon-γ in a patient with chronic granulomatous disease. Clin Infect Dis. 2001. 32: E137-9
8. Seger R. Chronic granulomatous disease: Recent advances in pathophysiology and treatment. Neth J Med. 2010. 68: 334-40
9. Stasia MJ, Li XJ. Genetics and immunopathology of chronic granulomatous disease. Semin Immunopathol. 2008. 30: 209-35