Indian Journal of Medical Microbiology Medknow Publications on behalf of Indian Association of Medical Microbiology ISSN: 0255-0857 EISSN: 1998-3646 Vol. 28, Num. 3, 2010, pp. 269-270

Indian Journal of Medical Microbiology, Vol. 28, No. 3, July-September, 2010, pp. 269-270

Correspondence

Recurrent infections with Aspergillus require exclusion of defects in the phagocyte NADPH oxidase pathway

S Khan

Path Links Immunology, Scunthorpe General Hospital, Scunthorpe, DN15 7BH, United Kingdom
Correspondence Address: S Khan, Path Links Immunology, Scunthorpe General Hospital, Scunthorpe, DN15 7BH, United Kingdom, sujoy.khan@nlg.nhs.uk

Date of Submission: 02-Dec-2009
Date of Acceptance: 29-Apr-2010

Code Number: mb10085

PMID: 20644327
DOI: 10.4103/0255-0857.66483

Dear Editor,

The case report by S. Mohapatra and colleagues on recurrent primary cutaneous aspergillosis with an apparent ′intact immunological status′ requires further clarification as neutrophil function tests were not reported. ^[1] The patient had non-healing ulcer due to Aspergillus niger for 10 years and a defect in the NADPH oxidase pathway should have been excluded. Neutrophils with an intact NADPH oxidase pathway, on appropriate stimulation, reduce the yellow dye nitroblue tetrazolium to an insoluble blue formazan precipitate (NBT test). This does not occur if there is a defect in superoxide generation (chronic granulomatous disease (CGD) patients), and the dye stays yellow.

CGD patients have recurrent infections with catalase producing pathogens (Aspergillus, Staphylococcus, Serratia marcescens, Nocardia species and Burkholderia cepacia). Pneumonia, lymphadenitis, skin/liver/perianal abscesses, osteomyelitis, granulomas causing outlet obstruction, Crohns-like inflammatory bowel disease occur in CGD. ^[2] Some patients generate low levels of reactive oxidants and NBT test may be normal, so if clinical suspicion of CGD is high the flow cytometry test using dihydrorhodamine 123 is recommended, as it is extremely sensitive for detection of intracellular hydrogen peroxide production. ^[2] Mutations in the genes encoding gp91 ^phox account for 65% of CGD (X-linked CGD), and mutations in p22 ^phox , p47 ^phox , p67 ^phox , p40 ^phox , Rac2 genes account for autosomal recessive cases. Prophylactic trimethoprim-sulfamethoxazole, itraconazole, or interferon gamma therapy (subcutaneous infusions three times a week) are usually enough to prevent infections, and gene therapy is being actively pursued. ^[3]

The references of cutaneous aspergillosis quoted by Mahapatra et al. also did not report neutrophil function, while two previous reports of cutaneous aspergillosis and alternariosis had underlying X-CGD, both of whom required oral fluconazole for 6-7 months. ^[4],[5] Collaboration with Immunologists is vital, as correct diagnosis and effective prophylaxis can prevent life threatening infections and timely stem cell transplantation could offer permanent cure.

References

1.	Mohapatra S, Xess I, Swetha JV, Tanveer N, Asati D, Ramam M, et al. Primary cutaneous aspergillosis due to Aspergillus niger in an immunocompetent patient. Indian J Med Microbiol 2009;27:367-70.  Back to cited text no. 1  [PUBMED]
2.	Lekstrom-Himes JA, Gallin JI. Immunodeficiency diseases caused by defects in phagocytes. N Engl J Med 2000;343:1703-14.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.	Kang EM, Malech HL. Advances in treatment for chronic granulomatous disease. Immunol Res 2009;43:77-84.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.	Chatzipanagiotou S, Takou K, Perogamvros A. Cutaneous purulent aspergillosis in a young man with chronic granulomatous disease. Mycoses 1998;41:379-82.  Back to cited text no. 4  [PUBMED]
5.	Uenotsuchi T, Moroi Y, Urabe K, Fukagawa S, Tsuji G, Matsuda T, et al. Cutaneous alternariosis with chronic granulomatous disease. Eur J Dermatol 2005;15:406-8.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]

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