1. Infections in Chronic Granulomatous Disease: 22 years' single centre experience from
North India
Vignesh Pandiarajan, Amit Rawat, Avinash Sharma, Deepti Suri, Anju Gupta, Surjit Singh
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Introduction
Figures B A
Chronic Granulomatous Disease (CGD) is a rare phagocytic disorder due to defective NADPH oxidase complex- characterized by recurrent infections with catalase positive organisms (1)
Data on infection patterns and causative microorganisms provide added information to the spectrum of infections in CGD
Objective
To study the infection patterns and microbiological profile in CGD
Design and methods
Case records of 30 children with CGD, who were diagnosed and followed up from the period of August 1993 to May 2015, in Pediatric Immunodeficiency Clinic, Advanced Pediatrics Centre, PGIMER, Chandigarh, were retrieved and analyzed
Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either nitroblue tetrazolium test or flow cytometry based dihydrorhodamine (DHR) 123 assay
Genetic confirmation of diagnosis was available for 18 of the 30 cases
Blood counts, immunoglobulin profile, blood cultures, chest X ray and abdominal ultrasound were performed in all cases
Chest computerized tomography (CT), fine needle aspiration from tissues, other body fluid cultures, and blood fungal serology were performed based on clinical indication
Figure 1. Pie chart showing A) various bacterial infections isolated from CGD patients, B) fungal infections isolated from CGD patients
Figure 2. Sagittal T2 (A), T1 (B) and post contrast T1 (C) weighted MR images of cervico-dorsal region showing features of vertebral osteomyelitis in a child with X linked CGD
Figure 3. Cutaneous ulcer and cellulitis over left upper cheek in a child with X linked CGD. Culture from the pus grew Pseudomonas aeruginosa
Results
Common sites of infections were lung (pneumonia) (90%), followed by lymph nodes (56.7%), and skin & subcutaneous tissue (43.3%) (Table 1)
Aspergillus was the commonest organism isolated; Staphylococcus aureus followed by Pseudomonas aeruginosa were the commonest among culture proven bacterial infections (Fig. 1)
Burkholderia cepacia lymphadenitis and Pseudomonas aeruginosa skin ulcers were some peculiar infections noted (Fig. 3)
Pattern of infections were similar in X-linked recessive and autosomal recessive groups of CGD; however, X-linked CGD had an earlier age of onset and more frequent episodes of infections (Table 2)
Nine (9) of the 30 (30%) children succumbed to illness at the time of analysis; pneumonia and septicemia were the predominant causes for mortality
Discussion
Patients with X-linked CGD had more frequent and severe infections
Four cases of Pseudomonas infections were documented- 2 septicemia, 1 pneumonia, 1 skin ulcer; this organism has not been frequently reported in CGD
Apparently low incidence of BCG and Mycobacterium tuberculosis infection in our cohort of CGD patients could be due to under detection (3)
With prophylactic cotrimoxazole and itraconazole, and prompt management of breakthrough infections, we were able to achieve 70% survival rates on follow up
Increased mortality could be due to- a) Non-availability of interferon γ; b) Increased exposure to infectious agents resulting in breakthrough infections; c) Lack of readily available facility- bone marrow transplant (4)
Table 1. Infectious illness in patients with CGD
Pattern of infections
No. of patients (%)
No. of episodes
No. of patients with > 1 episode
% of patients with > 1 episode
Pneumonia
27 (90%) 66 21
70%
Skin/subcutaneous abscess
13 (43.3%) 36 10
33.3%
Lymphadenitis
17 (56.7%) 40 13
43.3%
Liver abscess
5 (16.7%) 12 2
6.7%
Septicemia
9 (30%) 4
13.3%
Ear infection
3 (10%) 5
Bone/ joint (Fig. 2)
Urinary tract infection
1 (3.3%) 1 -
Onychomycosis
Meningitis
Conclusion
One of the largest series from a developing country which looked into the infection profile in CGD
Fungal pneumonia is the most common infection at diagnosis of CGD
Infections with Pseudomonas aeruginosa are not uncommon in our series
References
1. Winkelstein JA, Marino MC, Johnston Jr RB, Boyle J, Curnutte J, Gallin JI, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 2000;79(3):155–69.
2. Marciano BE, Spalding C, Fitzgerald A, Mann D, Brown T, Osgood S, et al. Common severe infections in chronic granulomatous disease. Clin Infect Dis 2015 ;60(8):1176–83.
3. Lee PP, Chan KW, Jiang L, Chen T, Li C, Lee TL, et al. Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous
disease: a review of 17 patients living in a region endemic for tuberculosis. Pediatr Infect Dis J 2008;27(3):224–30.
4. Rawat A, Singh S, Suri D, Gupta A, Saikia B, Minz RW, et al. Chronic granulomatous disease: two decades of experience from a tertiary care centre in North West India. J Clin Immunol 2014;34(1):58-67.
Table 2. Infections and mortality among CGD subtypes
Type of CGD
No. of patients
Patients with <5 infections
Patients with 5 or more infections
Mortality (%)
gp91 15
2/ 15
13/ 15
4/15 (26.67%)
p47phox 8
6/ 8
2/ 8
2/8 (25%)
P67phox 3
0/ 3
3/ 3
1/3 (33.33%)