Severe Multisystem Involvement of Chronic Granulomatous Disease in a Pediatric Patient

Severe Multisystem Involvement of Chronic Granulomatous Disease in a Pediatric Patient Abstract Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder identified by recurrent pyogenic and fungal infections infections secondary to defective nicotinamide adenine dinucleotide phosphate oxidase enzyme. In the present study, we demonstrated a case with a history of multiple segmental lung resections because of invasive bronchopulmonary aspergillosis, multifocal hepatic and splenic granulomas, bilateral adnexal calcific foci presumed to be related with old granulomatous infection and finally gastric outlet obstruction secondary to the involvement of the stomach wall thickening with granulomatous tissue. This is an extremely severe case of CGD with multiorgan involvement within a 10-year period after the diagnosis. Gastric antral involvement may mimic inflammatory bowel diseases in such cases, and intestinal involvement can reliably be demonstrated via ultrasonography. Spontaneous resolution of the antral involvement was observed in the follow-up. antrum, lung, liver, computed tomography, chronic granulomatous disease INTRODUCTION Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex, responsible for the respiratory burst in phagocytic leukocytes, resulting in serious infections especially by catalase-positive bacteria and fungi. CGD can either be inherited in an X-linked or autosomal recessive pattern. The reported incidence of CGD in the USA and Europe is around 1 in 200 000–250 000 live births, which increases in the countries with the high frequency of consanguinity marriages [1]. Clinical presentation includes recurrent infections with a narrow spectrum of bacteria, fungi. The majority of the overwhelming infections in patients with CGD are related to catalase-positive organisms such as Aspergillus species, Staphylococcusaureus, Burkholderia (Pseudomonas) cepacia complex, Serratia marcescens and Nocardia species, whereas severity was mostly related to infection with Burkholderia species [2]. Fungal infections have been identified as the major contributors to mortality [3]. Recurrence of bacterial infections may contribute to the chronic lung, liver or kidney disease [4]. CASE REPORT A 6-year-old girl having a past history of frequent infections, including a heel abscess in the newborn period and superficial inguinal abscess at 7 months of age, presented with an abscess in the right axillary region. Diagnostic and therapeutic aspiration of the material yielded fungal hyphae. Elevation of lactate dehydrogenase level was (322 U/l) presumed to be associated with sequential pulmonary damage because of multiple granulomatous infections. She was the daughter of a second-degree consanguineous marriage and diagnosed as CGD based on the nitroblue tetrazolium (NBT) test (NBT: 0, sNBT: %4). She was started on subcutaneous interferon (IFN)-gamma therapy (100 mcg/m2 subcutaneously three times per week). Partial regression was observed after empiric antimicrobial treatment, and she continued to have oral voriconazole, trimethoprim–sulfamethoxazole and IFN-gamma prophylaxis after discharge. However, the patient underwent segmental lung resection at 7 years of age because of the fungal consolidation in the right lung. Five years later, she underwent removal of the posterior segment of left lung, because of fungal consolidation. Histopathology revealed suppurative granulomatous inflammation and periodic-acid-Schiff (PAS)-positive fungal hyphae. At 14 years of age, she presented with infraclavicular and intercostal soft tissue swelling. Computerized chest tomography demonstrated focal consolidations located in the periphery of upper lobe of the right lung with extension to the intercostal muscular layers and subcutaneous tissue in addition to nodular consolidation in the left lung. Subcarinal granulomatous calcified lymph nodes, peribronchial thickening and tubular bronchiectasis were detected (Figs 1 and 2). Histopathological evaluation revealed granulomatous inflammation with multinucleated giant cells. She was given parenteral voriconazole treatment and continued to have secondary prophylaxis with oral posaconazole. Two years after the last thoracotomy, subcutaneous abscess requiring surgical excision was found in the location of the last thoracotomy area. Fig. 1. View largeDownload slide Axial section of the chest CT demonstrates recurrent fungal lung consolidation (closed arrow) and calcified lymph nodes (open arrow). Fig. 1. View largeDownload slide Axial section of the chest CT demonstrates recurrent fungal lung consolidation (closed arrow) and calcified lymph nodes (open arrow). Fig. 2. View largeDownload slide Axial section of the chest CT presents air trapping, traction bronchiectasis and interstitial cuffing confirming interstitial fibrosis. Fig. 2. View largeDownload slide Axial section of the chest CT presents air trapping, traction bronchiectasis and interstitial cuffing confirming interstitial fibrosis. At 15 years of age, she was admitted to the emergency department with the complaint of chronic right upper quadrant discomfort and groin and hip pain. Abdominal computed tomography (CT) demonstrated bilateral adnexal focal millimetric calcifications, which were considered old granulomas, and no other etiology was found (Fig. 3). Also, multiple calcific granulomas in both lobes of the liver and in the upper pole of the spleen were found (Fig. 4). A hepatic wedge resection revealed granuloma. Fig. 3. View largeDownload slide Axial section of the pelvic CT exhibits bilateral adnexal millimetric calcific foci considering granulomatous inflammation. Fig. 3. View largeDownload slide Axial section of the pelvic CT exhibits bilateral adnexal millimetric calcific foci considering granulomatous inflammation. Fig. 4. View largeDownload slide Axial section of the upper abdominal CT shows multiple calcified granulomas (closed arrows). Fig. 4. View largeDownload slide Axial section of the upper abdominal CT shows multiple calcified granulomas (closed arrows). Her final clinical presentation was persistent vomiting at 17 years of age. Gastric antral asymmetrical thickening without any pathological lymph nodes was depicted on abdominal ultrasound and confirmed with contrast enhanced abdominal CT (Fig. 5). Endoscopic biopsy revealed Helicobacterpylori-negative chronic gastritis negative for granuloma. Radiological findings were highly suggestive of antral involvement of CGD. The regression of involvement was confirmed via ultrasonography after 6 weeks. Fig. 5. View largeDownload slide Contrast enhanced upper abdominal CT demonstrates gastric antral involvement exhibiting hypodense expansion of submucosal and muscular layers. Fig. 5. View largeDownload slide Contrast enhanced upper abdominal CT demonstrates gastric antral involvement exhibiting hypodense expansion of submucosal and muscular layers. DISCUSSION Respiratory tract involvement is common in CGD and accounts for approximately 50% of the cases [5]. Furthermore, chronic interstitial inflammation in CGD may mimic hypersensitivity pneumonitis and also result in interstitial lung disease [6]. In the present case, there were severe interstitial fibrotic thickenings, emphysematous changes and traction bronchiectasis compatible with chronic interstitial lung disease. Histopathological evaluation of CGD cases with the suspicion of hepatic abscess demonstrates nonspecific inflammatory changes in the majority of the cases, while typical granulomas and numerous classical pigmented macrophages within the hepatic sinusoids were depicted in a few cases [5]. Similarly, in the bowels, active, predominantly eosinophilic or neutrophilic colitis (71%) was found to be the most commonly encountered finding followed in the frequency by classical pigment-containing macrophages within the gastrointestinal tract lamina propria (57%). Fewer cases (34%) have exhibited noncaseating granulomas located in the upper gastrointestinal tract. Multiple consecutive gastrointestinal biopsies could demonstrate involvement in CGD [7]. Marciano et al. [8] have analyzed a wide series of CGD patients and found that 46 of 140 were symptomatic and had endoscopy-proven inflammatory bowel disease. Though histopathological evaluation reported only chronic inflammation in the antrum in the presented case, the obvious antral thickening depicted via ultrasonography, endoscopy and computed tomography was highly suggestive of granulomatous involvement of CGD. Reports of obstructive findings were rarely presented in the literature among the higher prevalence of gastrointestinal involvement reported particularly in X-linked type [7]. Persistent vomiting secondary to gastric outlet involvement that was managed conservatively was a severe manifestation of the disease in our case. Although it has been reported that inflammatory involvement in multiple sites is uncommon for CGD patients, yet, in a recent report, pulmonary with antro-pyloric involvement in the form of eosinophilic infiltration of the mucosa and submucosa has been described [9]. Bilateral adnexal calcific foci were seen in the patient with menstrual irregularities as well as inguinal and pelvic pain. Though histopathological confirmation was not performed, ovarian parenchymal calcifications were considered as CGD involvement. As far as we know, no previous data regarding ovarian granulomatous involvement have been reported. In female CGD patients, menstrual irregularities may be observed because of immunosuppressive drugs or ovarian inflammatory changes. Both obstructions and palliative operations because of the mural CGD involvement would cause complications as extralumination, fistula or abscess formation. Pathophysiology of the chronic gastrointestinal inflammation is explained by defective myeloperoxidase-halide-hydrogen peroxide system that is not able to inactivate chemoattractants [10]. Both published reviews and clinical guidelines consider corticosteroids as first-line choice in CGD patients with fungal infection, even more if intestinal obstruction is present [11, 12]. Immunomodulatory therapy with IFN-gamma is an important part of the disease management together with antibacterial and antifungal chemoprophylaxis. Although some authors suggest IFN-gamma replacement only during active infection, others recommend long-term prophylaxis [1]. Finally, hematopoietic cell transplantation (HCT) remains the definitive cure for CGD [13]. Our case has been using IFN-gamma therapy since the time of diagnosis, but she could not undergo HCT, as she had multiple comorbidies. In conclusion, CGD is a genetic disorder with serious life-threathening infections and multisystem granulomatous disorders. Antimicrobial and immunomodulatory therapy together with surgery for selected cases prolongs survival in the cases when HCT is not possible. References 1 Arnold DE, Heimall JR. A review of chronic granulomatous disease. Adv Ther  2017; 34: 2543. Google Scholar CrossRef Search ADS PubMed  2 Marciano BE, Spalding C, Fitzgerald A, et al.   Common severe infections in chronic granulomatous disease. Clin Infect Dis  2015; 60: 1176. Google Scholar CrossRef Search ADS PubMed  3 Falcone EL, Holland SM. Invasive fungal infection in chronic granulomatous disease: insights into pathogenesis and management. Curr Opin Infect Dis  2012; 25: 658– 69. Google Scholar CrossRef Search ADS PubMed  4 Greenberg DE, Goldberg JB, Stock F, et al.   Recurrent Burkholderia infection in patients with chronic granulomatous disease: 11-year experience at a large referral center. Clin Infect Dis  2009; 48: 1577– 9. Google Scholar CrossRef Search ADS PubMed  5 Levine S, Smith VV, Malone M, et al.   Histopathological features of chronic granulomatous disease (CGD) in childhood. Histopathology  2005; 47: 508– 16. Google Scholar CrossRef Search ADS PubMed  6 Moghtaderi M, Kashef S, Rezaei N. Interstitial lung disease in a patient with chronic granulomatous disease. Iran J Pediatr  2012; 22: 129– 33. Google Scholar PubMed  7 Mohandas S, Toh J, Arora P, et al.   Noninfectious enterocolitis as initial presentation of chronic granulomatous disease. Clin Pediatr  2017; 54: 1353– 6. Google Scholar CrossRef Search ADS   8 Marciano BE, Rosenzweig SD, Kleiner DE, et al.   Gastrointestinal involvement in chronic granulomatous disease. Pediatrics  2004; 114: 462. Google Scholar CrossRef Search ADS PubMed  9 Labrosse R, Abou-Diab J, Blincoe A, et al.   Very early-onset inflammatory manifestations of X-linked chronic granulomatous disease. Front Immunol  2017; 8: 1167. Google Scholar CrossRef Search ADS PubMed  10 Ohno Y, Buescher ES, Roberts R, et al.   A re-evaluation of cytochrome b and flavin adenine dinucleotide in neutrophils from patients with chronic granulomatous disease and description of a family with probable autosomal recessive inheritance of eytochrome b deficiency. Blood  1986; 67: 1132– 8. Google Scholar PubMed  11 Chin TW, Stiehm ER, Falloon J, et al.   Corticosteroids in treatment of obstructive lesions of chronic granulomatous disease. J Pediatr  1987; 111: 349– 52. Google Scholar CrossRef Search ADS PubMed  12 Siddiqui S, Anderson VL, Hilligoss DM, et al.   Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis  2007; 45: 673– 81. Google Scholar CrossRef Search ADS PubMed  13 Seger RA. Hematopoietic stem cell transplantation for chronic granulomatous disease. Immunol Allergy Clin North Am  2010; 30: 195– 208. Google Scholar CrossRef Search ADS PubMed  © The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Tropical Pediatrics Oxford University Press

Severe Multisystem Involvement of Chronic Granulomatous Disease in a Pediatric Patient

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Abstract

Abstract Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder identified by recurrent pyogenic and fungal infections infections secondary to defective nicotinamide adenine dinucleotide phosphate oxidase enzyme. In the present study, we demonstrated a case with a history of multiple segmental lung resections because of invasive bronchopulmonary aspergillosis, multifocal hepatic and splenic granulomas, bilateral adnexal calcific foci presumed to be related with old granulomatous infection and finally gastric outlet obstruction secondary to the involvement of the stomach wall thickening with granulomatous tissue. This is an extremely severe case of CGD with multiorgan involvement within a 10-year period after the diagnosis. Gastric antral involvement may mimic inflammatory bowel diseases in such cases, and intestinal involvement can reliably be demonstrated via ultrasonography. Spontaneous resolution of the antral involvement was observed in the follow-up. antrum, lung, liver, computed tomography, chronic granulomatous disease INTRODUCTION Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex, responsible for the respiratory burst in phagocytic leukocytes, resulting in serious infections especially by catalase-positive bacteria and fungi. CGD can either be inherited in an X-linked or autosomal recessive pattern. The reported incidence of CGD in the USA and Europe is around 1 in 200 000–250 000 live births, which increases in the countries with the high frequency of consanguinity marriages [1]. Clinical presentation includes recurrent infections with a narrow spectrum of bacteria, fungi. The majority of the overwhelming infections in patients with CGD are related to catalase-positive organisms such as Aspergillus species, Staphylococcusaureus, Burkholderia (Pseudomonas) cepacia complex, Serratia marcescens and Nocardia species, whereas severity was mostly related to infection with Burkholderia species [2]. Fungal infections have been identified as the major contributors to mortality [3]. Recurrence of bacterial infections may contribute to the chronic lung, liver or kidney disease [4]. CASE REPORT A 6-year-old girl having a past history of frequent infections, including a heel abscess in the newborn period and superficial inguinal abscess at 7 months of age, presented with an abscess in the right axillary region. Diagnostic and therapeutic aspiration of the material yielded fungal hyphae. Elevation of lactate dehydrogenase level was (322 U/l) presumed to be associated with sequential pulmonary damage because of multiple granulomatous infections. She was the daughter of a second-degree consanguineous marriage and diagnosed as CGD based on the nitroblue tetrazolium (NBT) test (NBT: 0, sNBT: %4). She was started on subcutaneous interferon (IFN)-gamma therapy (100 mcg/m2 subcutaneously three times per week). Partial regression was observed after empiric antimicrobial treatment, and she continued to have oral voriconazole, trimethoprim–sulfamethoxazole and IFN-gamma prophylaxis after discharge. However, the patient underwent segmental lung resection at 7 years of age because of the fungal consolidation in the right lung. Five years later, she underwent removal of the posterior segment of left lung, because of fungal consolidation. Histopathology revealed suppurative granulomatous inflammation and periodic-acid-Schiff (PAS)-positive fungal hyphae. At 14 years of age, she presented with infraclavicular and intercostal soft tissue swelling. Computerized chest tomography demonstrated focal consolidations located in the periphery of upper lobe of the right lung with extension to the intercostal muscular layers and subcutaneous tissue in addition to nodular consolidation in the left lung. Subcarinal granulomatous calcified lymph nodes, peribronchial thickening and tubular bronchiectasis were detected (Figs 1 and 2). Histopathological evaluation revealed granulomatous inflammation with multinucleated giant cells. She was given parenteral voriconazole treatment and continued to have secondary prophylaxis with oral posaconazole. Two years after the last thoracotomy, subcutaneous abscess requiring surgical excision was found in the location of the last thoracotomy area. Fig. 1. View largeDownload slide Axial section of the chest CT demonstrates recurrent fungal lung consolidation (closed arrow) and calcified lymph nodes (open arrow). Fig. 1. View largeDownload slide Axial section of the chest CT demonstrates recurrent fungal lung consolidation (closed arrow) and calcified lymph nodes (open arrow). Fig. 2. View largeDownload slide Axial section of the chest CT presents air trapping, traction bronchiectasis and interstitial cuffing confirming interstitial fibrosis. Fig. 2. View largeDownload slide Axial section of the chest CT presents air trapping, traction bronchiectasis and interstitial cuffing confirming interstitial fibrosis. At 15 years of age, she was admitted to the emergency department with the complaint of chronic right upper quadrant discomfort and groin and hip pain. Abdominal computed tomography (CT) demonstrated bilateral adnexal focal millimetric calcifications, which were considered old granulomas, and no other etiology was found (Fig. 3). Also, multiple calcific granulomas in both lobes of the liver and in the upper pole of the spleen were found (Fig. 4). A hepatic wedge resection revealed granuloma. Fig. 3. View largeDownload slide Axial section of the pelvic CT exhibits bilateral adnexal millimetric calcific foci considering granulomatous inflammation. Fig. 3. View largeDownload slide Axial section of the pelvic CT exhibits bilateral adnexal millimetric calcific foci considering granulomatous inflammation. Fig. 4. View largeDownload slide Axial section of the upper abdominal CT shows multiple calcified granulomas (closed arrows). Fig. 4. View largeDownload slide Axial section of the upper abdominal CT shows multiple calcified granulomas (closed arrows). Her final clinical presentation was persistent vomiting at 17 years of age. Gastric antral asymmetrical thickening without any pathological lymph nodes was depicted on abdominal ultrasound and confirmed with contrast enhanced abdominal CT (Fig. 5). Endoscopic biopsy revealed Helicobacterpylori-negative chronic gastritis negative for granuloma. Radiological findings were highly suggestive of antral involvement of CGD. The regression of involvement was confirmed via ultrasonography after 6 weeks. Fig. 5. View largeDownload slide Contrast enhanced upper abdominal CT demonstrates gastric antral involvement exhibiting hypodense expansion of submucosal and muscular layers. Fig. 5. View largeDownload slide Contrast enhanced upper abdominal CT demonstrates gastric antral involvement exhibiting hypodense expansion of submucosal and muscular layers. DISCUSSION Respiratory tract involvement is common in CGD and accounts for approximately 50% of the cases [5]. Furthermore, chronic interstitial inflammation in CGD may mimic hypersensitivity pneumonitis and also result in interstitial lung disease [6]. In the present case, there were severe interstitial fibrotic thickenings, emphysematous changes and traction bronchiectasis compatible with chronic interstitial lung disease. Histopathological evaluation of CGD cases with the suspicion of hepatic abscess demonstrates nonspecific inflammatory changes in the majority of the cases, while typical granulomas and numerous classical pigmented macrophages within the hepatic sinusoids were depicted in a few cases [5]. Similarly, in the bowels, active, predominantly eosinophilic or neutrophilic colitis (71%) was found to be the most commonly encountered finding followed in the frequency by classical pigment-containing macrophages within the gastrointestinal tract lamina propria (57%). Fewer cases (34%) have exhibited noncaseating granulomas located in the upper gastrointestinal tract. Multiple consecutive gastrointestinal biopsies could demonstrate involvement in CGD [7]. Marciano et al. [8] have analyzed a wide series of CGD patients and found that 46 of 140 were symptomatic and had endoscopy-proven inflammatory bowel disease. Though histopathological evaluation reported only chronic inflammation in the antrum in the presented case, the obvious antral thickening depicted via ultrasonography, endoscopy and computed tomography was highly suggestive of granulomatous involvement of CGD. Reports of obstructive findings were rarely presented in the literature among the higher prevalence of gastrointestinal involvement reported particularly in X-linked type [7]. Persistent vomiting secondary to gastric outlet involvement that was managed conservatively was a severe manifestation of the disease in our case. Although it has been reported that inflammatory involvement in multiple sites is uncommon for CGD patients, yet, in a recent report, pulmonary with antro-pyloric involvement in the form of eosinophilic infiltration of the mucosa and submucosa has been described [9]. Bilateral adnexal calcific foci were seen in the patient with menstrual irregularities as well as inguinal and pelvic pain. Though histopathological confirmation was not performed, ovarian parenchymal calcifications were considered as CGD involvement. As far as we know, no previous data regarding ovarian granulomatous involvement have been reported. In female CGD patients, menstrual irregularities may be observed because of immunosuppressive drugs or ovarian inflammatory changes. Both obstructions and palliative operations because of the mural CGD involvement would cause complications as extralumination, fistula or abscess formation. Pathophysiology of the chronic gastrointestinal inflammation is explained by defective myeloperoxidase-halide-hydrogen peroxide system that is not able to inactivate chemoattractants [10]. Both published reviews and clinical guidelines consider corticosteroids as first-line choice in CGD patients with fungal infection, even more if intestinal obstruction is present [11, 12]. Immunomodulatory therapy with IFN-gamma is an important part of the disease management together with antibacterial and antifungal chemoprophylaxis. Although some authors suggest IFN-gamma replacement only during active infection, others recommend long-term prophylaxis [1]. Finally, hematopoietic cell transplantation (HCT) remains the definitive cure for CGD [13]. Our case has been using IFN-gamma therapy since the time of diagnosis, but she could not undergo HCT, as she had multiple comorbidies. In conclusion, CGD is a genetic disorder with serious life-threathening infections and multisystem granulomatous disorders. Antimicrobial and immunomodulatory therapy together with surgery for selected cases prolongs survival in the cases when HCT is not possible. References 1 Arnold DE, Heimall JR. A review of chronic granulomatous disease. Adv Ther  2017; 34: 2543. Google Scholar CrossRef Search ADS PubMed  2 Marciano BE, Spalding C, Fitzgerald A, et al.   Common severe infections in chronic granulomatous disease. Clin Infect Dis  2015; 60: 1176. Google Scholar CrossRef Search ADS PubMed  3 Falcone EL, Holland SM. Invasive fungal infection in chronic granulomatous disease: insights into pathogenesis and management. Curr Opin Infect Dis  2012; 25: 658– 69. Google Scholar CrossRef Search ADS PubMed  4 Greenberg DE, Goldberg JB, Stock F, et al.   Recurrent Burkholderia infection in patients with chronic granulomatous disease: 11-year experience at a large referral center. Clin Infect Dis  2009; 48: 1577– 9. Google Scholar CrossRef Search ADS PubMed  5 Levine S, Smith VV, Malone M, et al.   Histopathological features of chronic granulomatous disease (CGD) in childhood. Histopathology  2005; 47: 508– 16. Google Scholar CrossRef Search ADS PubMed  6 Moghtaderi M, Kashef S, Rezaei N. Interstitial lung disease in a patient with chronic granulomatous disease. Iran J Pediatr  2012; 22: 129– 33. Google Scholar PubMed  7 Mohandas S, Toh J, Arora P, et al.   Noninfectious enterocolitis as initial presentation of chronic granulomatous disease. Clin Pediatr  2017; 54: 1353– 6. Google Scholar CrossRef Search ADS   8 Marciano BE, Rosenzweig SD, Kleiner DE, et al.   Gastrointestinal involvement in chronic granulomatous disease. Pediatrics  2004; 114: 462. Google Scholar CrossRef Search ADS PubMed  9 Labrosse R, Abou-Diab J, Blincoe A, et al.   Very early-onset inflammatory manifestations of X-linked chronic granulomatous disease. Front Immunol  2017; 8: 1167. Google Scholar CrossRef Search ADS PubMed  10 Ohno Y, Buescher ES, Roberts R, et al.   A re-evaluation of cytochrome b and flavin adenine dinucleotide in neutrophils from patients with chronic granulomatous disease and description of a family with probable autosomal recessive inheritance of eytochrome b deficiency. Blood  1986; 67: 1132– 8. Google Scholar PubMed  11 Chin TW, Stiehm ER, Falloon J, et al.   Corticosteroids in treatment of obstructive lesions of chronic granulomatous disease. J Pediatr  1987; 111: 349– 52. Google Scholar CrossRef Search ADS PubMed  12 Siddiqui S, Anderson VL, Hilligoss DM, et al.   Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis  2007; 45: 673– 81. Google Scholar CrossRef Search ADS PubMed  13 Seger RA. Hematopoietic stem cell transplantation for chronic granulomatous disease. Immunol Allergy Clin North Am  2010; 30: 195– 208. Google Scholar CrossRef Search ADS PubMed  © The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Journal of Tropical PediatricsOxford University Press

Published: May 7, 2018

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