Pulmonary BCG/TB infection in patients with chronic granulomatous disease - imaging characteristics from a single center in Shanghai, China

doi:10.21203/rs.3.rs-1505528/v1

Download PDF

Article

Pulmonary BCG/TB infection in patients with chronic granulomatous disease - imaging characteristics from a single center in Shanghai, China

https://doi.org/10.21203/rs.3.rs-1505528/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: In China, tuberculosis (TB) is epidemic and the Bacillus Callmette-Güerin (BCG) vaccine is administered to all the newborns, which may lead to BCG infection in patients with chronic granulomatous disease (CGD). Infection of BCG/TB in CGD patients can be fatal and pulmonary is the most affected organ. Our objective was to assess the imaging of pulmonary BCG/TB infection in CGD.

Methods: We screened 169 CGD patients and identified the patients with pulmonary BCG/TB infection. BCG infection was diagnosis according to the vaccination history, local infection manifestation, and acid-fast bacilli staining. PPD, T-SPOT and acid-fast bacilli staining were used for diagnosis of TB.

Results: Totally 58 patients were identified, including TB (n = 7), solely BCG (n = 18), BCG + bacterial (n = 20), and BCG + fungi (n = 13). The onset of BCG disease was much early than TB. For those patients only with BCG, lymphadenopathy was the first and most prevalent feature. The most found location was the left axilla, followed by the ipsilateral cervical areas and mediastinal or hilar area. On chest CT, ground-glass opacities, multiple nodules and pulmonary scarring were the most common findings. For TB patients, the pulmonary infections were more serious, including large masses, severe lymphadenopathy, and extensive pulmonary fibrosis.

Conclusion: Lymphadenopathy, especially in the left axillary was the most common feature. Pulmonary infection of BCG were more common than TB in CGD patients, but much less severe.

Mycobacteria

Bacillus Callmette-Güerin

chronic granulomatous disease

tuberculosis

primary immunodeficiency

computed temography

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease (PID) characterized by the deficiency of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to produce reactive oxygen species. Five types are the most common types according to the mutation of genes: gp91phox (CYBB) and p22phox (CYBA), the cytosolic subunits p47phox (NCF1), p67phox (NCF2), and p40phox (NCF4). ^{1, 2}

Patients usually experience recurrent infections caused by a relatively specific set of pathogens, mainly bacterial and fungal infections (Aspergillus, Burkholderia, Nocardia, and Staphylococcus species). In China, tuberculosis (TB) is epidemic and lung is the most affected organ. ³ In 2015, the incidence of pulmonary TB in children (0–14 years old) of China was 3.03 per 100,000. ⁴ To prevent severe TB infection, Bacillus Callmette-Güerin (BCG) vaccination is routinely administered to every newborn. It is one of the most widely used vaccines in over 150 countries and proved to be save in immunocompetent hosts. ^{5, 6} However, for PID patients including CGD, it will lead to BCG infection. Most present with local BCG disease, mainly regional lymphadenitis. ^{5, 6} Disseminated BCG with CGD is extremely rare but fatal with a mortality rate of 60–80%. ^{7, 8} So in China, in addition to the commonly pathogens, BCG and TB infection should also be considered in the clinical work. ^{2, 9–11}

We have performed retrospective reviews on the clinical manifestation of CGD patients and identified the high incidence of BCG and TB infection, which can also be found in other countries in Asia, south Africa and Latin America. ^{2, 9, 10} Patients with BCG and TB infection all present positive in PPD tests and prolonged and recurrent pulmonary infection, which sometimes hard to be distinguished in the clinical work. Chest CT is the routine exam for GCD patients and can afford useful information for identifying the pathogens. ¹² However, for pulmonary BCG/TB infection, researches focusing on imaging findings are limited due to the low morbidity. This is the first research to summarize the imaging manifestations of pulmonary mycobacterial infection and compare the severity between BCG and TB.

Subjects

Our institution is a university teaching hospital, and pediatric immunology department is a tertiary referral center for patients with PID. From 1999 to 2019, we screened for pulmonary mycobacterial infection in 169 CGD patients. The clinical and imaging data were reviewed. Informed consent forms were signed by the parents and ethics approval was approved by the institutional review boards of the institutions. All methods were performed in accordance with the relevant guidelines and regulations. CGD was diagnosed as described before. ¹² The defective respiratory burst was detected by dihydrorhodamine-1,2,3 (DHR) test. Decreased protein level of gp91 was tested by flow cytometry-based extracellular staining with Moab 7D5, and gene mutations were identified by Sanger sequencing, including CYBB, CYBA, NCF1, and NCF2. Our analysis focused mainly on the imaging manifestations of pulmonary mycobacterial infections. The accompanied infection of other organs was also evaluated. Mycobacterial infections were diagnosed according to the published papers. ^{2, 10, 13} BCG infection was diagnosis according to the vaccination history, local infection manifestation, and evidence of acid-fast bacilli staining. PPD, T-SPOT and acid-fast bacilli staining were used for diagnosis of TB. PPD positive was defined as the diameter of > 5 mm after 48–72 h.

BCG infection was classified in three groups according to the affected organs and location ¹⁰: (I) local BCG infection: lymphadenitis near the injection site; (II) regional BCG infection: regional lymphadenopathy or other lesions beyond the vaccination site (e.g., ipsilateral axillary, supraclavicular, cervical lymph nodes); and (III) disseminated BCG infection: infections in remote sites or proved by blood or bone marrow culture.

The results of G ((1–3)-β-D-glucan) tests and GM (galactomannan) tests were used as evidences for fungal disease. GM index was defined as positive when > 0.5. G index was defined as positive when > 100 pg/ml⁸. GM test was highly sensitive to the infection of Aspergillus. ¹⁰

Imaging Modalities

All CT studies were performed with conventional techniques on a 64-slice CT (GE Healthcare, Princeton, NJ). Chest protocol included the following parameters: tube current 80-100mAs, tube voltage 80-100kV and gantry rotation time 350 milliseconds, a matrix of 512×512, reconstructed width 0.625mm. Omnipaque (iodine content 300mg/mL) was injected at the dose of 1.5-2ml/kg by power injector at the rate of 0.8-1ml/s. Reconstructions were made in the coronal and sagittal planes.

Two experienced radiologists analyzed the CT findings. If there were discrepant readings, they discussed and got the common decision. The observers evaluated: consolidation, nodules, ground-glass opacity, mass, abscess, cavity, tree-in bud opacities, interlobular septal thickening, pulmonary scarring, bronchiectasis, emphysema, pleural thickening, mediastinal or hilar lymphadenopathy, axillary lymphadenopathy, chest wall invasion, calcification in the mediastinal or hilar lymph nodes and pulmonary parenchyma. The radiographic definitions were defined by the Fleischner Society nomenclature.¹⁴ Consolidation appeared as a homogeneous increase lesion of lung. A nodule was defined as a rounded opacity, well or poorly defined, up to 3 cm in diameter while a mass more than 3 cm in diameter. Ground-glass opacity was hazy increased opacity in pulmonary parenchyma, with bronchial and vascular margins visible inside. Bronchiectasis was defined as localized or diffuse dilatation of a bronchus. A cavity presented as a gas-filled space, within pulmonary consolidation, a mass, or a nodule. Emphysema was a focal area of low attenuation, usually without visible walls. Mediastinal or hilar lymphadenopathy was defined by the short-axis diameter of the lymph nodes more than 10 mm.

Statistical analysis

Data were presented in a descriptive way. Continuous parameters were presented as mean ± standard deviation and inter-quartile range (IQR). Categorized data were expressed as number and percentages. Unpaired Student's t-test was used to compare the age of patients in two groups. The degree of inter-observer agreement was evaluated by Fleiss’ κ values: κ < 0.40, poor agreement; 0.40 < κ < 0.75, fair to good agreement and 0.75 < κ < 1.00, excellent agreement.

Demographic and clinical features

The flow chart was listed in Fig. 1. Among all the 169 CGD patients in recent 20 years, 58 patients with pulmonary mycobacterial infection and chest CT examinations were included in this study. Fifty-seven (96.55%) cases were male, and 1 (3.44%) was female, indicating a high proportion of X-linked CGD. CYBB was identified as the main gene type. Of all the patients, 51 (87.93%) cases presented with BCG infection and 7 (12.07%) patients with TB. The average stimulation index was similar in both groups. The average age at BCG diagnosis was significantly lower than that of TB (6.33 ± 9.84 vs. 58.14 ± 65.85 respectively, p < 0.05). In BCG group, apart from the patients with other bacterial (n = 20) and fungal (n = 13) infections, 18 patients presented solely with BCG disease. No other pathogens were found in TB group. The demographic and clinical features of subjects involved in the two groups were listed in Table 1.

Table 1

Distribution of genetic data and clinical infection
Sex
male	57
female	1
Gene type
CYBB	53
CYBA	4
unknow	1
BCG	58
Age at BCG diagnosis (month)	6.33 ± 9.84 (IQR, 2–12)
Stimulation index	5.13 ± 3.66
TB
Age at TB diagnosis (month)	58.14 ± 65.85 (IQR, 29–89)
Stimulation index	5.87 ± 5.46
BCG only	18
TB only	7
BCG + bacteria	20
BCG + fungi	13
BCG: Bacillus Callmette-Güerin; TB: tuberculosis

BCG imaging findings

To avoid the disturbance of bacterial and fungal infection, we only included the 18 patients solely with BCG disease for imaging analysis. For those infected with only BCG (n = 18), local BCG infection lymphadenopathy was the first and most prevalent feature. The most common site was the mediastinal or hilar (n = 15) (Fig. 2B), the left axilla (n = 18) (Fig. 2C), and the ipsilateral cervical areas (n = 8). CT revealed a majority of hypodense lesions with slight enhancement. Four cases had abscess formation with ring enhancement and one was accompanied by fistula, presented as enhanced strips extending to the skin. Twelve had sand-like, streak-like or nodular calcification within the enlarged lymph nodes. Nine patients who had a follow-up CT scan after antituberculosis therapy (Isoniazid, rifampicin and ethambutol) were found with a decrease in the size of lymphadenopathy and an increase in calcification.

As disseminated BCG with CGD is extremely rare and the chest imaging data are limited, we further summarized the chest CT findings of 18 cases only with BCG disease in detail (Table 2). The presence of ground-glass opacities, multiple nodules and pulmonary scarring was most common among all the 108 pulmonary segments of 18 patients. The imaging showed small bilateral patchy ground-glass opacities without obvious propensity. 1-3mm nodular lesions were mainly presented in the lower lobes beneath the pleura (Fig. 2A). Mild local pulmonary scarring was accompanied by slight tractive bronchiectasis and emphysema. Mass and patchy consolidation were found mostly in the bilateral upper lobes with multiple small cavities less than 3mm in 2 cases. Small nodular calcification in the pulmonary parenchymal was identified in 20 segments of 7 patients without predominantly lobar location while one demonstrated chest wall invasion and surrounding soft-tissue mass (Fig. 2D), which was adjacent to the infectious mass in the left upper lobe.

Table 2. Number and location of main pulmonary CT manifestations in the 108 pulmonary segments of BCG infection (n=18)

	RUL (%)	RML (%)	RLL (%)	LUL (%)	Lingula (%)	LLL (%)	N (%)
consolidation	6 (5.56)	2 (1.85)	1 (0.93)	5 (4.63)	1 (0.93)	1 (0.93)	16 (14.81)
nodules	3 (2.78)	3 (2.78)	7 (7.41)	2 (1.85)	4 (3.70)	9 (8.33)	28 (25.93)
cavity	2 (1.85)	0	0	0	0	0	2 (1.85)
ground-glass opacity	9 (8.33)	7 (7.41)	8 (44.44)	9 (8.33)	7 (7.41)	10 (9.26)	50 (46.30)
tree-in bud opacities	1 (0.93)	2 (1.85)	0	0	0	0	3 (2.78)
bronchiectasis	3 (2.78)	0	1 (0.93)	2 (1.85)	0	1 (0.93)	7 (6.48)
emphysema	6 (5.56)	2 (1.85)	5 (4.63)	4 (3.70)	2 (1.85)	6 (5.56)	25 (23.15)
pulmonary scarring	10 (9.26)	5 (4.63)	7 (7.41)	6 (5.56)	5 (4.63)	7 (7.41)	40 (37.04)
mass	3 (2.78)	1 (0.93)	0	0	2 (1.85)	2 (1.85)	8 (7.41)
interlobular septal thickening	1 (0.93)	2 (1.85)	3 (2.78)	0	0	3 (2.78)	9 (8.33)
pulmonary calcification	3 (2.78)	3 (2.78)	4 (3.70)	3 (2.78)	2 (1.85)	5 (4.63)	20 (18.52)

RUL: right upper lobe; RML: right middle lobe; RLL: right lower lobe; LUL: left upper lobe; LLL: left lower lobe; Lingula: left lingula lobe.

Other Visceral involvement included hepatosplenomegaly (n = 5), abscesses in the liver (n = 3), calcaneus osteomyelitis (n = 1) and enteritis (n = 1) (Fig. 3). In patients with hepatic abscess, contrast-enhanced CT scanning demonstrated the presence of multiple nodules with a central, low-attenuated mass, most of which were less than 5mm. Patients with enteritis showed markedly thickened and enhanced intestinal wall on abdominal CT, accompanied by a small amount of ascites. One child was detected with skeletal infection in the calcaneal. Multiple osteolytic lesions showed periosteal reaction and cortical disruption, all of which regressed following appropriate anti-tuberculosis treatment.

TB imaging findings

The percentage of all thoracic lesions in patients with TB infections were listed and compared with BCG in Fig. 4. Patients with TB infections showed multiple forms of pulmonary manifestation than those with BCG infection. Masses and nodules of different sizes at various levels of heterogeneous enhancement in bilateral pulmonary field were identified in 6 patients while nodular calcification was observed in three patients, with the biggest mass being up to 5cm in diameter (Fig. 5A, 5B). Consolidation and ground-grass opacity were common in bilateral fields, some with multiple small cavities and necrosis inside. CT showed extensive pulmonary fibrosis in 14 segments from 5 patients, among which 2 patients were found with volume loss (Fig. 5C). Six patients were found with remarkable mediastinal or hilar lymphadenopathy while one patient was identified with TB granuloma of the bronchial mucosa under bronchoscopy. Chest wall invasion was found in 1 patient accompanied with thoracic vertebrae destruction and paravertebral abscess, extending to the spinal canal and compressing the thoracic spinal cord on MR.

The other involved sites included hepatosplenomegaly (n = 2), kidney abscess (n = 1), right tibiofibular bone and foot osteomyelitis (n = 1), cerebral abscess (n = 1) and enteritis (n = 1) (Fig. 6). The imaging features of enteritis were similar to BCG infection, including extensive intestinal dilation and thickened intestinal wall on CT. One patient had multiple small cerebral abscesses in the left parietal and occipital lobes, showing high signal on T1WI and DWI, low signal on T2WI sequence and annular enhancement, indicating the possibility of caseous necrosis. The patient also had osteomyelitis in the right tibiofibular joint and foot, demonstrating local bone erosions and swelling of the surrounding soft tissue. All patients were treated with multiple-drug therapy (Isoniazid, rifampicin and ethambutol) and INF- therapy.

Inter-observer correlation

Agreement between the two radiologists was strong for determining the main chest CT features. For the diagnosis of pathogens, the agreement of fungal infections (κ value of 0.89) and BCG infection (κ value of 0.76) was good. There was moderate agreement between TB infections (κ value of 0.52), and weak agreement in the diagnosis of bacterial infections (κ value of 0.38).

BCG vaccine has existed for 80 years and has been proved highly useful in preventing severe TB infections. In China, neonatal BCG vaccination has become a routine as suggested by the World Health Organization. According to the literature, the incidence of BCG complication is less than 1% in immunocompetent hosts, most of which are presented as local lymph nodes diseases. ^{5, 6} However, there are concerns about the safety of BCG among PID patients including CGD. Deffert reported that in 297 cases of CGD patients with mycobacterial infections, BCG was most commonly identified in 220 (74%) patients, while TB was reported in only 59 (20%) patients.¹⁵ Francesca examined 71 patients with CGD from 20 countries and found 31 (44%) patients had tuberculosis, and 53 (75%) presented adverse reaction to BCG. ¹³ The BCG infection usually occurs in the first decade of life, especially within 1 year after vaccination, much earlier than the onset of TB. ^{16, 17} The finding was consistent with previous studies. In the research, BCG has a high incidence of complication and earlier onset than TB, with the earliest presentation of BCG disease 1 month after birth.

The impaired granulocytic phagocytosis would cause the infection to spread in the lymphatic and the blood system, with the lymphatic system being most vulnerable to infections. ^{11, 18} In the cohort, lymphadenopathy, whether regional or disseminated, was the most common feature. The most common location was in the left axillary ipsilateral to the injection site, followed by the ipsilateral cervical areas that develop along the lymphatic system. ¹⁹ The central abscess and rim enhancement could be regarded as a sign of progress, indicating caseous necrosis. After treatment, serial CT studies have been used to document the resolution of BCG-related lymphadenopathy, including changes in size and calcification, which are similar to the lymphadenopathy of tuberculosis.

Patients with PID usually have more severe BCG infection than patients without PID. Disseminated BCG involves multiple systems with fatal consequences in most cases. ¹⁷ The incidence is estimated to be 0.59 per 1 million and almost occurs in children with immunodeficiency disorders. ^{20, 21} The lung has been proved to be the most common site and may be the first involved visceral organ. However, the lack of typical imaging characteristics could lead to inaccurate diagnosis. ^22–24 Nodules and exudation have been reported as the most common manifestations, and some are characterized by small nodular calcification in the pulmonary parenchyma and lymphoid nodes. ²⁵ In the cohort, pulmonary lesions presented multiple manifestations, including granulomas forming pathologically characterized by multiple nodules and masses mainly in the bilateral lower lobes, bearing similarities with the infection of fungus like aspergillus and candida, while the incidence of calcification is relatively lower in the fungal infection. The regions of ground-grass opacity and consolidation vary from subtle patches to bilateral multi-segment distribution. Other lesions like interstitial pneumonia and fibrotic changes were local and mild without obvious volume loss.

In TB-endemic countries, children with CGD are at high risk of infection. In Argentina, Hong Kong, and Iran, up to 11%, 54.5%, and 31.7% of patients with CGD were found to have TB infection respectively. ²⁵ We also observed a high incidence of TB in our cohort, most of which presented more severe infections than BCG group. Radiologic manifestations varied including heterogeneous patchy of consolidation, large masses with cavitation, multiple nodules, and obvious lymphadenopathy. Miliary disease has not been found in our group. Progressive fibrosis with volume loss and tractive bronchiectasis in the upper lobes occurred in almost 1/3 of patients, much severe than BCG. Lymphadenopathy is another feature of TB, which larger in size and most seen in the bilateral hilar area. Compared with TB infection, BCG lymphadenitis is more generalized and dispersed. TB mostly affects the elderly, and children below 15 years old only constitute less than 5% of all cases. ^25–27 In the paper, the BCG group has a much younger average age than the TB group.

In CGD patients, mycobacterial Infection also affects other visceral organs in a disseminated pattern, with liver and spleen as the most common infected organs. ²⁸ Hepatosplenomegaly and multiple small abscesses have been observed, unlike the abscess of other pyogenic infection. Osteomyelitis, central nervous system infection and intestinal involvement have also been reported in the published literatures, but with relatively lower morbidity. The bone infection of BCG and TB has similar radiographic appearance characterized by osteolytic destruction and periosteal reaction, usually in the epiphysis and metaphysis of the long bone. ²⁹ In the small or irregular bones, osteolytic destruction and dilation can be found with soft-tissue swelling. ^{30, 31}

As an attenuated live vaccine, BCG presents lower pathogenicity and better response to anti-tuberculous treatment than TB. However, BCG has a higher incidence, and BCG disease might be the first sign of CGD caused by mandatory vaccination after birth, earlier than bacteria or fungi. Therefore, it is suggested that an evaluation of underlying immunodeficiency should be given for infant and children diagnosed as BCG disease. ³² In addition, for neonate with a family history of PIDs, BCG vaccination should be delayed until PID is excluded.

In our cohort, the onset of BCG disease was much early than TB, which might be the first sign of PID. Lymphadenopathy, especially in the left axillary ipsilateral to the injection site and the ipsilateral cervical areas was the most common feature, which may regress and form calcification after treatment. The pulmonary manifestation of BCG infection was less marked than that of TB, but with higher incidence. TB infections in CGD patients usually bear serious consequences (fibrosis with volume loss and tractive bronchiectasis) and leads to multiple drug resistance. The involvements of other systems were also common. For CGD patients, radiologists should be alert to the imaging features for early recognition of mycobacterial infections.

Figure 1 Study flowchart. CGD: chronic granulomatous disease, BCG: Bacillus Callmette-Güerin, TB: tuberculosis

Figure 2 Pulmonary CT of BCG infection. A: Chest CT of a 9-month-old boy showed multiple pulmonary nodules in the bilateral lower lobe beneath the pleura (long arrow). B: Coronal reformatted CT image of a 1-year-old boy demonstrated multiple nodular calcification within the mediastinal and hilar lymph nodes (long arrow). The calcified nodule in the right lower lobe was also found (short arrow). C: The left axillary calcification ipsilateral to the BCG injection site was found in a 1-year-old boy (long arrow). D: A 8-month-old boy with chest wall invasion. CT demonstrated a large chest wall mass with patchy areas of low density inside, suggesting the forming of abscess (star).

Figure 3 Abdominal visceral involvements of BCG infection. A: Coronal post-contrast CT showed hepatosplenomegaly with homogeneous enhancement in a 1-year-old boy. B: A 8-month-old boy with hepatic abscess. CT scan demonstrated the presence of multiple low-attenuated lesions in the left lobe (long arrow). Most lesions were less than 5mm and some with ring enhancement. Edema around the left portal vein were also noticed. C and D: A 1-year-old boy with enteritis. The widely thickened intestinal wall and effusion within the lumen were found on abdominal CT. The small amount of ascites also accompanied. The enlargement of mesenteric lymph nodes was noticed (Fig D, long arrow).

Figure 4 Percent of thoracic lesions in patients with BCG and TB infections

Figure 5 Pulmonary CT of TB infection. A and B: 16-year-old boy with TB infection. A: Post-contrast CT showed a large mass in the right lower lobe, about 5 cm in diameter (star). Multiple small cavities were found in the adjacent area of consolidation. B: A nodule in the right bronchus led to atelectasis of the right lung, which was identified as TB granuloma formation by bronchoscopy (long arrow). The right pleural effusion was also found. C: In a 3-year-old boy, axial CT scan showed scarring, segmental atelectasis and volume loss in the right upper lobe (long arrow). Slight bronchiectasis could be found inside the area of consolidation.

Figure 6A 5-year-old boy with infection of TB. A ~ D: MRI showed multiple small cerebral abscesses (long arrow) in the left parietal and occipital lobes, which had low intensity on T1WI (A) and T2WI (B), high intensity on DWI sequence (C) and annular enhancement on post-contrast T1WI (D), suggesting the presence of caseous necrosis. Extensive cerebral edema could be found around the lesions. E, F: Osteomyelitis in the right tibia and foot was found in the same patient, demonstrating local bone erosions and osteosclerosis in the lower metaphysis of the tibia, the calcaneal and the 2nd-4th metatarsal bones (long arrow). Periosteal thickening along the metatarsal bones and swelling soft tissue of the right ankle and foot were found.

CGD：chronic granulomatous disease; PID: primary immunodeficiency disease; NADPH: nicotinamide adenine dinucleotide phosphate; TB: tuberculosis; BCG: Bacillus Callmette-Güerin

Ethics approval and consent to participate

Informed consent forms were signed by the parents and ethics approval was approved by the institutional review boards of the Children’s Hospital of Fudan Uninversity.

Consent for publication

Not applicable

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests

Funding

The National Key Research and Development Program of China (2016YFC1000500)

Authors' contributions:

Concept and design: Qiong Yao

Acquisition of data: Qiong Yao and Qin-hua Zhou

Analysis and interpretation of data: Quan-li Shen
Drafting the article: Qiong Yao and Quan-li Shen

Revising the article: Xi-hong Hu and Xiao-chuan Wang

Final approval of the version to be published: Xi-hong Hu and Xiao-chuan Wang

Acknowledgements:

Qiong Yao and Qin-hua Zhou contributed equally to the work.

Xi-hong Hu and Xiao-chuan Wang contributed equally to the work.

Pulmonary BCG/TB infection in patients with chronic granulomatous disease - imaging characteristics from a single center in Shanghai, China

Matute, J. D. et al. A New Genetic Subgroup of Chronic Granulomatous Disease with Autosomal Recessive Mutations in P40 Phox and Selective Defects in Neutrophil NADPH Oxidase Activity. Blood. 114, 3309–3315 (2009).
Zhou, Q. et al. A Cohort of 169 Chronic Granulomatous Disease Patients Exposed to BCG Vaccination: A Retrospective Study From a Single Center in Shanghai, China (2004–2017). J. Clin. Immunol. 38, 260–272 (2018).
Jabado, N. et al. Invasive Pulmonary Infection Due to Scedosporium Apiospermum in Two Children with Chronic Granulomatous Disease. Clin. Infect. Dis. 27, 1437–1441 (1998).
Tao, N. N. et al. Epidemiological Characteristics of Pulmonary Tuberculosis Among Children in Shandong, China, 2005–2017. BMC Infect. Dis. 19, 408 (2019).
Zwerling, A. et al. The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices. PLoS Med. 8, e1001012 (2011).
Krysztopa-Grzybowska, K., Paradowska-Stankiewicz, I. & Lutyńska, A. The Rate of Adverse Events Following BCG Vaccination in Poland. Przegl Epidemiol. 66, 465–469 (2012).
Li, T. et al. Genetic and Clinical Profiles of Disseminated Bacillus Calmette-Guérin Disease and Chronic Granulomatous Disease in China. Front Immunol. 10, 73 (2019).
Sadeghi-Shanbestari, M. et al. Immunologic Aspects of Patients with Disseminated Bacille Calmette-Guerin Disease in North-West of Iran. Ital. J. Pediatr. 35, 42 (2009).
Winkelstein, J. A. et al. Chronic Granulomatous Disease. Report On a National Registry of 368 Patients. Medicine (Baltimore). 79, 155–169 (2000).
Ying, W. et al. Clinical Characteristics and Immunogenetics of BCGosis/BCGitis in Chinese Children: A 6 Year Follow-Up Study. PLoS One. 9, e94485 (2014).
Marciano, B. E. et al. BCG Vaccination in Patients with Severe Combined Immunodeficiency: Complications, Risks, and Vaccination Policies. J Allergy Clin Immunol. 133, 1134–1141 (2014).
Mahdaviani, S. A. et al. Pulmonary Computed Tomography Scan Findings in Chronic Granulomatous Disease. Allergol Immunopathol (Madr). 42, 444–448 (2014).
Conti, F. et al. Mycobacterial Disease in Patients with Chronic Granulomatous Disease: A Retrospective Analysis of 71 Cases. J Allergy Clin Immunol. 138, 241–248 (2016).
Hansell, D. M. et al. Fleischner Society: Glossary of Terms for Thoracic Imaging. Radiology. 246, 697–722 (2008).
Deffert, C. et al. Bacillus Calmette-Guerin Infection in NADPH Oxidase Deficiency: Defective Mycobacterial Sequestration and Granuloma Formation. PLoS Pathog. 10, e1004325 (2014).
Rezai, M. S., Khotaei, G., Mamishi, S., Kheirkhah, M. & Parvaneh, N. Disseminated Bacillus Calmette-Guerin Infection After BCG Vaccination. J Trop Pediatr. 54, 413–416 (2008).
Afshar, P. S., Siadati, A., Mamishi, S., Tabatabaie, P. & Khotaee, G. Disseminated Mycobacterium Bovis Infection After BCG Vaccination. Iran J Allergy Asthma Immunol. 5, 133–137 (2006).
Yang, C. S., Yuk, J. M. & Jo, E. K. The Role of Nitric Oxide in Mycobacterial Infections. Immune Netw. 9, 46–52 (2009).
Rigouts, L. Clinical Practice: Diagnosis of Childhood Tuberculosis. Eur. J. Pediatr. 168, 1285–1290 (2009).
Roos, D. et al. Hematologically Important Mutations: The Autosomal Recessive Forms of Chronic Granulomatous Disease (Second Update). Blood Cells Mol Dis. 44, 291–299 (2010).
Köker, M. Y. et al. Clinical, Functional, and Genetic Characterization of Chronic Granulomatous Disease in 89 Turkish Patients. J Allergy Clin Immunol. 132, 1156–1163 (2013).
Shrot, S., Barkai, G., Ben-Shlush, A. & Soudack, M. BCGitis and BCGosis in Children with Primary Immunodeficiency - Imaging Characteristics. Pediatr. Radiol. 46, 237–245 (2016).
Kido, J., Mizukami, T., Ohara, O., Takada, H. & Yanai, M. Idiopathic Disseminated Bacillus Calmette-Guerin Infection in Three Infants. Pediatr. Int. 57, 750–753 (2015).
Kawashima, H. et al. Hazards of Early BCG Vaccination: BCGitis in a Patient with Chronic Granulomatous Disease. Pediatr. Int. 49, 418–419 (2007).
Lee, P. P. 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. 27, 224–230 (2008).
Howie, S. et al. Tuberculosis in New Zealand, 1992–2001: A Resurgence. Arch. Dis. Child. 90, 1157–1161 (2005).
Lamb, G. S. & Starke, J. R. Tuberculosis in Infants and Children. Microbiol Spectr. 5, (2017).
Andronikou, S. & Wieselthaler, N. Modern Imaging of Tuberculosis in Children: Thoracic, Central Nervous System and Abdominal Tuberculosis. Pediatr. Radiol. 34, 861–875 (2004).
Hugosson, C. & Harfi, H. Disseminated BCG-osteomyelitis in Congenital Immunodeficiency. Pediatr. Radiol. 21, 384–385 (1991).
Teo, H. E. & Peh, W. C. Skeletal Tuberculosis in Children. Pediatr. Radiol. 34, 853–860 (2004).
Han, T. I., Kim, I. O., Kim, W. S. & Yeon, K. M. Disseminated BCG Infection in a Patient with Severe Combined Immunodeficiency. Korean J. Radiol. 1, 114–117 (2000).
Boisson-Dupuis, S. et al. Inherited and Acquired Immunodeficiencies Underlying Tuberculosis in Childhood. Immunol. Rev. 264, 103–120 (2015).

No competing interests reported.

Download PDF

Editorial decision: Major revision
01 Jun, 2022
Reviews received at journal
15 May, 2022
Reviewers agreed at journal
12 May, 2022
Reviewers invited by journal
24 Apr, 2022
Editor assigned by journal
24 Apr, 2022
Editor invited by journal
05 Apr, 2022
Submission checks completed at journal
05 Apr, 2022
First submitted to journal
30 Mar, 2022

You are reading this latest preprint version

Pulmonary BCG/TB infection in patients with chronic granulomatous disease - imaging characteristics from a single center in Shanghai, China

Status:

Version 1

Abstract

Figures

Background

Methods

Subjects

Imaging Modalities

Statistical analysis

Results

Demographic and clinical features

BCG imaging findings

TB imaging findings

Inter-observer correlation

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1