Differential diagnosis of primary immunodeficiency in patients with BCGitis and BCGosis: A single‐centre study

Aytekin, Elif Soyak; Keskin, Armağan; Tan, Çağman; Yalçın, Ebru; Özçeli̇k, Uğur; Ki̇per, Nural; Tezcan, İlhan; Çağdaş, Deniz

doi:10.1111/sji.13084

Cited by 12 publications

(3 citation statements)

References 21 publications

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“…BCG is used to prevent severe tuberculosis, and the WHO recommends that newborns born in areas with high tuberculosis incidence should be vaccinated [10][11][12] . The incidence of severe tuberculosis has been reduced after BCG vaccination, but BCG disease still occurs occasionally [6] and can even be fatal [13][14][15] . In recent years, there have been few large-sample updated clinical data about BCG disease, and no studies have focused on differences in BCG disease in different types of PID and between PID and non-PID patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characteristics of BCG Disease in Chinese Children: a Retrospective Study

et al. 2023

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Summarize the characteristics of the largest cohort of BCG disease and compare differences in clinical characteristics and outcomes among different genotypes and between primary immunode ciency disease (PID) and non-PID patients. MethodsWe collected information on patients with BCG disease in our center from January 2015 to December 2020 and divided them into four groups: chronic granulomatous disease (CGD), Mendelian susceptibility to mycobacterial disease (MSMD), severe combined immunode ciency disease (SCID) and unspeci ed pathogenic group. ResultsA total of 134 patients were reviewed, and most of them had PID. A total of 112 (83.6%) patients had 19 different types of pathogenic gene mutations, most of whom (91.1%) were classi ed with CGD, MSMD and SCID. CYBB was the most common gene mutation (53/112). BCG disease behaves differently in individuals with different PIDs. Signi cant differences in sex (P < 0.001), age at diagnosis (P = 0.019), frequency of recurrent fever (P = 0.003) and infection severity (P = 0.038) were noted among the four groups. The CGD group had the highest rate of males and the oldest age at diagnosis. The MSMD group had the highest probability of disseminated infection (46.4%). The course of anti-tuberculosis treatment and the survival time between PID and non-PID patients were similar. ConclusionGreater than 80% of BCG patients have PID; accordingly, gene sequencing should be performed in patients with BCG disease for early diagnosis. BCG disease behaves differently in patients with different types of PID. Non-PID patients had similar outcomes to PID patients, which hints that they may have pathogenic gene mutations that need to be discovered. tend to suffer from BCG disease with an incidence of approximately 1:10,000-1:1,000,000 or even disseminated BCG disease, which is a rare and serious adverse reaction [4] . In 2015, Aishwarya Venkataraman et al. observed sixty children who presented with adverse reactions and found that twothirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications, and 54% had received anti-tuberculous therapy and/or a procedure [5] . With the increasing use of gene sequencing, some pathogenic genes have been discovered in some BCG diseases [6] . Rina Yue Ling Ong et al. reported that 10 patients likely had underlying PID -four with SCID, three with MSMD, one with anhidrotic ectodermal dysplasia with PID (EDA-ID), one with combined immunode ciency (CID), and one with a STAT-1 gain-of-function mutation [7] . A previous study enrolled 74 con rmed cases of BCGosis/BCGitis in our center in 2014. Thirty-two patients (43.2%) had de nitive PID, and CGD was the most common PID (n = 23, accounting for 71.9% of all PID patients) [6] .However, limited updated clinical data on large-sized samples of BCG disease have been reported, and differences among different genotypes and between PID and non-PID patients have not been described.This study aims to analyze the clinical and genetic characteristics of the largest cohort of BCG...

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Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characteristics of BCG Disease in Chinese Children: a Retrospective Study

et al. 2023

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“…Granulomas caused by Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) are significantly prevalent in IEIs due to phagocytic disorders, and T cell signaling disorders including defects in IFN- γ /Il-12 signaling ( 7 , 77 ). In endemic areas where the Bacille Calmette-Guérin (BCG) vaccine, containing live-attenuated Mycobacterium bovis bacilli is administered, IEI patients may present with localized granulomatous inflammation termed BCG-itis or disseminated “BCG-osis” ( 77 – 79 ). This may be the first presentation of CGD or SCID and may present challenges in patient management if HSCT is considered since pre-transplant infection and/or inflammation is associated with poor outcomes.…”

Section: Introductionmentioning

confidence: 99%

Granulomatous inflammation in inborn errors of immunity

Sacco

Gazzin²,

Notarangelo³

et al. 2023

Front. Pediatr.

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Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and T cells. The three-dimensional spherical structure typically consists of a central core of tissue resident macrophages which may merge into multinucleated giant cells surrounded by T cells at the periphery. Granulomas may be triggered by infectious and non-infectious antigens. Cutaneous and visceral granulomas are common in inborn errors of immunity (IEI), particularly among patients with chronic granulomatous disease (CGD), combined immunodeficiency (CID), and common variable immunodeficiency (CVID). The estimated prevalence of granulomas in IEI ranges from 1%–4%. Infectious agents causing granulomas such Mycobacteria and Coccidioides presenting atypically may be ‘sentinel’ presentations for possible underlying immunodeficiency. Deep sequencing of granulomas in IEI has revealed non-classical antigens such as wild-type and RA27/3 vaccine-strain Rubella virus. Granulomas in IEI are associated with significant morbidity and mortality. The heterogeneity of granuloma presentation in IEI presents challenges for mechanistic approaches to treatment. In this review, we discuss the main infectious triggers for granulomas in IEI and the major forms of IEI presenting with ‘idiopathic’ non-infectious granulomas. We also discuss models to study granulomatous inflammation and the impact of deep-sequencing technology while searching for infectious triggers of granulomatous inflammation. We summarize the overarching goals of management and highlight the therapeutic options reported for specific granuloma presentations in IEI.

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“…In addition, herpes virus family infections are common and can be severe, including herpes simplex virus (HSV) type 1 and 2, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Bacillus Calmette-Guerin (BCG) infection and disseminated BCG infection are seen quite frequently in MSMD disorders because of reduced IL-12 and IFN-γ cytokines (1). IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, IRF8, CYBB, and NEMO genes are the best-known disease-causing genes underlying MSMD disorders, all of which are related to IFN-γ mediated immunity (2,3).…”

Section: Introductionmentioning

confidence: 99%

Genetic and Clinical Profiling of Mendelian Susceptibility to Mycobacterial Disease Patients; Single Center Experience

Nepesov¹,

Fırtına²,

Aygün³

et al. 2022

jarhs

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This work is licensed under Creative Commons Attribution-NonCommercial 4.0 International License ÖZ Amaç: Mikobakteriyel hastalığa (MSMD) Mendel duyarlılığı, Bacille Calmette-Guérin (BCG) aşısı veya tüberküloz dışı mikobakteriyel enfeksiyonlarla gelişen primer immün yetmezliklerin bir alt grubudur. Klinik semptomlar, lokalize enfeksiyondan yayılmış enfeksiyona kadar geniş bir spektruma sahiptir. Gereç ve Yöntem: Bu çalışmada; MSMD fenotipli 13 hastada tüm ekzom dizileme (WES) yaptık. Tüm varyantlar Sanger dizileme ile doğrulandı. Bizim kohortumuzda ortalama yaş 8.41 yıl (en az 3 -en fazla 14 yıl) ve ortalama semptom başlangıç yaşı 4.6 idi. Bulgular: Dokuz hastada; IFNGR1 (n=2), IFNGR2 (n=1), TYK2 (n=1), IL12RB1 (n=1) ve CYBB (n=1) gen varyantları bulduk. Hastalarımızda en çok lenfadenit (%61,5), osteomiyelit (%38) ve miliyer tüberküloz (%31) mevcuttu. Biri hariç tüm hastalara BCG aşısı yapıldı. İki hastada aşılamadan sonra BCGitis gelişti. Üç hasta, yayılmış BCG enfeksiyonundan (BCGosis) muzdaripti. Sonuç: Bulgularımız, enfeksiyon hastalıklarının genetik temelinin anlaşılmasında ve tedavi seçeneklerine karar verilmesinde bir yaklaşım olarak ağır enfeksiyonlu hastalarda moleküler tanının önemini göstermektedir. IFN aracılı bağışıklık genlerinin eksikliği, MSMD'nin patogenezinde çok önemli bir rol oynar ve BCGitis'li pediatrik hastalarda düşünülmelidir.

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Differential diagnosis of primary immunodeficiency in patients with BCGitis and BCGosis: A single‐centre study

Cited by 12 publications

References 21 publications

Clinical and Genetic Characteristics of BCG Disease in Chinese Children: a Retrospective Study

Clinical and Genetic Characteristics of BCG Disease in Chinese Children: a Retrospective Study

Granulomatous inflammation in inborn errors of immunity

Genetic and Clinical Profiling of Mendelian Susceptibility to Mycobacterial Disease Patients; Single Center Experience

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