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JMM Case Reports Aug 2018Guillain Barré Syndrome (GBS) has rarely been associated with tuberculosis and has been previously reported after Bacille Calmette Guérin (BCG) vaccination, but we...
INTRODUCTION
Guillain Barré Syndrome (GBS) has rarely been associated with tuberculosis and has been previously reported after Bacille Calmette Guérin (BCG) vaccination, but we report an association of GBS with intra-vesical BCG instillations followed by the clinical picture of disseminated BCGosis.
CASE PRESENTATION
A 68-year-old man with bladder carcinoma had a transurethral tumour resection followed by repeated BCG instillations. Catheterization for his eighth dose was traumatic, causing frank haematuria. Ten days later he presented with fevers, myalgia and dyspnoea. Chest X-ray on admission showed micronodular shadowing and a computed tomography scan showed miliary changes in the lungs. Disseminated BCGosis infection was suspected and his symptoms did improve after starting rifamipicin, isoniazid and ethambutol. Over 2 weeks post-admission he developed an unsteady gait, reduced pin-prick sensation below both knees and fingertips, reduced proprioception in both toes and ankles, with absent reflexes in his lower limbs and diminished reflexes in his upper limbs. Nerve conduction studies showed a purely demyelinating sensori-motor peripheral neuropathy in upper and lower limbs, characteristic of GBS.
CONCLUSION
To our knowledge this is the first case report of GBS following bladder instillation of BCG. Given the millions of cases of tuberculosis and millions of doses of administered BCG, GBS must be a very rare adverse effect.
PubMed: 30323939
DOI: 10.1099/jmmcr.0.005164 -
The Journal of Infection Jun 2012Primary immunodeficiency diseases (PIDs) are a group of inherited disorders, characterized by defects of the immune system predisposing individuals to variety of... (Review)
Review
Primary immunodeficiency diseases (PIDs) are a group of inherited disorders, characterized by defects of the immune system predisposing individuals to variety of manifestations, including recurrent infections and unusual vaccine complications. There are a number of PIDs prone to Bacillus Calmette-Guérin (BCG) complications. This review presents an update on our understanding about the BCGosis-susceptible PIDs, including severe combined immunodeficiency, chronic granulomatous disease, and Mendelian susceptibility to mycobacterial diseases.
Topics: BCG Vaccine; Humans; Immunologic Deficiency Syndromes; Tuberculosis
PubMed: 22430715
DOI: 10.1016/j.jinf.2012.03.012 -
EJVES Vascular Forum 2023Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for bladder carcinomas; however, extravesical BCG infection may occur in remote organs in patients...
INTRODUCTION
Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for bladder carcinomas; however, extravesical BCG infection may occur in remote organs in patients with underlying primary immunodeficiency and is a potentially serious complication in 3-5% of cases. It includes granulomatous pneumonia, hepatitis as well as specific dermatological, ophthalmic, and haematopoietic manifestations. Diagnosis is difficult and often based on high clinical suspicion as in many cases is not isolated. This report presents a rare case of BCGaortitis treated in a tertiary care centre.
REPORT
A 74 year old man, with a history of bladder cancer treated with BCG therapy over a year ago, presented with malaise, abdominal pain, anorexia, and significant weight loss for several months associated with acute on chronic renal failure and a tender aneurysm. He was diagnosed with hepatic BCGitis and pararenal BCGaortitis. He was considered too high risk for open surgery after a multidisciplinary team meeting and was treated with a four vessel physician modified endograft (PMEG) and antituberculous therapy. At seven month follow up, he was clinically well and control computed tomography showed a patent endograft with complete exclusion of the aortic aneurysm.
DISCUSSION
Infectious BCG complications after intravesical BCG administration for bladder carcinomas can lead to severe early and late complications. In the present case, the patient presented with both liver and aortic BCG infection. The lack of positive microbiological data should not discourage clinicians from considering BCG infection even if several months have passed since the last BCG instillation.
PubMed: 36949865
DOI: 10.1016/j.ejvsvf.2023.02.003 -
Frontiers in Immunology 2021Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in...
Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated -Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), , fungi, parasites like and some viruses, in otherwise healthy individuals. Mutations in the gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with and non-typhi (13%), (11%), (7%), NTM (4%), and (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.
Topics: Adolescent; Adult; BCG Vaccine; Child; Child, Preschool; Coinfection; Female; Genetic Predisposition to Disease; Humans; Immunity, Innate; India; Infant; Infant, Newborn; Male; Mutation; Mycobacterium Infections; Phenotype; Receptors, Interleukin-12; Retrospective Studies; Young Adult
PubMed: 33732252
DOI: 10.3389/fimmu.2021.631298 -
CVIR Endovascular 2018Intravesicular Bacillus Calmette-Guérin (BCG) is an effective adjunctive therapy for superficial bladder cancer that has been shown to delay recurrence and progression...
BACKGROUND
Intravesicular Bacillus Calmette-Guérin (BCG) is an effective adjunctive therapy for superficial bladder cancer that has been shown to delay recurrence and progression of disease. Serious side effects are relatively rare but are difficult to diagnose and are often overlooked. Vascular complications are particularly rare.
CASE PRESENTATION
We report two cases of mycotic aortic aneurysms secondary to BCG treatment, one managed with endovascular stent-graft placement and the other with open surgical repair. The present understanding of disseminated BCGosis, including a literature review, will be discussed.
CONCLUSION
The incidence of mycotic aneurysms from BCG treatment is rare and very few cases have been reported in the literature. These cases further expand the current knowledge on vascular complications related to BCG treatment. In the absence of formal guidelines, we recommend a multidisciplinary approach involving vascular surgery, diagnostic and interventional radiology, and infectious disease to manage these patients.
PubMed: 30652159
DOI: 10.1186/s42155-018-0036-y -
Asian Pacific Journal of Allergy and... Dec 2023Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency, caused by non-tuberculous mycobacteria or Bacillus Calmette-Guerin (BCG)... (Review)
Review
BACKGROUND
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency, caused by non-tuberculous mycobacteria or Bacillus Calmette-Guerin (BCG) vaccine and characterized by severe diseases in childhood.
OBJECTIVE
In this study, we examined eight years followed-up 12 Turkish children with genetically proven MSMD and we tried to evaluate the survival rate with succesfull disease management, rate of consanguinity, molecular, cellular and clinical features of patients. In addition, we wanted to emphasize the importance of early diagnosis before administration of BCG vaccine in countries where this vaccine is routinely used.
METHODS
Twelve patients diagnosed with molecular studies [IFNγR1 complete (n = 1), IFNγR2 partial (n = 3), IL12Rβ1 (n = 6), NEMO (n = 1), STAT1 mutation (n = 1)] were included.
RESULTS
Ten patients (83%) were born from consanguineous parents and frequency of family history for the primary immunodeficiency was 58% (n = 7). All the cases had been immunized with BCG vaccine (Mycobacterium bovis) due to lack of early diagnosis. Two patients had BCG-itis and four patients had "BCG-osis". Survival rate was 75% after successful disease management with antibiotics, anti-tuberculous agents and recombinant IFN-γ.
CONCLUSIONS
It was concluded that MSMD must be differentiated from different forms of primary immunodeficiencies, so clinicians should be aware of MSMD especially in patients with BCG vaccine complications and non-tuberculous mycobacterial infection.
Topics: Humans; Child; BCG Vaccine; Follow-Up Studies; Mycobacterium Infections; Mycobacterium bovis; Mutation; Genetic Predisposition to Disease
PubMed: 33638623
DOI: 10.12932/AP-271219-0726 -
Frontiers in Immunology 2021Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an...
Phenomic Analysis of Chronic Granulomatous Disease Reveals More Severe Integumentary Infections in X-Linked Compared With Autosomal Recessive Chronic Granulomatous Disease.
BACKGROUND
Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms.
METHODS
We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients.
RESULTS
XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. species, , and were the most frequent pathogens to be found.
CONCLUSION
Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.
Topics: Alleles; Disease Management; Female; Genes, Recessive; Genes, X-Linked; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Granulomatous Disease, Chronic; Humans; Infections; Male; Phenomics; Phenotype; Sequence Analysis, DNA
PubMed: 35140711
DOI: 10.3389/fimmu.2021.803763 -
Scandinavian Journal of Immunology May 2021World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The...
World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.
Topics: BCG Vaccine; Female; Granulomatous Disease, Chronic; Humans; India; Infant; Male; Mycobacterium tuberculosis; Severe Combined Immunodeficiency; Treatment Outcome; Tuberculosis, Pulmonary; Vaccination
PubMed: 33325540
DOI: 10.1111/sji.13010 -
Frontiers in Immunology 2019Disseminated Bacillus Calmette-Guérin disease (D-BCG) in children with chronic granulomatous disease (CGD) can be fatal, while its clinical characteristics remain... (Observational Study)
Observational Study
Disseminated Bacillus Calmette-Guérin disease (D-BCG) in children with chronic granulomatous disease (CGD) can be fatal, while its clinical characteristics remain unclear because both diseases are extremely rare. The patients with CGD receive BCG vaccination, because BCG vaccination is usually performed within 24 h after delivery in China. We prospectively followed-up Chinese patients with CGD who developed D-BCG to characterize their clinical and genetic characteristics. The diagnoses were based on the patients' clinical, genetic, and microbiological characteristics. Between September 2009 and September 2016, we identified 23 patients with CGD who developed D-BCG. Their overall 10-year survival rate was 34%. We created a simple dissemination score to evaluate the number of infected organ systems and the survival probabilities after 8 years were 62 and 17% among patients with simple dissemination scores of ≤3 and >3, respectively ( = 0.0424). Survival was not significantly associated with the CGD stimulation index or interferon-γ treatment. Eight patients underwent umbilical cord blood transplantation and 5 of them were successfully treated. The genetic analyses found mutations in (19 patients), (1 patient), (1 patient), and (1 patient). We identified 6 novel highly likely pathogenic mutations, including 4 mutations in and 2 mutations in . D-BCG is a deadly complication of CGD. The extent of BCG spreading is strongly associated with clinical outcomes, and hematopoietic stem cell transplantation may be a therapeutic option for this condition.
Topics: BCG Vaccine; Child; Child, Preschool; China; Female; Follow-Up Studies; Genetic Testing; Genotype; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Humans; Interferon-gamma; Kaplan-Meier Estimate; Male; Mutation; Mycobacterium bovis; NADPH Oxidase 2; NADPH Oxidases; Prospective Studies; Rhodamines; Survival Rate; Treatment Outcome; Tuberculosis; Vaccination
PubMed: 30761141
DOI: 10.3389/fimmu.2019.00073 -
Frontiers in Immunology 2017Primary immunodeficiency disorders (PIDs) render patients vulnerable to infection with a wide range of microorganisms and thus provide good models for the assessment of...
Primary immunodeficiency disorders (PIDs) render patients vulnerable to infection with a wide range of microorganisms and thus provide good models for the assessment of immune responses during infectious challenges. Priming of the immune system, especially in infancy, depends on different environmental exposures and medical practices. This may determine the timing and phenotype of clinical appearance of immune deficits as exemplified with early exposure to Bacillus Calmette-Guérin (BCG) vaccination and dissemination in combined immunodeficiencies. Varied phenotype expression poses a challenge to identification of the putative immune deficit. Without the availability of genomic diagnosis and data analysis resources and with limited capacity for functional definition of immune pathways, it is difficult to establish a definitive diagnosis and to decide on appropriate treatment. This study describes the use of exome sequencing to identify a homozygous recessive variant in , NIK, in a patient with combined immunodeficiency, disseminated BCG-osis, and paradoxically elevated lymphocytes. Laboratory testing confirmed hypogammaglobulinemia with normal CD19, but failed to confirm a definitive diagnosis for targeted treatment decisions. NIK is predicted to be deleterious and pathogenic by two prediction tools and is situated in a gene crucial for effective functioning of the non-canonical nuclear factor-kappa B signaling pathway. Functional analysis of NIK- versus NIK-transfected human embryonic kidney-293T cells showed that this mutation significantly affects the kinase activity of NIK leading to decreased levels of phosphorylated IkappaB kinase-alpha (IKKα), the target of NIK. BCG-stimulated RAW264.7 cells transfected with NIK also presented with reduced levels of phosphorylated IKKα, significantly increased p100 levels and significantly decreased p52 levels compared to cells transfected with NIK. Ideally, these experiments would have been conducted in patient-derived immune cells, but we were unable to source these cells from the patient. The functional analysis described in this paper supports previous illustrations of the importance of NIK in human immune responses and demonstrates the involvement of function-altering mutations in in PIDs. The genomic approach used for this patient demonstrates its value in the diagnosis of an unusual PID and as a tool for detecting rarer mutations to help guide treatment approaches.
PubMed: 29230214
DOI: 10.3389/fimmu.2017.01624