Periprosthetic joint infection (PJI) can present challenges in diagnosis and treatment, particularly in the setting of atypical causative organisms such as fungi and mycobacteria. Herein, we present a case and provide a review of the diagnosis and treatment of an unusual PJI caused by bacillus Calmette-Guérin, administered during the treatment of bladder cancer 3 years prior to total knee arthroplasty and subsequent PJI. Although the patient\'s history of bladder cancer was known, neither his Bacillus Calmette-Guérin treatment nor its potential for distant site spread that could lead to PJI were appreciated, leading to a prolonged diagnostic evaluation and treatment course.

Bacillus Calmette-Guierin (BCG) vaccination complications are common in inborn errors of immunity (IEI) due to the inability to clear live attenuated Mycobacterium bovis. Various BCG-vaccine strains are used worldwide, and the profile of the Russian BCG strain vaccine complications in IEI is poorly characterized.
To evaluate risks of BCG infection in a large cohort of patients with IEI vaccinated with the Russian BCG strain.
We evaluated 778 patients with IEI vaccinated with the Russian BCG strain.
A total of 114 (15%) developed BCG infection, 41 (36%) with local, 19 (17%) with regional, and 54 with (47%) disseminated disease. BCG infection was seen in 58% of the patients with severe combined immunodeficiency (SCID), 82% with chronic granulomatous disease, 50% with innate immune defects, 5% with combined immunodeficiency, and 2% with other IEI. BCG infection presented at a median age of 4 to 5 months in SCID, chronic granulomatous disease, combined immunodeficiency, and other IEI groups versus 12 months in patients with innate immune defects (P < .005). We found no influence of specific genetic defects, CD3+ and natural killer cell numbers in SCID, or dihydrorhodamine test stimulation index values in chronic granulomatous disease on the BCG-infection risks. All patients with SCID received antimycobacterial therapy at SCID diagnosis even in the absence of active BCG infection. More antimycobacterial agents were required in disseminated relative to local or regional infection (P < .0001). Only 1 of 114 patients (with SCID) died of BCG-related complications (<1%).
BCG infection is common in patients with IEI receiving BCG vaccination. Rational early antimycobacterial therapy, combined with anticytokine agents for posttransplant inflammatory syndrome prevention, and treatment in SCID may prevent BCG-related mortality.

Intra-vesical instillations with bacillus Calmette-Guerin (BCG) are the established adjuvant therapy for superficial bladder cancer. Although generally safe and well tolerated, they may cause a range of different, local, and systemic complications. We present a patient treated with BCG instillations for three years, who was admitted to our hospital due to fever, hemoptysis, pleuritic chest pain and progressive dyspnea. Chest computed tomography (CT) showed massive bilateral ground glass opacities, partly consolidated, localized in the middle and lower parts of the lungs, bronchial walls thickening, and bilateral hilar lymphadenopathy. PCR tests for SARS-CoV-2 as well as sputum, blood, and urine for general bacteriology-were negative. Initial empiric antibiotic therapy was ineffective and respiratory failure progressed. After a few weeks, a culture of M. tuberculosis complex was obtained from the patient\'s specimens; the cultured strain was identified as Mycobacterium bovis BCG. Anti-tuberculous treatment with rifampin (RMP), isoniazid (INH) and ethambutol (EMB) was implemented together with systemic corticosteroids, resulting in the quick improvement of the patient\'s clinical condition. Due to hepatotoxicity and finally reported resistance of the BCG strain to INH, levofloxacin was used instead of INH with good tolerance. Follow-up CT scans showed partial resolution of the pulmonary infiltrates. BCG infection in the lungs must be taken into consideration in every patient treated with intra-vesical BCG instillations and symptoms of protracted infection.

BCG infections occur more frequently in patients with underlying primary immunodeficiency disease (PIDD). In this study, we aimed to evaluate the ratio of PIDD in the patients with BCG infections. Patients with BCG infections were analyzed in a tertiary referral centre in the 2015-2020 period. Forty-seven patients with BCGitis/BCGosis were evaluated; thirty-four (72.3%) had BCGitis, and 13 (27.7%) had BCGosis. Common tissue and organs affected are lymph nodes (57.4%), skin and subcutaneous tissue (48.9%), lungs (23.4%) and liver (17%). PIDD was shown in 26 patients (55.3%), including 92.3% of patients with BCGosis and 41.2% of patients with BCGitis. Ten patients had Mendelian susceptibility to Mycobacterial disease (MSMD) (21.2%), six had predominantly antibody deficiency (PAD) (12.7%), five had severe combined immunodeficiency (SCID) (10.6%), three had CGD (6.3%), and two had CID (4.2%). Mortality was reported in two patients (4.2%) with CID (ZAP70 deficiency (n = 1) and PIK3R1 deficiency (n = 1)). Parental consanguinity (84%), axillary lymphadenopathy (65%), mycobacterial lung disease (42%), hepatomegaly (30%) and growth retardation (19%) were significantly high in patients with PIDD diagnosis. Isolated vaccination site infection was also recorded in patients with PIDD (CID (n = 1), SCID (n = 1), PAD (n = 5)). BCG vaccination should be planned with caution for the cases with suspected PIDD. This study indicates that almost all patients (92.3%) with BCGosis and one in every two patients (41.2%) with BCGitis have an underlying PIDD. Parental consanguinity, axillary lymphadenopathy, mycobacterial lung disease, hepatomegaly and growth retardation (19%) are important clinical features in the differential diagnosis of PIDD.

Chronic granulomatous disease (CGD) is an inborn error of immunity that affects the functionality of phagocytosis; specifically, there\'s lack of production of oxygen-free radicals by NADPH oxidase. CGD manifests as severe and recurring bacterial and fungal infections, as well as local and systemic hyperinflammation. In countries where tuberculosis is endemic and the BCG vaccine is mandatory at birth, patients with CGD may present local or systemic reactions to this vaccine as first manifestation; besides, recurrent infections by M. tuberculosis may be present throughout their life. The susceptibility of these patients to mycobacteria is due to the excessive production of pro-inflammatory cytokines and the formation of granulomas that are inefficient in containing mycobacteria. In developed countries, patients with CGD do not present this type of infectious manifestations, except for migrants who come from developing countries. In this review, we present the characteristics of infections by BCG, M. tuberculosis, and other types of mycobacteria. Interestingly, there are no guidelines regarding anti-tuberculosis treatments in patients with CGD, so we propose the realization of a consensus by experts in order to establish guidelines for the treatment of mycobacterial disease in CGD.
La enfermedad granulomatosa crónica (ECG) es un error innato de la inmunidad que afecta la funcionalidad de la fagocitosis, específicamente hay una falta de producción de radicales libres de oxígeno por la NADPH oxidasa. La EGC se manifiesta con infecciones bacterianas y fúngicas, recurrentes y graves e hiperinflamación local y sistémica. En países en donde la tuberculosis es endémica y la vacuna BCG es obligatoria al nacer, los pacientes con EGC pueden presentar como primera manifestación las reacciones locales o sistémicas a esta vacuna y además a lo largo de su vida infecciones recurrentes por M. tuberculosis. La susceptibilidad de estos pacientes a micobacterias es debida a la producción excesiva de citocinas proinflamatorias y la formación de granulomas ineficientes en la contención de la micobacteria. En los países desarrollados, los pacientes con EGC no presentan este tipo de manifestaciones infecciosas, salvo los migrantes de países en desarrollo. En esta revisión, presentamos las características de las infecciones por BCG, M. tuberculosis y otras micobacterias. Interesantemente no existen lineamientos en cuanto a los tratamientos antituberculosos en pacientes con EGC, por lo que proponemos realizar un consenso por expertos para establecer lineamientos para el tratamiento de la enfermedad por micobacterias en EGC.

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.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects patients younger than 5 years. In the absence of an available, affordable diagnostic test, detailed clinical history and physical examination are still fundamental to make a diagnosis.
METHODS: We present five representative cases with KD-like presentations: systemic onset juvenile idiopathic arthritis, mycoplasma-induced rash and mucositis, staphylococcal scalded skin syndrome, BCGosis, and the recently described multisystemic inflammatory syndrome in children (MIS-C) associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus.
RESULTS: Rash, fever, and laboratory markers of inflammation can be present in several childhood diseases that may mimic KD.
CONCLUSIONS: The term \'Kawasaki syndrome\' instead of \'Kawasaki disease\' may be more appropriate. Physicians should consider an alternative diagnosis that may mimic KD, particularly considering MIS-C during the present pandemic, as an aggressive diagnostic and therapeutic approach is needed.

BACKGROUND: Bacille Calmette-Guerin (BCG) vaccination has a great impact on the prevention of severe complications of tuberculosis. However, in patients with primary immunodeficiencies (PID), it can lead to severe complications such as severe combined immunodeficiency, chronic granulomatous disease, and Mendelian susceptibility to mycobacterial disease. This study highlights the demographics, clinical complications and laboratory parameters among PID patients associated with BCG vaccination side effects.
METHODS: One hundred and thirty-seven PID patients with BCGosis were evaluated in this study, based on the complications following BCG vaccination.
RESULTS: The mean age of the patients with BCG complications at the time of the first visit was five years. The within-group comparison of patients showed a highly significant incidence of pneumonia and hepatomegaly in severe combined immunodeficiency patients. Furthermore, the immunologic data showed an increase in the overall rates of lymphocytes such as CD3+, CD4+ and CD8 + T cells in Mendelian susceptibility to mycobacterial disease patients. The level of immunoglobulins has also increased in chronic granulomatous disease patients.
CONCLUSIONS: The high rate of undiagnosed PIDs predisposes individuals to a high risk of severe side effects as a result of BCG vaccination, as well as infants that are less than one month of age. Therefore, there is a need for early screening and diagnosis of PIDs before exposing unknown PID status patients to BCG vaccination. The benefits of screening and early diagnosis of PID cannot be overemphasized, especially in patients with a previous family history of immunodeficiency.

Intra-vesical Bacillus Calmette-Guérin (BCG) immunotherapy is an effective treatment for high-risk bladder cancer. Less well known is that fewer than 1% of patients receiving BCG treatment can develop disseminated BCG. The reaction can range from a mild flu-like illness to a systemic disorder with a fulminant course which in the most severe cases can lead to death. The diagnostic yield is low and diagnosis is often made after a comprehensive exclusion of more common causes of pyrexia of unknown origin. A high level of suspicion is therefore required in those who may be at risk. We report a case of disseminated BCG in an older patient for whom early involvement of his family was pertinent to determining the precipitant for delirium.

BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs).
METHODS: A 15-year retrospective review was conducted in KK Women\'s and Children\'s Hospital in Singapore, from January 2003 to October 2017.
RESULTS: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%.
CONCLUSIONS: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.