Diagnostic value of the reaction at the bacillus calmette-guérin vaccination site in kawasaki disease / Utilidade diagnóstica da reação do sítio de vacinação bacillus calmette-guérin na doença de kawasaki

ABSTRACT Objective: To describe the case of an infant - diagnosed with incomplete Kawasaki disease - who developed BCG scar reactivation. Case description: A 6-month-old patient was admitted to hospital with fever associated with ocular hyperemia, cervical lymphadenopathy, and hyperemic lips, and remained hospitalized for 12 days. The physical examination revealed an inflammatory reaction at the site of the BCG scar, leading to the diagnosis of incomplete Kawasaki disease. The patient was treated with venous immunoglobulin, but presented recurrence of Kawasaki disease, with subsequent onset of coronary artery disease. Comments: BCG scar reactivation is an important finding in countries where the vaccine is routinely given and may be a useful marker for early diagnosis of Kawasaki disease, especially in its incomplete form.

RESUMO Objetivo: Descrever o caso de um lactente - com diagnóstico de Doença de Kawasaki incompleta - que desenvolveu reativação da cicatriz da vacina BCG. Descrição do caso: Um paciente de 6 meses de idade foi admitido no hospital com febre, associada à hiperemia ocular, linfadenomegalia cervical e fissuras labiais, permanecendo hospitalizado por 12 dias. Apresentava, no exame físico, reação inflamatória no local da cicatriz da vacina BCG, tendo sido feito o diagnóstico de Kawasaki incompleto. O paciente foi tratado com imunoglobulina venosa, mas apresentou recorrência da doença, com posterior surgimento de coronariopatia. Comentários: A reativação da BCG é um achado importante na doença de Kawasaki em países onde a vacina é aplicada de forma rotineira e pode ser um marcador útil para o diagnóstico precoce da doença de Kawasaki, principalmente em sua forma incompleta.

Osteomielitis de tibia secundaria a la vacuna BCG en un paciente pediátrico inmunocompetente: Reporte de un caso / Tibia osteomyelitis secondary to BCG vaccination in an immunocompetent infant. Case report

Introducción: La vacuna BCG (bacilo de Calmette-Guérin) para prevenir las formas graves de tuberculosis, es la vacuna más difundida en el mundo. Los efectos adversos asociados a la vacunación son poco frecuentes, y la mayoría de ellos ocurren en el sitio de inoculación. Presentamos un caso de osteomielitis de tibia secundaria a la vacuna BCG en un paciente pediátrico inmunocompetente. Conclusiones: El compromiso óseo secundario a la vacuna BCG en pacientes previamente sanos es muy raro. Es importante sospecharlo, para diagnosticarlo y administrar el tratamiento adecuado. Se obtuvieron buenos resultados administrando fármacos antituberculosos, sin necesidad de limpieza quirúrgica. Nivel de Evidencia: IV

Introduction: The Bacillus Calmette-Guérin (BCG) vaccine, used to prevent severe forms of tuberculosis (TB), is the most extensively used vaccine worldwide. Adverse events associated with BCG vaccination are rare, and most of them occur at the inoculation site. We present a tibia Osteomyelitis case secondary to BCG vaccination in an immunocompetent infant. Conclusions: Bone involvement secondary to BCG vaccination in previously healthy patients is extremely rare. Healthcare providers must consider such settings in order to make the diagnosis and institute the appropriate treatment. Antituberculous drugs produced good therapeutic results with no need for surgical toilette. Level of Evidence: IV

Investigation of the frequency of COVID-19 in patients treated with intravesical BCG

SUMMARY INTRODUCTION In this retrospective study, we aimed to investigate the frequency of COVID-19 in patients with and without BCG application due to bladder tumors. METHODS The presence of COVID-19 was investigated in 167 patients with BCG and 167 without bladder cancer. All patients were compatible with COVID-19 infection. Patients with RT-PCR positive for SARS-CoV-2 and/or Chest CT positive for viral pneumonia between March and May 2020 were included in the study. RESULTS A total of 334 patients were included in the study. The mean age of the 167 patients in the study group was 71.1±14.2 1 (min. 38.0- max. 98.0 years), 141 (84.4%) were male. The mean age of the 167 patients in the control group was 70.5±13.8 years (min. 41.0- max. 96.0 years), and 149 were male (p> 0.05). COVID-19 was detected in 5 patients in the BCG group and in 4 patients in the control group (P> 0.05). CONCLUSION Intravesical BCG administration does not decrease the frequency of COVID-19 infection.

RESUMO INTRODUÇÃO Neste estudo retrospectivo, objetivou-se investigar a frequência de COVID-19 em pacientes com e sem aplicação de BCG por tumor de bexiga. MÉTODOS A presença de COVID-19 foi investigada em 167 pacientes com BCG e 167 sem câncer de bexiga. Todos os pacientes compatíveis para infecção por COVID-19. Resumidamente, os pacientes foram incluídos no estudo com RT-PCR positivo para Sars-CoV-2 e/ou TC de tórax positivo para pneumonia viral entre março e maio de 2020. RESULTADOS Um total de 334 pacientes foi incluído no estudo. A idade média dos 167 pacientes no grupo de estudo foi de 71,1±14,2 1 (min. 38,0 - máx. 98,0 anos), 141 (84,4%) eram do sexo masculino; 167 pacientes do grupo controle tinham idade média de 70,5±13,8 (min. 41,0 - máx. 96,0 anos) e 149 eram do sexo masculino (p>0,05). A COVID-19 foi detectada em cinco pacientes no grupo BCG e em um no grupo controle (p>0,05). CONCLUSÃO A administração intravesical de BCG não diminui a frequência da infecção por COVID-19.

Vacunación BCG e inmunodeficiencias primarias: ¿es momento de un cambio? / BCG vaccine administration schedule and primary immunodeficiencies: Is it time for a change?

Resumen: Los pacientes con Inmunodeficiencias primarias (IDP) tienen un riesgo elevado de complicaciones severas por la vacuna BCG, incluso mortalidad. Es necesario evaluar periódicamente el riesgo versus beneficio de la vacunación universal BCG en el periodo neonatal. Chile es un país con baja incidencia de tuberculosis (TB) pero cuya epidemiología ha cambiado recientemente con un aumento de los casos. Cambios en esquemas de vacunación BCG en países con incidencias mayores o similares de TB y con coberturas de vacunación menores han sido posibles sin aumento de los casos graves de TB que son los que previene la BCG. El cambio ha evitado complicaciones graves en pacientes con IDP. Creemos que un análisis crítico de la fecha de vacunación BCG debe realizarse hoy en Chile. Más aún dada la posibilidad técnica de realizar screening neonatal de IDP.

Abstract: Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.

Enfermedad por bacilo de Calmette-Guérin a distancia en un lactante: Presentación de un caso / Distant bacillus Calmette-Guérin disease in an infant: Case report

La vacuna con el bacilo de Calmette-Guérin es una vacuna atenuada utilizada para prevenir formas graves de tuberculosis. Se aplica a los recién nacidos en países con alta prevalencia de tuberculosis. Pueden presentarse, después de su aplicación, complicaciones a nivel local, como supuración o adenopatías regionales. La enfermedad por diseminación del bacilo es infrecuente y ocurre, por lo general, en pacientes con alteraciones inmunitarias subyacentes. Se presenta el caso de un niño de 5 meses que ingresó por un cuadro de 2 meses de evolución con detención del aumento de peso y nódulos subcutáneos. Se sospechó enfermedad por diseminación del bacilo y se diagnosticó por la biopsia de las lesiones. Se realizó el tratamiento con tres drogas antituberculosas, y se recuperó clínicamente. Si bien se realizaron estudios inmunológicos, no logró demostrarse ninguna inmunodeficiencia como afección predisponente.

The bacillus Calmette-Guérin vaccine is an attenuated vaccine historically used to prevent severe forms of tuberculosis. It is applied to all newborns in countries with high prevalence of tuberculosis. Local complications, such as suppuration or regional adenopathies, may occur after application. Disease due to the spread of the bacillus is infrequent, usually occurring in a patient with an underlying immune alteration. We present the case of a 5-month-old child who was admitted due to a 2-month evolution with weight loss and subcutaneous nodules. Disease was suspected to be due to bacillus Calmette-Guérin dissemination, being diagnosed by biopsy of the lesions. Treatment was carried out with three antituberculous drugs, evolving towards clinical recovery. Although immunological studies were carried out, no immunodeficiency could be demonstrated as a predisposing condition.

Tuberculosis cutánea a forma de lupus vulgar causada por vacuna de bacilo Calmette-Guérin. A propósito de un caso pediátrico / Lupus vulgaris as a form of cutaneous TB caused by the Bacille Calmette-Guérin vaccine. A pediatric case / Tuberculose cutânea sob forma de lúpus vulgar causada pela vacina de bacilo Calmette- Guérin. A propósito de um caso pediátrico

La tuberculosis cutánea es una enfermedad infecciosa crónica y poco frecuente ocasionada por Mycobacteriun tuberculosis. Existen varias formas de la infección cutánea, siendo el lupus vulgar la más frecuente y común en los países industrializados. Las variantes clínicas dependerán de la vía de llegada del bacilo a la piel, del estado inmunológico del paciente y del medio ambiente. En el lupus vulgar, además de M. tuberculosis puede estar implicado M. bovis y menos frecuentemente el bacilo de Calmette y Guérin. Esta entidad presenta una evolución crónica, es de carácter progresivo y es rara de ver en niños. Se presenta el caso de una niña en la cual se diagnosticó una forma de tuberculosis cutánea denominada lupus vulgar provocada por el bacilo de Calmette y Guérin. Caso clínico: niña de 10 años que presentaba lesiones cutáneas de diferentes características, de evolución tórpida y asintomáticas; la de mayor tamaño se localizaba en la cara externa del deltoides derecho en forma de placa eritematosa de 20 por 10 cm con bordes sobreelevados presentando en su centro micropápulas que coalescen dejando una zona de atrofia central. Esta había comenzado en etapa neonatal luego de la vacunación por el bacilo de Calmette y Guérin. Desde hacía tres años presentaba una segunda lesión más pequeña en cara externa de muslo derecho de similares características y otras de carácter múltiple en dorso con forma de micropápulas rojo vinosas. Los exámenes de valoración general fueron normales, al igual que la radiografía de tórax y de los miembros. El test de la tuberculina mostró una induración de 15 mm y las baciloscopias fueron negativas. La biopsia de la lesión de piel del deltoides mostró granulomas caseosos y las técnicas moleculares diagnosticaron Mycobacterium bovis atenuado. Con ese diagnóstico, recibió tratamiento antituberculoso por diez meses con buena tolerancia y con mejoría de las lesiones.

Cutaneous TB is a rather unusual chronic infectious disease caused by Mycobacteriun tuberculosis. There are several forms of cutaneous infection, lupus vulgaris being the most frequent and ordinary one in developed countries. Clinical variations will depend on the site of infiltration of the skin by the bacillus, the patient's immune condition and the environment. In the case of lupus vulgaris, apart from Mycobacteriun tuberculosis, M. bovis may be involved, and the Bacille Calmette Guérin involvement is less frequent. The latter presents a chronic evolution, being progressive and unusual in children. The study presents the case of a girl who was diagnosed with a form of cutaneous tuberculosis called lupus vulgaris caused by the Bacille Calmette-Guérin vaccine. Clinical case: a 10 year old girl who evidenced skin lesions of different kinds, of slow evolution and asymptomatic: the largest one was in the external part of the right deltoid muscle as an erythematous plaque of 20 by 10 cm with higher borders evidencing micro papules in the center that coalesce leaving a central atrophy zone. The latter had started in the neonatal stage after the Bacille Calmette-Guérin vaccine. For three years she had evidenced a second smaller lesion in the outer face of the right thigh of similar characteristics and other multiple lesions in the back with the shape of vinous red micro papules. Assessment tests were generally normal, as well as the chest and limbs X-ray. The tuberculin test evidenced a 15 mm induration and smears were negative. The deltoid muscle skin lesion biopsy showed caseous granulomas and molecular techniques diagnosed attenuated Mycobacteriumbovis. Given that diagnose the patient received anti-TB treatment during 10 months, tolerance being good and the lesions improved.

A tuberculose cutânea é uma doença infecciosa crônica e pouco frequente causada pelo Mycobacteriun tuberculosis. Existem várias formas de infecção cutânea, sendo o lúpus vulgar a mais frequente e comum nos países industrializados. As variantes clínicas dependerão da via de entrada do bacilo à pele, do estado imunológico do paciente e do ambiente. No lúpus vulgar, além do M. tuberculosis podem estar implicados o M. bovis e mais raramente o bacilo de Calmette-Guérin. Esta entidade apresenta uma evolução crônica, é progressiva e é rara em crianças. Apresenta-se o caso de uma paciente de sexo feminino com 10 anos que foi diagnosticada com uma forma de tuberculose cutânea denominada lúpus vulgar provocada pelo bacilo de Calmette-Guérin. Caso clínico: paciente de sexo feminino com 10 anos que apresentava lesões cutâneas de diferentes características, com evolução letárgica e assintomática; a maior lesão estava localizada na face externa do deltoide direito sob a forma de placa eritematosa de 20 x 10 cm com bordes sobrelevados apresentando no centro micropápulas que coalescem deixando una zona de atrofia central. Esta lesão começou na etapa neonatal depois da vacinação com o bacilo de Calmette-Guérin. Desde 3 anos apresentava uma segunda lesão menor na face externa da coxa direita com características similares e outras múltiplas no dorso com forma de micropápulas com coloração de manchas em vinho do Porto. Os exames de avaliação geral foram normais, bem como as radiografias de tórax e de membros. O teste da tuberculina mostrou uma induración de 15 mm e as baciloscopias foram negativas. A biopsia da lesão de pele dos deltoides mostrou granulomas caseosos e as técnicas moleculares diagnosticaram Mycobacterium bovis atenuado. Com esse diagnóstico recebeu tratamento antituberculoso por 10 meses com boa tolerância e melhoria das lesões.

Infección diseminada por Bacilo Calmette-Guérin en un lactante con inmunodeficiencia: reporte de caso / Disseminated infection by Bacillus Calmette-Guérin in an immunodeficient infant: case report

RESUMEN La vacuna Bacillus Calmette-Guerin (BCG) que se administra a los recién nacidos de países con alta incidencia de tuberculosis puede ocasionar reacciones locales hasta infección diseminada en pacientes inmunocomprometidos. Reportamos el caso de un lactante varón de seis meses con antecedente de haber recibido vacuna BCG al nacer, y presentar cuadros infecciosos a repetición, nódulos violáceos blandos en tronco y extremidades con presencia de bacilos ácido alcohol resistentes (BARR) en la histopatología y en cultivo de piel; el estudio molecular reportó la presencia de Micobacterium bovis BCG. En la tomografía se observó opacidades intersticiales en pulmones y en el lavado gástrico se identificó BAAR. El estudio genético del paciente y de la madre reveló la presencia de mutación en el gen IL2RG confirmando el diagnóstico de inmunodeficiencia combinada severa, recibe tratamiento con inmunoglubolina humana y esquema antituberculosis con isoniacida, rifampicina y etambutol. Presentamos el caso por la implicancia en el pronóstico de vida de estos pacientes y por la necesidad de un diagnóstico preciso y oportuno.

ABSTRACT The Bacillus Calmette-Guerin (BCG) vaccine given to newborns in countries with a high incidence of tuberculosis may cause local reactions up to disseminated infection in immunocompromised patients. We report the case of a six-monthold male infant with a history of having received the BCG vaccine at birth, and presenting repeated infectious, soft violet nodules in the trunk and extremities with the presence of acid-alcohol-resistant bacilli (BAAR) in histopathology and skin culture; the molecular study reported the presence of Mycobacterium bovis BCG. In the tomography, interstitial opacities were observed in the lungs and in the gastric lavage BAAR was identified. The genetic study of the patient and the mother revealed the presence of a mutation in the IL2RG gene confirming the diagnosis of severe combined immunodeficiency. Received treatment with human immunoglobulin and anti-tuberculosis scheme with isoniazid, rifampicin, and ethambutol. We present the case because of the implication in the life prognosis of these patients and because of the need for an accurate and timely diagnosis

BCG 1948 – 2014: la misma cepa? / BCG 1948 – 2014: is the same strain yet?

Tuberculosis remains a public health problem and its control is a global health priority. One of the most successful tools to control infectious diseases has been the use of vaccines. Bacille Calmette-Guérin is one of the oldest available vaccines used today, the only licensed against tuberculosis. It has been administered to billions of people, as part of national immunization programs around the world. Immunological mechanisms by which it induces protection are not fully understood, but a role in the innate immune system maturation and the activation of T CD4 + and CD8 +, have been considered. Its effectiveness in terms of pulmonary tuberculosis is variable and controversial but highly cost - efficient to control tuberculous meningitis and miliary dissemination. However, it has not been enough to solve the global problem of tuberculosis, especially in countries with high rates, so that scientific development aiming at getting a new vaccine remains active.

La tuberculosis sigue siendo un problema de salud pública mundial y su control es una prioridad de salud global. Una de las herramientas más exitosas que se han utilizado para controlar enfermedades infecciosas ha sido el uso de vacunas. El bacilo de Calmette-Guérin es una de las vacunas más antiguas disponibles utilizadas en la actualidad, la única licenciada contra tuberculosis. Ha sido administrada en miles de millones de personas, siendo parte de distintos programas de vacunación nacionales en el mundo. Los mecanismos inmunológicos por los cuales induce protección aún no son completamente comprendidos, planteándose un rol sobre la maduración del sistema inmune innato y activación de células T CD4+ y CD8+. Su eficacia respecto de tuberculosis pulmonar es variable y controvertida, pero altamente costo eficiente para controlar meningitis tuberculosa y diseminación miliar, sin embargo no ha sido suficiente para resolver el problema global de la tuberculosis, especialmente en los países con endemias más altas, por lo que el desarrollo científico en miras de obtener una nueva vacuna se mantiene vigente.

Cistectomia com reconstrução de neobexiga ortotópica ileal para tratamento de bexiga contraída após aplicação de bacilo de Calmette-Guérin intravesical / Cystectomy with orthotopic ileal neobladder reconstruction for treatment of bladder contracture after intravesical bacillus Calmette-Guerin therapy

O câncer de bexiga é um importante problema de saúde mundial, tanto pelas elevadas taxas de prevalência, quanto pelos custos relacionados ao tratamento. Desde a introdução da imunoterapia intravesical adjuvante com bacilo Calmette-Guérin, vem sendo observada diminuição na taxa de recorrência. As principais complicações são de pequeno porte e simples resolução a partir de medidas locais e orientações. A bexiga contraída, uma complicação local rara e grave, mas incapacitante em alguns casos, é observada principalmente em doentes com um programa de manutenção. Relatamos aqui o caso de um paciente masculino submetido a ressecção transuretral da bexiga por um carcinoma urotelial T1 de alto grau, que desenvolveu tal complicação durante tratamento com bacilo Calmette-Guérin, sendo portanto submetido à cistoprostatectomia com realização de neobexiga ortotópica ileal.

Bladder cancer is an important health problem worldwide due to high prevalence rates and costs related to treatment. A reduction in recurrence rates has been observed since the introduction of adjuvant intravesical immunotherapy with bacillus Calmette-Guerin. There are mild complications that are easily solved by local measures and orientations. Bladder contracture, a rare and severe local complication, in some cases leading to disability, is observed primarily in patients in a maintenance program. In this article we reported the case of a male patient who underwent transurethral resection of the bladder because of a high-grade T1 urothelial carcinoma and developed this complication during treatment with bacillus Calmette-Guerin. For this reason he was submitted to cystoprostatectomy with orthotopic ileal neobladder reconstruction.

Enfermedad por bacilo de Calmette-Guérin (BCG) y deficiencia del receptor β-1 de interleuquina 12: Experiencia clínica de dos casos en una familia y un caso aislado / Bacillus Calmette-Guérin (BCG) disease and interleukin 12 receptor β1 deficiency: Clinical experience of two familial and one sporadic case

BCG disease has been reported in primary and secondary immunodeficiency and as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Investigation of this syndrome has led to the identifications of a series of genetic, inherited defects in the IL-12/IFN-γ axis. MSMD-causing mutations have been found in seven autosomal and two X-linked genes. In these patients, local or disseminated vaccine BCG infections are common. We report a clinical series including two infants with left axillary adenitis ipsilateral to the site of neonatal BCG immunization; one of them member of a family with two previously reported cases and a single sporadic case. All of them were diagnosed sequentially in Puerto Montt, Chile. The aim of this report is to notify the first Chilean disseminated BCG patients without previous immunodeficiency, in whom it was possible to identify an underlying immunodeficiency, although specific tests for IL-12/IFN-γ axis was no performed in our country. Clinical suspicion and international collaboration permitted to confirm IL12-Rβ1 deficiency in 2 of 3 familial cases and a sporadic case.

La enfermedad por el bacilo de Calmette-Guérin (BCG) ha sido reportada en relación a inmunodeficiencias primarias, secundarias y en el síndrome clínico denominado susceptibilidad mendeliana a enfermedades micobacterianas. La investigación de este síndrome ha llevado a la identificación de defectos en el eje interleuquina (IL)- 12/ interferón gamma (IL-12/IFN-γ), habiéndose identificado hasta hoy mutaciones en siete genes autosómicos y dos ligados al cromosoma X. En estos pacientes, las infecciones localizadas o generalizadas por BCG vacunal son comunes. Reportamos una serie clínica constituida por dos lactantes con adenomegalia axilar izquierda recurrente secundaria a vacunación BCG al nacer; uno de ellos integrante de una familia con dos casos reportados previamente y un caso aislado, diagnosticados consecutivamente en Puerto Montt, Chile, con el objetivo de notificar los primeros casos chilenos de diseminación BCG en niños sin inmunodeficiencia previa conocida, en los que se logró identificar la deficiencia inmune subyacente pese a no disponer en el país del estudio específico del eje (IL-12/IFN-γ). La sospecha diagnóstica y colaboración internacional permitieron identificar en dos de los tres casos familiares y en el caso aislado, la deficiencia del receptor β1 de IL 12 (IL12Rβ1).

Linfadenitis por vacuna BCG / Lymphadenitis due to BCG

La linfadenitis secundaria a la vacunación con BCG (Bacilo Calmette Guérin) mal llamada becegeitis, es un proceso inflamatorio localizado provocado por el bacilo en ganglios linfáticos regionales. Se indica el uso de la ecografía como primer método de diagnóstico por imágenes.

Lymphadenitis caused by infection with an isoniazid- and rifampin-resistant strain of Mycobacterium bovis BCG in an infant with IFN-γ/IL-12 pathway defect / Linfadenite por Mycobacterium bovis BCG resistente a isoniazida e rifampicina em lactente com defeito no eixo IFN-γ/IL-12

We report a rare case in a female infant (age, 3.5 months) with primary immunodeficiency (IFN-γ/IL-12 pathway defect) who presented with suppurative lymphadenitis after Mycobacterium bovis BCG vaccination. The strain of M. bovis BCG identified was found to be resistant to isoniazid and rifampin. The patient was treated with a special pharmacological regimen involving isoniazid (in a limited, strategic manner), ethambutol, streptomycin, and IFN-γ, after which there was complete resolution of the lesions.

Relatamos um caso raro em uma lactente com três meses e meio de idade, portadora de imunodeficiência primária (defeito no eixo IFN-γ/IL-12), que apresentou linfadenite supurativa após a vacinação por Mycobacterium bovis BCG, cepa essa resistente a isoniazida e rifampicina. Após o tratamento com um esquema medicamentoso especial com isoniazida (de forma estratégica e limitada), etambutol, estreptomicina e IFN-γ, houve a cura completa das lesões.