Sarcoidosis cutánea. Presentación de un caso

La sarcoidosis es una enfermedad granulomatosa sistémica de causa desconocida, con mayor prevalencia en el sexo femenino, entre los 20 a 40 años de edad; caracterizada por la formación de granulomas no caseificantes en distintos órganos. La afectación cutánea de forma exclusiva es rara, pues se describe solo en el 4-5 % de los pacientes, ya que las lesiones en piel pueden aparecer antes o después del compromiso sistémico, o bien coincidir con este. Se presenta el caso de una paciente de 35 años con lesiones en piel de cuatro años de evolución. Considerando el cuadro clínico y la histopatología, se concluyó con el diagnóstico de sarcoidosis cutánea, crónica y asintomática. Se trata de una enfermedad muy polimorfa en sus manifestaciones cutáneas, lo cual la convierte en una gran simuladora, y su diagnóstico constituye un reto para el dermatólogo.

Sarcoidosis is a systemic granulomatous disease of unknown cause, with a higher prevalence in females, between 20 and 40 years of age; characterized by the formation of non-caseating granulomas in different organs. Exclusive skin involvement is rare, as it is described in only 4-5% of patients, since skin lesions may appear before or after systemic involvement, or coincide with it. The case of a 35-years-old patient with skin lesions of four years of evolution is presented. Considering the clinical case and histopathology, the diagnosis of chronic and asymptomatic cutaneous sarcoidosis was concluded. It is a very polymorphic disease in its skin manifestations, which makes it a great simulator, and its diagnosis constitutes a challenge for the dermatologist.

Case for diagnosis. Eyelid edema and erythematous papules disseminated on the face

Abstract Lupus miliaris disseminatus faciei or acne agminata is a chronic inflammatory disorder of the skin, considered an intriguing entity due to its pathogenesis, which is still largely speculative. It has been linked to tuberculosis, sarcoidosis, rosacea, and other granulomatous diseases, but it is considered an independent entity.

Cutaneous sarcoidosis: clinico-epidemiological profile of 72 patients at a tertiary hospital in São Paulo, Brazil,

Abstract Background: Sarcoidosis is a multisystem disease of unknown cause that is characterized by the presence of granulomas in various organs. Cutaneous involvement is common and the reported incidence has varied from 9% to 37%. Studies on cutaneous sarcoidosis in Brazil are lacking. Objectives: To describe the clinical and epidemiological aspects of patients with cutaneous sarcoidosis diagnosed at the Department of Dermatology of the University of São Paulo, from May 1994 to March 2018. Methods: Clinical data of patients with confirmed cutaneous sarcoidosis were retrospectively reviewed and classified according to gender, ethnicity, age at diagnosis, cutaneous presentation, systemic involvement and treatment. Results: Cutaneous sarcoidosis was diagnosed in 72 patients with a female predominance (74%). The mean age at diagnosis was 49.6 years and most of the patients were white (61%). Papules and plaques were the most common lesions. Systemic sarcoidosis was detected in 81% of patients, affecting mainly the lungs and thoracic lymph nodes (97%). Typically, cutaneous lesions were the first manifestation (74%). Systemic therapy was necessary for 72% of patients; the dermatologist managed many of these cases. Oral glucocorticoids were the most commonly used systemic medication (92%). The mean number of systemic drugs used was 1.98 per patient. Limitations: Insufficient data in medical records. Conclusions: This series highlights the dermatologist role in recognizing and diagnosing cutaneous sarcoidosis, evaluating patients for systemic disease involvement and treating the skin manifestations. Cutaneous sarcoidosis was once considered exceedingly infrequent in Brazil in comparison to infectious granulomatous diseases; however, the present series seems to suggest that the disease is not so rare in this region.

Actinomicosis renal en adolescente inmunocomprometido / Renal actinomycosis in immune compromised teenager

RESUMEN Fundamento: la actinomicosis es una enfermedad granulomatosa crónica poco común. El compromiso renal es raro y el diagnóstico suele ser posterior a la nefrectomía. Objetivo: presentar el caso de un adolescente con actinomicosis renal. Caso clínico: adolescente femenina, raza blanca, 13 años de edad, con antecedentes de asma bronquial e inmunocomprometida. Hace seis meses ingresó en el Hospital Pediátrico Eduardo Agramonte Piña de Camagüey debido a amigdalitis pultácea y se le indicó tratamiento antimicrobiano con una evolución favorable. Hace una semana comenzó con fiebre de 39 grados centígrados, vómitos, toma del estado general y dolor lumbar derecho por lo que reingresa para diagnóstico y tratamiento. Conclusiones: dado que la actinomicosis renal se presenta como una lesión sólida que invade estructuras vecinas es confundida con frecuencia con enfermedades neoplásicas. Menos del 10 % de los casos son diagnosticados antes de la cirugía, las pruebas complementarias son de escaso valor diagnóstico. El diagnóstico definitivo se basa en la identificación histológica o en cultivos en medios anaerobios del Actinomyces.

ABSTRACT Background: actinomycosis is a rare chronic granulomatous disease. Renal involvement is rare and the diagnosis is usually after nephrectomy. Objective: to present a case suffering from renal actinomycosis in a teenage patient. Clinical Case: caucasian, female, 13-years-old adolescent, who has a previous history of Bronchial Asthma and also immunocompromised. Six months ago she was admitted in the Pediatric Hospital Eduardo Agramonte Piña of Camagüey suffering from Tonsillitis and antimicrobial treatment was imposed with a favorable outcome. A week ago she started with 39 degrees fever, vomiting, general condition and right back lower pain. She was admitted in the Pediatric Hospital again to achieve a proper diagnosis and treatment. Conclusions: given that Renal Actinomycosis presents as a solid lesion that invades neighboring structures, the usual behavior is frequently confused with neoplastic conditions. Less than 10% of cases are diagnosed before surgery, with complementary tests of little diagnostic value. The definitive diagnosis is based on the histological identification or cultures in anaerobic media of Actinomyces.

A case report of neonatal-onset chronic granulomatosis disease with aspergillus infection and literature review / 中国新生儿科杂志

Objective To study the clinical features,diagnosis,treatment and genetic characteristics of chronic granulomatosis disease (CGD) in neonates,and to improve the understanding of CGD.Method Clinical manifestations and treatments of one patient with CGD and aspergillus infection in our hospital were analyzed.Key words including "infant","newborn","chronic granulomatous disease","lung abscess",and "aspergillus infection"were searched in Chinese medical databases,PubMed and Embase until 2018 September.The clinical features and genetic mutations of CGD reported in literature were summarized.Result The patient in our hospital was a full-term male infant naturally delivered with birth weight of 3 400 g.The onset of the disease was on the 19th day after birth,and the initial clinical manifestations included fever,cough,and then pulmonary abscess,diarrhea,recurrent skin infection,and aspergillus infection.Anti-infection and symptom-alleviating treatments were not effective,and weight gain was poor.Laboratory examination indicated bacterial and fungal infection.The neutrophil respiratory burst test was positive and indicated CGD.Hetero-zygotic frameshift mutation [c.1599-1602delAGTTt (p.V534Sfs* 12)] of CYBB gene 13 exon was detected and the diagnosis of CGD was confirmed.The mother carried the heterozygous mutation and the father didn't.Antifungal therapy was continued after the children got better and discharged from hospital.The patient was followed up until 3-month-old and his condition was stable.Our literature review revealed 28 reports including 108 cases of CGD infants,including 79 male cases (73.1％) and 21 female cases (19.4％).Most of the CGD infants (79/108,73.1％) had the onset within 2 weeks of life.The main clinical features included pneumonia/pulmonary abscess/pleural effusion (87.0％),diarrhea (58.3％),perianal abscess (35.2％),skin infection (53.7％),aspergillus infection (41.7％),and tuberculosis infection (26.9％).75 cases had positive neutrophil respiratory burst test (69.4％),and 95 cases were diagnosed using genetic tests (88.0％).Over 300 loci of the CYBB gene mutation had been reported contributing to the disease.28 cases had abnormal family history (25.9％),19 cases received hematopoietic stem cell transplantation (17.6％),41 cases had clinical improvement (38.0％),and 35 cases died (32.4％).Conclusion CGD is rare in neonatal period.The main clinical manifestations included recurrent infection with pathogens like aspergillus,tuberculosis and others.CGD can be diagnosed based on recurrent multiple bacterial or fungal infections,neutrophil respiratory burst test and gene tests.CGD should be considered among children with recurrent infections at early life stage,especially those with poor maternal history or positive family history.

Malacoplaquia renal. Presentación de caso / Renal Malakoplakia. Case report

Introducción: La malacoplaquia es una enfermedad granulomatosa multisistémica crónica caracterizada por una o múltiples placas blancas en varios órganos del cuerpo, precedida por alguna infección crónica bacteriana. En la mayoría de los casos estudiados se encuentra que la E. Coli contribuye en aproximadamente el 80 % de ellos. Objetivo: Dar a conocer la existencia de esta enfermedad y sus características mediante una revisión de tema, y exponer un caso de malacoplaquia renal en una mujer de 65 años de edad con múltiples comorbilidades asociadas a dicha entidad; se describe la utilización de los métodos diagnósticos, así como su desenlace. Discusión: La malacoplaquia es una patología que se encuentra frecuentemente en el tejido urinario, a pesar de que puede desarrollarse en otros órganos. Su etiopatología no ha sido totalmente explicada; sin embargo, se asume que se da por un defecto en la actividad fagolisosomal, al parecer por alteración en la concentración de guanosín monofosfato cíclico intracelular (cGMP) en macrófagos y monocitos. Los pacientes que cursan con esta patología pueden ser asintomáticos o presentar síntomas inespecíficos. Conclusión: La malacoplaquia es una entidad que, aunque poco frecuente en la población general, debe tenerse en cuenta cuando existe compromiso uni o multifocal del parénquima renal en pacientes con factores de riesgo. Las imágenes pueden no ser concluyentes y hacer sospechar patología tumoral; sin embargo, el estudio histopatológico de la muestra permite un diagnóstico definitivo, lo cual les da la oportunidad a los pacientes de recibir manejo oportuno con excelentes resultados.

Introduction: Malakoplakia is a chronic multisystemic granulomatous disease characterized by the presence of one or multiple white plaques in various organs of the body, preceded by some chronic bacterial infection. In most reported cases it is found that E. coli contributes in approximately 80% of cases. Objective: The objective of this article is to show a case report of this disease and its characteristics through a review of the subject. We present a case of renal Malakoplakia in a 65-year-old woman with multiple comorbidities associated with this entity. We emphasize on the use of the diagnostic methods, as well as the outcome. Discussion: Malakoplakia is a pathology that is usually found in the urinary tissue, although it may develop in other organs. Its cause has not been fully explained and it is assumed to be due to a defect in phagolysosome activity, apparently by alteration in the concentration of intracellular cyclic guanosine monophosphate (Cgmp) in macrophages and monocytes. Patients with this pathology may be asymptomatic or have non-specific symptoms. Conclusion: Malakoplakia is an entity that although rare in the general population should be taken into account when there is uni or multifocal involvement of the renal parenchyma in patients with the potential risk where the role of imaging is to provide a first work-up of the extension, with the final work-up taking place through histopathological studies, giving patients the opportunity to receive timely treatment with excellent results.

Case for diagnosis. Metastatic Crohn's disease

Abstract: Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin.

Reconstitución inmune exitosa mediante trasplante de células madre hematopoyéticas en un paciente colombiano afectado con enfermedad granulomatosa crónica / Successful immune reconstitution by means of hematopoietic stem cell transplantation in a Colombian patient with chronic granulomatous disease

Introducción. La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en los genes que codifican para las proteínas del sistema de la oxidasa de NADPH ( Nicotinamide Adenine Dinucleotide Phosphate ) de las células fagocíticas, las cuales afectan la producción de especies reactivas del oxígeno y la actividad microbicida. Actualmente, la única terapia curativa para esta enfermedad es la reconstitución inmune mediante el trasplante de células madre hematopoyéticas. Objetivo. Reportar la caracterización clínica y molecular de un paciente con enfermedad granulomatosa crónica ligada al cromosoma X y su reconstitución inmunitaria exitosa mediante el trasplante de células madre hematopoyéticas. Materiales y métodos. El estallido respiratorio en neutrófilos de sangre periférica se midió por citometría de flujo mediante la prueba de oxidación de la dihidrorrodamina 123 (DHR 123). El análisis de las mutaciones del gen CYBB se hizo mediante reacción en cadena de la polimerasa (PCR) en el ADN complementario y la secuenciación e hibridación genómica comparativa en el ADN genómico. En el trasplante se emplearon células madre del hermano menor con HLA idéntico, y previamente se hizo un acondicionamiento de intensidad reducida. La reconstitución inmunitaria después del trasplante se evaluó periódicamente con hemoleucogramas y la prueba DHR 123 en neutrófilos de sangre periférica. Resultados. El diagnóstico de la enfermedad granulomatosa crónica ligada al cromosoma X se estableció como resultado de una deleción hemicigota en la banda Xp21.1 que implicó la deleción completa del CYBB . La toma de injerto postrasplante para plaquetas y neutrófilos fue en los días 10 y 11, respectivamente. En el día 30 después del trasplante se logró la reconstitución hematológica completa y en los tres años siguientes no se observaron complicaciones ni infecciones. Conclusión. El trasplante de células madre hematopoyéticas permite la reconstitución completa de la función inmunitaria relacionada con la actividad microbicida de las células fagocíticas de pacientes con enfermedad granulomatosa crónica ligada al cromosoma X.

Introduction: Chronic granulomatous disease is a primary immunodeficiency that results from mutations in proteins of the NADPH oxidase system that affect the microbicidal activity of phagocytes. Immune reconstitution by hematopoietic stem cell transplantation is currently the only curative therapy for this disease. Objective: To describe the clinical and molecular characterization of a patient with X-linked chronic granulomatous disease and the successful immune reconstitution by means of a hematopoietic stem cell transplantation. Materials and methods: The respiratory burst was measured by flow cytometry using the dihydrorodamine 123 (DHR) oxidation test in neutrophils of peripheral blood. Mutational analysis of CYBB was performed by PCR amplification in complementary DNA, as well as sequencing and comparative genomic hybridization in genomic DNA. HLA-identical stem cells from the patient´s younger brother were used for the transplantation and reduced intensity pre-transplantation conditioning was administered. Post-transplantation immune reconstitution was evaluated periodically by serial complete blood counts and DHR 123 in peripheral blood neutrophils. Results: The diagnosis of X-linked chronic granulomatous disease resulted from a hemizygous deletion affecting Xp21.1 that included the entire CYBB . Post-transplantation engraftment was documented in platelets and peripheral blood neutrophils at days 10 and 11, respectively. Total hematological reconstitution was achieved by day 30 post-transplantation and no complications or infections have been observed in the three years since the transplantation. Conclusion: Hemopoietic stem cell transplantation allows for total reconstitution of the immune function related to microbicidal activity of phagocytic cells from patients with X-linked chronic granulomatous disease.

Botriomicose cutânea - relato de caso em Minas Gerais, Brasil / Skin botryomycosis - case report in Minas Gerais, Brazil

Botriomicose é doença infecciosa crônica granulomatosa e supurativa causada por bactérias Gram-positivas e Gram-negativas que formam grãos pseudomicóticos. As lesões cutâneas sãoplacas e tumores multinodulares com ulceração e formação de fístulas que podem eliminar grãos. A infecção acomete a pele, com possível disseminação para vísceras. É doença relativamente rara e seu diagnóstico pode ser alcançado por meio de biópsia das lesões e culturados grânulos nas secreções positivas para cocos Gram-positivos ou Gram-negativos. Esta descrição apresenta a botriomicose cutânea em brasileiro causada por Staphylococcus aureus.

Botryomycosis is a chronic infectious suppurative and granulomatous disease caused by Gram-positive and Gram-negative bacteria that form pseudo mycotic grains. The skin lesions are plaques and multinodular tumors with ulceration and formation of fistulae thatcan eliminate grains. The infection affects the skin, with possible dissemination to viscerae. It is relatively rare, and its diagnosis can be achieved through the biopsy of lesions and culture of granules from positive Gram-positive and Gram-negative cocci secretions. This description shows a case of skin botryomycosis in Brazil caused by Staphylococcus aureus.

Musculoskeletal and cutaneous sarcoidosis: exuberant case report

Sarcoidosis is a multisystem granulomatous disease of unknown cause. The osteoarticular involvement in sarcoidosis is rare and is often associated with cutaneous and long-standing chronic multisystem disease. More common in black women, osseous sarcoidosis is difficult to diagnose, with an incidence of 3 to 13%. The most characteristic radiological clinical picture evidences rounded, well-defined cysts, with no periosteal reaction and without peripheral sclerosis. The small bones of hands and feet are the most frequently involved sites. This report aims to demonstrate a rare case of osteoarticular sarcoidosis with characteristic clinical presentation, and highlight the importance of detecting osteoarticular involvement in this pathology.

Autoimmune thyroiditis presenting as interstitial granulomatous dermatitis / Dermatite intersticial granulomatosa como apresentação de tireoidite autoimune

A 54-year-old female presented with recurrent, widespread, erythematous, painful plaques, over a 3-month period. Skin biopsy was compatible with interstitial granulomatous dermatitis. Additional investigation revealed hypothyroidism and positive anti-thyroid antibodies. Normalization of thyroid function and high-potency topical corticosteroids provided only transitory improvement of the dermatosis. Interstitial granulomatous dermatitis is a histologic inflammatory reaction, with variable cutaneous expression. It has been reported in association with several drugs, lymphoproliferative diseases and autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus and vasculitis, but association with autoimmune thyroiditis is rare. Optimal therapy for this condition is yet to be established, but topical corticosteroids have been a mainstay of treatment. In most cases, this disease is characterized by flares and remissions.

Uma doente de 54 anos foi avaliada por placas eritematosas, dolorosas, disseminadas, recorrentes, com 3 meses de evolução. A biopsia cutânea foi compatível com dermatite intersticial granulomatosa. Os restantes exames laboratoriais revelaram hipotiroidismo e anticorpos anti-tiroideus positivos. Apesar da normalização da função tiroideia e de tratamento com corticóide tópico de alta potência, a dermatose melhorou apenas parcialmente. Dermatite intersticial inflamatória é um diagnóstico histopatológico, com expressão clínica variável. Tem sido associada a vários fármacos, doenças linfoproliferativas e autoimunes, nomeadamente artrite reumatóide, lupus eritematoso sistémico e vasculites, mas a associação com tireoidite autoimune é rara. Até ao momento, não foi definido nenhum tratamento específico, mas os corticóides tópicos são dos fármacos mais utilizados. A doença caracteriza-se por períodos de agravamento e remissão.

Imunofenotipagem e remodelamento da matriz extracelular na sarcoidose pulmonar e extrapulmonar / Immunophenotyping and extracellular matrix remodeling in pulmonary and extrapulmonary sarcoidosis

OBJETIVO: Investigar o significado de marcadores de imunidade celular e de componentes elásticos/colágeno da matriz extracelular em estruturas granulomatosas em biópsias de pacientes com sarcoidose pulmonar ou extrapulmonar. MÉTODOS: Determinações qualitativas e quantitativas de células inflamatórias, de fibras de colágeno e de fibras elásticas em estruturas granulomatosas em biópsias cirúrgicas de 40 pacientes com sarcoidose pulmonar e extrapulmonar foram realizadas por histomorfometria, imuno-histoquímica, e técnicas de coloração com picrosirius e resorcina-fucsina de Weigert. RESULTADOS: A densidade de linfócitos, macrófagos e neutrófilos nas biópsias extrapulmonares foi significativamente maior do que nas biópsias pulmonares. Os granulomas pulmonares apresentaram uma quantidade significativamente maior de fibras de colágeno e menor densidade de fibras elásticas que os granulomas extrapulmonares. A quantidade de macrófagos nos granulomas pulmonares correlacionou-se com CVF (p < 0,05), ao passo que as quantidades de linfócitos CD3+, CD4+ e CD8+ correlacionaram-se com a relação VEF1/CVF e com CV. Houve correlações negativas entre CPT e contagem de células CD1a+ (p < 0,05) e entre DLCO e densidade de fibras colágenas/elásticas (r = -0,90; p = 0,04). CONCLUSÕES: A imunofenotipagem e o remodelamento apresentaram características diferentes nas biópsias dos pacientes com sarcoidose pulmonar e extrapulmonar. Essas diferenças correlacionaram-se com os dados clínicos e espirométricos dos pacientes, sugerindo que há duas vias envolvidas no mecanismo de depuração de antígenos, que foi mais eficaz nos pulmões e linfonodos.

OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Doença de Jorge Lobo de localização labial exclusiva / Jorge Lobo's disease with restricted labial presentation

Doença de Jorge Lobo (DJL) é infecção granulomatosa cutânea crônica produzida pelo fungo Lacazia loboi, cujas lesões mais típicas têm aspecto queloidiano, com localizações preferenciais em membros e orelhas. As lesões restringem-se à pele, havendo apenas uma referência, do conhecimento dos autores, à localização em semimucosa labial. Apresenta-se caso de doença de Jorge Lobo em paciente masculino, com lesão papulonodular no vermelhão do lábio superior, à esquerda, de dez anos de evolução, exitosamente submetida a tratamento cirúrgico, sem recidiva após oito anos.

Jorge Lobo's Disease (JLD) is a chronic granulomatous cutaneous mycosis caused by Lacazia loboi. The most typical lesions are keloid-like growths preferentially located on limbs and ears. To the best of the authors' knowledge, only one labial case has previously been reported. We describe the case of a man who presented with a left-sided papulonodular lesion of 10 years' duration on the vermillion border of the upper lip. A successful surgical resection of the lesion was performed and there was no recurrence in eight years of follow-up.

Doença granulomatosa crônica: diagnóstico no primeiro episódio infeccioso / Chronic granulomatous disease: diagnosis on the first infection episode

OBJETIVO: Relatar caso ilustrativo de doença granulomatosa crônica cujo diagnóstico ocorreu durante o aparecimento do primeiro episódio infeccioso, colaborando com a iniciativa do Brazilian Group for Immunodeficiency para a sensibilização do pediatra geral em relação ao diagnóstico precoce das imunodeficiências primárias, o que está associado a melhor qualidade de vida e maior sobrevida desses indivíduos. DESCRIÇÃO DE CASO: Paciente do sexo masculino, 39 dias de vida, admitido em pronto-socorro pediátrico por febre alta há cinco dias e irritabilidade. No dia seguinte, observou-se abscesso cervical, isolando-se Staphylococcus aureus comunitário. Durante a internação, ocorreram outros abscessos superficiais e em cadeias ganglionares profundas, além de resposta lenta aos antimicrobianos. Solicitou-se investigação para imunodeficiências, que confirmou a hipótese de doença granulomatosa crônica por quantificação dos ânions superóxido e teste de redução do nitrobluetetrazolio. Paciente foi encaminhado a serviço especializado, no qual identificou-se doador de medula óssea compatível, realizando-se o transplante seis meses após o diagnóstico. Quatro meses após o transplante, ocorreu normalização do burst oxidativo, indicando sucesso. COMENTÁRIOS: O paciente mostrou apresentação típica da doença, o que permitiu seu diagnóstico por pediatras gerais já na primeira infecção, tendo como consequência o acompanhamento por especialistas em imunodeficiências primárias, a introdução da profilaxia antimicrobiana e a procura bem sucedida de doador de medula HLA-compatível.

OBJECTIVE: To report a case of chronic granulomatous disease diagnosed during the first infectious episode in order to collaborate with the Brazilian Group for Immunodeficiency, in sensitizing the general pediatrician that the early diagnosis of primary immunodeficiency results in better quality of life and longer life expectancy for the patients. CASE DESCRIPTION: Male patient, 39 days, admitted to the pediatric emergency ward with fever for the last five days and irritability. On the following day, a cervical abscess was noted and a community Staphylococcus aureus was isolated. During hospital stay, other abscesses were observed in the skin and in the deep ganglia chains, with a slow response to antibiotics. Investigation of immunodeficiency was requested and chronic granulomatous disease was confirmed by quantification of superoxide anions and nitrobluetetrazolium tests. The patient was transferred to a specialized clinic for bone marrow transplantation, performed six months after diagnosis. Four months afterwards, the normalization of oxidative burst was noted, indecating the success of the transplantation. COMMENTS: The patient showed a typical presentation of the disease, which allowed its diagnosis by general pediatricians on the first infection, allowing the follow-up by experts in primary immunodeficiencies, the introduction of antimicrobial chemoprophylaxis, and the successful search for an HLA-compatible bone marrow donor.

Comparison of Various Detection Methods of Mycobacterium Species in Formalin-Fixed Paraffin-Embedded Tissue with Chronic Granulomatous Inflammation

BACKGROUND: To determine the most effective method for detecting mycobacteria in formalin- fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR). METHODS: We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpobeta were done. RQ-PCR with the IS6110/Rpobeta primer was done in 51 cases. RESULTS: Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpobeta (73.3%). Specificity was higher in all PCR experiments (79.5-82.1%) than in RQ-PCR (69.4%) experiments. The false negative rate was lowest for RQ-PCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpobeta (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpobeta (20.5%). CONCLUSIONS: RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.

Genetic Analysis of 10 Unrelated Korean Families with p22-phox-deficient Chronic Granulomatous Disease: An Unusually Identical Mutation of the CYBA Gene on Jeju Island, Korea

Chronic granulomatous disease (CGD) is a rare hereditary disorder characterized by recurrent life-threatening bacterial and fungal infections. The underlying defect in CGD is an inability of phagocytes to produce reactive oxygen species as a result of defects in NADPH oxidase. Considering that CGD generally affects about 3-4 in 1,000,000 individuals, it is surprising that the prevalence of CGD on Jeju Island is 20.7 in 1,000,000 individuals. We performed genetic analysis on 12 patients from 10 unrelated families and found that all patients had an identical homozygous single-base substitution of C to T in exon 1 (c.7C>T) of the CYBA gene, which was expected to result in a nonsense mutation (p.Q3X). Because Jeju Island has long been a geologically isolated region, the high prevalence of CGD on Jeju Island is presumably associated with an identical mutation inherited from a common ancestor or proband.

Lacaziose (doença de Jorge Lobo): revisão e atualização / Lacaziosis (Jorge Lobo’s disease): review and update

Lacaziose ou doença de Jorge Lobo é micose crônica, granulomatosa, causada por implantação traumática do fungo Lacazia loboi - patógeno não cultivável até o presente - nos tecidos cutâneo e subcutâneo, manifestando-se clinicamente por lesões nodulares queloidianas predominantes, envolvendo sobretudo pavilhões auriculares, face, membros superiores e inferiores, e não comprometendo as mucosas. A maioria dos casos humanos está registrada em países da América do Sul. Entretanto, a enfermidade apresenta aspectos epidemiológicos destacados, como o aparecimento em tribo Caiabi, no Brasil Central e em mamíferos não humanos, golfinhos de duas espécies (Tursiops truncatus e Sotalia guianensis) capturados na costa da Flórida (EUA), na foz do rio Suriname, na costa de Santa Catarina (Brasil), no golfo de Gasconha (baía de Biscaia-Europa), com manifestações cutâneas e achados histopatológicos muito similares às encontradas no homem. O artigo objetiva abordar características do fungo e sua taxonomia, e aspectos históricos, ecoepidemiológicos, clínicos, imuno-histoquímicos, histopatológicos, ultra-estruturais e terapêuticos.

Lacaziosis, also known as Jorge Lobo’s disease, lobomycosis and keloidal blastomycosis, is a chronic cutaneous and subcutaneous fungal granulomatous disease, caused by Lacazia loboi - an uncultivated fungal pathogen - characterized by the development of nodular keloidal lesions, particularly on the pinnae, face, upper and lower limbs, and with no involvement of mucous membranes. Most cases in humans were reported in South America, including the Caiabi Indians, in Central Brazil. The disease was described in non-human mammals, such as two species of dolphins (Tursiops truncatus and Sotalia guianensis) inhabiting the coasts of Florida (USA), South America (Suriname River estuary, Santa Catarina-Brazil coast) and Gulf of Gascony (Biscaya Bay, in Europe). The histopathological findings in dolphins were very similar to those observed in humans. The aspects related to the history, etiology, epidemiology and ecology, clinical manifestations, differential diagnosis, immunohistochemistry, pathology, ultrastructural, laboratory diagnosis and therapy of lacaziosis, are presented.

Molecular Analysis of X-linked Chronic Granulomatous Disease in Five Unrelated Korean Patients

Chronic granulomatous disease (CGD) is a fatal genetic disorder in which phagocytes fail to produce antimicrobial superoxide because of NADPH oxidase deficiency. Molecular defects in CYBB gene causing X-linked CGD are responsible for about 70% of all cases. This study was done to confirm genetic defects of CYBB gene in five Korean patients who were highly suggestive of having CGD by clinical history. We performed initial screening for five unrelated Korean patients using single strand conformation polymorphism (SSCP) and then selective sequencing for the regions involving the abnormal bands. Activated NBT tests revealed that all patients were X-linked. SSCP analysis for CYBB gene showed abnormal bands in all patients. The molecular defects of five patients were as follows: c.1663insT, c.1111-1G>T, c.39_40insG, c.927delC and c.434T>C mutation. This result will help the families with prenatal diagnosis or genetic counseling.

Idiopathic Hypertrophic Spinal Pachymeningitis: A Case Report

Idiopathic hypertrophic pachymeningitis (IHP) is a rare, chronic nonspecific and granulomatous inflammatory disorder of the dura with unknown etiology. The diagnosis can be established by open biopsy and exclusion of all other specific granulomatous and infectious diseases. We report a typical case of spinal IHP occurring in a long segment of cervical and thoracic dura from C6 to T8. The patient was 56-yr-old female, who had been suffered from pain on her upper back and both arms for 3 months and recent onset motor weakness of both legs. During the 9 months of follow-up period, she experienced the improvement of her neurologic symptoms with combined therapy of partial excision and corticosteroid medication. Since early surgical intervention and subsequent pulse ste-roid therapy are mandatory for this disease to avoid irreversible damage of nervous system, the identification of this unique disease entity is essential on frozen diagnosis. A few cases have been reported in Korean literature.