RESUMEN
The immune system is composed of innate humoral defence and adaptive immunity. One of the key mechanisms of the innate humoral defence is through complement activation. Mutations of certain enzyme may affect the complement activation and result in decreased defence against microorganisms. Mannan-binding lectin serine protease 2 (MASP-2) mutation was associated with recurrent infections and autoimmune diseases. Tuberculosis (TB) has been linked with mannose-binding lectin and MASP-2 gene polymorphism. We report a case of a paediatric patient with MASP-2 deficiency with classical and atypical features associated with Crohn's, onychomycosis and severe cutaneous infections including TB. We also report the presence of a new mutation variant in MASP-2 reported in whole exome sequencing of our patient.
Asunto(s)
Enfermedad de Crohn/genética , Enfermedad de Crohn/microbiología , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/deficiencia , Onicomicosis/genética , Tuberculosis Cutánea/genética , Niño , Humanos , Masculino , Mutación , Onicomicosis/microbiología , Tuberculosis Cutánea/microbiologíaRESUMEN
Interferon-γ receptor-1 (IFNγR1) deficiency is caused by mutations in the IFNγR1 gene and is characterized mainly by susceptibility to mycobacterial disease. Herein, we report an 8-month-old boy with complete recessive IFNγR1 deficiency, afflicted by recurrent mycobacterial diseases with Mycobacterium bovis, Mycobacterium tuberculosis, Mycobacterium avium intracellulare and Mycobacterium fortuitum. Genetic analysis showed a homozygous mutation (106insT) in the IFNγR1 gene leading to complete IFNγR1 deficiency. In addition, he had atypical mycobacterial skin lesions caused by M. avium intracellulare and developed scrotal and lower limb lymphedema secondary to compression of large and fixed inguinal lymphadenopathies. Hematopoietic stem cell transplantation was performed from a matched unrelated donor at 5 years of age; however, he died at 9 months post-transplant. To our knowledge, the patient is the first case with IL-12/IFN-γ pathway defect and severe lymphedema. We have also reviewed and summarized the literature related with IFNγR1 deficiency.
Asunto(s)
Granuloma/inmunología , Hipergammaglobulinemia/inmunología , Linfedema/inmunología , Infección por Mycobacterium avium-intracellulare/inmunología , Mycobacterium/inmunología , Receptores de Interferón/genética , Tuberculosis Cutánea/inmunología , Niño , Preescolar , Consanguinidad , Análisis Mutacional de ADN , Resultado Fatal , Granuloma/genética , Granuloma/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Hipergammaglobulinemia/genética , Hipergammaglobulinemia/terapia , Lactante , Extremidad Inferior/patología , Linfedema/genética , Linfedema/terapia , Masculino , Infección por Mycobacterium avium-intracellulare/genética , Infección por Mycobacterium avium-intracellulare/terapia , Linaje , Escroto/patología , Eliminación de Secuencia/genética , Tuberculosis Cutánea/genética , Tuberculosis Cutánea/terapia , Receptor de Interferón gammaRESUMEN
The non-specific clinical findings and variable histopathological features of cutaneous tuberculosis and non-tuberculous mycobacterial infections often make it difficult to establish a diagnosis and initiate appropriate therapy. We investigated 25 patients diagnosed with mycobacterial infections of the skin in Hanyang University Hospital between 2001 and 2011. Skin biopsy specimens were re-evaluated by various histopathological criteria and molecular studies. To identify the mycobacteria, we performed staining for acid-fast bacilli and also completed polymerase chain reaction analysis. The non-tuberculous mycobacterium species were identified by genetic sequencing of formalin-fixed, paraffin-embedded tissues. Immunocompromised status was more frequent in non-tuberculous mycobacterial infections than in tuberculosis (p = 0.017) while disease duration was longer in tuberculosis (p = 0.026). Microscopically, neutrophil infiltration, interstitial granuloma, small vessel proliferation and increased numbers of bacilli were found to be associated with non-tuberculous mycobacterial infections (all p < 0.05). In contrast, giant cells, plasma cells, tuberculoid granulomas and necrosis were associated with tuberculosis (all p < 0.05). There were no species-specific histopathological findings in non-tuberculous mycobacterial infections. The significant histopathological differences between cutaneous tuberculous and non-tuberculous mycobacterial infections are helpful in considering differential diagnoses. In addition, molecular techniques together with clinico-pathological findings may assist in making accurate diagnoses of cutaneous non-tuberculous mycobacterial infections.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas/patología , Tuberculosis Cutánea/patología , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Granuloma de Células Gigantes/microbiología , Granuloma de Células Gigantes/patología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/genética , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infiltración Neutrófila , Micobacterias no Tuberculosas/genética , Células Plasmáticas/patología , Reacción en Cadena de la Polimerasa/métodos , Estudios Retrospectivos , Tuberculosis Cutánea/genética , Tuberculosis Cutánea/microbiologíaRESUMEN
Acute primary cutaneous leishmaniasis typically presents microscopically with a lymphohistiocytic infiltrate containing admixed plasma cells, parasitized macrophages and abundant organisms. Tuberculoid granulomatous changes may occur in the later phases of primary infection. A 23-year-old male presented 1 month after visiting Peru with classic clinical findings of acute primary cutaneous leishmaniasis, while histopathology showed a tuberculoid granulomatous process that lacked any organisms in hematoxylin-eosin and fungal stains. Polymerase chain reaction (PCR) analysis and tissue cultures confirmed the diagnosis of cutaneous leishmaniasis with Leishmania (Viannia) panamensis infection. A pauci-organism tuberculoid granulomatous process may uncommonly be the presenting histopathology in the acute infectious phase of cutaneous leishmaniasis. Clinicians and dermatopathologists should be aware of this atypical presentation, which may cause diagnostic confusion and delay proper treatment. PCR testing should be employed in cases with high clinical suspicion when histopathology is not definitive.
Asunto(s)
Dermatitis , Granuloma , Leishmania guyanensis/genética , Leishmaniasis Mucocutánea , Reacción en Cadena de la Polimerasa , Tuberculosis Cutánea , Adulto , Dermatitis/genética , Dermatitis/parasitología , Dermatitis/patología , Diagnóstico Diferencial , Granuloma/genética , Granuloma/parasitología , Granuloma/patología , Humanos , Leishmaniasis Mucocutánea/genética , Leishmaniasis Mucocutánea/parasitología , Leishmaniasis Mucocutánea/patología , Masculino , Perú , Tuberculosis Cutánea/genética , Tuberculosis Cutánea/parasitología , Tuberculosis Cutánea/patologíaRESUMEN
BACKGROUND: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Interacciones Huésped-Patógeno/genética , Enfermedades Cutáneas Infecciosas/genética , Histoplasmosis/genética , Humanos , Leishmania/genética , Leishmaniasis/genética , Lepra/genética , Mycobacterium leprae/genética , Paracoccidioidomicosis/genética , Factores de Riesgo , Sífilis Cutánea/genética , Tuberculosis Cutánea/genéticaRESUMEN
BACKGROUND: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection.
INTRODUÇÃO: Durante a era pré-microbiológica, era comum a visão de que doenças, hoje sabidamente infecciosas, eram hereditárias. Com a descoberta dos microorganismos e seu papel na patogênese de diversas patologias, chegou-se a propor que a exposição ao patógeno era condição suficiente para explicar infecção. Hoje, está claro que infecção é o resultado de uma complexa interação entre patógeno e hospedeiro, dependendo portanto, em última análise, do make-up genético de ambos os organismos. A dermatologia oferece diversos exemplos de doenças infecciosas em diferentes graus de entendimento de suas bases moleculares. Nesta revisão, resumimos os principais avanços na direção da dissecção do componente genético controlando suscetibilidade do ser humano a doenças infecciosas de importância na dermatologia. Doenças amplamente estudadas, como a hanseníase e a leishmaniose, são discutidas sob o ponto de vista da genética tanto do hospedeiro quanto do patógeno. Outras, como micobacterioses raras, micoses e sífilis, são apresentadas como boas oportunidades para pesquisa na área de genética de infecção.
Asunto(s)
Humanos , Predisposición Genética a la Enfermedad/genética , Interacciones Huésped-Patógeno/genética , Enfermedades Cutáneas Infecciosas/genética , Histoplasmosis/genética , Leishmania/genética , Leishmaniasis/genética , Lepra/genética , Mycobacterium leprae/genética , Paracoccidioidomicosis/genética , Factores de Riesgo , Sífilis Cutánea/genética , Tuberculosis Cutánea/genéticaAsunto(s)
Tuberculosis Cutánea , Adulto , Humanos , Ganglios Linfáticos , Masculino , Cuello , Tuberculosis Cutánea/genéticaRESUMEN
BACKGROUND: Most cutaneous tuberculosis lesions contain few bacilli, so identification of Mycobacterium tuberculosis in conventional laboratory tests is difficult. In vitro amplification of specific DNA sequences using polymerase chain reaction (PCR) has become a valuable tool in the rapid detection of slow-growing organisms like M. tuberculosis. AIM: To investigate the presence of M. tuberculosis DNA in cutaneous tuberculosis. METHODS: Twenty-two archival biopsy specimens diagnosed as cutaneous tuberculosis were investigated for the presence of M. tuberculosis DNA by PCR. Normal skin samples of 29 healthy patients were used as a control. RESULTS: Amplification of the M. tuberculosis DNA was observed in one of the cutaneous tuberculosis specimens and in a healthy control. CONCLUSION: Although PCR is a rapid diagnostic method, fixation procedures may decrease its sensitivity.
Asunto(s)
Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Adhesión en Parafina , Reacción en Cadena de la Polimerasa , Tuberculosis Cutánea/genética , Tuberculosis Cutánea/microbiología , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The objective of this study was to explore the role of the polymerase chain reaction (PCR) fo the detection of Mycobacterium tuberculosis DNA as a diagnostic aid in cutaneous tuberculosis using routinely processed skin biopsy specimens. METHODS AND RESULTS: A wide range of clinical specimens representing different forms of cutaneous tuberculosis and so-called tuberculids were studied. A sensitive and specific PCR assay targeting the sequence IS6110 of Mycobacterium tuberculosis complex was used. The specimens were categorized as follows. 1 Acid-fast bacilli (AFB) positive on biopsy (nine specimens from seven patients who were immunocompromised). PCR was positive in five specimens. Of these, one specimen was culture positive and three specimens were culture negative. 2 AFB negative on biopsy: (a) tuberculosis verrucosa cutis (23 specimens); (b) lupus vulgaris (three specimens); (c) cutaneous tuberculosis clinically suspected (six specimens). PCR was negative in all specimens. 3 Tuberculids.' (a) erythema induratum/nodular vasculitis (20 specimens); (b) papulonecrotic tuberculid (two specimens); (c) erythema nodosum (20 specimens). PCR was negative in all specimens. CONCLUSIONS: The role of PCR in clinical dermatologic practice, at this stage, may be in differentiating between cutaneous tuberculosis and atypical mycobacterial infections in the context of an immunocompromised patient where AFB can be demonstrated on biopsy and cultures may be negative. In this clinical situation, PCR allows the prompt diagnosis and early institution of appropriate therapy. We have not found PCR to be a useful complement to the clinical and histologic diagnosis of "paucibacillary" forms of cutaneous tuberculosis.
Asunto(s)
ADN Bacteriano/análisis , Mycobacterium tuberculosis/genética , Tuberculosis Cutánea/genética , Adulto , Anciano , ADN Bacteriano/genética , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Piel/metabolismo , Piel/microbiología , Piel/patología , Tuberculosis Cutánea/microbiología , Tuberculosis Cutánea/patologíaRESUMEN
Families with multiple cases of leprosy were tested for HLA (histocompatibility leukocyte antigen)-linked control of susceptibility to tuberculoid leprosy and association with HLA-DR2. Thirty-one non-HLA genetic markers were also examined for indications of non-HLA-linked genetic factors that might control susceptibility to tuberculoid leprosy. A significant (P = 0.002) preferential inheritance of HLA-DR2 by siblings affected with tuberculoid leprosy, but not by healthy siblings nor by siblings affected with lepromatous leprosy, was observed. In addition, combined family data showed a significant (P less than 0.0025) excess of identical HLA haplotypes inherited from healthy parents by siblings affected with tuberculoid leprosy. Segregation on non-HLA polymorphisms did not deviate significantly from what would have occured randomly. These data are compatible with a recessive inheritance of HLA-linked susceptibility to tuberculoid leprosy. The preferential segregation of DR2 observed in children with tuberculoid leprosy (P less than 0.001 for the combined data from India) indicates that the HLA-linked susceptibility gene is either DR2 or in linkage disequilibrium with it.