Association between erythema nodosum/erythema induratum of Bazin and Mycobacterium tuberculosis infection in Koreans

Background: Erythema nodosum and erythema induratum of Bazin are similar inflammatory diseases of the lower extremities. These are clinically distinguishable entities, though overlap can occur. Both diseases are reported to be related to Mycobacterium tuberculosis infection, but it is very difficult to identify Mycobacterium tuberculosis in skin lesions. Aim: This study aimed to develop a new nested polymerase chain reaction targeting the IS6110 insertion sequence of M. tuberculosis to improve the M. tuberculosis detection rate in skin lesions of erythema nodosum or erythema induratum of Bazin. Methods: From May 2016 to Jan 2018, 14 patients with clinically suspicious erythema nodosum or erythema induratum were enrolled in the study. Two cases were classified as erythema nodosum and 12 as erythema induratum. Individual patients were subjected to a 4-mm punch biopsy, and their venous whole blood was sampled immediately after diagnosis. Results: Eight patients were tested for M. tuberculosis using QuantiFERON, of which seven (87.5%) were positive. IS6110-nested polymerase chain reaction on all 14 patients identified 11 (78.6%) positive cases. Four of the eight (50%) individuals tested with QuantiFERON were also positive in the IS6110 nested polymerase chain reaction. The difference between the outcomes of the QuantiFERON and the IS6110-nested polymerase chain reaction tests was not statistically significant. There was also no significant agreement between the results of both assays. Sequencing the IS6110-nested polymerase chain reaction products showed a 97%–100% nucleotide sequence identity with the H37Rv genome. Conclusion: It is important to test for tuberculosis in patients with multiple tender subcutaneous nodules on their lower extremities in high-burden tuberculosis countries like Korea. Limitations: We need to register more suspicious patients to verify the association between erythema nodosum/erythema induratum of Bazin and M. tuberculosis. Furthermore, it is neces

Unusual recurrent skin lesions: Bazin's disease

A 46 year old Iraqi Kurd female patient was presented with recurrent round erythematous skin lesions on her upper and lower extremities mainly calves, lower abdomen, and buttock for 3 years. Routine laboratory investigations were unremarkable; however, based on strongly positive tuberculin skin test, positive interferon gamma release assay, histo-pathological findings and a response to anti-TB treatment, she was diagnosed with Erythem Induratum of Bazin (EIB). The patient was treated successfully with combination anti-TB drugs. The skin lesions disappeared after 2 months of the treatment. There was no recurrence of the lesions over a 6 month follow up period.

Relato da ocorrência simultânea de escrofuloderma, eritema indurado de Bazin e tuberculide pápulo-necrótica em paciente imunocompetente / Report of simultaneous occurrence of scrofuloderma, Bazin's indurated erythema and papulonecrotic tuberculid on an immunocompetent patient

Modelo do estudo: relato de caso Importância do problema: A tuberculose é um grave problema de saúde no nosso país, no entanto poucos profissionais sabem identificar as formas extrapulmonares da doença, que são responsáveis por 23,3% dos óbitos por tuberculose no Brasil. Das formas extra-pulmonares, apenas 1-2% representam formas cutâneas. É importante que o médico generalista conheça as formas cutâneas de tuberculose, uma vez que pode ser a única manifestação da doença. O seu diagnóstico é um desafio, pois os exames tradicionais têm menor sensibilidade e especificidade para a apresentação cutânea em relação à forma pulmonar. No entanto, novos exames vêm sendo implantados como o GeneXpert. Comentários: Relatamos um caso raro de tuberculose cutânea em paciente imunocompetente, com a manifestação de três formas clínicas simultaneamente ­ escrofuloderma, tubercúlide papulonecrótica e eritema indurado de Bazin. A ocorrência de duas formas simultâneas é descrita na literatura mas a ocorrência de três formas simultâneas é inédita. Essa manifestação atípica foi de difícil diagnóstico clínico por simular outras doenças e os exames tradicionais como o RX de tórax, baciloscopia e cultura não evidenciaram o diagnóstico. A identificação do Mycobacterium tuberculosis só foi possível por meio da pesquisa de PCR com o GeneXpert, que mostrou positividade no escarro pulmonar e no exsudato do escrofuloderma, possibilitando iniciar o tratamento precocemente. Este novo exame de alta sensibilidade e especificidade no diagnóstico da tuberculose pulmonar mostrou-se de grande utilidade no diagnóstico deste caso atípico de tuberculose cutânea onde os exames tradicionais não definiram o diagnóstico. (AU)

Study: Case Report Importance: Tuberculosis is a serious health problem in Brazil. Nevertheless, only few physicians know how to identify the non-pulmonary cases of this disease, which can represent up to 23,3% of deaths caused by tuberculosis in Brazil. Among the non-pulmonary cases, only 1-2% affect the skin. It is important for the general physician to understand the cutaneous presentations of tuberculosis, once it can be the only symptom that the patient presents. Diagnosing cutaneous tuberculosis is a challenge, because traditional laboratory tests have smaller sensitivity and specificity for the cutaneous form in contrast to pulmonary tuberculosis. However, implementation of new exams such as GeneXpert may come in hand. Comments: We report a rare case of cutaneous tuberculosis on an immunocompetent patient, with three different simultaneous presentations - scrofuloderma, papulonecrotic tuberculids and Bazin's indurated erythema. Occurrence of two simultaneous presentations has been reported, however, three simultaneous forms have not. Diagnosing this atypical manifestation was very hard because the clinical presentation often mimics other dermatological conditions, and traditional laboratory testing such as chest X-ray, bacilloscopy and culture did not evidence infection. Identification of Mycobacterium tuberculosis was only possible due to positive PCR testing through GeneXpert on pulmonary and scrofuloderma fluids, allowing rapid treatment initiation. This new high sensitivity and specificity exam proved to be of great value when diagnosing this atypical cutaneous tuberculosis case, in which diagnose was not possible through traditional laboratory testing. (AU)

A Case of Drastically Aggravated Erythema Induratum due to Co-existing Peripheral Arterial Occlusive Disease / 대한피부과학회지

A 72-year-old woman presented with recurrent painful erythematous nodules and ulcers on both legs. Latent tuberculosis was proven by a positive interferon-gamma release assay, and a histopathology examination revealed septolobular panniculitis with vasculitis. The initial diagnosis was erythema induratum associated with tuberculosis, but the leg ulcers became worse despite anti-tuberculosis medication and wound dressing. Computed tomography angiography showed occlusion of the superficial femoral and popliteal arteries bilaterally, supporting that the vascular event contributes to the ulcers according to the vascular territories. Under the diagnosis of peripheral arterial occlusive disease, she was treated with percutaneous transluminal angioplasty and antiplatelet medication. The skin ulcers were resolved. Elderly patients with erythema induratum have a risk of coincidental peripheral arterial occlusive disease, therefore dermatologists should be aware of the possibility of underlying vascular disease, so even minor trauma like skin biopsy can evoke serious condition shown in this patient. Here, we report a case of drastically aggravated erythema induratum due to co-existing peripheral arterial occlusive disease, which resolved with vascular intervention after not responding to antituberculosis medication.

Update on cutaneous tuberculosis

Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction.

Cutaneous tuberculosis: diagnosis, histopathology and treatment - Part II

The evolution in the knowledge of tuberculosis' physiopathology allowed not only a better understanding of the immunological factors involved in the disease process, but also the development of new laboratory tests, as well as the establishment of a histological classification that reflects the host's ability to contain the infectious agent. At the same time, the increasing bacilli resistance led to alterations in the basic tuberculosis treatment scheme in 2009. This article critically examines laboratory and histological investigations, treatment regimens for tuberculosis and possible adverse reactions to the most frequently used drugs.

Eritema indurado de Bazin-vasculitis nodular / Erythema induratum of Bazin-nodular vasculitis

Comunicamos un caso de eritema indurado de Bazin-vasculitis nodular en una mujer de 22 años, con una reacción fuertemente positiva al test de la tuberculina, lesiones ulceradas y una buena respuesta a la terapia anti tuberculosa hasta el momento. Se discute la ubicación nosológica de esta entidad y se enfatiza sobre la necesidad de una biopsia amplia adecuada.

A 22-old woman with an erythema induratum de Bazin-nodular vasculitis was reported, the tuberculin test was strongly positive measuring 17 mm of diameter. The patient had indolent ulcerated lesions, the therapy with four anti-tuberculous drugs results effective until now. The existence of the entity as unique or not as well the need of a wide biopsy is discussed.

Eritema indurado de Bazin: uma manifestação de tuberculose cutânea / Erythema induratum of Bazin: a manifestation of cutaneous tuberculosis

O eritema indurado de Bazin caracteriza-se por nódulos nas extremidades inferiores, as quais podem apresentar úlceras e cicatrizes atrófi cas. Esse tipo de paniculite apresenta associação bem estabelecida com tuberculose, mas casos idiopáticos ou induzidos por outros agentes infecciosos podem ocorrer. Neste estudo, nosso objetivo foi relatar o caso de um paciente de 15 anos com derivado proteico purifi cado da cultura de Mycobacterium tuberculosis fortemente reator e apresentação clínica e histopatológica típica dessa forma de tuberculose cutânea.

The erythema induratum of Bazin is characterized by nodules in the lower extremities, which may have ulcers and atrophic scars. This type of panniculitis presents well-established association with tuberculosis, but idiopathic cases or induced by other infectious agents may happen. In this study, our aim was to report the case of 15-year-old patient with highly reactive purifi ed protein derivative of Mycobacterium tuberculosis culture and typical clinical and histopathological presentation of this form of cutaneous tuberculosis.

Cutaneous tuberculosis: epidemiologic, etiopathogenic and clinical aspects - Part I

Cutaneous tuberculosis (CTB) is the result of a chronic infection by Mycobacterium tuberculosis, M. ovis and occasionally by the Calmette-Guerin bacillus. The clinical manifestations are variable and depend on the interaction of several factors including the site of infection and the host's immunity. This article revises the current knowledge about this disease's physiopathology and immunology as well as detailing the possible clinical presentations.

Eritema indurado de Bazin asociado a infección por Mycobacterium tuberculosis / Erythema induratum of Bazin associated to Mycobacterium tuberculosis infection

El eritema indurado de Bazin es poco frecuente en la edad pediátrica. Presentamos el caso de una niña de 12 años procedente de China remitida para estudio por sospecha de eritema nudoso de larga evolución y prueba de tuberculina positiva (20 mm). La paciente no presentaba otros síntomas. En la exploración física se observaban nódulos violáceos, localizados en ambas regiones pretibiales, pero también en ambas pantorrillas. La radiografía de tórax fue normal. Se obtuvo muestra para biopsia, que mostró una paniculitis de predominio lobulillar con presencia de granulomas. La detección de micobacterias mediante cultivo y reacción en cadena de la polimerasa en la muestra fue negativa. Se aisló Mycobacterium tuberculosis en una de tres muestras de jugo gástrico. Se trató con isoniacida, rifampicina, pirazinamida y etambutol con curación de las lesiones. Este caso resalta la importancia de sospechar eritema indurado en las formas atípicas de eritema nudoso y de investigar exhaustivamente la existencia de una tuberculosis activa en estos casos.

Erythema induratum of Bazin is uncommon in children. We report the case of a 12 year-old girl from China, referred by her pediatrician with long lasting lesions of erythema nodosum and a positive tuberculin skin test (20 mm). She had no other symptoms. Physical examination showed purple nodular lesions located on both legs, mostly on the pretibial areas but also on her calves. A chest X-ray was normal. A skin biopsy was obtained, showing granulomata and septolobular panniculitis. Attempts to identify Mycobacterium tuberculosis by culture and PCR were negative. M. tuberculosis was isolated in one of three gastric aspirate samples. She was treated with isoniazid, rifampin, pyrazinamide and ethambutol. There was complete remission of the lesions. This case highlights the importance of considering erythema induratum in atypical cases of erythema nodosum and the need to perform a thorough investigation in search of active tuberculosis.

Erythema induratum of Bazin associated with Addison's disease: first description / Eritema indurado de Bazin associado à doença de Addison: primeira descrição

CONTEXT: Erythema induratum of Bazin (EIB) is considered to be a tuberculid reaction and consists of recurrent painful nodules. The differential diagnosis includes diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. CASE REPORT: We report the case of a woman with EIB who developed Addison's disease during treatment with anti-tuberculosis drugs with good response to glucocorticoid replacement. The diagnosis was obtained through the clinical picture, positive tuberculin test and positive BCG (bacillus Calmette-Guérin) test on the histological sample. Anti-tuberculosis drugs and glucocorticoid replacement led to disappearance of the signs and symptoms. CONCLUSIONS: This is the first description of an association between EIB and Addison's disease. It should be borne in mind that tuberculosis is an important etiological factor for Addison's disease.

CONTEXTO: O eritema indurado de Bazin (EIB) é considerado uma reação tuberculoide e consiste de nódulos dolorosos recorrentes. O diagnóstico diferencial inclui doenças como vasculite nodular, perniose, poliarterite nodosa e eritema nodoso. RELATO DE CASO: Nós reportamos o caso de uma mulher com EIB que desenvolveu doença de Addison durante tratamento com drogas tuberculostáticas e com boa resposta com reposição de glicocorticoide. O diagnóstico foi realizado pela apresentação clínica, teste tuberculínico positivo e positividade para BCG (bacilo Calmette-Guérin) no espécime histológico. A reposição de glicocorticoides e drogas tuberculostáticas levou ao desaparecimento dos sinais e sintomas. CONCLUSÕES: Este é o primeiro caso reportando a associação entre EIB e doença de Addison. Tuberculose é um importante agente etiológico da doença de Addison.

Recurrent nodules in the calves: A sign of tuberculosis / Recurrent nodules in the calves: A sign of tuberculosis

Aims: To describe a case of erythema induratum of Bazin, classified as a tuberculid, or skin lesion with similar histological features to true cutaneous tuberculosis, in which the relation with Mycobacterium tuberculosis cannot be easily demonstrated.Case Description: A 60-year-old woman presented with recurrent multiple nodules in the legs. Skin examination revealed violaceous painless nodules, some of them ulcerated, with a serous fluid, located on both legs in an asymmetric way, predominantly in the calves. Lesions disappeared spontaneously for brief periods. Skin biopsies revealed septal and lobular panniculitis with epithelioid granulomata and vascular necrosis. Tuberculin skin test was positive. Culture of the cutaneous lesions and polymerase chain reaction to Mycobacterium tuberculosis were negative, but mediastinal lymph nodes collected through mediastinoscopy were cultivated and positive to Mycobacterium tuberculosis. Therapy with isoniazid, rifampicin, pyrazinamide and ethambutol were administered. After two months under therapy the skin lesions healed. The clinical and histopathological features and the strong positive tuberculin skin test have strongly suggested the diagnosis of erythema induratum of Bazin. Positive culture for Mycobacterium tuberculosis and the remission of the lesions with antituberculosis therapy confirmed the diagnosis.Conclusions: Clinicians must be aware of the differential diagnosis of recurrent skin lesions, including the erythema induratum of Bazin. In this case, association with tuberculosis was confirmed by positive culture of mediastinal lymph nodes for Mycobacterium tuberculosis and remission of the lesions with antituberculosis therapy.

Objetivos: descrever um caso de eritema induratum de Bazin, classificado como tubercúlide, lesão cutânea com características histológicas semelhantes à tuberculose cutânea, mas na qual a relação entre o Mycobacterium tuberculosis não é facilmente demonstrada.Descrição do Caso: uma mulher de 60 anos de idade apresentou-se com múltiplos nódulos recorrentes nos membros inferiores. O exame da pele revelou nódulos indolores, violáceos, alguns deles ulcerados, com um líquido seroso, localizados em ambas as pernas, de forma assimétrica e com predomínio nas panturrilhas. As lesões apresentavam um aparecimento paroxístico, com remissão espontânea por breves períodos. Foi realizada biópsia cutânea que revelou paniculite septal e lobular com granulomas epitelióides e necrose vascular. O teste tuberculínico foi positivo. A cultura das lesões cutâneas e a reação em cadeia da polimerase para Mycobacterium tuberculosis foram negativos, mas foi realizada biópsia de linfonodos por mediastinoscopia, cuja cultura foi positiva para Mycobacterium tuberculosis. Foi iniciada terapêutica específica com isoniazida, rifampicina, pirazinamida e etambutol. Após dois meses de tratamento houve remissão das lesões. As características clínicas e histopatológicas e o teste tuberculínico fortemente positivo sugeriram o diagnóstico de eritema indurado de Bazin, sendo este confirmado pela cultura de linfonodos positiva para Mycobacterium tuberculosis e pela remissão das lesões com a terapêutica antituberculose.Conclusões: o clínico precisa estar atento para o diagnóstico diferencial de lesões cutâneas recorrentes, incluindo neste o eritema induratum de Bazin. Neste caso, a associação com a tuberculose ficou confirmada pela cultura dos linfonodos mediastinais positiva para Mycobacterium tuberculosis e remissão das lesões com a terapêutica antituberculose.

A retrospective analysis of tuberculosis screening by interferon-gamma release assay at National Skin Centre, Singapore

Objective The T-Spot.TB is an interferon-gamma release assay (IGRA) which is increasingly used in dermatology as a screen for latent TB before initiation of biologics and for confirming diagnosis of tuberculids. This study aims to explore its concordance with tuberculin skin tests (TST) and eventual diagnosis of latent TB. Study design This is a retrospective review of all patients in NSC who had a TB T-spot test done between 2008 and 2010. We looked at the dermatological diagnosis, results of T-Spot.TB and TST, chest radiograph findings, tuberculosis status and treatment of TB. Result 51 TB T spot tests were ordered in National Skin Centre between 1 January 2008 and 9 June 2010. 31 tests were for patients with psoriasis with the intention of initiating biologics; 5 were for patients with suspected tuberculids and tuberculosis verrucosa cutis; 3 were done as part of work-up for possible erythema nodosum; 3 tests were part of screening for latent TB in hospital staff and 9 tests were performed for other reasons. There were a total of 13 patients eventually diagnosed with latent or active TB infection. All of whom had a positive T-Spot.TB result except for 1 patient with an indeterminate result. On the other hand, out of these 13 patients, only 5 showed a positive TST, 2 had negative TST and 4 patients did not have a TST done. There were a total of 14 positive T-Spot.TB results for which 12 eventually received antituberculous therapy. All patients with erythema induratum had a positive test result. Six patients’ T-Spot.TB tests were borderline, indeterminate or could not be interpreted due to insufficient lymphocyte yield. Conclusion Our study shows the utility of T-Spot. TB test in various conditions seen in dermatology clinics in a local setting. We suggest that the T-spot test can supplant the tuberculin skin test in screening latent TB for psoriasis patients for whom biologics are intended and in erythema induratum. The high incidence of borderline and indeterminate results should not be ignored. This should be taken into account when interpreting the IGRA especially if patients are on immunosuppressive therapy.

Erythema induratum - A type of cutaneous tuberculosis.

We report a case of erythema induratum recently encountered in our centre. A 14-year male presented with history of fever, weight loss and multiple, painful, hyperpigmented patches over both legs and dorsum of foot, since six months. FNAC showed evidence of granulomatous inflammation. Biopsy of the lesion showed skin with inflammatory infiltrate in the deep dermis composed predominantly of epithelioid granulomas, Langhan’s giant cells and mature lymphocytes. A strongly positive Mantoux test and elevated TB IgG and IgM antibody levels suggested tuberculosis . The patient responded well to a course of anti-tuberculous therapy with marked resolution of the lesions.

Erythema Induratum of Bazin / 대한피부과학회지

Erythema induratum of Bazin (EIB) belongs to a group of diseases characterized by inflammatory nodules of the leg which primarily involve the lower legs. EIB is considered to be a reactive disorder related to several etiologic factors. In Korea, most dermatologists accept the tuberculosis as one of the most common etiology of EIB. As the number of EIB cases is decreasing in Korea in accordance with the decreased incidence of tuberculosis, EIB can be easily mistaken for any of the disease that produces chronic nodular eruptions on the legs. In Korea, important factors to make a correct diagnosis of EI include clinicopathologic observations coupled with the identification of hypersensitivity to tuberculous antigen and successful treatment of anti-tuberculous medication.

Application of the QuantiFERON(R)-TB Gold Test in Two Cases of Erythema Induratum of Bazin / 대한피부과학회지

Erythema induratum of Bazin is a chronic, nodular subcutaneous eruption usually occurring on the lower legs of young women. Erythema induratum of Bazin hasbeen regarded as a tuberculide, a hypersensitivity response to Mycobacterium tuberculosis. The pathogenesis of erythema induratum of Bazin associated with tuberculosis is still debatable because mycobacteria cannot be cultured from the skin lesions. QuantiFERON(R)-TB Gold test detects INF-gamma released by T cells in response to Mycobacterium tuberculosis-specific antigens, which offers an improved diagnostic test of latent tuberculosis infection. We experienced two cases of erythema induratum of Bazin, which showed normal chest X-ray and negative TB-PCR. However the QuantiFERON(R)-TB Gold test was positive which led us to a diagnosis of latent tuberculosis infection. Both patients were treated with anti-tuberculosis medications, which was followed by successful resolution of the skin lesions. Therefore, we report the application of the QuantiFERON(R)-TB Gold test for the confirmation of latent tuberculosis infection in erythema induratum of Bazin patients.

Application of the QuantiFERON(R)-TB Gold Test in Two Cases of Erythema Induratum of Bazin / 대한피부과학회지

Erythema induratum of Bazin is a chronic, nodular subcutaneous eruption usually occurring on the lower legs of young women. Erythema induratum of Bazin hasbeen regarded as a tuberculide, a hypersensitivity response to Mycobacterium tuberculosis. The pathogenesis of erythema induratum of Bazin associated with tuberculosis is still debatable because mycobacteria cannot be cultured from the skin lesions. QuantiFERON(R)-TB Gold test detects INF-gamma released by T cells in response to Mycobacterium tuberculosis-specific antigens, which offers an improved diagnostic test of latent tuberculosis infection. We experienced two cases of erythema induratum of Bazin, which showed normal chest X-ray and negative TB-PCR. However the QuantiFERON(R)-TB Gold test was positive which led us to a diagnosis of latent tuberculosis infection. Both patients were treated with anti-tuberculosis medications, which was followed by successful resolution of the skin lesions. Therefore, we report the application of the QuantiFERON(R)-TB Gold test for the confirmation of latent tuberculosis infection in erythema induratum of Bazin patients.

A Case of Papulonecrotic Tuberculid Combined with Erythema Induratum / 대한피부과학회지

We report a rare case in which two tuberculids, erythema induratum and papulonecrotic tuberculid, occured together. A 15-year-old Korean girl had two types of clinically distinct lesions; painful subcutaneous nodules on the legs and pruritic necrotic papules on the trunk and extremity. Mantoux test showed a strong positive reaction. Histopathologic findings of the subcutaneous nodule and necrotic papule were consistent with erythema induratum and papulonecrotic tuberculid, respectively. There was no extracutaneous focus of tuberculosis. Polymerase chain reaction for tuberculosis bacilli in both lesions revealed negative results. Antituberculous therapy brought a rapid clinical improvement of lesions within a month.

The clinical and histopatholgical study of erythema induratum and erythema nodosum / 대한피부과학회지

Erythema induratum and erythema nodosum are both inflammatory disorders of the panniculus. However they are often difficult to distinguish because of clinical variations and similarity of histopathologic features. We investigated the clinical and histopathologic features of 30 cases of erythema induratum and 38 cases of erythema nodosum in order to define discrimination of clinical and histopathologic features. The results show that presence of ulceration is clinically important in differentiating erythema induratum from erythema nodosum. Histopathologic findings which suggest erythema induratum include lobular panniculitis or lobuloseptal panniculitis, necrosis and necrotizing vasculitis while erythema nodosum is characterized by predominantly septal panniculitis without necrosis and necrotizing vasculitis.