The continuing search for Mycobacterium tuberculosis involvement in sarcoidosis: a study on archival biopsy specimens (original) (raw)
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Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis
European Respiratory Journal, 2007
The aetiology of sarcoidosis is currently unknown. Due to the clinical and histological similarities between sarcoidosis and tuberculosis, the role of mycobacteria has been repeatedly investigated as an aetiological agent for sarcoidosis. The current meta-analysis aimed to evaluate the available molecular evidence on the possible role of mycobacteria in the development of sarcoidosis.
Current Respiratory Medicine Reviews, 2018
Background: Sarcoidosis is a granulomatous inflammatory disorder with unknown etiology and its relation with Mycobacterium tuberculosis (M. tuberculosis) has been debated for years. In this study, we have investigated the presence of mycobacterial DNA in sarcoidosis tissue samples. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 33 patients with sarcoidosis were analyzed for the presence of mycobacterial DNA. Genomic DNA extraction was done by QIAamp DNA FFPE Tissue Kit. Polymerase chain reaction using insertion element IS6110 of M. tuberculosis complex (MTC) was applied by commercial kits (GeneProof) for all individuals. The results were compared with 27 patients with tuberculosis and 5 other patients associated with granulomatous disease of the lung. All cases had confirmed granulomatous inflammation in their histopathological examination. Results: In this study, the IS6110 repetitive DNA element of (MTC) was not detected in any of the tissue samples from the patients with sarcoidosis. Of the 33 sarcoidosis patients, 30 (90.1%) had negative results for IS6110 and despite the repeated attempts of DNA extraction for three patients (9.1%), strong inhibitor made constant negative outcomes. In contrast, in patients with tuberculosis, 22 (81.5%) had positive results, three had (11.1%) negative results and 2 patients (7.4%) showed negative results with strong inhibitor. IS6110 was not found in any of the control group patients. Discussion: This study does not support the presence of M. tuberculosis in tissues of patients with sarcoidosis as a microbial pathogen or trigger of the immune response. Due to difficulties in diagnosis of sarcoidosis and different methods for diagnosis of M. tuberculosis, the impact of M. tuberculosis as a possible aetiological agent in sarcoidosis has been the point of debate.
Journal of Clinical Microbiology, 2002
ABSTRACTThe cause(s) of sarcoidosis is unknown.Mycobacteriumspp. are suspected in Europe andPropionibacteriumspp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes ofPropionibacterium acnes,Propionibacterium granulosum,Mycobacterium tuberculosis,Mycobacterium aviumsubsp.paratuberculosis, andEscherichia coli(as the control) were counted by quantitative real-time PCR. EitherP. acnesorP. granulosumwas found in all but two of the sarcoid samples.M. aviumsubsp.paratuberculosiswas found in no sarcoid sample.M. tuberculosiswas found in 0 to 9% of the sarcoid samples but in 65 to 100% ...
Identification of Mycobacterium avium complex in sarcoidosis
Journal of Clinical Microbiology, 1996
Cell wall-defective bacteria which later reverted to acid-fast bacilli have been isolated from sarcoid tissue. These have not been conclusively shown to be mycobacteria. Specific PCR assays were applied to identify mycobacterial nucleic acids in these cultured isolates and in fresh specimens obtained from patients with sarcoidosis. Positive amplification and hybridization were observed with Mycobacterium avium complex-and/or Mycobacterium paratuberculosis-specific probes in five of the six cultured isolates and two fresh skin biopsy samples and one cerebrospinal fluid specimen. There was no amplification or hybridization with Mycobacterium tuberculosis or M. avium subsp. silvaticum probes, respectively. Patients' sera were also tested for antibody reactivities by immunoblotting with M. paratuberculosis recombinant clones expressing the 36,000-molecularweight antigen (36K antigen) (p36) and the 65K heat shock protein (PTB65K). All seven sarcoidosis, four of six tuberculosis, and all six leprosy patient serum specimens showed strong reactivity with p36 antigen. In contrast, 13 of 38 controls showed only weak reactivity with p36 (P ؍ 0.002 for controls versus sarcoidosis samples). Similarly, PTB65K reacted with high intensity with sera from 5 of 5 sarcoidosis, 5 of 6 tuberculosis, and 5 of 6 leprosy patients, compared with its low-intensity reaction with 5 of 22 controls (P ؍ 0.001 for controls versus sarcoidosis samples). This study demonstrates the isolation and/or identification of M. paratuberculosis or a closely related M. avium complex strain from sarcoid skin lesions and cerebrospinal fluid. Furthermore, the reactivity of antibodies in sarcoid patient sera against p36 and PTB65K antigens was comparable to the reactivity of sera obtained from patients with known mycobacterial diseases. Collectively, these data provide further support for the theory of the mycobacterial etiology of sarcoidosis. MATERIALS AND METHODS Bacterial strains and growth. The bacterial strains used in this study were obtained from the Veterans Administration Medical Center (VAMC), Houston, Tex.; the American Type Culture Collection (ATCC), Rockville, Md.
Sarcoidosis is a multi-system granulomatous diseases of undetermined etiology characterized by activation of lymphocytes and mononuclear phagocytes at the site of the disease (I). Seen most often between 30-40 years of age, it can effect any race, though less common in tropics. It involves lungs in 80-90% of cases (2), although it is a multi-organ disease and can present to any of the medical or surgical discipline (3). In areas endemic for Tuberculosis like Pakistan there may be lot of difficulty in excluding Mycobacterial infection, since both the diseases have similar clinico-radiological, biochemical and pathological features (4). Clinical and epidemiological features favor the hypothesis that it results from environmental exposure. possibly infective agents. An updated review of the subject is presented.
Disseminated nontuberculous infections with Mycobacterium genavense during sarcoidosis
European Respiratory Review, 2009
Sarcoidosis is a chronic disease characterised by the development and accumulation of granulomas in multiple organs. We report two observations of disseminated Mycobacterium genavense infection in patients with proven sarcoidosis. High fever and abdominal pain appeared at 8 and 18 months following the initiation of immunosuppressive therapy. Abdominal computed tomography scans of the patients showed diffuse mesenteric lymphadenitis and splenomegaly. The diagnosis was obtained on bone marrow specimens for both patients with numerous acid-fast bacteria at direct examination and positive specific mycobacterial identification by nucleic acid amplification test. Despite prompt antimycobacterial therapy, occurrence of complications (peritonitis post-splenectomy surgery and lung carcinoma) resulted in a fatal outcome for both patients. These cases highlight that opportunistic infections like M. genavense or other nontuberculous mycobacterial infections should be considered for long-standing immunocompromised patients with sarcoidosis.
Respiration, 2006
Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. The presence of mycobacterial nucleic acid components in patients with sarcoidosis has been demonstrated with varying degrees of success. Objectives: The aim of this study was to estimate the presence of Mycobacterium tuberculosis DNA in tissues from sarcoidosis patients, in Catalonia, Spain, as well as to assess the long-term clinical course in these patients. Methods: Fifty-eight paraffin-embedded tissue biopsies corresponding to cases of sarcoidosis (n = 23), lung neoplasm (n = 23), and lung tuberculosis (n = 12) available in 1996 were analyzed in a retrospective study by means of a nested polymerase chain reaction using primers corresponding to the insertion element IS6110 of M. tuberculosis complex. For greater sensitivity, Southern blot hybridization was performed. Clinical data were recorded prior to and after PCR analysis (follow-up reported until 2002). Results:M. tuberculosis DNA was present i...
Diagnostic Dilemma of Sarcoidosis: A Case Report Masquerading as Tuberculosis
Bangladesh Journal of Medicine, 2017
Sarcoidosis is a chronic multisystem disorder of unknown etiology characterized by formation of granulomata within affected organs and consequent distortion of their normal architecture. Typically, these are non-caseating epithelioid granulomata involving organized collections of activated macrophages and T lymphocytes. In countries where tuberculosis is endemic, sarcoidosis is often misdiagnosed and mistreated as tuberculosis. We present case report of a 47-year-old female who presented with 2 years history of recurrent, multiple nodules with occasional joint pain & fever and had received anti-tubercular therapy without any improvement. A diagnosis of sarcoidosis is made finally and she was managed accordingly.
Sarcoidosis: Challenging Diagnostic Aspects of an Old Disease
The American Journal of Medicine, 2012
Over the past few years, there have been substantial advances in our understanding of sarcoidosis immunopathogenesis. Conversely, the etiology of the disease remains obscure for a number of reasons, including heterogeneity of clinical manifestations, often overlapping with other disorders, and insensitive and nonspecific diagnostic tests. While no cause has been definitely confirmed, there is increasing evidence that one or more infectious agents may cause the disease, although the organism may no longer be viable. Here we present 2 cases, in which sarcoidosis preceded tuberculosis and non-Hodgkin lymphoma. Development of new lesions in a patient with chronic/remitting sarcoidosis should be looked at with suspicion and promptly investigated in order to rule out an alternative/concomitant diagnosis. In such cases, tissue confirmation from the most accessible site, and bone marrow biopsy-if lymphoma is in the differential diagnosis-should be performed. In conclusion, we strongly advise that physicians be ready to reconsider the diagnosis of sarcoidosis in the presence of atypical manifestations or persistent/progressive disease despite conventional therapy.