Sarcoidosis of the upper respiratory tract and its association with lupus pernio. (1/11)

In a series of 34 patients with sarcoidosis affecting the upper respiratory tract and nose, 26 had lupus pernio (LP) and 17 had sarcoidosis of the upper respiratory tract (SURT). In nine patients these features coexisted. A patient presenting with SURT carried a 50% risk of developing LP although one feature could be present without the other. Both were disorders of women of the child-bearing years of life. SURT, like LP, was an indicator of chronic fibrotic sarcoidosis, developing insidiously and progressing indolently over the years. It was complicated by ulceration, septal perforation, and LP. Three patients had nasal septal perforations, in two instances following submucous resection. This operation is contraindicated in patients with active sarcoidosis, particularly when granulomas are found on nasal biopsy. The Kveim-Siltzbach skin test was positive in all patients with SURT, making it invaluable in the differential diagnosis of granuloma of the nasal cavity.  (+info)

Potential etiologic agents in sarcoidosis. (2/11)

The etiology of sarcoidosis remains uncertain. The hallmark of sarcoidosis is the epithelioid granuloma, which serves as a necessary starting point for considering disease etiology. Any etiologic agent of sarcoidosis must also explain the typical clinical behaviors and characteristic immunopathologic features of the disease. One clinical observation that serves as a bridge to the etiology of sarcoidosis is the Kveim reaction. In this reaction, local epithelioid granulomas develop several weeks after the intradermal injection of homogenates of sarcoidosis tissue. Our group capitalized on the known properties of the Kveim reagent to search for candidate pathogenic tissue antigens in sarcoidosis without other a priori hypotheses regarding possible microbial or autoimmune etiologies. Using a limited proteomics approach based on the physicochemical properties of Kveim reagent, we detected a limited number of poorly soluble antigenic proteins in sarcoidosis tissues by protein immunoblotting, using sarcoidosis sera. Matrix-associated laser desorption/ionization-time of flight mass spectrometry identified one of these antigens to be the Mycobacterium tuberculosis catalase-peroxidase protein (mKatG). We found IgG responses to recombinant mKatG in more than 50% of patients with sarcoidosis but rarely in purified protein derivative (PPD)-negative control subjects. These findings support the conclusion that mKatG is a tissue antigen and target of the adaptive immune response in sarcoidosis, providing further evidence of a mycobacterial etiology in a subset of sarcoidosis. More generally, the approach used in these studies might be employed to discover and validate other candidate pathogenic antigens in sarcoidosis or other granulomatous disorders.  (+info)

Observations on the Kveim reaction using an animal model of granulomatous bowel disease. (3/11)

Striking differences were observed between the visceral and cutaneous responses after tests with validated Kveim and normal spleen suspensions in a guinea pig model of granulomatous bowel disease. Five of six animals sensitised with BCG showed positive responses at the ileal Kveim test site whereas all six had negative cutaneous Kveim tests. Conversely, two of six animals sensitised with irradiated Mycobacterium leprae showed positive cutaneous Kveim tests and only one a positive response in the ascending colon. All six showed negative responses at the ileal Kveim test site. No positive visceral or cutaneous responses were observed in either group of animals after tests with normal spleen suspension. These findings are discussed in relation to the positive Kveim responses previously reported among patients with Crohn's disease, tuberculoid and lepromatous leprosy, and among seemingly healthy BCG vaccinated subjects. The findings provide further evidence in support of a possible mycobacterial aetiology for sarcoidosis and Crohn's disease.  (+info)

Sarcoidosis presenting with stroke. (4/11)

A 25-year-old black man with sarcoidosis presented with transient ischemic attacks followed by sudden, persistent right hemiparesis. He gave a history of recent, recurrent lower motor neuron facial palsy. Computed tomography demonstrated an infarct in the left internal capsule. Chest x-ray film showed bilateral hilar and mediastinal lymphadenopathy and multiple opacities in the lung fields. Serum angiotensin converting enzyme concentration was raised, and a Kveim test was positive for sarcoidosis. Despite clear pathologic reports of cerebral vasculitis in neurosarcoidosis, the occurrence of stroke is extremely rare.  (+info)

Early cellular responses to intradermal injection of Kveim suspension in normal subjects and those with sarcoidosis. (5/11)

In a detailed controlled study of the cellular response to Kveim suspension in vivo we used immunohistological and histochemical methods to examine cryostat sections of immature Kveim biopsy specimens in subjects with sarcoidosis and normal controls. Changes seen at 48 hours, at which time papular reactions have sometimes been reported, are described. Eight cases of sarcoidosis previously confirmed by a positive Kveim test were studied, in five of whom the test remained positive; plus two subjects with sarcoidosis studied prospectively; and four healthy controls. There were two main features of the 48 hour response: collagen disruption with associated histiocytes, which showed increased acid phosphatase activity; and perivascular infiltrates of lymphocytes and small groups of dendritic cells. The T4:T8 ratios in the infiltrates were similar to those found in the peripheral blood of the subjects, and few lymphocytes showed evidence of activation. T lymphocytes were also seen free in the dermis and migrating to the epidermis. Small juxtacapillary clumps of dendritic cells, identified by NA1/34 (= OKT6; Langerhans' cells) and RFD1 (interdigitating cell) monoclonal antibodies, were found. The Langerhans' cells in the epidermis were, however, normal in number and distribution. These features, which were found in all groups, are not consistent with pre-existing hypersensitivity to Kveim suspension in sarcoidosis. Subsequent differences between sarcoid and normal subjects in the development of granulomas in the Kveim response may therefore relate to the different handling of the foreign material by the cells affected, rather than to differences in the early non-specific recruitment of the cells to the test site.  (+info)

Sarcoidosis: histopathological definition and clinical diagnosis. (6/11)

Sarcoidosis is best defined in histopathological terms as 'a disease characterised by the presence in all of several affected organs and tissues of non-caseating epithelioid-cell granulomas, proceeding either to resolution or to conversion into hyaline connective tissue'. Although the defining characteristics are thus histopathological, diagnosis during life depends largely upon clinical, radiological, and immunological findings. The amount of support required from histology varies greatly from case to case. Though histology from one site cannot in itself establish the diagnosis of sarcoidosis, a generalised disease, detailed histological study of biopsy tissue makes an important and often essential contribution. In many instances, complete lack of necrosis, an intact reticulin pattern, and failure to demonstrate infective agents permit an unequivocal statement of compatibility with this diagnosis; however, a compatible clinical picture and absence of evidence of known causes of local granulomatous reactions or of other generalised granulomatous diseases are required for definitive diagnosis. In some, the histological pattern deviates in some particular from the accepted 'typical' pattern; there may be a little necrosis, the follicular pattern of the granuloma may be less than perfect, and exclusion of known infective agents can never be absolute. In such instances, subsequent surveillance, including possible response to treatment, may show a clinical course justifying a diagnosis of sarcoidosis, and necropsy may establish it; but it must be recognised that in a few cases, particularly those in which the clinical evidence of disease is confined to one organ, diagnosis is likely to remain in doubt for long periods. Reports on the histology of the Kveim test should be made without knowledge of clinical findings and in terms of the presence and quality of granulomatous response. A granulomatous reaction to a validated test suspension makes a contribution to diagnosis similar to the finding of granulomas in an additional organ or tissue.  (+info)

The distribution of lymphoid and macrophage like cell subsets of sarcoid and Kveim granulomata: possible mechanism of negative PPD reaction in sarcoidosis. (7/11)

Immunohistological observations of lymphoid and non-lymphoid cell subsets in biopsies of sarcoid skin granulomas have been compared with positive Kveim tests and the sites of PPD injection in sarcoid patients. Monoclonal antibodies have been used in indirect immunofluorescence often in combination with histochemical methods for the detailed characterization of the cells involved. The antibodies used included two new reagents, RFD-1 and RFD-2, which react with interdigitating cells and acid phosphatase positive macrophages, respectively. Sarcoid granulomas had a distinctive pattern of organization though there was a heterogeneity of macrophage like and T lymphoid cells. In the centre, predominantly HLA-DR+, acid phosphatase positive macrophages (RFD-2+) were seen and the lymphoid cells were almost exclusively T4+. At the periphery of the granulomas the HLA-DR+ dendritic cells were ACP negative and RFD-1+. Here T8+ cells were admixed with the T4+ population. The Kveim granuloma had fewer RFD-2+, macrophages and therefore the RFD-1+ cells were more evenly distributed, but the other cells showed a similar distribution to the established lesions. The PPD injection sites contained fewer T cells than the normal control infiltrates in PPD positive healthy individuals. The T4+/T8+ ratios were about 3:2. The most likely explanation for the PPD anergy in sarcoidosis is the sluggish traffic of T4+ cells which could be due to the sequestration of T4+ cells in sites of ongoing inflammation.  (+info)

Chronic intrahepatic cholestasis due to sarcoidosis. (8/11)

Two West Indian patients with Kveim-biopsy proven sarcoidosis developed chronic cholestatic liver disease, clinically and biochemically similar to primary biliary cirrhosis. Liver histology revealed multiple granulomas with reduction in bile ducts and, in one patient, progression to biliary cirrhosis. Portal hypertension was present in both patients leading to severe variceal haemorrhage in one. Mitochondrial antibody was negative in both patients and when used in conjunction with the Kveim-Siltzbach skin test serves to differentiate chronic intrahepatic cholestasis secondary to sarcoidosis from primary biliary cirrhosis.  (+info)

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