Kveim Test Research Articles

The Kveim test in leprosy

Summary From the older literature it has been claimed that a significant proportion of patients with the tuberculoid, but not the lepromatous, form of the disease, gave positive Kveim reactions. It is concluded, however, from a review of this older literature that none of the claims are based on studies using a validated Kveim antigen and that the majority of the readings were based on macroscopic, rather than microscopic assessment. The International Study by Siltzbach on Kveim tests in leprosy patients using a validated antigen and assessed microscopically reveal no positive reactions among fifty-seven patients with all types of leprosy from Finland, Israel, Italy and Turkey. However, this same study on Japanese patients gave two positive and five equivocal Kveim reactions among ten lepromatous patients and one equivocal reaction among three tuberculoid patients. Our own studies in Malaysia with the same validated Kveim antigen used by Siltzbach and assessed microscopically gave one weak positive Kveim reaction among twenty-one lepromatous patients and four equivocal Kveim reactions among nine tuberculoid patients. It is concluded from these results that, with the possible exception of Chinese and Japanese patients, false positive Kveim reactions are extremely rare in patients with all types of leprosy. Therefore in parts of the world where leprosy is endemic the Kveim reaction can still be accepted as an important confirmatory diagnostic test for sarcoidosis. It is suggested that further surveys of Kveim reactivity be undertaken on Chinese and Japanese leprosy patients, since both have a similar ethnic origin, in order to determine whether such patients are more liable to elicit a granulomatous reaction to Kveim antigen.

An attempt to demonstrate a transmissible agent from sarcoid material.

Summary The results of a controlled experiment in which an attempt was made to transmit sarcoidosis by inoculation of sarcoid and non-sarcoid lymph node homogenates into the footpads of normal and immunologically deficient mice, are reported. The early and late changes in the footpads were assessed microscopically. A substantial proportion of the footpads of mice receiving sarcoid homogenate showed the histological characteristics typical of sarcoidosis in man and evolved fully only after a period of 6-8 months following inoculation. Moreover, positive Kveim tests were confined to a proportion of those mice given sarcoid homogenates and were all associated with a sarcoid granuloma in the footpad. Conversely, the inflammatory lesions seen in the early histology of the footpads of mice inoculated with non-sarcoid homogenate were no longer apparent in the late histology and Kveim tests in all mice given non-sarcoid homogenate were negative.

Evaluation of the clinical and histological features of paratracheal and hilar gland enlargement.

Summary Sixty-nine patients with a chest radiograph showing enlargement of the hilar and/or paratracheal lymph nodes were analysed. Ten of these, mainly Asian, were found to be suffering from tuberculosis. Of the remaining fifty-nine, who had sarcoidosis, 12% were tuberculin-positive. All the cases diagnosed as sarcoidosis had either a positive Kveim test and/or mediastinal lymph node histology compatible with sarcoidosis. 10% of cases with sarcoidosis showed evidence of uveitis and 10% showed bone cysts and there was also a high proportion of other extrathoracic lesions. From these studies we conclude that, whilst the currently accepted radiological staging of sarcoidosis serves as a convenient form of reference, these stages do not in any way relate to the clinical stage of disease, or to the histological appearance of affected lymph node tissue. There is a correlation between a strongly positive Kveim test of three or more granulomas and mediastinal lymph nodes showing confluent granulomata (predominantly of the epithelioid cell-type) with fibrosis. The presence of intra- or peri-granulomatous fibrosis, or even gross diffuse fibrosis, does not seem in itself to be related to the nature of onset, clinical or accepted radiological staging of disease. However the mediastinal lymph nodes in patients with erythema nodosum were predominantly of giant cell-type; these patients were also Kveim-positive. Similar instances of giant cell predominance in the mediastinal lymph nodes were seen in each of the groups examined. Further studies are required to determine whether these cellular characteristics, or other histological features in the mediastinal lymph nodes, might be of prognostic significance.

AGENT TRANSMISSIBLE FROM CROHN'S DISEASE TISSUE

The results of a controlled experiment in which an attempt was made to transmit Crohn's disease by inoculation of homogenates from Crohn gut or lymph-node tissue and from non-Crohn lymph-node into the footpads of normal and immunologically deficient mice, are reported. The early and late changes in the footpads were assessed microscopically. A significant proportion of the footpads of mice receiving homogenates prepared from Crohn's disease tissues showed the histological characteristics typical of the focal granulomas of Crohn's disease in man. The granulomas evolved fully only 6-24 months after inoculation. Conversely, the early inflammatory reactions seen in a small proportion of the footpads of mice inoculated with non-Crohn's homogenates could no longer be seen in the late examination. Moreover, although positive Kveim tests were found in a proportion of mice given homogenates from Crohn's disease tissues and were all associated with granulomas in the footpads, all Kveim tests were negative in mice given non-Crohn's homogenates.

The definitive evaluation of sarcoidosis.

Thirty patients with clinical, roentgenographic, and histologic manifestations of sarcoidosis on biopsy of peripheral tissues were subjected to exhaustive diagnostic study in an attempt to establish a definitive diagnosis other than sarcoidosis. This was accomplished in 27 patients. The most rewarding diagnostic procedure was open lung biopsy, which proved to be the definitive diagnostic procedure in 16 patients. Additional diagnostic procedures included cultures of secretions and biopsied tissues, special staining techniques, chemical analysis of biopsy specimens, and immunologic studies. In the patient with suspected intrathoracic sarcoidosis, the diagnosis cannot be established without open thoracotomy unless preliminary cultures or biopsies of peripheral tissue reveal evidence of another pathologic process known to cause a granulomatous reaction. The presence of sarcoid in a patient with an abnormal chest film cannot be confirmed by scalene node biopsy, a Kveim test, or absence of bacteriologic eviden...

Lymphography in Sarcoidosis: Comparison with Roentgen Findings in the Chest

THE PREVALENCE of sarcoidosis in Japan is 5.6 per 100,000. This is far lower than that of other countries, e.g., 64.0 in Sweden and 26.7 in Norway (1, 2). Schaumann considered sarcoidosis a systemic disease, attacking particularly the reticuloendothelial system, but Iwai and Oka (3) found in autopsy studies that only the tracheomediastinal lymph nodes are uniformly involved. This study is concerned primarily with the lymphographic findings in patients with this granulomatous disease of unknown etiology. The characteristic lymphographic appearance is described and compared with the chest roentgenograms, especially in respect to hilar node enlargement. Methods and Materials From May 1965 to June 1968, lymphography was performed in 15 cases of sarcoidosis, all with pulmonary lesions. Radiographs were taken immediately and twenty-four hours after the injection of 10 ml of Ethiodol into the dorsum of each foot by Kinmonth's method, with visualization of the major retroperitoneal lymph node groups. The diagnostic criterion of sarcoidosis was based on three major factors: chest findings specific for sarcoidosis (bilateral peribronchial lymph node enlargement and/or parenchymal lesions), the Kveim test, and organ biopsy (presence of epithelioid cell tubercles showing little or no necrosis), supported by such data as uveitis, negative tuberculin test, hyper-globulinemia, and hypercalcemia. The 15 cases which constitute the present series were grouped according to the system proposed at the Second International Conference on Sarcoidosis as follows: Group I, in which both the Kveim test and organ biopsy were positive (5 cases) ; Group II, in which the Kveim test was positive and organ biopsy was negative or omitted (1 case) ; Group III, in which organ biopsy was positive and the Kveim test was negative or omitted (6 cases) ; Group IV, in which both the Kveim test and organ biopsy were negative or omitted (3 cases). Chest findings were based on routine roentgen examination supplemented by laminagraphy and magnification roentgenography. To follow the course of the disease, films of the chest made prior to the diagnosis of sarcoidosis were retrospectively studied as far as available, and the course subsequent to lymphography was observed, especially to record the effects of steroid therapy. Results Lymphographic Findings (a) Abnormal Findings in the Lymphadenograms of the Retroperitoneal and Iliac Nodes: These can be classified into the following three patterns : 1. A marked enlargement of retroperitoneal nodes (Fig. 1, CASE 1) comparable in size to the hilar adenopathy. The nodes show sharply defined multiple central filling defects (see full description, CASE 1).

THE KVEIM TEST IN CROHN'S DISEASE

Kveim tests were done on 48 patients with Crohn's disease. Of 45 with definite or probable Crohn's disease 23 had a positive Kveim test. This finding could be explained: ( a) by cross-reactivity between sarcoidosis and Crohn's disease antigens, ( b) by an ætiological agent common to the two diseases, or ( c) by a property of the Kveim test material used in this series.

A comparison of the results of mediastinal lymph node biopsy and of simultaneous Kveim tests in patients with sarcoidosis

A comparison of the results of mediastinal lymph node biopsy and of simultaneous Kveim tests in patients with sarcoidosis

A TRANSMISSIBLE AGENT FROM SARCOID TISSUE

The results of a controlled experiment in which an attempt was made to transmit sarcoidosis by inoculation of sarcoid and non-sarcoid lymph-node homogenates into the footpads of normal and immunologically deficient mice, are reported. The early and late changes in the footpads were assessed microscopically. A substantial proportion of the footpads of mice receiving sarcoid homogenate showed the histological characteristics typical of sarcoidosis in man and evolved fully only after 6-8 months following inoculation. Moreover, positive Kveim tests were confined to a proportion of those mice given sarcoid homogenates and were all associated with a sarcoid granuloma in the footpad. Conversely, the inflammatory lesions seen in the early histology of the footpads of mice inoculated with non-sarcoid homogenate were no longer apparent in the late histology and Kveim tests in all mice given non-sarcoid homogenate were negative.

A Study of Sarcoidosis and Leprosy in Turkey Employing the Kveim Reaction

Twenty-one patients with sarcoidosis and 38 patients with leprosy in Istanbul, Turkey, received an intracutaneous Kveim test with a standardized (Chase-Siltzbach type 1) Kveim suspension. A microscopically positive Kveim reaction was obtained in 81 percent of the patients with sarcoidosis and no false positive reactions were observed among 38 patients with leprosy. Because leprosy and tuberculosis are still being encountered in Turkey, the Kveim test may be decisive in the differentiation of sarcoidosis from these two granulomatous disorders.

The Enigma of Sarcoidosis

Its etiology and pathogenesis are undetermined, its manifestations are extremely varied, and its course is often silent. Accurate diagnosis is thus a difficult task in sarcoidosis. Given a suspicious chest x-ray, diagnosis can be confirmed by a positive Kveim test and biopsy of affected tissue. Since the disease tends to regress spontaneously, therapy is directed primarily to suppression of symptoms.

The diagnosis of sarcoidosis.

A diagnosis of sarcoidosis should usually be supported by demonstration of sarcoid granulomas in an excised tissue or Kveim nodule. Kveim test material has not been readily available to American physicians due to difficulties in production of splenic extracts that are potent, specific, and stable. Kveim reactions occur most consistently in patients whose sarcoidosis is manifested by erythema nodosum. It is also valuable in other fresh cases with few or no symptoms; an unequivocal Kveim reaction may be obtained in 60 to 80% of such patients, making hospitalization for biopsy procedures unnecessary. The test is less useful in hospitalized patients. Biopsy procedures developed in recent years more rapidly and more consistently provide histologic evidence of sarcoidosis. Atypical sarcoidosis may be difficult to distinguish from unusual mycobacterial or fungal disease, but emphasis on pitfalls that are rarely encountered should not obscure the fact that with careful study accurate diagnosis is achieved in most cases. Greater precision is unlikely until the active fraction in Kveim test material is identified or the cause of sarcoidosis discovered.

Chloroquine in the treatment of sarcoidosis: A report from the Research Committee of the Bristish Tuberculosis Association

Summary A double-blind trial was undertaken of the effect of chloroquine on pulmonary sarcoidosis. Eligible patients had lung shadowing of at least six months' duration and had not been treated with corticosteroids. Fifty seven patients from many centres were allocated treatment at random with inert tablets or chloroquine sulphate 600 mg. daily for 8 weeks and 400 mg. daily for 8 weeks. Assessments were made at 1, 2, 4, 6 and 12 months. Five patients were excluded from the analysis for various reasons. Compared with the chloroquine group, the control group contained more older women and more patients with histological or Kveim test support for the diagnosis. The control group also contained more patients with lesions which were considered to be only partly reversible. Radiographic assessments by independent observers showed that there was a significant improvement in the chloroquine group compared with the control group at four and six months. These findings were supported by improvement in dyspnoea and ventilatory tests. Detailed analysis showed that the differences could not be attributed to the disparity in ages and other factors between the groups. After six months there was some deterioration in the chloroquine group and some spontaneous improvement in the control group, so that there was no significant difference between them at 12 months. The effect of chloroquine is therefore believed to be suppressive rather than curative. The side effects are recorded. The toxic effects of chloroquine are described in detail so that a rational assessment can be made of the risks of treatment.

Present Diagnostic Approach to Sarcoidosis in Japan

Sarcoidosis is a rare disease in Japan. Bilateral hilar adenopathy is suggestive of malignant tumor rather than sarcoidosis. Hematology and plasma chemistry offer no clues to the diagnosis of sarcoidosis. The Kveim test is still poor in reliability even in biopsy-confirmed patients in this country. One-third of patients with bilateral hilar node swelling or pulmonic mottled silhouette alone are left undiagnosed even after Daniels' scalene lymph node biopsy. Sarcoidosis was discovered in 18 patients among those who underwent thoracotomy biopsy to exclude definitely the possibility of malignancy.

"Residual bodies" in sarcoid and sarcoid-like granulomas.

A MORPHOLOGICAL AND HISTOCHEMICAL STUDY WAS MADE OF EPITHELIOID CELL GRANULOMAS: (a) classical sarcoid type, namely, sarcoidosis, Kveim tests, tuberculosis, farmer's lung, and Crohn's syndrome; (b) sarcoid-like granulomas, often distinguishable from (a) by the presence of extracellular mucin or bile, namely, ulcerative colitis, diverticulitis, cholecystitis, cholangitis, carcinoma of the rectum and lymph nodes, draining tumours. All these granulomas showed similar, numerous cytoplasmic granules in epithelioid and giant cells with the properties of residual bodies, i.e., end products of activated lysosomes. The presence of residual bodies demonstrates the following features the morphological similarity of the granulomas studied, and the phagocytic nature of the affected cells. It suggests a common mechanism of granuloma formation but does not identify any particular exogenous cause. The findings suggest that Boeck's sarcoidosis may be caused by unidentified exogenous agents.

Sarcoidosis and the Malignant Lymphoreticular Diseases

The case of a 49-year-old Negro man is described in whom sarcoidosis was followed by mycosis fungoides and a fatal lymphoma of mixed cell type. A review of the literature revealed 14 previously reported cases in which sarcoidosis and a malignant lymphoreticular disease were associated in the same individual. Of these, however, only one appears to have had both diagnoses adequately documented. In the present study, Kveim tests were performed on 21 additional patients with proved lymphoreticular malignancies of various types. Only one of these patients produced a positive reaction. As this patient had little other evidence of systemic sarcoidosis, the Kveim test in this instance may represent a false-positive reaction. The possibility of a relationship between sarcoidosis and the malignant lymphoreticuloses is discussed.

Unusual immunologic alterations in sarcoidosis during repeated Kveim testing

A thirty-eight year old woman, suffering from lymphonodal sarcoidosis, displayed exceptionally strong, rapid skin responses to several Kveim antigens, including an autologous antigen. During the initial Kveim tests the number of plasma cells in her lymph nodes increased, and marked hypergammaglobulinemia ensued. At the same time her blood showed a profound monocytosis and reactivity in flocculation tests for syphilis and in the latex flocculation test for rheumatoid factor. On the day following the second test with the most potent Kveim antigen, her blood displayed marked eosinophilia and strong complement-fixing activity against this antigen. During prednisone treatment the eosinophil count dropped abruptly, while flocculation reactions for syphilis disappeared more gradually, simultaneously with normalization of the level of gamma globulins and regression of Kveim papules and lymph nodes to a nonpalpable state. The serum, however, retained its complement-fixing activity against the repeatedly tested Kveim antigens for a longer time. The interrelations of these unusual immunologic alterations and their connection with repeated Kveim testing are discussed.

JOINT INVOLVEMENT IN SARCOIDOSIS WITH SPECIAL REFERENCE TO THE COEXISTANCE OF SARCOIDOSIS AND RHEUMATOID ARTHRITIS.

SummaryIn a group of 94 cases of sarcoidosis one definite and one probable case of rheumatoid arthritis was found. Additionally, the x-ray findings in some of the patients were similar to those in rheumatoid arthritis. Signs of rheumatoid arthritis were no more frequent than would be expected in a group of subjects of equal size without sarcoidosis.The most common form of joint involvement in sarcoidosis was migratory polyarthritis, which in cases of subacute sarcoidosis had an incidence of 33 per cent, and in association with erythema nodosum 57 per cent. Difficulties of differential diagnosis will arise mostly with respect to rheumatic fever, especially when the disease begins with joint symptoms and fever. In such atypical cases of arthritis the Kveim test is of diagnostic value.

A study of Crohn's syndrome using tissue extracts and the Kveim and Mantoux tests.

The vesicular glutamate transporters (VGLUTs) package glutamate into synaptic vesicles, and the two principal isoforms VGLUT1 and VGLUT2 have been suggested to influence the properties of release. To understand how a VGLUT isoform might influence transmitter release, we have studied their trafficking and previously identified a dileucine-like endocytic motif in the C terminus of VGLUT1. Disruption of this motif impairs the activity-dependent recycling of VGLUT1, but does not eliminate its endocytosis. We now report the identification of two additional dileucine-like motifs in the N terminus of VGLUT1 that are not well conserved in the other isoforms. In the absence of all three motifs, rat VGLUT1 shows limited accumulation at synaptic sites and no longer responds to stimulation. In addition, shRNA-mediated knockdown of clathrin adaptor proteins AP-1 and AP-2 shows that the C-terminal motif acts largely via AP-2, whereas the N-terminal motifs use AP-1. Without the C-terminal motif, knockdown of AP-1 reduces the proportion of VGLUT1 that responds to stimulation. VGLUT1 thus contains multiple sorting signals that engage distinct trafficking mechanisms. In contrast to VGLUT1, the trafficking of VGLUT2 depends almost entirely on the conserved C-terminal dileucine-like motif: without this motif, a substantial fraction of VGLUT2 redistributes to the plasma membrane and the transporter9s synaptic localization is disrupted. Consistent with these differences in trafficking signals, wild-type VGLUT1 and VGLUT2 differ in their response to stimulation.

Le Test De Kveim : Signification Clinique Et Immunolocique (*)1

SummaryKveim test was carried out in patients with sarcoidosis as well as in normal subjects.Nine extracts were prepared but five among them proved to be inert or unspecific. The four other antigens gave positive reactions in 79,4 % of the cases of subacute sarcoidosis, and 2,4 % of false positive reactions.The passive transfer of a positive Kveim test to normal subjects was carried out by means of leukocytes of patients with sarcoidosis. It was unsuccessful with serum of the same patients o Kveim test appears therefore as an hypersensitivity reaction of cellular or delayed type.