Negative Tuberculin Test Research Articles

La tuberculose ganglionnaire en France chez l'adulte non immunodéprimé : une pathologie qui reste d'actualité

Lymph node tuberculosis is more frequent in Africa or in HIV-infected patients. We review results that were obtained in 18 patients with lymph node tuberculosis but without infection by HIV. Eight French native patients (mean age: 69 years) and ten African patients (mean age: 32.5 years) were included into the study. Of the 18 patients, 14 had exclusively hematopoietic localizations, two with medullar involvement and two with either liver or spleen involvement. Normal erythrocyte sedimentation rate was found in two out of 18 cases and normal C-reactive protein levels in seven out of 17 cases. Lymph node biopsy revealed lesions typically associated with tuberculosis in 12 out of 14 patients, two of them had no necrosis. Inflammatory syndrome was inconstant, tuberculin test sometimes negative. A favorable outcome was seen in all cases after 6, 12 or 18 months of treatment, depending on clinical appreciation. Tuberculous lymphadenopathy in non-HIV-infected patients may occur without inflammatory syndrome, with sometimes negative tuberculin test and without lymph node necrosis.

Reliability of anergy skin testing in persons with HIV infection. The pulmonary Complications of HIV Infection Study Group.

Testing with antigens that elicit delayed-type cutaneous hypersensitivity reactions is commonly used to evaluate immune competence in persons infected with the human immunodeficiency virus; however, the reliability of such testing has not been determined. We performed serial testing with tuberculin, mumps, and Candida antigens in 491 HIV-infected persons and found that 30% of persons who initially had no reaction (0 mm) to any of the three antigens, and, thus, were considered to be anergic, had reaction to the mumps or Candida antigen when they were retested 12 months later. We also examined the results of mumps antigen tests in 50 subjects who had a negative tuberculin tests after an initial positive test. The mumps antigen test was positive in 39% of the subjects when the tuberculin test was falsely negative. We conclude that tests commonly used to define anergy cannot reliably identify the anergic state. Moreover, using the mumps antigen to aid in the interpretation of the tuberculin test will often lead to erroneous conclusions. These data indicate that the results of anergy testing should not be used to make individual patient decisions concerning preventive therapy for tuberculosis.

Does Crohn's disease need differentiation from tuberculosis?

Crohn's disease (CD) and tuberculosis (TB) of the gastrointestinal tract pose major diagnostic problems for clinicians where these conditions coexist. Clinically and radiologically, the diseases are similar. In the West, TB is considered in the differential diagnosis of all suspected cases of CD, particularly among Asian migrants. Earlier age of presentation, perianal disease and enteric fistulae favour a diagnosis of CD. Aphthoid ulceration, pseudopolyps and filiform mucosa at endoscopy are suggestive of CD and a negative tuberculin test us useful. The final diagnosis depends largely on histopathology and the presence or absence of acid fast bacilli. Tuberculosis is more common in developing countries and intestinal TB frequently coexists with pulmonary tuberculosis. TB is known to affect all age groups and fistulous communication, although uncommon, does occur. In addition to radiology and endoscopy, laparotomy may be required to establish the diagnosis. In developing countries, CD is uncommon and remains largely a diagnosis of exclusion. A trial of anti-tuberculosis therapy may often be prescribed before definitely diagnosing CD. The development of molecular biology techniques had led to a revival of interest in mycobacteria as a possible aetiological agent in CD. DNA from Mycobacterium paratuberculosis and Mycobacterium kansaii have both been identified in CD cases but the significance of this finding has not been established. However, in the near future polymerase chain reaction will become increasingly useful in differentiating CD from intestinal TB because it allows the amplification and identification of very small quantities of mycobacterium DNA.

Tuberculin reactivity in Bacillus Calmette-Guérin vaccinated subjects

Setting: The Centre for Prevention and Control of Tuberculosis in Barcelona, Spain, where the staff appointed to Training Centers are examined. Aims: To check for tuberculin sensitivity due to Bacillus Calmette-Guérin (BCG) vaccine and ascertain its duration. Method: We compared the results of a tuberculin test (TT) on vaccinated and non-vaccinated subjects. The induration diameter and the time elapsed between BCG vaccination and the TT were determined. Results: Of the 2424 vaccinated subjects, 1489 (61.4%) reacted to TT (≥ 5 mm) and of the 3135 non-vaccinated, 905 (28.9%) reacted, a significant difference. Of 1978 subjects vaccinated between 6 and 14 years of age, 63.3% were TT reactors, compared to 23.9% of the 1948 non-vaccinated. Induration diameters ≥ 15 mm amounted to 11% for vaccinated subjects and 8% for those not vaccinated, a significant difference. The time from vaccination to TT was 13–25 years. Of the 446 subjects vaccinated at birth, 237 were reactors (53.1%); of the 887 non-vaccinated subjects of the same age, 154 (17.4%) reacted. Reactors ≥ 15 mm amounted to 40 (9%) for vaccinated subjects and 46 for non-vaccinated (5.2%), a significant difference. The time elapsed between vaccination and TT was 20–25 years. For 124 vaccinated subjects with a previous negative TT, a second test was positive for 87 (70.2%), and for 257 non-vaccinated it was positive for 64 (24.9%). The difference is due to a booster effect. Conclusions: BCG vaccination at birth and for school age children causes a reactivity to tuberculin which persists for 20 to 25 years. An induration diameter of ≥ 15 mm does not exclude a vaccinal origin. For vaccinated subjects with a previous negative TT, it is necessary to exclude the booster effect.

The negative tuberculin test: tuberculin, HIV, and anergy panels.

The negative tuberculin test: tuberculin, HIV, and anergy panels.

The negative tuberculin test. Tuberculin, HIV, and anergy panels.

"The negative tuberculin test. Tuberculin, HIV, and anergy panels.." American journal of respiratory and critical care medicine, 149(6), pp. 1699–1709

A prospective study of the risk of tuberculosis among HIV-infected patients

To evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. Prospective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration > or = 5 mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. Active TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +/- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +/- 103 x 10(6)/l (range, 1-400 x 10(6)/l). Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 10(6)/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.

Synovite sarcoïdosique: A propos d'un cas de localisation au niveau des tendons fléchisseurs des doigts

Sarcoidosis without bone involvement or sarcoid dactylitis, is a very unusual cause of flexor synovitis. Our reported patient initially presented with chronic arthralgia of the knees and ankles. The initial diagnosis of rheumatoid arthritis was incorrect. A surgical flexor synovectomy was performed to release painful compression of the median nerve due to the synovitis. The correct diagnosis was suggested by the histopathological examination showing noncaseating epithelioid granulomas. The diagnosis was confirmed by the association of a negative tuberculin test and raised angiotensin converting enzyme. No recurrence of synovitis occurred after surgical excision and colchicine therapy but arthralgia persisted.

Coincidence of Deficient Delayed Hypersensitivity and Intestinal Protozoa in Homosexual Men

Stool samples of 134 subjectively and apparently healthy male homosexual volunteers were studied, and in 86 men (64.2%) 190 parasite infestations, up to 6 per host, were identified. The most frequent species were Endolimax nana (40), Entamoeba coli (38), Entamoeba histolytica (34), Entamoeba hartmanni (32), and Iodamoeba bütschlii (22); Cryptosporidium was not found. All 11 isolates of Entamoeba histolytica analysed belonged to a noninvasive zymodeme: 10 were of zymodeme I and I of zymodeme III. In 172 healthy control adults 6 parasite infestations were found. In the homosexual men, a negative tuberculin test was more frequent in the presence than in the absence of parasites. Entamoeba histolytica (p = 0.005) Entamoeba coli (p = 0.013) and Iodamoeba bütschlii (p = 0.004) were associated with the anergy.

False negative tuberculin tests: check your Heaf gun.

False negative tuberculin tests: check your Heaf gun.

Four-year follow-up on the Albany experience with intrapleural BCG in lung cancer

One hundred sixty-nine patients were entered into randomized controlled studies of intrapleural bacille Calmette Guérin (BCG) immunotherapy after surgical resection of lung cancer. Long-term follow-up of our initial series of BCG-treated patients with Stage I disease continues to indicate that this treatment was superior to that given to control patients. The recurrence rate in the control population was high, 62% at 3 years. The recurrence rate was 33% at 3 years in the BCG-treated group. A negative preoperative tuberculin test and squamous cell histologic type were favorable prognostic factors for BCG-treated patients. The survival of patients with more advanced disease was not improved by BCG immunotherapy.

Miliary tuberculosis in association with chronic cutaneous tuberculosis

A case of miliary tuberculosis associated with two different forms of cutaneous tuberculosis and a negative Heaf tuberculin test is reported. The value of skin biopsy and culture in helping to establish an early diagnosis is discussed. The unusual finding of a negative Heaf tuberculin test is commented upon.

Assessment of Tuberculin Screening in an Urban Pediatric Clinic

The American Lung Association (ALA) and Center for Disease Control (CDC) have stated that routine screening of children is an inefficient and ineffective method for detection of tuberculosis in the United States. This is at variance with prior recommendations. Our objective, therefore, was to assess prospectively tuberculin screening for our urban, primarily low socioeconomic, clinic population. A prior chart review revealed that only 36% of tuberculin tests had written documentation of results. The following improvements were made: (1) One trained technician administered all tests and recorded data. (2) One hospital mail box was used for receiving tuberculin test postcard results. (3) Telephone follow-up was begun. This resulted in an increase of results documented to 84% (P .001). After these improvements, we prospectively studied the next 1,233 routine screening tests over a period of eight months. The written documentation rate during the study was 90%. Thirteen positive tuberculin tests were found. Three patients had subsequent negative tuberculin tests. One patient received Calmette-Guérin bacillus (BCG) as an infant and had multiple positive tuberculin tests in the past. One patient was lost to follow-up. Eight positive patients were confirmed as new converters. Of these eight patients, six had histories of prior positive tuberculin tests, recent TB exposure, foreign travel, or symptoms. We conclude that: (1) Prior to the study, recording of tuberculin tests was severely deficient. (2) Reorganization significantly increased the documentation rate. (3) Of 1,233 consecutive tests, eight unsuspected cases were found. This is below the 1% conversion rate recommended by the CDC for routine TB screening in children. (4) The data support the ALA-CDC statement regarding the low yield of routine tuberculin testing of healthy children. (5) However, abandoning tuberculin screening of healthy children would leave undetected a few children with unsuspected tuberculosis infection, who would then be in danger of developing serious illness.

AN OUTBREAK OF HISTOPLASMOSIS AT AN ARKANSAS COURTHOUSE, WITH FIVE CASES OF PROBABLE REINFECTION

An outbreak of histoplasmosis occurred at a county courthouse in Arkansas in July, 1975. Fifty cases were identified by symptoms and positive complement fixation (CF) tests and 18 others by the clinical findings alone. Only three positive CF tests (greater than or equal to 1:8) were found in a control group of 55 unexposed persons of the same age. The attack rate for 84 courthouse employees was 52%. Histoplasma capsulatum was isolated from the sputum of two cases, and from bird droppings which had been dumped from the roof of the courthouse two weeks before the epidemic's peak. Window air conditioners apparently helped to distribute infectious particles throughout the building. Nine exposed people had pulmonary calcifications and a negative tuberculin test that were taken as presumptive evidence of previous histoplasmosis. Five (55%) of these became ill. Exposed persons without pulmonary calcifications had an attack rate of 85%. The reinfected cases during convalescence had higher serum CF titers but not larger histoplasmin skin test diameters than the rest of the cases. A microdroplet aerosol of cooking oil was used to simulate air flow patterns during the exposure, and the results agreed with the hypothesized means of infection.

Sarcoidosis with mandibular involvement: Report of a case

A case of mandibular involvement in sarcoidosis is presented. The diagnosis was based on positive chest roentgenograms, involvement of superficial and mediastinal lymph nodes of epithelioid tubercles, negative tuberculin test, and negative results of an examination with respect to tubercle bacilli. Mandibular involvement was diagnosed tentatively roentgenographically and verified by histopathologic examination. The mandibular lesion was treated surgically, and the defect healed uneventfully after less than 1 year. Almost complete normalization of the pulmonary lesions had taken place after 2 years.

Tuberculin anergy in patients with Mycoplasma pneumoniae infection.

Skin testing for delayed hypersensitivity to tuberculin was performed in 36 patients with pneumonia associated with Mycoplasma pneumoniae infection. 22 of these patients had a negative tuberculin reaction when first tested. The tuberculin reaction was negative in 13 out of 16 cases tested during the first 2 weeks after onset of illness, in 6 out of 11 cases tested 15-28 days after onset of illness and in 3 out of 9 cases tested 29-45 days after clinical onset. In 19 patients with a negative tuberculin test in the early phase after onset of illness the test was repeated several weeks or months later. 16 of these cases had a positive tuberculin reaction at the later time period. Two of these cases showed prolonged tuberculin anergy for more than 5 months.

Tuberculin sensitivity in tuberculosis.

SummaryIt is generally accepted that patients suffering from Mycobacterium tuberculosis infections show positive tuberculin skin tests, with certain rare exceptions. Recognized causes of these exceptions include extreme illness, whether due to extensive tuberculosis or to other severe disease, and certain viral infections, notably measles. It is not so generally recognized that a few patients with pulmonary tuberculosis, generally of rather indolent type, who are not acutely ill, persistently fail to react to tuberculin; and that the range of tuberculin sensitivity observed in patients with the more usual forms of tuberculosis is very wide.The effect of cortisone in diminishing the size of tuberculin reactions in patients with pulmonary tuberculosis is directly related to the degree of sensitivity; reactions produced by small doses of tuberculin in patients with high sensitivity are greatly diminished or inhibited, while those produced by 100 T.U. in patients with low sensitivity are not significantly altered. Patients with tuberculosis can be desensitized to tuberculin by increasing injections of tuberculin under chemotherapy cover. In patients who have been so desensitized, the addition of cortisone to tuberculin in an intradermal test produces positive reactions in 70%. Among patients with sarcoidosis giving no reaction to 100 T.U., about half react when cortisone is added.These observations show that in patients with sarcoidosis, a negative tuberculin test cannot be taken to exclude M. tuberculosis infection.

Tuberculin Skin Test Conversion

To the Editor.— Dr. Edwards in her reply to a question (212:1219, 1970) has stated that isoniazid chemoprophylaxis is recommended for anyone of any age whose tuberculin reaction from negative to positive and that appearance of a positive reaction signals the occurrence of tuberculous infection. Thus a 62-year-old physician whose reaction converted seven months after a negative tuberculin test was advised chemoprophylaxis for one year. We have shown1,2that a tuberculin test itself converts a negative tuberculin reaction to a positive one in a substantial number of persons in the absence of tuberculous infection. Such conversions as a result of the previous tuberculin test increased in frequency with age and could be more frequent in areas with high prevalence of nonspecific sensitivity. The physician given the advice came from New York, an area from which 15% to 19% of the life-time Navy recruits gave 4-mm or larger reactions

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).

Calcification in intrathoracic nodes in Hodgkin's disease.

HODGKIN'S DISEASE is an entity of unknown etiology and uncertain nature which exhibits traits suggesting infection, immune reaction, and neoplasia. It often involves the intrathoracic nodes and particularly those tissues lying behind the sternum. Disease that is limited to or predominant in the thorax is commonly of a nodular sclerotic type and often follows a slow clinical course. Many patients suffering from well-differentiated forms of Hodgkin's disease live for many years, especially following radiation therapy to the thorax (1, 2). In some long-term survivors of this disease, calcification may appear in intrathoracic lymph nodes following irradiation. The first occurrence of such calcification was noted by us in 1951. Since then we have collected an additional 8 examples of calcified lymph nodes in the chest. In most of these, it was possible to follow the events from the appearance of uncalcified enlarged lymph nodes in the mediastinal, paratracheal, and hilar areas through the regression of these nodes following external roentgen therapy to the development of increasingly evident foci of calcification within the nodes. In our 9 cases, consisting of 4 males and 5 females, the calcification appeared from one to fourteen years after treatment (Table I). Radiation dosages, which could not be ascertained accurately in some instances, ranged from 1,000 to 6,000 R. No correlation could be drawn between the type or amount of treatment and the degree of calcification. One patient received 2 courses to the mediastinal lymph nodes; one received 3 courses; the others each received 1 course. No specific characteristics of the lymph node calcification were recognized. The nodes most commonly involved lay behind the middle and upper sternum, and less often in the paratracheal and hilar regions. In some cases, the diseased nodes were initially observed to be enlarged though not calcified, but they shrank in size following x-irradiation. Several months or years later, they were found to be partly calcified; with the passage of several more months or years, these calcifications became more and more dense, and the nodes seemed to shrink still further with increasing conglomeration of these calcific densities (Fig. 1). Most often the calcification was diffuse, finely stippled, or irregular and nodular. In two instances the periphery was accentuated in an eggshell pattern reminiscent of the calcification in silicosis (Fig. 2). As the calcific densities enlarged, more conglomeration occurred, with the formation of irregular masses (Fig. 1, C). None of our patients was known to have tuberculosis, histoplasmosis, or other associated inflammatory processes. One had a negative tuberculin test; the others were not tested for tuberculosis and fungi. These patients have been followed for relatively long periods of time. One was studied for thirty-two years, while others were observed for twenty-six, twenty-three, twenty-two, and seventeen years.