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Year : 2007  |  Volume : 24  |  Issue : 3  |  Page : 83-86 Table of Contents   

Tuberculous sarcoidosis

Department Of Chest Disease, Jaslok Hospital And Research Center, 15, Dr. G. Deshmukh Marg, Mumbai 400026., India

Correspondence Address:
J R Shah
Department Of Chest Disease, Jaslok Hospital And Research Center, 15, Dr. G. Deshmukh Marg, Mumbai 400026.
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This presentation is to define tuberculous sarcoidosis as a distinct clinical en­tity quite separate from tuberculosis or sarcoidosis. Evidence is also presented to postulate that altered mycobacterial infection or its biodegraded products can reasonably be considered as the aetiologic cause of Tuberculous Sarcoidosis.

How to cite this article:
Shah J R. Tuberculous sarcoidosis. Lung India 2007;24:83-6

How to cite this URL:
Shah J R. Tuberculous sarcoidosis. Lung India [serial online] 2007 [cited 2020 Apr 6];24:83-6. Available from: http://www.lungindia.com/text.asp?2007/24/3/83/44220

   Introduction Top

Clinical set up of tuberculosis and sarcoidosis has close similarity. In practice on one end of the narrow spectrum we find patients with definite diagnostic criteria of pulmonary tuberculosis and at the other end those of undisputed diagnostic criteria of pulmonary sarcoidosis. In between is the gray zone wherein we find patients that fulfill diagnostic criteria both of tuberculosis and sarcoidosis. There is no doubt that in patients with tuberculosis individual lesion can be found exactly which resemble sarcoid tubercle. Scadding [1] was so impressed by patients in the gray zone that he introduced the term tuberculous sarcoidosis for this category of patients. Our experience of sarcoidosis of the last three decades as also the published work on the subject leads us to emphasize that tuberculous sarcoidosis should be clinically recognized as a well defined and distinct disease condition separate from tuberculosis and sarcoidosis.

Over the centuries tuberculous bacilli which were originally earthen saprophytes evolved first into pathogenic bovine strain and then as typical invasive mycobacteria to cause tuberculous disease. Over the period of time thereafter population also underwent adaptive evolutionary changes to strengthen their defense mechanism against infective organism. This is evident by the cell wall deficient mycobacteria grown from the blood of subjects with sarcoidosis [2] . There is also evidence of residual genetic material of tubercular bacilli by positive PCR in several cases of sarcoidosis [3] .

It is postulated in this article that the weakened tuberculous pathogenicity and altered immuno­defense mechanism in select individuals results in non­caseating granulomatous sarcoidosis instead of caseating granulomatous tuberculosis. This provides an explanation for the grey-zone of tuberculous sarcoidosis, a state of transition through which tuberculosis demerges and evolves as sarcoidosis. In support follows review in brief of the literature of epidemiology, immunology, bacteriology and case reports published on this specific aspect connecting tuberculosis to sarcoidosis. First however the description of tuberculous sarcoidosis.

Tuberculous Sarcoidosis :

Set-up of tuberculous sarcoidosis shows three patterns (1) patients who has had tuberculosis and develop sarcoidosis,(2) patients who present with co-existent sarcoidosis and tuberculosis and (3) patients of chronic sarcoidosis who develop overt tuberculosis. Tuberculous sarcoidosis has clinical manifestations of both diseases but the course is different and so also the treatment which is the combinations of steroids in large doses prescribed for the specific treatment of sarcoidosis with anti tuberculosis drugs.

The following case histories illustrate the clinical set-up of tuberculous sarcoidosis.

1. At the age of 17 years, this College girl student had cough, low grade fever, loss of weight and raised ESR. X-ray chest showed tuberculous infiltration in right upper lobe. She was given anti-tubercular drugs. Lesions on x-ray chest disappeared completely by 6 weeks. Anti-tubercular drugs was continued for total period of 9 months. During the next 6 years she kept very well and completed her studies for M.B.A. Soon thereafter she developed fever, cough, breathlessness, loss of weight and extensive infiltrative lesions occupying both lung fields. Sputum showed AFB. She was again given anti-tubercular drugs but without improvement. Her condition progressively deteriorated over next five months. She was admitted in hospital. Sputum smear was positive for AFB and culture for drug sensitivity did not show resistance to drugs. Repeat x-ray chest showed rapid progression of infiltrative but non­cavitating lesions. After considerable evaluation steroids was added in specifically adequate dosage for treatment of sarcoidosis. Her moribound condition improved almost miraculously and progressively. Anti-tubercular drugs were discontinued after 6 months, but steroids were continued for a further period of ten months until all the lesions cleared out. About a year later she migrated to Switzerland on a job and her diagnosis of sarcoidosis was accepted by the health department concerned with immigration.

2. A 32 year old male was investigated for fever, loss of weight and enlarged right cervical lymphadenopathy with cold abscess in neck by a senior physician in Lucknow. X-ray chest showed bilateral hilar and right paratracheal lymphadenopathy. The abscess was drained and he was put on anti-tubercular drugs. About six weeks later he again developed cold abscess. Thereafter he showed in the hospital. Cold abscess was incised and enlarged cervical gland were resected which on histopathology showed caseating tubercular granulomas and areas with distinct multiple noncaseating granuloma characteristic of sarcoidosis. Tuberculin test was positive, ESR was raised and SACE was markedly raised. He was treated with methyl prednisolone in doses required for treatment of sarcoidosis in addition to Anti tuberculosis drugs. He improved rapidly and enlarged cervical and intrathoracic lymph nodes regressed remarkably. Anti-tubercular drugs were discontinued after 3 months. Steroid was continued in maintenance dosage for seven months till complete clearance of intra thoracic lymph nodes.

   Epidemiology Top

Sarcoidosis was not recognized in developing countries like India earlier for reasons of lack of awareness and inadequate diagnostic facilities. Worldwide epidemiologic studies [4] have shown that sarcoidosis follows the population which has emerged from the scourge of tuberculosis. Asymptomatic or latent sarcoidosis is more frequently found in areas where tuberculosis incidence has been reduced. The eleven-city survery team of sarcoidosis analysed data concerning patients in 9 countries with varying populations and the results were surprisingly similar in 3 different continents. There is also evidence from a South African survey [4] that sarcoidosis is more frequent not only in the waning of tuberculosis but also after the eradication of leprosy. In much of the world transmission of tubercular infection is declining.

   Immunology Top

A controlled study of tuberculin sensitivity in sarcoidosis by Hoyle et all [5] found that 44 per cent of patients with sarcoidosis were insensitive whereas only 21 per cent of the control group were insensitive. Citron [6] studied results of addition of cortisone to tuberculin test. In healthy persons and in tuberculous patients previously positive tuberculin test was converted to negative. In sarcoidosis 50% of patients with previously negative test were converted to positive. Depression of skin sensitivity to tuberculosis is not a specific feature of sarcoidosis. Positive skin tuberculin test therefore does not rule out the diagnosis of sarcoidosis. Conversion of negative to positive reaction by addition of cortisone to tuberculin test is useful supportive evidence for diagnosis of sarcoidosis. If positive tubercular sensitivity in patients indicates previous infection with tubercular bacilli, the above observations would tend to support the view that sarcoidosis is also a manifestation of previous tuberculosis.

Gupta [7] has reported unusual sarcoid granulomatous reaction at the site of tuberculin test in a few patients. We had 4 patients who similarly reacted with acute erythema surrounding the nodule following tuberculin test which developed into granulomatous growth that proved sarcoidosis on histopathologic examination.

   Bacteriology Top

Ustvedt [8] reviewing 59 necropsies in cases of sarcoidosis found that tuberculosis was the cause of death in 11.Based on a continual investigation of 160 cases of sarcoidosis including 30 autopsies, Longcope and Frieman [9] in their study found considerable evidence for suspecting tubercular etiology.

Their concept was based on results of necropsy series in which mycobacterium tuberculosis was isolated in 25% cases.

Renewed interest in the infective nature of sarcoidosis followed the discovery of tuberculous bacilli in small groups in histologically proven and acceptable cases of sarcoidosis by Vanek [10] . Mitchell and Rees [11] also succeeded in producing sarcoid lesions in the footpads of mice by injecting a homogenate prepared from human sarcoid lesions and were able to use the mouse lesions to reproduce further lesions in other mice. Their discovery received support from the electron-microscopic studies of Green berg et al [12] , who found that the epithelioid cells in the centers of the sarcoidal granulomas contained cytoplasmic inclusion with structure compatible with an acid-fast organism. Several case reports describe isolation of either M. tuberculosis or atypical mycobacteria from tissue of patients who clinically have sarcoidosis. Kent and coworkers [13] , for example, reported that 14 of 30 cases initially diagnosed with sarcoidosis had positive mycobacterial cultures (12 with M. tuberculosis) when open lung biopsies were cultured carefully.

   Clinical Material Top

Many clinicians in Europe believed that sarcoidosis was related to tuberculosis. Pinner had earlier reported that acid-fast bacilli were occasionally found in sarcoidosis but that normally they were rapidly destroyed. Riley [14] reported the development of overt tuberculosis in 18 out of 52 cases of sarcoidosis. Scadding reported 34 cases of tuberculous sarcoidosis. Eleven cases had caseating tuberculosis that preceded the development of sarcoidosis. In 5 cases, sarcoidosis was followed by caseating tuberculosis. In remaining 18 cases, tubercle bacilli were isolated during the course of sarcoidosis although clinical, immunological and radiological features remained characteristic of sarcoidosis. We have collected 27 patients. 6 patients initially had tuberculosis who later on developed sarcoidosis. Thirteen patients had sarcoidosis and tuberculosis together when presented to us whereas 8 patients had sarcoidosis initially and later developed tuberculosis.

In a recent case report [15] of a patient histologically and bacteriologically confirmed as tubercular lymphadenitis. After 15 months of anti-tubercular drugs and despite resolution of lymph node, developed exertional dyspnoea. Histologically findings from tissue obtained via transbronchial biopsy and open lung biopsy proved sarcoidosis but also showed the presence of mycobacterium DNA by PCR. She subsequently showed good response clinically, radiologically, biochemically after one year of corticosteroid treatment for her sarcoidosis and remained relapse free afterwards.

In another recent Indian case report [16] of a 48 year old female housewife, who presented with moderate right sided lymphocytic exudative pleural effusion showed lymphadenopathy on chest skiagram, treated with anti­tubercular drugs. At the end of 4 months CT scan showed bilateral hilar and mediastinal lymphadenopathy. Serum ACE level was 150 µl/ml and tuberculin test was negative. Transbronchial lung biopsy revealed non-caseating granuloma consistent with the diagnosis of sarcoidosis.

   Discussion Top

The tubercle bacillus has frequently been cited as a possible cause of sarcoidosis. In a direct search for the presence of mycobacteria, few studies detected presence of acid-fast bacilli in tissues from sarcoid patients. Mycobacteria, however, may also be present in the 'cell wall deficient' or the 'L' forms. Mattman and co-workers [2] found cell wall deficient bacteria grown from blood of patients with sarcoidosis stained with monoclonal antibody raised against M.tuberculosis whole cell antigen. Certain studies [3] observed five fold greater amount of M.tuberculosis RNA in splenic tissue from patients with sarcoidosis. Others demonstrated presence of bacterial components and tuberculostearic acid in patients with sarcoidosis. suggesting that bacteria are mycobacterial in origin. More recently, molecular biologic techniques have been applied to the search for infectious agent in sarcoidosis.

Wong et al [14] reported a case of sarcoidosis in a patient previously treated for culture-proven M tuberculosis and showed that one of the mechanisms of developing sarcoidosis is a continued reaction of M tuberculosis. It is known that mycobacterial infection leading to a positive skin test but with no viable organisms may still have positive PCR reactions that would imply that the organism has been effectively killed but its genetic material remains dormant in the lung. Mycobacteria can cause a granulomatous reaction and may cause a reaction indistinguishable from sarcoidosis.

   Conclusion Top

Normally clinicians tend to place disease process of a patient into one or other neat category of diagnosis. With combined features of a disease process arises confusion unless it can be placed in a recognized category. This is so strikingly shown by Marc Noppen [17] who described the case histories of three patients with "overlap features" of both disorders, and in whom extensive diagnostic workup and response to therapy did not allow unequivocal classification into diagnosis of either sarcoidosis or tuberculosis.

From review of literature and material seen in clinical chest practice it seems fair to conclude that Tuberculous sarcoidosis, a term originally introduced by Scadding [1] should be considered as a definite clinical entity and that tuberculous sarcoidosis is a state of transition through which tuberculosis evolves into sarcoidosis in these patients.

   References Top

1.Scadding J G The relation between sarcoidosis and tuberculosis Brompton hospital case reports. Lloyed-Luke 1962; volume 31:34.  Back to cited text no. 1    
2.Mattman, M Lesser, A Johnson, P L Almenoff. Growth of acid fast L forms from the blood of patients with sarcoidosis. Thorax 1996; 51: 530-533.  Back to cited text no. 2    
3.Mitchell I C Turk J L Mitchell D.N. Detection of mycobacterial RNA in sarcoidosis with liquid-phase hybridization. Lancet 1992;339:1015-17.  Back to cited text no. 3    
4.James D G Neville E, Siltzbach E. A Worldwide review of Sarcoidosis. Ann N Y Acad Sci 1976; 278:321-333.  Back to cited text no. 4    
5.Hoyale C, Dawson J and Mather G. Skin sensitivity in Sarcoidosis. Lancet 1954; 2:164  Back to cited text no. 5    
6.Citron K M and Scadding J G The effect of Cortisone upon the reaction of skin to tuberculin in Tuberculosis and in Sarcoidosis.Quart J Med. 1957; 26:277.  Back to cited text no. 6    
7.Gupta S K, Mitra K, Roy M, Dutta S K Mantoux test site granuloma in sarcoidosis in India. Sarcoidosis 1986; 3:153 (Abstract).  Back to cited text no. 7    
8.Ustvedt H J Necropsies in cases of sarcoidosis. Tubercle (London)1948; 29:107.  Back to cited text no. 8    
9.Longcope WT, Freeman DG. A study of Sarcoidosis based on combined investigation of 16 cases including 30 autopsies fiom John Hopkins Hospital and Massachusetts General Hospital. Med 1952; 26:277.  Back to cited text no. 9    
10.Vaneck J, Schwarz J. Demonstration of acid fast rods in Sarcoidosis. Am Rev Respir Dis 1970; 101:395.  Back to cited text no. 10    
11.Mitchell D N, Rees R J W, Goswami K K A. Transmissible agents from human sarcoid and Crohn's disease tissue. Lancet 1976;761.  Back to cited text no. 11    
12.Greenberg DS, Gyorkey F, Wes J et al. The ultrastructure of pulmonary granuloma in sarcoid. Am Rev Respir Dis 1970;102:648  Back to cited text no. 12    
13.Kent D, Houk V, Elliott R. The definativeevaluationofsarcoidosis.Am Rev Respir Dis 1970; 101:721.  Back to cited text no. 13    
14.Riley E. Boeck's Sarcoid. A review based upon the clinical study of 52 cases. Am Rev Tuberc 1952; 62:231.  Back to cited text no. 14    
15.Wong CF, Wing WY, Joseph L. A case of concomitant tuberculosis and sarcoidosis with mycobacterial DNA present in sarcoid lesion.Chest 1998; 114:626-629.  Back to cited text no. 15    
16.Bedi GS and Bedi RS. Indian J Tuberc 2004; 51:112-115.  Back to cited text no. 16    
17.Noppen M. Difficult diagnosis in granulomatous lung disease:sarcoidosis, tuberculosis or both? Eur J Intern Med 1994;5:283­-286.  Back to cited text no. 17    


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