- Email: [email protected]
The treatment of superficial tuberculous lymphadenitis
Tubercle (1990) 71, l-3 @ Longman Group UK Ltd 1990
0041-3879/90/0071-0001/$10.00
Leading article
The treatment lymphadenitis
of superficial
tuberculous
Mycobacterial infection and inflammation of the cervical, axillary, chest wall or inguinal lymph nodes in adults is almost always caused by Mycobacterium tuberculosis. In children, the infecting organisms are usually atypical mycobacteria (opportunist mycobacteria), more often M. avium-intracellulare than any of the other atypical species [l]. Such infections in children are usually cured by removal of the affected node [2]. In Great Britain, tuberculous lymphadenitis is much commoner among the immigrant population from the Indian sub-continent than among the indigenous white population [3-51. In the Asian group it is predominantly a disease of the younger and middle-aged groups, with women affected more often than men, whilst in the white British the condition is commoner among late middle-aged or older people. The onset of tuberculous lymphadenitis is usually slow and painless but can sometimes be acute with pyrexia and perinodal reaction. If left untreated the glands usually become caseous. Occasionally they appear to settle completely and calcify but there is always the risk of later reactivation. Before the middle 1970s the treatment of tuberculous lymphadenitis had not been studied as systematically as that of pulmonary tuberculosis. Practice included surgical excision, anti-tuberculosis chemotherapy for varying durations and various combinations of surgery and chemotherapy. Reports in the literature were based on retrospective and uncontrolled data [6, 71. In 1957 Kilpatrick and Douglas [8] reviewed the Edinburgh experience in the early chemotherapy era and
recommended that chemotherapy with two drugs should be given for at least 12-18 months, with aspiration or incision if there was obvious fluctuation. They advised the removal of isolated, large gland masses which had failed to respond after 46 weeks of chemotherapy. Fourteen years later Newcombe claimed that a policy of longer-term chemotherapy (18-24 months) with two antituberculosis drugs and early excision of the affected glands was an effective means of treatment, basing his opinion on a retrospective analysis of the results in 45 patients treated in that manner [9]. Reviewing the Westminster Hospital (London) experience between 1965 and 1973, Iles and Emerson showed that 10 out of 12 patients treated by excision alone relapsed while there were no relapses among 24 patients treated by excision plus chemotherapy [lo]. It was against this background that the British Thoracic Association (latterly the British Thoracic Society) set up a series of controlled trials which aimed not only to document the behaviour of this disease during and after treatment but also to compare various regimens of chemotherapy. First prospective study
In this study 18 months of rifampicin and isoniazid was compared with 18 months of ethambutol and isoniazid, both regimens supplemented initially with 2 months of streptomycin. The regimens were allocated in random order in each of three strata, depending on how the patient had been managed up to the point of diagnosis (total excision, diagnostic biopsy or clinical picture plus 1
CAMPBELL
2 positive tuberculin test). Standard doses of the drugs were used. Clinical reviews were performed monthly up to 3 months and 3 monthly thereafter up to 3 years. At the end of chemotherapy, 108 patients were available for analysis. In 65% there had been smooth resolution of the enlarged nodes. Fresh nodes appeared in 12% and existing nodes enlarged in 13% during chemotherapy. Fluctuation developed in ll%, 7% discharged and excision or aspiration was performed in 19%. At the end of chemotherapy there was a persistent sinus or unhealed scar in 2% but 18 months later these had healed. At the end of chemotherapy 13% had been left with residual nodes, but, 18 months later, in half of these patients the nodes had disappeared, in a quarter they had remained the same or shrunk further and in a quarter they were actually larger; New nodes appeared transiently in 2%) whilst in 4% of patients nodes reappeared after chemotherapy at previously involved sites. Hypersensitivity to tuberculoprotein was thought a likely explanation for these phenomena as there was no bacteriological relapse and no further treatment was deemed necessary in any patient. There was no difference in the efficacy of the two regimens of chemotherapy [ll, 121. Second prospective study While the first study was in progress it became apparent that short-course chemotherapy produced good results in the treatment of pulmonary tuberculosis, provided that it included rifampicin and isoniazid [13, 141. In 1980 Summers and McNicol published a retrospective survey describing 239 patients with tuberculous lymphadenitis in the London borough of Brent: only 4 patients relapsed after the end of treatment in a follow-up period extending from 14 years. A considerable proportion of their patients had been treated with rifampicin and isoniazid for 9 months, plus initial ethambutol, and none of these had relapsed [15]. In the second study by the British Thoracic Association short course chemotherapy, i.e. 9 months of rifampicin and isoniazid, was compared with 18 months therapy, both regimens including an initial 2 months of ethambutol. The design and methodology were similar to the previous study except that patients were followed up for a total of 5 years. In 74% of the total of 113 patients, the nodes resolved uneventfully during treatment. Again,
node enlargement (12%) and fresh nodes (12%)) were seen during treatment, fluctuation developing in 7%, whilst in 6% there was discharge or sinus formation or scar breakdown. At the end of chemotherapy 9% had residual nodes. After chemotherapy nodes enlarged transiently in 10% or appeared afresh in 4%. One node became fluctuant. At 5 years, 4% had residual nodes. There was no microbiological or clinical relapse. Initial surgery or aspiration eventually conferred neither advantage nor disadvantage. The cosmetic results were considered perfect or adequate in 84% (in the other 16% the data were not available). In the comparisons of 9 months with 18 months of treatment no differences emerged [16,
171 Current trial It became apparent in further studies of shortcourse treatment in pulmonary tuberculosis that the addition of pyrazinamide to the initial intensive phase of the regimen allowed the duration of chemotherapy to be shortened to 6 months [18, 191. Furthermore, a retrospective study of patients with mediastinal lymph node tuberculosis showed that incorporation of pyrazinamide led to improved resolution of the lymphadenopathy 1201. Currently a prospective, multi-centre trial is under way, comparing three regimens: 9 months of rifampicin and isoniazid, plus ethambutol for the first 2 months; 9 months of rifampicin and isoniazid, plus pyrazinamide for the first 2 months; and 6 months of rifampicin and isoniazid, plus pyrazinamide for the first 2 months. Results of this study should be available in 1992. Summary Tuberculosis of the superficial lymph nodes responds well to chemotherapy, with uneventful resolution of the condition in 70% of patients. Nodes can appear afresh or enlarge during treatment but usually resolve. Fluctuation, discharge, sinus formation and scar breakdown occur in the minority. At the end of chemotherapy 10% may be left with residual nodes. After chemotherapy nodes can enlarge or appear afresh, usually transiently. Such events do not imply relapse, nor does the persistence of nodes presage relapse. Initial excision does not seem to affect outcome and surgical procedures should be reserved for the relief of discomfort caused by enlarged nodes or tense, fluctuant nodes.
3
SUPERFICIAL TUBERCULOUS LYMPHADENITIS
Nine months of rifampicin and isoniazid, supplemented by ethambutol for the first 2 months, is the current treatment of choice for tuberculous lymphadenitis. Shorter regimens are under investigation.
10. Iles PB, Emerson PA. Tuberculous lymphadenitis. Brit II Med J 1974; 1: 143-145.
Sully Hospital, Cardiff CF6 2YA, UK.
13
I. A. Campbell
References 1. Editorial. Scrofula today. Lancet 1983; 1: 335-336. 2. White MP, Bangash H, Goel KM, Jenkins PA. Nontuberculous mycobacterial lymphadenitis. Arch Dis Child 1986; 61: 368-371. 3. British Thoracic and Tuberculosis Association. A tuberculosis survey in England and Wales 1971; the influence of immigration and country of birth upon notifications. Tubercle 1973; 54: 249-260. 4. British Thoracic Association. Tuberculosis among immigrants in Britain. Brit Med J 1978: 1: 1038-1040. 5. Medical Research Council Tuberculosis and Chest Diseases Unit. National survey of tuberculous notifications in England and Wales 1978-9. Brit Med J 1980; 281: 895898. Gillam PMS, Knowles JP. The treatment of tuberculous lymphadenitis. Tubercle 1963; 44: 112-118. Kent DC. Tuberculous lymphadenitis: not a localised disease. Am J Med Sci 1967; 254: 866-874. Kilpatrick GS, Douglas AC. Superficial glandular tuberculosis treatment with chemotherapy. Brit Med J 1957; 2: 612-614. 9. Newcombe JF. Tuberculous cervical lymphadenopathy. Postgrad Med J 1971; 47: 713-717.
Campbell IA, Dyson AJ. Lymph node tuberculosis: a Tubercle 1977; 58: 171-179. Campbell IA, Dyson AJ. Lymph node tuberculosis: a comparison of treatments 18 months after completion of chemotherapy. Tubercle 1979; 60: 95-98. East African/British Medical Research Councils. Controlled clinical trial of four short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Lancet 1973; 1331-1339. British Thoracic and Tuberculosis Association. Shortcourse chemotherapy in pulmonary tuberculosis. Lancet 1976; 1102-1104. Summers GD, McNicol MW. Tuberculosis of superficial lymph nodes. Brit J Dis Chest 1980; 74: 369-373. British Thoracic Society Research Committee. Short course chemotherapy for tuberculosis of lymph nodes: a controlled trial. Brit Med J 1985; 290: 1106-1108. British Thoracic Society Research Committee. Short course chemotherapy for lymph node tuberculosis: final report at 5 years. Brit J Dis Chest 1988; 82: 282-284. Singapore Tuberculosis Service/British Medical Research Council. Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis: the results up to 30 months. Tubercle 1981; 62: 95-102. British Thoracic Society. A controlled trial of 6 months chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. Brit J Dis Chest 1984; 78: 330-336. Ormerod LP. A retrospective comparison of two drug regimens RHE2/RHlO and RHZ2/RHlO in the treatment of tuberculous mediastinal lymphadenopathy. Brit J Dis Chest 1988; 82: 274-281.
’ comparison of various methods of treatment. 12.
14.
1.5 16. 17.
18.
19.
20.
0041-3879/90/0071-0001/$10.00
Leading article
The treatment lymphadenitis
of superficial
tuberculous
Mycobacterial infection and inflammation of the cervical, axillary, chest wall or inguinal lymph nodes in adults is almost always caused by Mycobacterium tuberculosis. In children, the infecting organisms are usually atypical mycobacteria (opportunist mycobacteria), more often M. avium-intracellulare than any of the other atypical species [l]. Such infections in children are usually cured by removal of the affected node [2]. In Great Britain, tuberculous lymphadenitis is much commoner among the immigrant population from the Indian sub-continent than among the indigenous white population [3-51. In the Asian group it is predominantly a disease of the younger and middle-aged groups, with women affected more often than men, whilst in the white British the condition is commoner among late middle-aged or older people. The onset of tuberculous lymphadenitis is usually slow and painless but can sometimes be acute with pyrexia and perinodal reaction. If left untreated the glands usually become caseous. Occasionally they appear to settle completely and calcify but there is always the risk of later reactivation. Before the middle 1970s the treatment of tuberculous lymphadenitis had not been studied as systematically as that of pulmonary tuberculosis. Practice included surgical excision, anti-tuberculosis chemotherapy for varying durations and various combinations of surgery and chemotherapy. Reports in the literature were based on retrospective and uncontrolled data [6, 71. In 1957 Kilpatrick and Douglas [8] reviewed the Edinburgh experience in the early chemotherapy era and
recommended that chemotherapy with two drugs should be given for at least 12-18 months, with aspiration or incision if there was obvious fluctuation. They advised the removal of isolated, large gland masses which had failed to respond after 46 weeks of chemotherapy. Fourteen years later Newcombe claimed that a policy of longer-term chemotherapy (18-24 months) with two antituberculosis drugs and early excision of the affected glands was an effective means of treatment, basing his opinion on a retrospective analysis of the results in 45 patients treated in that manner [9]. Reviewing the Westminster Hospital (London) experience between 1965 and 1973, Iles and Emerson showed that 10 out of 12 patients treated by excision alone relapsed while there were no relapses among 24 patients treated by excision plus chemotherapy [lo]. It was against this background that the British Thoracic Association (latterly the British Thoracic Society) set up a series of controlled trials which aimed not only to document the behaviour of this disease during and after treatment but also to compare various regimens of chemotherapy. First prospective study
In this study 18 months of rifampicin and isoniazid was compared with 18 months of ethambutol and isoniazid, both regimens supplemented initially with 2 months of streptomycin. The regimens were allocated in random order in each of three strata, depending on how the patient had been managed up to the point of diagnosis (total excision, diagnostic biopsy or clinical picture plus 1
CAMPBELL
2 positive tuberculin test). Standard doses of the drugs were used. Clinical reviews were performed monthly up to 3 months and 3 monthly thereafter up to 3 years. At the end of chemotherapy, 108 patients were available for analysis. In 65% there had been smooth resolution of the enlarged nodes. Fresh nodes appeared in 12% and existing nodes enlarged in 13% during chemotherapy. Fluctuation developed in ll%, 7% discharged and excision or aspiration was performed in 19%. At the end of chemotherapy there was a persistent sinus or unhealed scar in 2% but 18 months later these had healed. At the end of chemotherapy 13% had been left with residual nodes, but, 18 months later, in half of these patients the nodes had disappeared, in a quarter they had remained the same or shrunk further and in a quarter they were actually larger; New nodes appeared transiently in 2%) whilst in 4% of patients nodes reappeared after chemotherapy at previously involved sites. Hypersensitivity to tuberculoprotein was thought a likely explanation for these phenomena as there was no bacteriological relapse and no further treatment was deemed necessary in any patient. There was no difference in the efficacy of the two regimens of chemotherapy [ll, 121. Second prospective study While the first study was in progress it became apparent that short-course chemotherapy produced good results in the treatment of pulmonary tuberculosis, provided that it included rifampicin and isoniazid [13, 141. In 1980 Summers and McNicol published a retrospective survey describing 239 patients with tuberculous lymphadenitis in the London borough of Brent: only 4 patients relapsed after the end of treatment in a follow-up period extending from 14 years. A considerable proportion of their patients had been treated with rifampicin and isoniazid for 9 months, plus initial ethambutol, and none of these had relapsed [15]. In the second study by the British Thoracic Association short course chemotherapy, i.e. 9 months of rifampicin and isoniazid, was compared with 18 months therapy, both regimens including an initial 2 months of ethambutol. The design and methodology were similar to the previous study except that patients were followed up for a total of 5 years. In 74% of the total of 113 patients, the nodes resolved uneventfully during treatment. Again,
node enlargement (12%) and fresh nodes (12%)) were seen during treatment, fluctuation developing in 7%, whilst in 6% there was discharge or sinus formation or scar breakdown. At the end of chemotherapy 9% had residual nodes. After chemotherapy nodes enlarged transiently in 10% or appeared afresh in 4%. One node became fluctuant. At 5 years, 4% had residual nodes. There was no microbiological or clinical relapse. Initial surgery or aspiration eventually conferred neither advantage nor disadvantage. The cosmetic results were considered perfect or adequate in 84% (in the other 16% the data were not available). In the comparisons of 9 months with 18 months of treatment no differences emerged [16,
171 Current trial It became apparent in further studies of shortcourse treatment in pulmonary tuberculosis that the addition of pyrazinamide to the initial intensive phase of the regimen allowed the duration of chemotherapy to be shortened to 6 months [18, 191. Furthermore, a retrospective study of patients with mediastinal lymph node tuberculosis showed that incorporation of pyrazinamide led to improved resolution of the lymphadenopathy 1201. Currently a prospective, multi-centre trial is under way, comparing three regimens: 9 months of rifampicin and isoniazid, plus ethambutol for the first 2 months; 9 months of rifampicin and isoniazid, plus pyrazinamide for the first 2 months; and 6 months of rifampicin and isoniazid, plus pyrazinamide for the first 2 months. Results of this study should be available in 1992. Summary Tuberculosis of the superficial lymph nodes responds well to chemotherapy, with uneventful resolution of the condition in 70% of patients. Nodes can appear afresh or enlarge during treatment but usually resolve. Fluctuation, discharge, sinus formation and scar breakdown occur in the minority. At the end of chemotherapy 10% may be left with residual nodes. After chemotherapy nodes can enlarge or appear afresh, usually transiently. Such events do not imply relapse, nor does the persistence of nodes presage relapse. Initial excision does not seem to affect outcome and surgical procedures should be reserved for the relief of discomfort caused by enlarged nodes or tense, fluctuant nodes.
3
SUPERFICIAL TUBERCULOUS LYMPHADENITIS
Nine months of rifampicin and isoniazid, supplemented by ethambutol for the first 2 months, is the current treatment of choice for tuberculous lymphadenitis. Shorter regimens are under investigation.
10. Iles PB, Emerson PA. Tuberculous lymphadenitis. Brit II Med J 1974; 1: 143-145.
Sully Hospital, Cardiff CF6 2YA, UK.
13
I. A. Campbell
References 1. Editorial. Scrofula today. Lancet 1983; 1: 335-336. 2. White MP, Bangash H, Goel KM, Jenkins PA. Nontuberculous mycobacterial lymphadenitis. Arch Dis Child 1986; 61: 368-371. 3. British Thoracic and Tuberculosis Association. A tuberculosis survey in England and Wales 1971; the influence of immigration and country of birth upon notifications. Tubercle 1973; 54: 249-260. 4. British Thoracic Association. Tuberculosis among immigrants in Britain. Brit Med J 1978: 1: 1038-1040. 5. Medical Research Council Tuberculosis and Chest Diseases Unit. National survey of tuberculous notifications in England and Wales 1978-9. Brit Med J 1980; 281: 895898. Gillam PMS, Knowles JP. The treatment of tuberculous lymphadenitis. Tubercle 1963; 44: 112-118. Kent DC. Tuberculous lymphadenitis: not a localised disease. Am J Med Sci 1967; 254: 866-874. Kilpatrick GS, Douglas AC. Superficial glandular tuberculosis treatment with chemotherapy. Brit Med J 1957; 2: 612-614. 9. Newcombe JF. Tuberculous cervical lymphadenopathy. Postgrad Med J 1971; 47: 713-717.
Campbell IA, Dyson AJ. Lymph node tuberculosis: a Tubercle 1977; 58: 171-179. Campbell IA, Dyson AJ. Lymph node tuberculosis: a comparison of treatments 18 months after completion of chemotherapy. Tubercle 1979; 60: 95-98. East African/British Medical Research Councils. Controlled clinical trial of four short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Lancet 1973; 1331-1339. British Thoracic and Tuberculosis Association. Shortcourse chemotherapy in pulmonary tuberculosis. Lancet 1976; 1102-1104. Summers GD, McNicol MW. Tuberculosis of superficial lymph nodes. Brit J Dis Chest 1980; 74: 369-373. British Thoracic Society Research Committee. Short course chemotherapy for tuberculosis of lymph nodes: a controlled trial. Brit Med J 1985; 290: 1106-1108. British Thoracic Society Research Committee. Short course chemotherapy for lymph node tuberculosis: final report at 5 years. Brit J Dis Chest 1988; 82: 282-284. Singapore Tuberculosis Service/British Medical Research Council. Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis: the results up to 30 months. Tubercle 1981; 62: 95-102. British Thoracic Society. A controlled trial of 6 months chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. Brit J Dis Chest 1984; 78: 330-336. Ormerod LP. A retrospective comparison of two drug regimens RHE2/RHlO and RHZ2/RHlO in the treatment of tuberculous mediastinal lymphadenopathy. Brit J Dis Chest 1988; 82: 274-281.
’ comparison of various methods of treatment. 12.
14.
1.5 16. 17.
18.
19.
20.