111 the position concerning control of infectious diseases. It is reasonable to assume that this document lists all the Statutory Requirements now in force for the control of infectious diseases, and there is an appendix table giving the relevant statutory provisions and administrative guidIn the statutory requireance relating to tuberculosis. ments I can find no evidence of any obligation to maintain a tuberoulosis register, and in the guidance the only recommendation about duration of supervision is that mentioned in your editorial (Nov. 30, p. 1298) to which Dr Edwards refers. Under these circumstances the duration of supervision of a patient with tuberculosis is a clinical decision to be made by the physician, unhampered by any statutory ses
PATIENTS AND DISEASE STATE BEFORE AND AFTER LEVAMISOLE TREATMENT
6
MONTHS OF
requirement. In fact, I suspect that there has not for some years been any statutory requirement for either the medical officer of health or the chest clinic to maintain a tuberculosis register. Some of us still find it useful to do so, and even in areas where a formal register has been abandoned it is to be hoped that many practices associated with a register will be
continued-e.g., contact tracing, and transferring information to colleagues when patients still on treatment (or under supervision) move to other areas. Finally, I have not been able to discover when the fiveyear follow-up became or ceased to be a statutory requirement. I would be most grateful to Dr Edwards if he would specify the Act to which he refers. Birmingham Chest Clinic, 151 Great Charles Street, Queensway, Birmingham B3 3HX.
V. H. SPRINGETT.
LEVAMISOLE IN RHEUMATOID ARTHRITIS
SIR,—Kåss et al.,l Rewald,2and Le Vay3suggest the possibility of treating rheumatoid arthritis by immunopotentiation, while Yu and Peter4 point out the role of cell-mediated immunity in the pathogenesis of rheumatoid arthritis.
Recently, a drug, levamisole was reported to restore delayed hypersensitivity reactions in anergic elderly subjects5 and in patients with cancer,6,7 to activate phagocytosis,8,9 and to increase resistance to challenge with Brucella abortus after previous exposure to a live or dead Brucella vaccine.10,11 Encouraging results in the treatment of aphthous u1cerations,12,I3 recurrent herpes labialis and genitalis,13, 14 HB Ag-associated chronic hepatitis, 15 and recurrent bacterial infections,16 further suggested the potential of the drug both to restore cell-mediated immunity cutaneous
and to eradicate chronic infection. As rheumatoid arthritis could be an inappropriate immune response to an invading pathogenit was tempting 1. 2. 3. 4. 5.
Kiss, E., Frøland, S. S., Natvig, J. B., Blichfeldt, P., Høyeraal, H. M. Lancet, 1974, i, 627. Rewald, E. ibid. 1974, ii, 785. Le Vay, D. ibid. p. 908. Yu, D. T. Y., Peter, J. B. Sem. Arthr. Rheum. 1974, 4, 25. Verhaegen, H., De Cree, J., Verbruggen, F., Hoebeke, J., De Brabander, M., Brugmans, J. Verh. dt. Ges. inn. Med. 1973, 79, 623.
Tripodi, D., Parks, L. C., Brugmans, J. New Engl. J. Med., 1973, 289, 354. 7. Hirshaut, Y., Pinsky, C., Marquardt, H., et al. Proc. Am. Ass. Cancer Res. 1973, 14, 109. 8. Hoebeke, J., Franchi, G. J. reticuloend. Soc. 1973, 14, 317. 9. Verhaegen, H., De Cree, J., De Cock, W., Verbruggen, F. New Engl. J. Med. 1973, 229, 1148. 10. Renoux, G., Renoux, M. C. r. Acad. Sci. Paris, 1971, 272, 349. 11. Renoux, G., Renoux, M. J. Immun. 1972, 109, 761. 12. Verhaegen, H., De Cree, J., Brugmans, J. Lancet, 1973, ii, 842. 13. Symoens, J., Brugmans, J. Br. med. J. 1974, iv, 592. 14. Kint, A., Verlinden, L. New Engl. J. Med. 1974, 291, 308. 15. De Cree, J., Verhaegen, H., De Cock, W., Brugmans, J. Digestion, 6.
1974, 10, 306. Cree, J., Verhaegen, H., De Cock, W., Vanheule, R., Brugmans, J., Schuermans, V. Lancet, 1974, ii, 294.
levamisole in the treatment of rheumatoid arthritis. 6 patients with classical or definite long-standing rheumatoid arthritis, who responded poorly to the usual anti-inflammatory and analgesic drugs, have been treated with levamisole for more than 6 months. None had received corticosteroids,
to use
or gold compounds for six months before the study. None had been in hospital for more than two weeks during the study. The anti-inflammatory and analgesic drugs were continued unchanged. The dosage of levamisole was 150 mg. once a day, until striking improvement occurred, and was then reduced to 150 mg. for three consecutive days every two weeks. The results are shown in the accompanying table. Striking objective and subjective improvement was seen within the first month of treatment. A noticeable finding was the conversion to negative of the previously highly positive (quantitatively determined) Rose-Waaler and Latex tests in 3 patients. A tentative conclusion of this pilot study is that levamisole might alter the natural course of rheumatoid arthritis. We will further explore this possibility, as well as the effect on phagocytosis and skin tests, in double-blind studies. Reumatologie, St. Jozefkliniek,
anti-malarials, cytostatics,
Mermansstraat 20, B-2300 Turnhout, Belgium.
Y. SCHUERMANS.
EPIPODOPHYLLOTOXIN IN MYCOSIS FUNGOIDES
SIR The similarity between mycosis fungoides and the histiocytic neoplasms, coupled with our recent experience in which VP 16-213 produced objective remission in 17 (63%) of 27 patients with late diffuse histiocytic lymphoma1 suggested that this epipodophyllotoxin may also be useful in the management of mycosis fungoides. The following case seems to support this cutaneous
assumption. A 53-year-old coloured male was referred to Groote Schuur Hospital because of extensive ulcerating mycosis. He had a sloughing necrotic tumour overlying his right patella measuring 12 x 8 x 5 cm. and a second such lesion at the angle of his left mandible measuring 10 x 53cm., which was discharging foul-smelling debris. There were, in addition, widespread ulcerating skin lesions, and biopsy of these tumours showed the uniform histological picture of mycosis fungoides. The patient received 60 mg. per sq. m. of VP 16-213 daily as an intravenous injection for five days, followed by a rest period of nine days: each treatment cycle therefore occupied two weeks. No significant side-effects were seen and only mild alopecia occurred. The response of the tumour was dramatic and rapid resolution of all the skin masses began immediately after the first cycle. At present he is in remission with healing of all skin lesions. Maintenance therapy is twice weekly injections of VP 16-213.
The
treatment
of mycosis
fungoides is
often difficult and
16. De
1.
Jacobs, P., King,
H.
S., Gordon,
W. S.
Afr. med. J. (in the press).
PATIENTS AND DISEASE STATE BEFORE AND AFTER LEVAMISOLE TREATMENT
6
MONTHS OF
requirement. In fact, I suspect that there has not for some years been any statutory requirement for either the medical officer of health or the chest clinic to maintain a tuberculosis register. Some of us still find it useful to do so, and even in areas where a formal register has been abandoned it is to be hoped that many practices associated with a register will be
continued-e.g., contact tracing, and transferring information to colleagues when patients still on treatment (or under supervision) move to other areas. Finally, I have not been able to discover when the fiveyear follow-up became or ceased to be a statutory requirement. I would be most grateful to Dr Edwards if he would specify the Act to which he refers. Birmingham Chest Clinic, 151 Great Charles Street, Queensway, Birmingham B3 3HX.
V. H. SPRINGETT.
LEVAMISOLE IN RHEUMATOID ARTHRITIS
SIR,—Kåss et al.,l Rewald,2and Le Vay3suggest the possibility of treating rheumatoid arthritis by immunopotentiation, while Yu and Peter4 point out the role of cell-mediated immunity in the pathogenesis of rheumatoid arthritis.
Recently, a drug, levamisole was reported to restore delayed hypersensitivity reactions in anergic elderly subjects5 and in patients with cancer,6,7 to activate phagocytosis,8,9 and to increase resistance to challenge with Brucella abortus after previous exposure to a live or dead Brucella vaccine.10,11 Encouraging results in the treatment of aphthous u1cerations,12,I3 recurrent herpes labialis and genitalis,13, 14 HB Ag-associated chronic hepatitis, 15 and recurrent bacterial infections,16 further suggested the potential of the drug both to restore cell-mediated immunity cutaneous
and to eradicate chronic infection. As rheumatoid arthritis could be an inappropriate immune response to an invading pathogenit was tempting 1. 2. 3. 4. 5.
Kiss, E., Frøland, S. S., Natvig, J. B., Blichfeldt, P., Høyeraal, H. M. Lancet, 1974, i, 627. Rewald, E. ibid. 1974, ii, 785. Le Vay, D. ibid. p. 908. Yu, D. T. Y., Peter, J. B. Sem. Arthr. Rheum. 1974, 4, 25. Verhaegen, H., De Cree, J., Verbruggen, F., Hoebeke, J., De Brabander, M., Brugmans, J. Verh. dt. Ges. inn. Med. 1973, 79, 623.
Tripodi, D., Parks, L. C., Brugmans, J. New Engl. J. Med., 1973, 289, 354. 7. Hirshaut, Y., Pinsky, C., Marquardt, H., et al. Proc. Am. Ass. Cancer Res. 1973, 14, 109. 8. Hoebeke, J., Franchi, G. J. reticuloend. Soc. 1973, 14, 317. 9. Verhaegen, H., De Cree, J., De Cock, W., Verbruggen, F. New Engl. J. Med. 1973, 229, 1148. 10. Renoux, G., Renoux, M. C. r. Acad. Sci. Paris, 1971, 272, 349. 11. Renoux, G., Renoux, M. J. Immun. 1972, 109, 761. 12. Verhaegen, H., De Cree, J., Brugmans, J. Lancet, 1973, ii, 842. 13. Symoens, J., Brugmans, J. Br. med. J. 1974, iv, 592. 14. Kint, A., Verlinden, L. New Engl. J. Med. 1974, 291, 308. 15. De Cree, J., Verhaegen, H., De Cock, W., Brugmans, J. Digestion, 6.
1974, 10, 306. Cree, J., Verhaegen, H., De Cock, W., Vanheule, R., Brugmans, J., Schuermans, V. Lancet, 1974, ii, 294.
levamisole in the treatment of rheumatoid arthritis. 6 patients with classical or definite long-standing rheumatoid arthritis, who responded poorly to the usual anti-inflammatory and analgesic drugs, have been treated with levamisole for more than 6 months. None had received corticosteroids,
to use
or gold compounds for six months before the study. None had been in hospital for more than two weeks during the study. The anti-inflammatory and analgesic drugs were continued unchanged. The dosage of levamisole was 150 mg. once a day, until striking improvement occurred, and was then reduced to 150 mg. for three consecutive days every two weeks. The results are shown in the accompanying table. Striking objective and subjective improvement was seen within the first month of treatment. A noticeable finding was the conversion to negative of the previously highly positive (quantitatively determined) Rose-Waaler and Latex tests in 3 patients. A tentative conclusion of this pilot study is that levamisole might alter the natural course of rheumatoid arthritis. We will further explore this possibility, as well as the effect on phagocytosis and skin tests, in double-blind studies. Reumatologie, St. Jozefkliniek,
anti-malarials, cytostatics,
Mermansstraat 20, B-2300 Turnhout, Belgium.
Y. SCHUERMANS.
EPIPODOPHYLLOTOXIN IN MYCOSIS FUNGOIDES
SIR The similarity between mycosis fungoides and the histiocytic neoplasms, coupled with our recent experience in which VP 16-213 produced objective remission in 17 (63%) of 27 patients with late diffuse histiocytic lymphoma1 suggested that this epipodophyllotoxin may also be useful in the management of mycosis fungoides. The following case seems to support this cutaneous
assumption. A 53-year-old coloured male was referred to Groote Schuur Hospital because of extensive ulcerating mycosis. He had a sloughing necrotic tumour overlying his right patella measuring 12 x 8 x 5 cm. and a second such lesion at the angle of his left mandible measuring 10 x 53cm., which was discharging foul-smelling debris. There were, in addition, widespread ulcerating skin lesions, and biopsy of these tumours showed the uniform histological picture of mycosis fungoides. The patient received 60 mg. per sq. m. of VP 16-213 daily as an intravenous injection for five days, followed by a rest period of nine days: each treatment cycle therefore occupied two weeks. No significant side-effects were seen and only mild alopecia occurred. The response of the tumour was dramatic and rapid resolution of all the skin masses began immediately after the first cycle. At present he is in remission with healing of all skin lesions. Maintenance therapy is twice weekly injections of VP 16-213.
The
treatment
of mycosis
fungoides is
often difficult and
16. De
1.
Jacobs, P., King,
H.
S., Gordon,
W. S.
Afr. med. J. (in the press).
