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The Treatment of Lupus Erythematosus with Mepacrine (Atabrine)1
THE TREATMENT OF LUPUS ERYTHEMATOSTJS WITH MEPACRINE (ATABRINE)* GEORGE HARVEY, M.B., Ca.B. AND THOMAS COCHRANE, B.Sc., M.D.
It is now little more than a year since Page (1) published his article on the treatment of lupus erythematosus with mepacrine. Sommerville, Devine, and Logan (2), Cramer and Lewis (3), Sawicky, Kanof, Silverberg, Braitman and Kalish (4) and Wells (5) reported on cases of lupus erythematosus treated with mepacrine (atabrine). During the past year we have used this drug in a number of cases of this disease. Our results varied somewhat from those observed by the above writers and we thought that it would be worth comparing our results with mepacrine with those obtained by the use of bismuth and mapharside. RESULTS OF TREATMENT
Table I gives the results of 20 previously untreated cases of lupus erythematosus who were given mepacrine. Forty-two cases all of whom had failed to respond to other forms of treatment were tried on mepacrine. Table II shows the results of treatment by mepacrine hydrochloride in the 62 cases of lupus erythematosus. Of the 62 cases 57 were typical chronic discoid lupus erythematosus, 4 were subacute cases of the disease with disseminated skin lesions and vague general malaise—2 had arthritic joint changes—and 1 was an acute disseminated case with widespread skin lesions, general malaise, pyrexia, albuminuria, leukopenia and spleriic enlargement. The dosage of mepacrine used varied slightly in different cases. The usual dosage was 200 mg. daily for one week and then 300 mg. for four weeks. The dose was then reduced to 200 mg. for four weeks and then to 100 mg. daily. The exact time of the reduction period varied with the degree of yellow staining. The duration of treatment varied from six weeks to eighteen weeks with an average duration of twelve weeks. Staining persisted for many weeks after withdrawal of the drug and was detectable by ifitered ultra violet light much longer than the naked eye. The staining was most evident around the hair follicles.
From Table II it will be seen that only 12 of the 20 previously untreated cases gave a satisfactory response to mepacrine treatment. Twenty-five of the 42 old cases showed a good response to the treatment. Three of the four subacute cases gave an excellent result but the youngest patient who presented typical lesions on the forehead, cheeks, nose, scalp, elbows, hands, fingers, knees, feet and chest, associated with general malaise and vague joint pains, did not improve on 200 mg. daily for ten weeks apart from the erythema of the lesions on the forehead becoming less intense. In 2 of the 3 successfully treated subacute cases although the skin cleared completely the arthritic joint changes were unaltered and the B.S.R. remained high. The skin lesions recurred in two and four months respectively after stopping treatment. The skin lesions of the one acute * From The
Department of Dermatology, Royal Infirmary, Glasgow, Scotland. Received for publication January 22, 1953. 99
NO.
59M
40F 59F 57F
11 12 13 14 15
41F
20
DISTRIBUTION
chest
Cheeks, nose
4Y
1Y
5Y 3M 6M 1M
ly
4Y 13Y Cheeks, nose Cheeks, forehead Cheeks, forehead, hands, 6M feet, elbows, knees,
Scalp
hands Hands, Cheeks Cheeks Cheeks, ears Cheeks, chest, arms Cheeks, forehead
9Y 2M
Cheek Cheeks, forehead, arms,
7
8
12 8 12 10
13 14 12 10 9
8
14 10
1Y
ly
13Y
11
7
11
WEEKS
IN
DORATION OP NEPACRINE
13 12 12
3Y
13Y
2Y 4M
ly
DORATION
Face, arms, hands, feet and body Cheek Cheek, nose Nose Cheeks, neck, fingers Cheeks, forehead
Cheeks, nose
Cheeks
* Subacute case.
14M
16 17 18 19*
22F 25F 32F
56M 34M
36M
10*
31F 50F 31M 50F 43F
71M 38F 49M
8 9
7
5 6
4
3*
2
1
CASE
ANO VATION
OBSER-
G
S
Nil
++
++
+++
3 3
++ ++
E
3
3
E
G
S
5
2
3
3
5
3
2
5
+++ +++ ++ +++ +++
++
+++ +++ +++ ++ +++ +++
+++ ++ +++
PERIOD IN STAINING MONTUS YELLOW
DEGREE
G Nil G
Nil E
E E
Nil
E
Nil
E
Nil
E
RESULT
TABLE I ____
Dermatitisstill present
E E
Relapse re-responding slowly 2nd course
G
Severe relapse
E
E
Relapse on Cheeks
E
Reactivity on face
E
PINAL RESULT
______________
Hyperkeratosis of palms and soles
Lichenoid dermatitis
Severe nausea and colic
TOXICREACTIONS
in
0
0
I-.
tn
0 0
101
MEPACRINE IN LUPTJS ERYTHEMATOSUS
case responded well to mepacrine but she now, four months after stopping treatment, shows very definite reactivity and is again on treatment. The response to treatment in our cases did not appear to be related so closely to the intensity of the yellow staining as was expected. In the 23 cases responding excellently to treatment 12 had moderate staining and 2 only mild staining. Of the 37 satisfactory cases no less than 12 cases relapsed during an observation period of from two to five months. Four of these 12 cases are now responding slowly to a further course of treatment. A comparison is made with the above figures and those from a series of cases treated with mapharside (3) and bismuth (4). No cases treated with gold are included as we have not used this heavy metal in the treatment of lupus erythematosus for many years on account of its high toxicity. The results of the three methods of treatment are summarised in Table
III. TABLE II RxSLTS OP TREATMENT TYPE OF CASE
RELAPSES
NUMBRR
Fresh cases Old cases
20
Total
Good
Slight
Nil
4
REACTIONS
8 15
10
2 5
6 12
4 8
3
42 62
23
14
7
18
12
8
RELAPSES
REACTIONS
12
8 3 4
5
TABLE III RESULTS OP TREATMENT METHOD OP TREATMENT
Mepacrine Bismuth Mapharside
NUMBER
62 117
56
Excellent
Good
Satisfactory
23 46 20
14
40
37 (59.7%) 86 (73.5%) 37 (66.2%)
17
9 5
To eliminate the possibility that mepacrine acted by its antimalarial properties two other drugs, used in the treatment of malaria, were given to a small series of cases. Chioroquine and paludrine were each used in the treatment of 10 cases of lupus erythematosus. With chioroquine 0.15G of chioroquine base was given every second day for two weeks and then 0.15G daily for two weeks. The dose was reduced to the original level for a further four to six weeks. With paludrine O.075G was given daily for 1 week than 0.1G daily for 1 week, 0.3G daily for 1 week and finally 0.1G daily for 6 weeks. The average duration of treatment was ten weeks. The results are tabulated in Table IV. No satisfactory results were obtained with paludrine. Two cases cleared completely with chioroquine. Both of these patients suffered from the disease for only a few months. One case has relapsed subsequently but the other patient still remains cured after five months observation. It is possible that these cases are examples of spontaneous remission which is not unknown in lupus erythematosus.
102
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
A 5 % mepacrine ointment and a 5 % aqueous paint were used as local treatment oniy in 6 cases but there was no obvious success. TABLE IV RESULTS OP TREATMENT METNOD OP TREATMENT
RELAPSES
NIflEBER
Excellent
Chioroquine Paludririe
10 10
2
—
Good
Nil
— —
10
8
1
—
REACTIONS
—
—
COMPLICATIONS
Complications from mepacrine treatment occurred in 8 of the cases: 3 developed typical lichenoid dermatitis, 2 had severe hyperkeratosis of the palms and soles and 1 an acute exfoliative dermatitis. This patient and 1 of the cases of lichenoid dermatitis were so severe as to warrant admission to the wards. Two patients suffered from severe nausea and abdominal colic related definitely to the mep-
acrine intake. Two patients, a man and a woman, refused further treatment after 3 weeks because of the yellow staining and 3 women refused mepacrine because of the discoloration which they had seen in other patients. One peculiar pseudocomplication occurred in a patient who spent seven weeks in bed with "yellow jaundice" after a most sucessful six weeks course of mepacrine. COMMENT
Of 62 cases of lupus erythematosus 37 responded satisfactorily to treatment with mepacrine. Sequeira, Ingram and Brain (8) state that sixty per cent of cases of lupus erythematosus respond to treatment. Our number of satisfactory results (37 or 59.7%) approximates closely to that figure but differs widely from the results obtained by Page (1) and Sommerville et al. (2). Nevertheless this number of successes in the treatment of such a capricious disease as lupus erythematosus can be regarded as satisfactory. It does not, however, make mepacrine the treatment of choice in this disease. This can be seen more clearly when the results obtained with mepacrine are compared with those from bismuth and mapharside. Mepacrine is only slightly below bismuth and mapharside in success in treatment but when the relapses and reactions of each drug are compared the differences between them become more emphasized and mepacrine becomes inferior to the other two. Page (1) does not state the reactions he observed with bismuth but remarks that they are well known. In a considerable experience of the use of bismuth we have had no reactions. Compared with gold we agree that mepacrine is a much more useful drug. Gold does produce an average number of satisfactory results in lupus erythematosus but it gave toxic reactions in no less than 22% of cases with several fatal issues (6). It has been stated by Page (1) that only 3 cases of lichenoid dermatitis were observed in several thousand troops receiving mepacrine. En only 62 cases we had 3 cases of lichenoid dermatitis, 1 case of exfoliative dermatitis and 2 of hyperkeratotic
MEPACRINE IN LIJPTJS EBYTHEMATOSIJS
103
dermatitis. Peterkin (9) is of the opinion that patients with previous skin disease are predisposed to lichenoid dermatitis. We agree with this suggestion and we are of the opinion that patients suffering from lupus erythematosus are unusually liable to develop skin complications in any treatment. This theory is supported by the dermal complications which occurred in the cases treated with mapharside. Three cases of arsenical dermatitis arose in 56 cases of lupus erythematosus while no skin complications have been seen in several hundred cases of syphilis treated with mapharside by one of us. We do not consider mepacrine our treatment of choice in lupus erythematosus. However since it did produce an excellent result in 15 of 42 cases which had resisted other forms of treatment and on account of the satisfactory results obtained in the fresh cases we feel that there is a definite place for it in the treatment of lupus erythematosus. Great care should be taken during its adminis-
tration to minimize the danger of producing a dermatitis which can last for many months and which can cause much more disability than the original discoid lupus erythematosus. The drug is easy to take, but control of the patient should be strict and the drug should be stopped immediately on the occurrence of pruritus. The yellow staining indicates that the tablets are being taken but we feel that it masks the lesions, because as the staining appears it is difficult to state the degree of erythema and the activity of the lesions. At first glance many lesions seem to be healing but as the yellow stain recedes on stopping the tablets the redness and activity resume their original intensity. We are of the opinion that assessment of cure should not be made until the yellow staining has been absent clinically from six to eight weeks. We intend to try the drug further in cases of acute disseminated lupus erythematosus. The good response of the subacute and acute cases resembles the action of ACTH in these cases but the joint manifestations did not improve. Currie (10) reported to us that he had no success with mepacrine in his clinic for rheumatoid arthritis. This would appear to be evidence that mepacrine does not exert its effect by an action similar to ACTH. The exact method by which it acts is unknown as in other drugs used in the disease. Although Page (1) states that it may reduce the light sensitivity of the skin we had no satisfactory response in a few cases of actinic dermatitis which were treated during the summer. Miller, Herrmann and Rubin (11) are of the opinion that mepacrine neither sensitizes nor desensitizes a patient to ultra violet light. STYMMARY
Sixty-two cases of lupus erythematosus were treated by mepacrine (atabrine) and a comparison made as regards cure, complications and relapses with series
of cases treated by bismuth and mapharside. Mepacrine is not so free from complications as was first thought, and is a potentially more toxic treatment than bismuth. Patients with lupus erythematosus appear to be more susceptible to dermatitis than normal individuals.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
104
REFERENCES (1) PAGE, F.: Treatment of lupus erythematosus with mepacrine. Lancet, 2: 775, 1951. (2) S0MMERvILLE, J., DEviN, D. C. AND LOGAN, J. C. P.: Lupus erythematosus treated with mepacrine. Brit. J. Dermat., 64:417, 1952. (3) CRAMER, JEAN A. AND LEWIs, GEORGE M.: Atabrine in the treatment of discoid lupus erythematosus. J. Invest. Dermat., 19: 393—395, 1952. (4) SAWIOXY, H. H., KANOF, NORMAN B., SILVERBERU, MABEL G., BRAITMAN, MAX AND
KALISH, BEATRICE: Therapeutic assays of the skin and cancer unit of the New York University Hospital. Assay VII. Quinacrine hydrochloride (atabrine hydrochloride) for chronic discoid lupus erythematosus. J. Invest. Dermat., 19: 397—404, 1952.
(5) WELLS, GEORGE C.: Treatment of chronic discoid lupus erythematosus with atabrine. J. Invest. Dermat., 19: 405—407, 1952.
(6) COCHEANE, T.: Mapharside treatment of 56 cases of lupus erythematosus discoides. Glasgow M. J., 80: 222, 1949.
(7) 000HEANE, T.: The treatment and early prognosis of lupus erythematosus. M.D. Thesis, University of Glasgow, 1950. (8) SEQUEIRA, J. M., INGRAM, J. T. AND BRAIN, R. T.: Diseases of the Skin, Churchill Ltd., Publishers, London, 254, 1947.
(9) PETERKIN, G. A. G.: Modern Practice of Dermatology, Butterworth & Co., Ltd., Publishers, London, 380, 1950. (10) CURRIE, J. P.: Personal Communication. (11) MILLER, 0. B., HERRMANN, F. AND RUBIN, J. : The effects of mepacrine hydrochloride (Atabrine) on the human skin. J. Invest. Dermat., 15: 445, 1951.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-
No warranty is given about the accuracy of the copy.
Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.
Cell Biol., 27: 603, 1965.
27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-
C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.
30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.
31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-
lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.
32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.
33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.
34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:
Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.
43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.
44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.
45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.
46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,
Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by
Res., 33: 176, 1964.
It is now little more than a year since Page (1) published his article on the treatment of lupus erythematosus with mepacrine. Sommerville, Devine, and Logan (2), Cramer and Lewis (3), Sawicky, Kanof, Silverberg, Braitman and Kalish (4) and Wells (5) reported on cases of lupus erythematosus treated with mepacrine (atabrine). During the past year we have used this drug in a number of cases of this disease. Our results varied somewhat from those observed by the above writers and we thought that it would be worth comparing our results with mepacrine with those obtained by the use of bismuth and mapharside. RESULTS OF TREATMENT
Table I gives the results of 20 previously untreated cases of lupus erythematosus who were given mepacrine. Forty-two cases all of whom had failed to respond to other forms of treatment were tried on mepacrine. Table II shows the results of treatment by mepacrine hydrochloride in the 62 cases of lupus erythematosus. Of the 62 cases 57 were typical chronic discoid lupus erythematosus, 4 were subacute cases of the disease with disseminated skin lesions and vague general malaise—2 had arthritic joint changes—and 1 was an acute disseminated case with widespread skin lesions, general malaise, pyrexia, albuminuria, leukopenia and spleriic enlargement. The dosage of mepacrine used varied slightly in different cases. The usual dosage was 200 mg. daily for one week and then 300 mg. for four weeks. The dose was then reduced to 200 mg. for four weeks and then to 100 mg. daily. The exact time of the reduction period varied with the degree of yellow staining. The duration of treatment varied from six weeks to eighteen weeks with an average duration of twelve weeks. Staining persisted for many weeks after withdrawal of the drug and was detectable by ifitered ultra violet light much longer than the naked eye. The staining was most evident around the hair follicles.
From Table II it will be seen that only 12 of the 20 previously untreated cases gave a satisfactory response to mepacrine treatment. Twenty-five of the 42 old cases showed a good response to the treatment. Three of the four subacute cases gave an excellent result but the youngest patient who presented typical lesions on the forehead, cheeks, nose, scalp, elbows, hands, fingers, knees, feet and chest, associated with general malaise and vague joint pains, did not improve on 200 mg. daily for ten weeks apart from the erythema of the lesions on the forehead becoming less intense. In 2 of the 3 successfully treated subacute cases although the skin cleared completely the arthritic joint changes were unaltered and the B.S.R. remained high. The skin lesions recurred in two and four months respectively after stopping treatment. The skin lesions of the one acute * From The
Department of Dermatology, Royal Infirmary, Glasgow, Scotland. Received for publication January 22, 1953. 99
NO.
59M
40F 59F 57F
11 12 13 14 15
41F
20
DISTRIBUTION
chest
Cheeks, nose
4Y
1Y
5Y 3M 6M 1M
ly
4Y 13Y Cheeks, nose Cheeks, forehead Cheeks, forehead, hands, 6M feet, elbows, knees,
Scalp
hands Hands, Cheeks Cheeks Cheeks, ears Cheeks, chest, arms Cheeks, forehead
9Y 2M
Cheek Cheeks, forehead, arms,
7
8
12 8 12 10
13 14 12 10 9
8
14 10
1Y
ly
13Y
11
7
11
WEEKS
IN
DORATION OP NEPACRINE
13 12 12
3Y
13Y
2Y 4M
ly
DORATION
Face, arms, hands, feet and body Cheek Cheek, nose Nose Cheeks, neck, fingers Cheeks, forehead
Cheeks, nose
Cheeks
* Subacute case.
14M
16 17 18 19*
22F 25F 32F
56M 34M
36M
10*
31F 50F 31M 50F 43F
71M 38F 49M
8 9
7
5 6
4
3*
2
1
CASE
ANO VATION
OBSER-
G
S
Nil
++
++
+++
3 3
++ ++
E
3
3
E
G
S
5
2
3
3
5
3
2
5
+++ +++ ++ +++ +++
++
+++ +++ +++ ++ +++ +++
+++ ++ +++
PERIOD IN STAINING MONTUS YELLOW
DEGREE
G Nil G
Nil E
E E
Nil
E
Nil
E
Nil
E
RESULT
TABLE I ____
Dermatitisstill present
E E
Relapse re-responding slowly 2nd course
G
Severe relapse
E
E
Relapse on Cheeks
E
Reactivity on face
E
PINAL RESULT
______________
Hyperkeratosis of palms and soles
Lichenoid dermatitis
Severe nausea and colic
TOXICREACTIONS
in
0
0
I-.
tn
0 0
101
MEPACRINE IN LUPTJS ERYTHEMATOSUS
case responded well to mepacrine but she now, four months after stopping treatment, shows very definite reactivity and is again on treatment. The response to treatment in our cases did not appear to be related so closely to the intensity of the yellow staining as was expected. In the 23 cases responding excellently to treatment 12 had moderate staining and 2 only mild staining. Of the 37 satisfactory cases no less than 12 cases relapsed during an observation period of from two to five months. Four of these 12 cases are now responding slowly to a further course of treatment. A comparison is made with the above figures and those from a series of cases treated with mapharside (3) and bismuth (4). No cases treated with gold are included as we have not used this heavy metal in the treatment of lupus erythematosus for many years on account of its high toxicity. The results of the three methods of treatment are summarised in Table
III. TABLE II RxSLTS OP TREATMENT TYPE OF CASE
RELAPSES
NUMBRR
Fresh cases Old cases
20
Total
Good
Slight
Nil
4
REACTIONS
8 15
10
2 5
6 12
4 8
3
42 62
23
14
7
18
12
8
RELAPSES
REACTIONS
12
8 3 4
5
TABLE III RESULTS OP TREATMENT METHOD OP TREATMENT
Mepacrine Bismuth Mapharside
NUMBER
62 117
56
Excellent
Good
Satisfactory
23 46 20
14
40
37 (59.7%) 86 (73.5%) 37 (66.2%)
17
9 5
To eliminate the possibility that mepacrine acted by its antimalarial properties two other drugs, used in the treatment of malaria, were given to a small series of cases. Chioroquine and paludrine were each used in the treatment of 10 cases of lupus erythematosus. With chioroquine 0.15G of chioroquine base was given every second day for two weeks and then 0.15G daily for two weeks. The dose was reduced to the original level for a further four to six weeks. With paludrine O.075G was given daily for 1 week than 0.1G daily for 1 week, 0.3G daily for 1 week and finally 0.1G daily for 6 weeks. The average duration of treatment was ten weeks. The results are tabulated in Table IV. No satisfactory results were obtained with paludrine. Two cases cleared completely with chioroquine. Both of these patients suffered from the disease for only a few months. One case has relapsed subsequently but the other patient still remains cured after five months observation. It is possible that these cases are examples of spontaneous remission which is not unknown in lupus erythematosus.
102
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
A 5 % mepacrine ointment and a 5 % aqueous paint were used as local treatment oniy in 6 cases but there was no obvious success. TABLE IV RESULTS OP TREATMENT METNOD OP TREATMENT
RELAPSES
NIflEBER
Excellent
Chioroquine Paludririe
10 10
2
—
Good
Nil
— —
10
8
1
—
REACTIONS
—
—
COMPLICATIONS
Complications from mepacrine treatment occurred in 8 of the cases: 3 developed typical lichenoid dermatitis, 2 had severe hyperkeratosis of the palms and soles and 1 an acute exfoliative dermatitis. This patient and 1 of the cases of lichenoid dermatitis were so severe as to warrant admission to the wards. Two patients suffered from severe nausea and abdominal colic related definitely to the mep-
acrine intake. Two patients, a man and a woman, refused further treatment after 3 weeks because of the yellow staining and 3 women refused mepacrine because of the discoloration which they had seen in other patients. One peculiar pseudocomplication occurred in a patient who spent seven weeks in bed with "yellow jaundice" after a most sucessful six weeks course of mepacrine. COMMENT
Of 62 cases of lupus erythematosus 37 responded satisfactorily to treatment with mepacrine. Sequeira, Ingram and Brain (8) state that sixty per cent of cases of lupus erythematosus respond to treatment. Our number of satisfactory results (37 or 59.7%) approximates closely to that figure but differs widely from the results obtained by Page (1) and Sommerville et al. (2). Nevertheless this number of successes in the treatment of such a capricious disease as lupus erythematosus can be regarded as satisfactory. It does not, however, make mepacrine the treatment of choice in this disease. This can be seen more clearly when the results obtained with mepacrine are compared with those from bismuth and mapharside. Mepacrine is only slightly below bismuth and mapharside in success in treatment but when the relapses and reactions of each drug are compared the differences between them become more emphasized and mepacrine becomes inferior to the other two. Page (1) does not state the reactions he observed with bismuth but remarks that they are well known. In a considerable experience of the use of bismuth we have had no reactions. Compared with gold we agree that mepacrine is a much more useful drug. Gold does produce an average number of satisfactory results in lupus erythematosus but it gave toxic reactions in no less than 22% of cases with several fatal issues (6). It has been stated by Page (1) that only 3 cases of lichenoid dermatitis were observed in several thousand troops receiving mepacrine. En only 62 cases we had 3 cases of lichenoid dermatitis, 1 case of exfoliative dermatitis and 2 of hyperkeratotic
MEPACRINE IN LIJPTJS EBYTHEMATOSIJS
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dermatitis. Peterkin (9) is of the opinion that patients with previous skin disease are predisposed to lichenoid dermatitis. We agree with this suggestion and we are of the opinion that patients suffering from lupus erythematosus are unusually liable to develop skin complications in any treatment. This theory is supported by the dermal complications which occurred in the cases treated with mapharside. Three cases of arsenical dermatitis arose in 56 cases of lupus erythematosus while no skin complications have been seen in several hundred cases of syphilis treated with mapharside by one of us. We do not consider mepacrine our treatment of choice in lupus erythematosus. However since it did produce an excellent result in 15 of 42 cases which had resisted other forms of treatment and on account of the satisfactory results obtained in the fresh cases we feel that there is a definite place for it in the treatment of lupus erythematosus. Great care should be taken during its adminis-
tration to minimize the danger of producing a dermatitis which can last for many months and which can cause much more disability than the original discoid lupus erythematosus. The drug is easy to take, but control of the patient should be strict and the drug should be stopped immediately on the occurrence of pruritus. The yellow staining indicates that the tablets are being taken but we feel that it masks the lesions, because as the staining appears it is difficult to state the degree of erythema and the activity of the lesions. At first glance many lesions seem to be healing but as the yellow stain recedes on stopping the tablets the redness and activity resume their original intensity. We are of the opinion that assessment of cure should not be made until the yellow staining has been absent clinically from six to eight weeks. We intend to try the drug further in cases of acute disseminated lupus erythematosus. The good response of the subacute and acute cases resembles the action of ACTH in these cases but the joint manifestations did not improve. Currie (10) reported to us that he had no success with mepacrine in his clinic for rheumatoid arthritis. This would appear to be evidence that mepacrine does not exert its effect by an action similar to ACTH. The exact method by which it acts is unknown as in other drugs used in the disease. Although Page (1) states that it may reduce the light sensitivity of the skin we had no satisfactory response in a few cases of actinic dermatitis which were treated during the summer. Miller, Herrmann and Rubin (11) are of the opinion that mepacrine neither sensitizes nor desensitizes a patient to ultra violet light. STYMMARY
Sixty-two cases of lupus erythematosus were treated by mepacrine (atabrine) and a comparison made as regards cure, complications and relapses with series
of cases treated by bismuth and mapharside. Mepacrine is not so free from complications as was first thought, and is a potentially more toxic treatment than bismuth. Patients with lupus erythematosus appear to be more susceptible to dermatitis than normal individuals.
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REFERENCES (1) PAGE, F.: Treatment of lupus erythematosus with mepacrine. Lancet, 2: 775, 1951. (2) S0MMERvILLE, J., DEviN, D. C. AND LOGAN, J. C. P.: Lupus erythematosus treated with mepacrine. Brit. J. Dermat., 64:417, 1952. (3) CRAMER, JEAN A. AND LEWIs, GEORGE M.: Atabrine in the treatment of discoid lupus erythematosus. J. Invest. Dermat., 19: 393—395, 1952. (4) SAWIOXY, H. H., KANOF, NORMAN B., SILVERBERU, MABEL G., BRAITMAN, MAX AND
KALISH, BEATRICE: Therapeutic assays of the skin and cancer unit of the New York University Hospital. Assay VII. Quinacrine hydrochloride (atabrine hydrochloride) for chronic discoid lupus erythematosus. J. Invest. Dermat., 19: 397—404, 1952.
(5) WELLS, GEORGE C.: Treatment of chronic discoid lupus erythematosus with atabrine. J. Invest. Dermat., 19: 405—407, 1952.
(6) COCHEANE, T.: Mapharside treatment of 56 cases of lupus erythematosus discoides. Glasgow M. J., 80: 222, 1949.
(7) 000HEANE, T.: The treatment and early prognosis of lupus erythematosus. M.D. Thesis, University of Glasgow, 1950. (8) SEQUEIRA, J. M., INGRAM, J. T. AND BRAIN, R. T.: Diseases of the Skin, Churchill Ltd., Publishers, London, 254, 1947.
(9) PETERKIN, G. A. G.: Modern Practice of Dermatology, Butterworth & Co., Ltd., Publishers, London, 380, 1950. (10) CURRIE, J. P.: Personal Communication. (11) MILLER, 0. B., HERRMANN, F. AND RUBIN, J. : The effects of mepacrine hydrochloride (Atabrine) on the human skin. J. Invest. Dermat., 15: 445, 1951.
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