British Journal of Dermatology (1978) 99, 303.
Treatment of pustular psoriasis with clofazimine THAVATCHAI CHUAPRAPAISILP AND THADA PIAMPHONGSANT Accepted for publication 14 January 1978 Institute of Dermatology, Bangkok 4, Thailand
SUMMARY
Two cases of generalized pustular psoriasis (von Zumbusch) were successfully treated with clofazimine. No side effects were noted except deep red staining of the skin which faded afterwards.
Many systemic treatments have been used for the treatment of generahzed pustular psoriasis especially in cases not undergoing spontaneous remission; for example, systemic corticosteroids, methotrexate, hydroxyurea and azathioprine (Baker, 1975). However, the well-known severe complications from these medications urge us to seek another treatment, especially in younger age patients. This commtmication describes the successful use of clofazimine in two young male patients with generalized pustular psoriasis (von Zumbusch). CASE REPORTS
Case I A 28-year-old male was admitted to the Institute of Dermatology in March, 1976 with a i month history of generalized skin pustulation. He had a io-year history of scaly plaques on his scalp. The pustules were first noted on his forearm i month prior to admission and rapidly spread to the whole body. He also had high fever. On admission, generahzed pustulation was seen all over his body, covering the entire skin surface except a few areas on the face, palms and soles. A geographical tongue was present. Nail dystrophy and onycholysis with subungual debris were also noted. The temperature was 39°C and a leukocytosis of 13,100 cells/mm^ was found. A skin biopsy from a pustule showed the histology of pustular psoriasis. Wet dressings with potassium permanganate for 5 weeks resulted in no improvement. New crops of pustules continued to appear nearly every 4 days. Dapsone 200 mg per day was given for 3 weeks, but methaemoglobinaemia developed and the lesions did not improve. Next trimethoprim-sulfamethoxazole was tried for 3 weeks without beneficial eflFect. Finally clofazimine 200 mg per day was given. Subsequently the pustulation rapidly disappeared in 4 days and the scales gradually diminished. The colour of the skin changed to a generalized bright erythema but there were no new pustules during the following 14 days. New crops of pustules were again seen when the dose of clofazimine was reduced to 100 mg per day. The dose was then increased again to 200 mg per day and the skin cleared in 8 days. Clofazimine was discontinued 3 weeks later without 0007-0963/78/0900-0303502.00 ©1978 British Association of Dermatologists
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any new pustulation developing. No side eflfects from the medication were noted except deep red staining of the skin due to deposition of the dye and which gradually faded after the drug was discontinued. During follow-up every 2 months for i year only mild scaling on the scalp was observed. Gase 2 A 20-year-old Thai male has had a history of three severe attacks of generalized pustulation accompanied by high fever and leukocytosis since 17 years of age. He also had ankylosing deformities of the finger joints of both hands. The histopathology from the skin biopsies was that of pustular psoriasis; the clinical impression was that of the von Zumbusch type. Recurrent pseudomonas infections in the middle ear seemed to be the precipitating cause. His symptoms and pustulation would persist if he was treated symptomatically without methotrexate. A single oral dose of 50 mg per week of methotrexate regularly controlled the eruption. Subsequently, he was maintained on a dose of 20 mg per week without skin pustulation for many months. Discontinuation of methotrexate would result in recurrence of a few crops of pustules. In December 1976, while he was receiving the maintenance dose, new crops of pustules recurred on the scalp, face, trunk and extremities accompanied by high fever and leukocytosis. A geographical tongue was also present. He was admitted and methotrexate was discontinued. Clofazimine 200 mg daily was given orally. The crops of pustules were reduced in numbers within 5 days and there were no new lesions within 21 days. The skin changed to a mild exfoliative dermatitis and improved with topical cold cream. He was discharged with clofazimine 200 mg daily for another 2 months after which medication was discontinued. No side eflFects were noted from the clofazimine except a deep red staining of the skin which gradually faded. He has been followed up for 5 months without recurrent skin pustulation.
DISCUSSION
Clofazimine, a phenazine imino-quinone derivative, has been used for the treatment of leprosy, discoid lupus erythematosus (Mackey & Barnes, 1974), pyoderma gangrenosum (Michaelsson et al., 1976), and palmo-plantar pustulosis (Molin, 1975). The mechanism of action in leprosy is possibly by bacteria-DNA binding activity (Morrison & Marley, 1976). In pyoderma gangrenosum and palmoplantar pustulosis it possibly acts by enhancing phagocytic activity of the leukocytes (Michaelsson et al., 1976; Molin, 1975). The mechanism of action in psoriasis is not known since no studies on DNA binding activity or on the eflFect on the migration of leukocytes have been done in this disease. In order to evaluate the eflScacy of new drugs, time should be allowed for spontaneous remission in any case of pustular psoriasis. Up till now the longest course of generalized pustular psoriasis observed at our Institute before spontaneous remission has been 52 days (Piamphongsant, 1977). In our first case, spontaneous remission was not observed even after 11 weeks. Once clofazimine was started, the pustules regressed in 4 days. It is possible that this could have been a spontaneous remission, but the fact that remission did not take place before clofazimine was instituted, favours the eflBcacy of the drug. Besides, when the dosage was reduced the pustules recurred and could be controlled again by reinstituting the higher dosage. The remission period was quite long. In our second pustular case, which was methotrexate dependent, clofazimine was substituted and discontinued without a recurrence of pustulation. Although the course of pustular psoriasis is variable and unpredictable, its response to treatment in our cases favoured the eflBcacy of clofazimine in treating certain cases of pustular psoriasis. It is interesting, however, that clofazimine was also tried in 6 cases of discoid psoriasis without success (Mackey, 1976).
Pustular psoriasis treated with clofazimine
305
REFERENCES BAKERJ H . (1975) Psoriasis: a review. II. Dermatologica, 150, 136. MACKEYJ J.P. & BARNES, J. (1974) Clofazimine in the treatment of discoid lupus erythematosus. British Journal of Dermatology, 93, 91. MACKEY, J.P. (1976) Clofazimine in Dermatology. International Journal of Dermatology, 15, 140. MICHAELSSON, G., MOLIN, L . , OHMAN, S., G I P , L . , LINDSTROM, B., SHOGH, M . & TROLIN, I. (1976) Clofazimine,
a new agent for the treatment of pyoderma gangrenosum. Archives of Dermatology, 112, 344. MOLIN, L . (1975) Clofazimine—enhanced phagocytosis in pustulosis palmaris et plantaris. Acta Dermatovenereologica, 55, 151. MORRISON, N . E . & MARLEY, G.M. (1976) The mode of action of clofazimine—DNA binding studies. International Journal of Leprosy and other Mycobacterial Diseases, 44, 133. PIAMPHONGSANT, T . (1977) Generalized non-discoid pustular psoriasis: Its hiitodynsLvaic. Journal of the Medical Association of Thailand (in press).
Treatment of pustular psoriasis with clofazimine THAVATCHAI CHUAPRAPAISILP AND THADA PIAMPHONGSANT Accepted for publication 14 January 1978 Institute of Dermatology, Bangkok 4, Thailand
SUMMARY
Two cases of generalized pustular psoriasis (von Zumbusch) were successfully treated with clofazimine. No side effects were noted except deep red staining of the skin which faded afterwards.
Many systemic treatments have been used for the treatment of generahzed pustular psoriasis especially in cases not undergoing spontaneous remission; for example, systemic corticosteroids, methotrexate, hydroxyurea and azathioprine (Baker, 1975). However, the well-known severe complications from these medications urge us to seek another treatment, especially in younger age patients. This commtmication describes the successful use of clofazimine in two young male patients with generalized pustular psoriasis (von Zumbusch). CASE REPORTS
Case I A 28-year-old male was admitted to the Institute of Dermatology in March, 1976 with a i month history of generalized skin pustulation. He had a io-year history of scaly plaques on his scalp. The pustules were first noted on his forearm i month prior to admission and rapidly spread to the whole body. He also had high fever. On admission, generahzed pustulation was seen all over his body, covering the entire skin surface except a few areas on the face, palms and soles. A geographical tongue was present. Nail dystrophy and onycholysis with subungual debris were also noted. The temperature was 39°C and a leukocytosis of 13,100 cells/mm^ was found. A skin biopsy from a pustule showed the histology of pustular psoriasis. Wet dressings with potassium permanganate for 5 weeks resulted in no improvement. New crops of pustules continued to appear nearly every 4 days. Dapsone 200 mg per day was given for 3 weeks, but methaemoglobinaemia developed and the lesions did not improve. Next trimethoprim-sulfamethoxazole was tried for 3 weeks without beneficial eflFect. Finally clofazimine 200 mg per day was given. Subsequently the pustulation rapidly disappeared in 4 days and the scales gradually diminished. The colour of the skin changed to a generalized bright erythema but there were no new pustules during the following 14 days. New crops of pustules were again seen when the dose of clofazimine was reduced to 100 mg per day. The dose was then increased again to 200 mg per day and the skin cleared in 8 days. Clofazimine was discontinued 3 weeks later without 0007-0963/78/0900-0303502.00 ©1978 British Association of Dermatologists
303
304
T.Ghuaprapaisilp and T.Piamphongsant
any new pustulation developing. No side eflfects from the medication were noted except deep red staining of the skin due to deposition of the dye and which gradually faded after the drug was discontinued. During follow-up every 2 months for i year only mild scaling on the scalp was observed. Gase 2 A 20-year-old Thai male has had a history of three severe attacks of generalized pustulation accompanied by high fever and leukocytosis since 17 years of age. He also had ankylosing deformities of the finger joints of both hands. The histopathology from the skin biopsies was that of pustular psoriasis; the clinical impression was that of the von Zumbusch type. Recurrent pseudomonas infections in the middle ear seemed to be the precipitating cause. His symptoms and pustulation would persist if he was treated symptomatically without methotrexate. A single oral dose of 50 mg per week of methotrexate regularly controlled the eruption. Subsequently, he was maintained on a dose of 20 mg per week without skin pustulation for many months. Discontinuation of methotrexate would result in recurrence of a few crops of pustules. In December 1976, while he was receiving the maintenance dose, new crops of pustules recurred on the scalp, face, trunk and extremities accompanied by high fever and leukocytosis. A geographical tongue was also present. He was admitted and methotrexate was discontinued. Clofazimine 200 mg daily was given orally. The crops of pustules were reduced in numbers within 5 days and there were no new lesions within 21 days. The skin changed to a mild exfoliative dermatitis and improved with topical cold cream. He was discharged with clofazimine 200 mg daily for another 2 months after which medication was discontinued. No side eflFects were noted from the clofazimine except a deep red staining of the skin which gradually faded. He has been followed up for 5 months without recurrent skin pustulation.
DISCUSSION
Clofazimine, a phenazine imino-quinone derivative, has been used for the treatment of leprosy, discoid lupus erythematosus (Mackey & Barnes, 1974), pyoderma gangrenosum (Michaelsson et al., 1976), and palmo-plantar pustulosis (Molin, 1975). The mechanism of action in leprosy is possibly by bacteria-DNA binding activity (Morrison & Marley, 1976). In pyoderma gangrenosum and palmoplantar pustulosis it possibly acts by enhancing phagocytic activity of the leukocytes (Michaelsson et al., 1976; Molin, 1975). The mechanism of action in psoriasis is not known since no studies on DNA binding activity or on the eflFect on the migration of leukocytes have been done in this disease. In order to evaluate the eflScacy of new drugs, time should be allowed for spontaneous remission in any case of pustular psoriasis. Up till now the longest course of generalized pustular psoriasis observed at our Institute before spontaneous remission has been 52 days (Piamphongsant, 1977). In our first case, spontaneous remission was not observed even after 11 weeks. Once clofazimine was started, the pustules regressed in 4 days. It is possible that this could have been a spontaneous remission, but the fact that remission did not take place before clofazimine was instituted, favours the eflBcacy of the drug. Besides, when the dosage was reduced the pustules recurred and could be controlled again by reinstituting the higher dosage. The remission period was quite long. In our second pustular case, which was methotrexate dependent, clofazimine was substituted and discontinued without a recurrence of pustulation. Although the course of pustular psoriasis is variable and unpredictable, its response to treatment in our cases favoured the eflBcacy of clofazimine in treating certain cases of pustular psoriasis. It is interesting, however, that clofazimine was also tried in 6 cases of discoid psoriasis without success (Mackey, 1976).
Pustular psoriasis treated with clofazimine
305
REFERENCES BAKERJ H . (1975) Psoriasis: a review. II. Dermatologica, 150, 136. MACKEYJ J.P. & BARNES, J. (1974) Clofazimine in the treatment of discoid lupus erythematosus. British Journal of Dermatology, 93, 91. MACKEY, J.P. (1976) Clofazimine in Dermatology. International Journal of Dermatology, 15, 140. MICHAELSSON, G., MOLIN, L . , OHMAN, S., G I P , L . , LINDSTROM, B., SHOGH, M . & TROLIN, I. (1976) Clofazimine,
a new agent for the treatment of pyoderma gangrenosum. Archives of Dermatology, 112, 344. MOLIN, L . (1975) Clofazimine—enhanced phagocytosis in pustulosis palmaris et plantaris. Acta Dermatovenereologica, 55, 151. MORRISON, N . E . & MARLEY, G.M. (1976) The mode of action of clofazimine—DNA binding studies. International Journal of Leprosy and other Mycobacterial Diseases, 44, 133. PIAMPHONGSANT, T . (1977) Generalized non-discoid pustular psoriasis: Its hiitodynsLvaic. Journal of the Medical Association of Thailand (in press).
