Clinical and Experimental Dermatology 1992; 17: 376-378.
Acrodermatitis continua responding to cyclosporin therapy C.C.HARLAND, P.E.KILBY AND K.L.DALZIEL Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK Accepted for publication 18 November 1991 Summary A 69-year-old man with painful, recalcitrant, localized acrodermatitis continua developed widespread pustulation which was resistant to high-dose methotrexate therapy. Low-dose cyclosporin induced a rapid and persistent remission. Acrodermatitis continua is a rare, chronic, sterile, pustular eruption ofthe digits. Trauma is usually a precipitating factor. Acute episodes of pustulation occur for no apparent reason, and may lead to skin atrophy and nail destruction.' Localized disease (dermatitis repens of Crocker) may become generalized (acrodermatitis continua of Hallopeau), the latter being associated with greater morbidity and mortality than generalized pustular psoriasis of Zumbusch-type." At present there is no single satisfactory treatment for either form of acrodermatitis continua.' We present a patient with acrodermatitis continua in association with plaque psoriasis who was treated with cyclosporin.
hospital for analgesia, bed-rest and methotrexate therapy. Histological examination of a pustular plaque of psoriasis showed dermal and epidermal collections of polymorphonuclear leucocytes with psoriasiform hyperplasia, consistent with pustular psoriasis. A liver biopsy was normal. Topical clobetasol propionate and oral methotrexate (0-25 mg/kg/week) resulted in partial disease remission, but relapses occurred despite escalating doses of twice weekly, high-dose intravenous methotrexate (up to 1-5 mg/kg/week; weeks 0-12) and the addition of
Case report A 69-year-old man suffered a traumatic fracture of the terminal phalanx of the left middle finger in June 1987. Pain, swelling and pustulation ofthe finger-tip persisted despite several courses of antibiotics, non-steroidal antiinflammatory drugs and surgical exploration of the nail bed. He was referred to our department in January 1988, when localized acrodermatitis continua was diagnosed (Fig. 1) in association with plaque psoriasis. Although temporary respite was achieved with oral oxytetracycline and topical 0-05% clobetasol propionate cream, episodic painful and debilitating pustulation continued for 12 months, the severity ofthe pain leading to the patient's demand for an amputation ofthe affected finger. In February 1989 the disease evolved to affect all digits, palms and soles (Fig. 2). Established psoriatic plaques also became pustular. He was admitted to Correspondence: Dr C.C.Harbnd, Department of E>ennatoiogy, St Helier Hospital, Wrythe Lane, Carshalton SM5 lAA, UK.
376
Figure \. Acrodermatitis tontinua of the finger. Note pustular eruption in association nith skin atrophy and nail loss.
ACRODKRMATITIS CONTINUA
?>11
Discussion
Figure 2. Acrodermatitis cimtinuii in evolution. Lakes of pus developing on the heel.
13-m-retinoic acid (15 mjc/kg/day; weeks 6-12) during 13 weeks of hospital admission. Oral cyclosporin (5 mg kg/day) was commenced in view of disease progression and abnormal Hver-function iest.s. Pustulation abated 3 days later; after 3 weeks it had completely resolved despite withdrawal of topical steroid, methotrexate and 13-r/5-retinoic acid. Pustular psoriasis of the acrodermatitis continua-type and plaque psoriasis remained in remission with low-dose cyclosporin (3-3~5() mg/kg/day) until June 1990. Owing to the development of mild renal impairment the dose did not exceed 3-3 mg/kg/day lor the following year; subsequently there have been regular outbreaks ofthe original, painful localized acropustuiosis. Attempts to sustain a complete disease rcmi.ssion have failed despite the addition of etretinalc (50 mg) and localized superficial radiotherapy. Only the combination of daily cyclosporin and a very potent topical steroid cream has been successful for control ofthe pain and extent of relapses.
Low-dose oral cyclosporin therapy (5 mg/kg/day) has been shown to be effective in controlling severe, chronic plaque psoriasis over long periods.^ Its role in the treatment of various patterns of pustular psoriasis is not established. Palmo-plantar pustular psoriasis has been shown to clear with cyclosporin therapy.^ Higher doses, which are associated with hypertension and renal dysfunction may be required for the suppression of generalized pustular psoriasis ol" lhe Zumbusch-type.'' Indeed, generalized pustular psoriasis has failed to respond to high doses used lor renal iransplanl patients.^ However, a patient with generalized pustular (von Zumbusch) psoriasi.s, who responded rapidly to cyclosporin, remained in remission on !()w-d()se therapy (< 4 mg/kg/day) for over 8 months.** Acrmlermatitis continua is thought to be a recalcitrant variant of pustular psoriasis.'There are four reports of its treatment with cyclosporin. None of these refer to prolonged therapy of this debilitating and sometimes lifethreatening condition. /achariae and Thestrup-Pederson successfully treated a case of severe pustular psoriasis of the acrodermatitis continua-type with cyclosporin.^ Their patient had already received courses of methotrexate, systemic steroids, etretinate, colchicine, hydroxj'urea and PU\"A over 10 years without sustained benefit. Cyclosporin (14 mg/ kg/day reduced to 7 5 mg/kg/day) produced complete remissi(m in 3 weeks. The authors were cautious not to advocate long-lerm low-dose cyclosporin for acrodermatitis continua as their patient had received therapy for only 3 months. Peter et al.y^^ on the other hand, found that lower doses of cyclosporin (4-8 mg/kg/day reducing to 2-1 mg/kg/day) were effective in clearing palmar acrodermatitis continua. Again, the duration of therapy was short (14 days). Korstanie et ai^^ described a patient with generalized acrodermatitis continua (Hallopeau) who required high doses (8 mg/kg/day) in combination with oral prednisolone in order to maintain a short-term remission. Pustule formation was arrested in another patient with involvement ofthe fingertips after 8 weeks of cyclosporin therapy (6 mg/kg/day).'In our case, painful localized acrodermatitis continua was evolving into generalized pustular psoriasis. Methotrexate, which is reportedly the most effective treatment of pustular psoriasis ofthe acrodermatitis continua-type,-^ failed to suppress pustulation, despite high doses in combination with systemic retinoid therapy. Low-dose cyclosporin (5 mg/kg/day) arrested disease progre.ssion, and subsequently appears to be the only effective treatment long-term. The addition of etretinate or superficial radiotherapy failed to reduce cyclosporin requirements, whereas the combination of cyclosporin
378
C.C.HARLAND, P.E.KILBY AND K.L.DALZIEL
(3-3 mg/kg/day) and potent topical corticosteroid has been used successfully for 30 months. The mechanism of action of cyclosporin on pustular psoriasis is unknown. Although it does not appear to have a direct effect on neutrophils, it may have an effect on the complex cytokine-mediated interaction between T-cells, keratinocytes and endothelial cells.'^ The fact that cyclosporin has been the only effective therapy in this case suggests that there is a differing pathogenesis for acrodermatitis continua compared with other types of pustular psoriasis. We conclude that low-dose cyclosporin may be a useful therapeutic option for both the short and long-term control of acrodermatitis continua. In some cases it may be the only effective therapy currently available. References
5. 6. 7.
8. 9. 10,
11, 1. Christophers E. Pustular eruption of palms and soles. In: Fitzpatrick TB, ed. Dermatology in General Medicine: McGrawHill, 1987, PP 604-610. 2. Baker H, Ryan TJ. Generalised pustular psoriasis. A clinical and 12. epidemiological study of 104 cases. British Journal of Dermatology 1968; 80: 771-793. 3. Baker H. Localized pustular psoriasis. In: Roenigk HH, Maibach 13. HI, eds. Psoriasis. New York: Dekker, 1986: pp 40-45. 4. Griffiths CEM, Powles AV, McFadden J et al. Long-term
eyclosporin for psoriasis. British Journal of Dermatology, 1989; 120: 253-260. Meinardi MMHM, de Rie MA, Bos JD. Oral cyelosporin A is effective in clearing persistent pustulosis palmaris et plantaris. Acta Dermato-Venereologtca (Stockh) 1990; 70: 77-79. Meinardi MMHM, Westerhof W, Bos JD. Generalized pustular psoriasis (von Zumbuseh) responding to cyclosporin A. British Journal o} Dermatology 1987; 116: 269-270. Coulson IH, Evans CD, Holden CA. Generalised pustular psoriasis after renal transplantation—failure to suppress with cyclosporin A, Cltmcat and Experimental Dermatology, 1988; 13: 416-417. Fradin MS, Ellis CN, Voorhees JJ. Rapid response of von Zumbusch psoriasis to cyclosporine. Journal of the .4merican Academy of Dermatology 1990; 23: 92.S-926. Zachariae H, Thestrup-Pedersen K, Ciclosporin A in acrodermatitis continua. Dermatologica 1987; 175: 29-32. Peter RU, Ruzicka T, Donhauser G, Braun-Falco O, Acrodermatitis continua-type of pustular psoriasis responds to low-dose cyclosporine. Journal of the American Academy of Dermatology, 1990; 3: 515-516. Korstanje MJ, Bessems PJMJ, Hulsmans RFHJ, Von de Staak WJBM. Pustular psoriasis and aerodermatitis continua (Hallopeau) need high doses of systemic ciclosporin A. Dermatologica 1989; 179:90-91. Gupta AK, Ellis CN, Nickoloff BJ et al. Oral cyclosporine in the treatment of inflammatory and non-inflammatory dermatoses. A clinical and immunopathologic analysis. Archives of Dermatology 1990; 126: 339-350. Borel JF. Mechanism of action and rationale for cyclosporin A in psoriasis. British Journal of Dermatology 1990; suppl., 36: 5-12.
Acrodermatitis continua responding to cyclosporin therapy C.C.HARLAND, P.E.KILBY AND K.L.DALZIEL Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK Accepted for publication 18 November 1991 Summary A 69-year-old man with painful, recalcitrant, localized acrodermatitis continua developed widespread pustulation which was resistant to high-dose methotrexate therapy. Low-dose cyclosporin induced a rapid and persistent remission. Acrodermatitis continua is a rare, chronic, sterile, pustular eruption ofthe digits. Trauma is usually a precipitating factor. Acute episodes of pustulation occur for no apparent reason, and may lead to skin atrophy and nail destruction.' Localized disease (dermatitis repens of Crocker) may become generalized (acrodermatitis continua of Hallopeau), the latter being associated with greater morbidity and mortality than generalized pustular psoriasis of Zumbusch-type." At present there is no single satisfactory treatment for either form of acrodermatitis continua.' We present a patient with acrodermatitis continua in association with plaque psoriasis who was treated with cyclosporin.
hospital for analgesia, bed-rest and methotrexate therapy. Histological examination of a pustular plaque of psoriasis showed dermal and epidermal collections of polymorphonuclear leucocytes with psoriasiform hyperplasia, consistent with pustular psoriasis. A liver biopsy was normal. Topical clobetasol propionate and oral methotrexate (0-25 mg/kg/week) resulted in partial disease remission, but relapses occurred despite escalating doses of twice weekly, high-dose intravenous methotrexate (up to 1-5 mg/kg/week; weeks 0-12) and the addition of
Case report A 69-year-old man suffered a traumatic fracture of the terminal phalanx of the left middle finger in June 1987. Pain, swelling and pustulation ofthe finger-tip persisted despite several courses of antibiotics, non-steroidal antiinflammatory drugs and surgical exploration of the nail bed. He was referred to our department in January 1988, when localized acrodermatitis continua was diagnosed (Fig. 1) in association with plaque psoriasis. Although temporary respite was achieved with oral oxytetracycline and topical 0-05% clobetasol propionate cream, episodic painful and debilitating pustulation continued for 12 months, the severity ofthe pain leading to the patient's demand for an amputation ofthe affected finger. In February 1989 the disease evolved to affect all digits, palms and soles (Fig. 2). Established psoriatic plaques also became pustular. He was admitted to Correspondence: Dr C.C.Harbnd, Department of E>ennatoiogy, St Helier Hospital, Wrythe Lane, Carshalton SM5 lAA, UK.
376
Figure \. Acrodermatitis tontinua of the finger. Note pustular eruption in association nith skin atrophy and nail loss.
ACRODKRMATITIS CONTINUA
?>11
Discussion
Figure 2. Acrodermatitis cimtinuii in evolution. Lakes of pus developing on the heel.
13-m-retinoic acid (15 mjc/kg/day; weeks 6-12) during 13 weeks of hospital admission. Oral cyclosporin (5 mg kg/day) was commenced in view of disease progression and abnormal Hver-function iest.s. Pustulation abated 3 days later; after 3 weeks it had completely resolved despite withdrawal of topical steroid, methotrexate and 13-r/5-retinoic acid. Pustular psoriasis of the acrodermatitis continua-type and plaque psoriasis remained in remission with low-dose cyclosporin (3-3~5() mg/kg/day) until June 1990. Owing to the development of mild renal impairment the dose did not exceed 3-3 mg/kg/day lor the following year; subsequently there have been regular outbreaks ofthe original, painful localized acropustuiosis. Attempts to sustain a complete disease rcmi.ssion have failed despite the addition of etretinalc (50 mg) and localized superficial radiotherapy. Only the combination of daily cyclosporin and a very potent topical steroid cream has been successful for control ofthe pain and extent of relapses.
Low-dose oral cyclosporin therapy (5 mg/kg/day) has been shown to be effective in controlling severe, chronic plaque psoriasis over long periods.^ Its role in the treatment of various patterns of pustular psoriasis is not established. Palmo-plantar pustular psoriasis has been shown to clear with cyclosporin therapy.^ Higher doses, which are associated with hypertension and renal dysfunction may be required for the suppression of generalized pustular psoriasis ol" lhe Zumbusch-type.'' Indeed, generalized pustular psoriasis has failed to respond to high doses used lor renal iransplanl patients.^ However, a patient with generalized pustular (von Zumbusch) psoriasi.s, who responded rapidly to cyclosporin, remained in remission on !()w-d()se therapy (< 4 mg/kg/day) for over 8 months.** Acrmlermatitis continua is thought to be a recalcitrant variant of pustular psoriasis.'There are four reports of its treatment with cyclosporin. None of these refer to prolonged therapy of this debilitating and sometimes lifethreatening condition. /achariae and Thestrup-Pederson successfully treated a case of severe pustular psoriasis of the acrodermatitis continua-type with cyclosporin.^ Their patient had already received courses of methotrexate, systemic steroids, etretinate, colchicine, hydroxj'urea and PU\"A over 10 years without sustained benefit. Cyclosporin (14 mg/ kg/day reduced to 7 5 mg/kg/day) produced complete remissi(m in 3 weeks. The authors were cautious not to advocate long-lerm low-dose cyclosporin for acrodermatitis continua as their patient had received therapy for only 3 months. Peter et al.y^^ on the other hand, found that lower doses of cyclosporin (4-8 mg/kg/day reducing to 2-1 mg/kg/day) were effective in clearing palmar acrodermatitis continua. Again, the duration of therapy was short (14 days). Korstanie et ai^^ described a patient with generalized acrodermatitis continua (Hallopeau) who required high doses (8 mg/kg/day) in combination with oral prednisolone in order to maintain a short-term remission. Pustule formation was arrested in another patient with involvement ofthe fingertips after 8 weeks of cyclosporin therapy (6 mg/kg/day).'In our case, painful localized acrodermatitis continua was evolving into generalized pustular psoriasis. Methotrexate, which is reportedly the most effective treatment of pustular psoriasis ofthe acrodermatitis continua-type,-^ failed to suppress pustulation, despite high doses in combination with systemic retinoid therapy. Low-dose cyclosporin (5 mg/kg/day) arrested disease progre.ssion, and subsequently appears to be the only effective treatment long-term. The addition of etretinate or superficial radiotherapy failed to reduce cyclosporin requirements, whereas the combination of cyclosporin
378
C.C.HARLAND, P.E.KILBY AND K.L.DALZIEL
(3-3 mg/kg/day) and potent topical corticosteroid has been used successfully for 30 months. The mechanism of action of cyclosporin on pustular psoriasis is unknown. Although it does not appear to have a direct effect on neutrophils, it may have an effect on the complex cytokine-mediated interaction between T-cells, keratinocytes and endothelial cells.'^ The fact that cyclosporin has been the only effective therapy in this case suggests that there is a differing pathogenesis for acrodermatitis continua compared with other types of pustular psoriasis. We conclude that low-dose cyclosporin may be a useful therapeutic option for both the short and long-term control of acrodermatitis continua. In some cases it may be the only effective therapy currently available. References
5. 6. 7.
8. 9. 10,
11, 1. Christophers E. Pustular eruption of palms and soles. In: Fitzpatrick TB, ed. Dermatology in General Medicine: McGrawHill, 1987, PP 604-610. 2. Baker H, Ryan TJ. Generalised pustular psoriasis. A clinical and 12. epidemiological study of 104 cases. British Journal of Dermatology 1968; 80: 771-793. 3. Baker H. Localized pustular psoriasis. In: Roenigk HH, Maibach 13. HI, eds. Psoriasis. New York: Dekker, 1986: pp 40-45. 4. Griffiths CEM, Powles AV, McFadden J et al. Long-term
eyclosporin for psoriasis. British Journal of Dermatology, 1989; 120: 253-260. Meinardi MMHM, de Rie MA, Bos JD. Oral cyelosporin A is effective in clearing persistent pustulosis palmaris et plantaris. Acta Dermato-Venereologtca (Stockh) 1990; 70: 77-79. Meinardi MMHM, Westerhof W, Bos JD. Generalized pustular psoriasis (von Zumbuseh) responding to cyclosporin A. British Journal o} Dermatology 1987; 116: 269-270. Coulson IH, Evans CD, Holden CA. Generalised pustular psoriasis after renal transplantation—failure to suppress with cyclosporin A, Cltmcat and Experimental Dermatology, 1988; 13: 416-417. Fradin MS, Ellis CN, Voorhees JJ. Rapid response of von Zumbusch psoriasis to cyclosporine. Journal of the .4merican Academy of Dermatology 1990; 23: 92.S-926. Zachariae H, Thestrup-Pedersen K, Ciclosporin A in acrodermatitis continua. Dermatologica 1987; 175: 29-32. Peter RU, Ruzicka T, Donhauser G, Braun-Falco O, Acrodermatitis continua-type of pustular psoriasis responds to low-dose cyclosporine. Journal of the American Academy of Dermatology, 1990; 3: 515-516. Korstanje MJ, Bessems PJMJ, Hulsmans RFHJ, Von de Staak WJBM. Pustular psoriasis and aerodermatitis continua (Hallopeau) need high doses of systemic ciclosporin A. Dermatologica 1989; 179:90-91. Gupta AK, Ellis CN, Nickoloff BJ et al. Oral cyclosporine in the treatment of inflammatory and non-inflammatory dermatoses. A clinical and immunopathologic analysis. Archives of Dermatology 1990; 126: 339-350. Borel JF. Mechanism of action and rationale for cyclosporin A in psoriasis. British Journal of Dermatology 1990; suppl., 36: 5-12.
