Ciclosporin

Abstract

Acrodermatitis continua of Hallopeau (ACH) is a rare form of pustular psoriasis which poses a challenge to treat and causes considerable pain and suffering for those afflicted. Tumor necrosis factor-alpha (TNF-[alpha]) is a pro-inflammatory cytokine involved in the pathogenesis of ACH and other forms of psoriasis. Inhibition of TNF-[alpha] has been shown to provide benefit in such inflammatory conditions as rheumatoid arthritis, psoriatic arthritis, and, most recently, plaque psoriasis. In this report, we present the case of a 65-year-old man with a 9-year history of recalcitrant ACH who demonstrated significant and sustained clinical improvement when etanercept, a competitive inhibitor of TNF-[alpha], was added to his treatment regimen of acitretin and topical corticosteroids over a 12-week period.

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Introduction

Acrodermatitis continua of Hallopeau (acrodermatitis continua suppurativa Hallopeau, dermatitis perstans, dermatitis repens Crocker), initially described by Crocker in 1888 and further defined by Hallopeau between 1890 and 1897, is a rare form of pustular psoriasis in which sterile pustules develop predominantly on the distal aspect of the upper extremities. The disease can, over time, expand proximally through local extension and coalescence of pustules into lakes of pus. (1,2) Trauma or infection may precede the initial outbreak of small pustules, which burst leaving a glossy erythematous base upon which new pustules form. Continuous pustulosis of the nail bed and matrix commonly occurs leading to onychodystrophy and eventual anonychia. Atrophy and sclerosis of underlying soft tissue and of the distal phalanx can also occur. (2) Annulus migrans of the tongue has been reported in association with ACH as well. The quality of life for patients suffering from ACH is greatly impaired as the fragility and tenderness of the skin on the hands limits activities of daily living. As with other forms of pustular psoriasis, ACH is very difficult to treat. Our patient underwent numerous different therapies with minimal to moderate relief, but has finally achieved sustained disease control with etanercept and acitretin combination therapy. A marked improvement in his quality of life has been noted as well.

Case Report

A 65-year-old Caucasian man, initially diagnosed with acrodermatitis continua of Hallopeau 9 years prior to our encounter with him, presented to our clinic with a physical examination remarkable for hyperkeratotic, scaly plaques and pustules covering the distal aspect of all 10 fingers, as well as the dorsal and palmar aspects of both hands and dorsal forearms. At the time of presentation, the disease did not involve the lower extremity, although the patient reported a distant history of similar eruptions involving his toes. He had no oral lesions. Examination of the upper extremities revealed anonychia of 4/10 fingernails with visible tapering of the distal phalanges (Figure 1). The patient reported great tenderness in his hands, which severely limited their use. He wore white cotton gloves during the day to protect his fingers from minor environmental trauma.

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Prior to this presentation, the patient had been treated with multiple regimens including topical steroids, topical calcipotriene, PUVA, cyclosporine, etretinate, and acitretin with mild to moderate improvement noted with each regimen. He was considered a poor candidate for methotrexate due to persistent consumption of alcoholic beverages. While each of these modalities brought some relief, the patient continued to experience multiple relapses.

Due to the recalcitrant nature of the patient's disease, we implemented etanercept at 25 mg injected subcutaneously twice weekly. The patient continued his routine of using occasional topical steroids, and he continued acitretin 75 mg a day with the intention of tapering off the acitretin as the new agent began to take effect.

Within 4 weeks of beginning treatment with etanercept, the patient displayed marked improvement in terms of decreased pustulation and scale and, subsequently, decreased tenderness of his hands and fingers. Six weeks into the treatment period, we increased the dose of etanercept to 50 mg SC twice weekly. The patient continued to improve and after 12 weeks of therapy demonstrated very limited disease with near normalization of skin on the distal extremities, some growth of nail tissue, and significant functional improvement in the use of his hands (Figures 3-5).

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Discussion

Our patient presented to the clinic with a 9-year history of acrodermatitis continua of Hallopeau, which had historically been quite difficult to treat and caused great distress to the patient on a daily basis. The patient's quality of life suffered greatly as use of his hands was markedly limited, particularly during flares. Topical steroids, calcipotriol, cyclosporine, and systemic retinoids have been reported as successful in the treatment of ACH. (2-6) In our patient, however, failure of the aforementioned therapies, as well as a lack of results with phototherapy, led us to introduce etanercept into his current medical treatment.

Etanercept (Enbrel[R]; Amgen, Inc., Thousand Oaks, CA) is one of many new biologic drugs recently indicated for the treatment of various immune-mediated disease processes. Initially, the FDA approved etanercept for the treatment of rheumatoid and psoriatic arthritis. A recent successful study on the efficacy of etanercept as monotherapy for the treatment of plaque psoriasis has led to FDA approval for this indication. (7) Tumor necrosis factor-alpha (TNF-[alpha]), a proinflammatory cytokine produced by type 1 helper T cells (Th1), is strongly linked to the development of psoriasis and psoriatic arthritis. Elevated levels have been found in psoriatic plaques and in the synovium of effected joints. (8-10) Etanercept is a recombinant, dimeric human fusion protein consisting of the TNF-[alpha] receptor linked to the Fc portion of immunoglobulin G1. It binds to TNF-[alpha] with great affinity and competitively inhibits TNF-[alpha] from binding to cell surface receptors, thus blocking the inflammatory processes seen in psoriasis without causing Th1 cell depletion. (7,11)

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Although ACH typically presents as a unique clinical picture, it is linked to psoriasis by its histologic compatibility with pustular psoriasis of the hands and feet and pustulosis palmaris et plantaris. (2,12) ACH is also linked by occasional transformation into, or co-existence with, other forms of psoriasis as well as by success with treatment regimens typically used for plaque type psoriasis.

We initiated etanercept therapy in our patient not only due to the reported successes of this drug in the treatment of various forms of psoriasis, but also due to the infrequent, biweekly dosing (our patient has a history of non-compliance) and the overall safety profile. (11)

The successful use of etanercept for treatment of psoriatic disease limited to the palms and soles has recently been reported. (13) We now report a case demonstrating successful treatment of yet another form of psoriasis effecting the distal extremities with combination therapy including etanercept. At the time of this publication, our patient continues to show sustained clinical improvement on etanercept therapy. He continues to occasionally use topical steroids on an as-needed basis, and he continues to take acitretin, though his dose has been reduced to one-third of the dose needed prior to starting etanercept. Such combination therapy has been reported previously for treatment of psoriasis and psoriatic arthritis, but not for the treatment of acrodermatitis continua of Hallopeau. (14) The success we have achieved in the management of this patient's challenging disease with etanercept lends further credence to the defining role of TNF-[alpha] in the development of not only psoriasis vulgaris but ACH as well, while offering another viable option for managing this historically difficult to control disease.

References

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9. Ettehadi P, et al. Elevated tumour necrosis factor-alpha (TNF-alpha) biological activity in psoriatic skin lesions. Clin Exp Immunol. 1994;96:146-151.

10. Partsch F, et al. Highly increased levels of tumor necrosis factor-alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid. J Rheumatol. 1997;24:518-523.

11. Goffe B, Cather JC. Etanercept: an overview. J Am Acad Dermatol. 2003;49(2 Suppl):S105-111.

12. Thormann J, Heilesen B. Recalcitrant pustular eruptions of the extremities. J Cutan Pathol. 1975;2(1):19-24.

13. Weinberg JM. Successful treatment of recalcitrant palmoplantar psoriasis with etanercept. Cutis. 2003;72(5):396-398.

14. Strober BE, Clarke S. Etanercept for the treatment of psoriasis: combination therapy with other modalities. J Drugs Dermatol. 2004;3(3):270-272.

Kimberly Kazinski 2LT USA MC, Kathleen M. Joyce Capt USAF MC, Darryl Hodson MAJ USA MC

Department of Dermatology, San Antonio Uniformed Services Health Education Consortium, Wilford Hall USAF Medical Center, San Antonio, TX

Address for Correspondence

Kathleen M. Joyce, MD

211 Argo Avenue

San Antonio, TX 78209

Phone: 210-601-3920

e-mail: Kathleen.kelly@amedd.army.mil

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