Managing Hyperkeratotic Eczema of the Hands and Feet

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By James Q. Del Rosso, D.O., F.A.O.C.D., and David E. Cohen, M.D., M.P.H.
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Hyperkeratotic eczema of the hands and/or feet is a well recognized yet poorly understood entity that is typically chronic and refractory to therapy. The eruption is characterized by dry, thick, gray plaques involving the palmar and/or plantar surfaces. Features of acute or subacute eczematous dermatitis are not observed. Pruritus is usually noted, and when present, deep fissuring may lead to pain. Treatment of hyperkeratotic hand-foot eczema is often challenging. Response to topical corticosteroids, with or without occlusion, is not consistent and potent “keratolytic” therapy tends to provide only partial benefit. The cause of hyperkeratotic eczema remains elusive in most cases; whether or not it is actually a variant of hand-foot psoriasis has been debated. Oral acitretin (Soriatane) has been reported to be effective in the treatment of chronic hyperkeratotic hand-foot eczema, with one study reporting results superior to topical corticosteroid and keratolytic therapy. An observational case collection series on the use of oral acitretin in the management of this disorder has been completed with results reported in this article. Disease State Overview Chronic hyperkeratotic eczematous dermatitis (eczema) is a common disorder characterized by dry, thickened, gray, hyperkeratotic plaques. The condition typically involves the palmar surfaces and sometimes the fingers.1 Plantar involvement may be present. Scaling is common, pruritus is often present, and superficial or deep fissuring may be noted. The cause of chronic hyperkeratotic eczema of hands and/or feet is usually not identifiable, and is likely to be multifactorial.1,2 Clinical features of plaque psoriasis (eg. brisk erythema and micaceous silver scales) and palmoplantar pustular psoriasis (eg. pustules in various stages) are absent. Visible signs of acute or subacute eczematous dermatitis seen with contact dermatitis or dyshidrotic eczema (eg. vesiculation, serous exudation and crusting) are absent or fleeting in nature. Both exogenous and endogeous (eg. personal or family history of atopy) factors may play a role in individual cases. From a clinical perspective, it is sometimes difficult to distinguish “chronic hand eczema” from “chronic hand psoriasis”.3 However, when classic features of psoriasis are present and/or psoriatic lesions involve other cutaneous sites, distinction between the disorders becomes much more apparent. It is believed that chronic hyperkeratotic eczema refers to the “clinical merging of a collection of heterogenous diseases” that occurs over time, with dry, hyperkeratotic skin changes representing the final common “reaction pattern.”3 Ultimately, affected palmar and/or plantar skin becomes “exceedingly hyperkeratotic and fissured to a disabling extent.”3 Although a cause and definitive diagnosis often cannot be found, “patients are suffering and need help.”3 Due to a marked propensity for relapse, exacerbations, chronicity and inconsistent response to therapy, finding an effective treatment regimen often poses a major challenge. Treatment of chronic hyperkeratotic hand eczema may involve use of several agents. Topical corticosteroids, topical calcineurin inhibitors, “keratolytic” agents, emollients and hand protectants are often used initially; combination topical therapy is frequently employed.3-6 Topical bexarotene gel has also been recommended in severe, poorly responsive cases of chronic hand dermatitis.7 Refractory severe eczematous dermatitis, especially when disabling, may be treated with phototherapy (eg. hand/foot PUVA) or systemic agents such as cyclosporine and azathioprine. The use of systemic retinoid therapy has also been recommended for chronic hyperkeratotic palmoplantar dermatitis.3,8 Role of Acitretin in Treating Chronic Hyperkeratotic Hand and Foot Eczema Acitretin, the major active metabolite of etretinate, is an oral retinoid agent which exhibits a much shorter half-life than its parent compound; within 3 weeks of cessation of intake, the cis- and trans- isomers of ingested acitretin are no longer detected in plasma (<5 ng/ml).9 Acitretin may be esterified to etretinate, especially after alcohol ingestion, leading to storage of etretinate in body fat for prolonged periods of time. Acitretin has proven to be effective as monotherapy for psoriasis vulgaris and pustular psoriasis, is highly effective when used in combination with phototherapy for psoriasis, and reduces development of squamous cell carcinoma in immunosuppressed patients such as renal transplant recipients.9-13 Systemic retinoid therapy has been suggested as “probably the most effective treatment choice” for hyperkeratotic eczema of the hands and feet, although scientific data has been limited.3,8 A recent single-blind, matched-sample trial compared acitretin 25 mg/day to 50 mg/day versus topical betamethasone 0.05%/salicylic acid 3% ointment applied twice daily in adult patients (n=42) with chronic hyperkeratotic palmoplantar dermatitis.3 Each therapy was sequentially utilized for 1 month by all patients (topical regimen first) and each was evaluated over a 5-month follow-up period. Based on changes in severity scores, acitretin proved to be significantly superior to the topical regimen after 1 month of therapy (p<0.0001), with greater persistence of improvement over the 5-month follow-up period also reported with acitretin use (p<0.0001). In addition, acitretin therapy produced a more rapid onset of improvement (p<0.0002), was not associated with disease rebound after discontinuation of use, and was clearly preferred over the topical regimen by patients. No significant adverse reactions or serum testing changes were associated with acitretin use and there were no study dropouts. As anticipated, mild cheilitis and skin dryness were observed during acitretin use. Although the mode of action of acitretin in the management of chronic hyperkeratotic hand and foot eczema is not known, several anti-inflammatory effects of retinoids have been noted.9 Systemic retinoids such as acitretin may cause alterations in serum lipids, are teratogenic, are occasionally associated with significant increases in hepatic enzymes, and may at times produce skeletal and ligamentous calcification after prolonged use (diffuse idiopathic skeletal hyperostosis).9,14 However, the overall favorable safety of acitretin is well established. Long-term administration of low-dose acitretin (25 mg/day or less) does not appear to cause significant side effects; evaluation of patients treated for at least 1 year (average 2.13 years) at a mean dose of 27.1 mg/day reported no radiographic evidence of skeletal hyperostosis, minimal changes in cardiovascular risk indices, and a low hepatotoxicity risk.14 The demonstration of favorable efficacy and safety of low-dose acitretin for chronic hyperkeratotic eczema of hands and feet warranted a further look at this therapeutic approach in cases with chronic hand involvement. Observational Experience with Acitretin Patient Inclusion. Twelve cases of adult patients with chronic hyperkeratotic hand eczema rated by the investigator as moderate-to-severe are included (seven males/five females). The average patient age was 49.5 years. In nine of 12 cases, patients had been using topical therapy up to the time of presentation with topical corticosteroids, topical calcineurin inhibitors, keratolytic agents and/or emollients with limited benefit; the remainder were off of any topical therapy for 3 to 6 months. The average duration of disease prior to presentation was 7.6 years. None of the patients had been treated with systemic therapy for the chronic hand eczema, except for two patients who were treated with short courses of systemic corticosteroids. Six patients had previously undergone patch testing with the standard series with negative results reported. Two patients were also affected by plantar involvement. A personal or family history of atopy (childhood eczema, seasonal rhinitis and/or asthma) was reported in five patients. None of the patients noted a personal or family history of psoriasis and none exhibited clinical evidence or suggestion of psoriatic skin lesions at other cutaneous sites. In eight cases, potassium hydroxide preparation and fungal culture (DTM) were performed from samples obtained from both hands and in one case from hands and feet. All fungal testing results were negative. Concomitant Medical Disorders/Medications. Five patients were under no treatment with systemic medications for concomitant medical disorders; the remaining seven patients utilized on a daily basis for at least the past 9 months a variety of agents for hyperlipidemia, hypertension, gastroesophageal reflux disease, allergic rhinitis, osteoarthritis or anxiety. In all cases, the medications used by patients were initiated after the onset of hand eczema. None of the patients had a history of using beta-blocker therapy. Of the five female patients, two said they were postmenopausal (with a negative urine pregnancy test at baseline), one had a history of hysterectomy, and one had undergone a tubal ligation years ago. Treatment Regimen. Of the 12 patients, three had not been using any therapy for their hand eczema at the time of presentation. Of the remaining nine patients, five were instructed to continue their current topical program; all patients not receiving any other topical agents were administered a designated moisturizer cream that did not contain any “therapeutic” additives such as ammonium lactate, glycolic acid, salicylic acid or urea. Acitretin was initiated at a dose of 10 mg to 25 mg daily based empirically on body weight and size. Patients were evaluated over a period of 8 to 12 weeks depending on response and availability; follow-up visits were scheduled every 2 to 4 weeks. Laboratory Testing. All patients underwent a baseline complete blood cell count and serum chemistry panel inclusive of lipid and hepatic profiles, which were repeated every 4 weeks during acitretin therapy. No significant abnormalities were noted at baseline or on follow-up laboratory testing. Investigator Evaluation (Table 1). At each visit, the investigator determined if the condition worsened, was unchanged, was mildly improved, moderately improved, significantly improved (almost clear) or completely improved (completely clear). Determination of improvement was based on a combination of visible and tactile assessment; both parameters would need to reach a given degree of improvement to be rated at that level, otherwise the next lower rating of improvement was reported. Adverse skin or systemic reactions were also reported. Patient Evaluation (Table 1). At each visit, the patient independently determined if the condition worsened, was unchanged, was mildly improved, moderately improved, significantly improved (almost clear) or completely improved (completely clear). Patients were informed to base their judgement on the appearance and roughness of their hands. Patients were asked at each visit about any suspected skin reactions, systemic reactions, and changes in review of systems, medical history or medications, including over-the-counter products of any kind. A Summary of Points • Low-dose acitretin has been reported to be effective and safe in the treatment of chronic hyperkeratotic eczema of hands and feet. Current clinical data and observational experience support the efficacy and safety of this approach. • The optimal duration of acitretin therapy for chronic hyperkeratotic hand eczema is not clear. Effective results are generally noted within 1 to 2 months with sustained benefit reported after discontinuation of use. Longer courses may provide further benefit, however, additional study is needed. • Based on data obtained from treatment of patients with psoriasis, long-term administration of low-dose acitretin (<25 mg daily) is associated with an excellent safety profile. Significant systemic adverse reactions are uncommon. Clinical and laboratory monitoring (serum lipid and hepatic profiles) appear to sufficiently allow for appropriate intervention should significant elevation in lipids or liver enzymes occur.

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