New and Existing Therapies for Chronic Hand Dermatitis

D. R. Thomas, MD, FRCPC¹ and C. E. Malcolm, MD, CCFP²
1. Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
2. Division of Dermatology, University of Toronto, Toronto, ON, Canada

Introduction

Hand dermatitis (HD) is a common skin disorder affecting individuals of all ages. HD broadly refers to any type of inflammation involving the skin of the hands that is characterized by a combination of redness, itching, scaling, and fissuring. Both genetic and environmental risk factors are important in its etiology. HD is well known for its recalcitrance, typically following a chronic relapsing course that progresses in severity and may resist conventional treatment. However, recent advances, particularly for chronic severe disease, have broadened the therapeutic landscape. A thorough understanding of pathogenesis, heritability, diagnosis, therapeutic options, and patient-related factors will aid in improving acute and long-term management, as well as treatment outcomes. For this review, the terms eczema and dermatitis are used interchangeably and refer to the same condition.

Prevalence and Prognosis

Most adult patients with dermatitis have involvement of the hands.

• An estimated 7-12% of the general population is affected by HD.¹
  • Approximately 5-7% of HD patients have chronic severe disease and 2-4% are refractory to topical treatment.²
• Prevalence is considerably higher among certain occupational groups, e.g., domestic workers, hairdressers, health care professionals, and workers in the agricultural, food-related, mechanical, metallurgic, or printing industries.
• HD is also twice as likely to occur in women than in men.³
• Strongest negative prognostic factors include extent of involvement, history of childhood dermatitis, and disease onset at < 20 years of age.⁴

Causes and Risk Factors

• Exogenous and endogenous factors contribute to the etiology of HD. This multiplicity makes identification of all causative elements very difficult.
• HD commonly progresses on a chronic path, even with avoidance of the initially implicated trigger.²
• Personal/familial history of atopy (asthma, allergic rhinitis, atopic dermatitis).
• HD can be caused or aggravated by occupational exposure from working in wet conditions, frequent hand washing, or using irritative substances.
  • Severity of occupational HD is associated with prolonged sick leave and increased risk of job loss.⁵

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Common Variants of Hand Dermatitis

An epidemiologic HD study observed irritant contact (35%), allergic contact (19%), and atopic (22%) dermatoses to be the most commonly classified forms; 15% of patients had unclassified eczema.⁶

Irritant Contact Dermatitis (ICD)

• ICD is caused by repeated or prolonged exposure to contactants, which inhibits epidermal barrier repair.
• Substances that can induce reactions: water, soaps, detergents, cleansers, solvents, degreasers, lubricants, oils, coolants, food products, fiberglass dust, metals, plastics, and resins, as well as mechanical trauma.
• Symptoms are usually symmetrical and affect the dorsal fingertips and webspaces.

Allergic Contact Dermatitis (ACD)

• Making a distinct diagnosis between ICD and ACD can be difficult.
• Reactivity occurs when previously sensitized individuals are re-exposed to the antigen.

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Treatment

Despite its prevalence and considerable disease burden, there are very few well-designed randomized controlled trials (RCTs) evaluating therapies for chronic hand dermatitis (CHD). Resultantly, most therapeutic recommendations are based on personal physician experience and the limited number of small studies. The EDEN survey by van Coevorden et al. assessed HD studies conducted between 1977 to 2003 and confirmed a lack of RCTs, with most exhibiting poor methodology and quality of reporting.⁷ Consequently, this dearth of evidence-based data fails to sufficiently guide therapeutic decisionmaking. The absence of clarity is even more evident for severe CHD, as therapeutic options are further restricted.⁸

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Topical Agents

Topical treatments may be used in combination or with systemic or light therapies.

Emollients

• The regimented use of emollients contributes to repair of the skin barrier.
• Adequate moisturization can support pharmacologic treatment by reducing the need for topical corticosteroids or immunomodulators, and mitigating side-effects from drug therapy.

Corticosteroids

• Topical steroids are used to reduce inflammation and are a mainstay of therapy.
• Ointments are generally more effective and contain fewer preservatives and additives than creams.
• The thick stratum corneum (e.g., palms, palmar aspects of fingers, and around nails) often requires higher potency preparations, such as clobetasol propionate 0.05% ointment 1-2 times daily for a few weeks and then 2-3 times a week thereafter, as needed.
• Topical steroids should be used on affected areas twicedaily until improvement is seen, then the dosage may be tapered to intermittent use for maintenance therapy.
• A poor response may indicate a corticosteroid allergy.
• Cross-reactions between groups of corticosteroids and flares with systemic steroids may complicate therapy.
• Limitations can include tachyphylaxis, skin atrophy, and systemic side-effects, especially if used long-term.

Topical Calcineurin Inhibitors (TCIs)

• TCIs are nonsteroidal immunomodulators that exert anti-inflammatory effects.
• Pimecrolimus and tacrolimus are beneficial when conventional agents fail or are unsuitable.
• Pharmacokinetic activities of TCIs include skin absorption, but they do not enter the bloodstream.
• Onset of effect is slower than corticosteroids.
• Common side-effects of TCIs include mild and transient itching and burning upon application.

Salicylic Acid and Coal Tar

• These agents are sometimes prescribed for hyperkeratotic areas to help soften skin, reduce thickness, and improve penetration of medications.
• Salicylic acid can cause irritation.
• Tars can have an unpleasant odour and cause irritation and staining. Potential carcinogenicity is also a concern.

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Systemic Agents

Antihistamines

• Sedating antihistamines (e.g., hydroxyzine or diphenhydramine) may be useful adjuncts when taken at bedtime for intractable itch, especially during flares.

Antibiotics

• Oral/topical antibiotics are used to treat infected lesions.
• Most infections are caused by Staphylococcus aureus colonization. Cephalexin is commonly prescribed at the dose of 500mg 4 times daily for 7 days.

Oral Corticosteroids

• Oral corticosteroids are effective in a short course for treating acute or widespread outbreaks.
• Prednisone may be initially prescribed at 0.5-1mg/kg or 20-40mg, then tapered over several weeks. Patients must be given information on side-effects (e.g., avascular necrosis of the hip) and precautions during dispensing.
• Long-term use is rarely advisable due to undesirable and potentially harmful side-effects.

Oral Immunosuppressive Agents for Severe HD

• Azathioprine may be used in AD, pompholyx, and psoriasis.
  • Side-effects include elevated liver enzymes, leucopenia, infections, and sun sensitivity.
  • Rare side-effects from long-term use include squamous cell cancers and non-hodgkins lymphoma.
• Cyclosporine suppresses inflammatory responses.
  • Long-term use can lead to severe side-effects, including organ damage.
• Methotrexate (MTX) has an immunomodulatory effect and is usually taken at a dose of 7.5-20mg weekly.
  • Side-effects of MTX include nausea, vomiting, diarrhea, liver fibrosis and cirrhosis, pulmonary fibrosis, and pancytopenia, as well as other severe adverse effects from long-term use.
  • Folic acid is generally co-prescribed, as this may reduce MTX associated side-effects.
  • During MTX treatment, alcohol avoidance is essential to prevent liver damage.
• Mycophenolate mofetil (MMF) may be used for patients who are nonresponsive or inadequate responders to other HD therapies.
  • There are concerns over MMF’s teratogenicity and long-term carcinogenicity.

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Phototherapy (Light Therapy)

For severe or treatment resistant HD, narrowband UVB light or oral/bath psoralen + long-wave UVA light therapy (PUVA) are helpful due to their local immunosuppressive effect.

• Long-term use of UV light therapies can cause skin damage and increase cancer risk.
• Patients may consider the required time commitment to be inconvenient.
• Access to clinic-based phototherapy may be limited.

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Therapeutic Advance for CHD

One of the few adequately controlled studies, which represents the largest HD trial to date, explored the oral use of alitretinoin in severe CHD refractory to standard care.¹ The investigation provides much-needed evidenced-based data and demonstrates the therapeutic potential for this nonimmunosuppressive agent.

Alitretinoin (9-cis retinoic acid) is a new oral retinoid that received regulatory approval in Canada in November 2009. It is the only systemic agent that is indicated for the treatment of adults with severe CHD that is refractory to high-potency topical steroids.

• Two randomized, double-blind, placebo-controlled, multicenter trials involving over 1300 patients treated with alitretinoin demonstrated significant clinical improvements in moderate to severe CHD.^1,9
• One study assessing once-daily use for 12 weeks showed a dose-dependent improvement in 53% of HD patients, who exhibited up to 70% mean reduction in disease signs and symptoms.⁹
• A second study looking at once-daily use for up to 24 weeks reported 48% of alitretinoin-treated patients achieved clear or almost clear hands, with up to 75% median reduction in disease signs and symptoms, compared with 17% of placebo. After cessation of therapy, the median time to relapse was 5.5-6.2 months.¹
• Alitretinoin was well-tolerated. Side-effects were dose-dependent and included headache, flushing, mucocutaneous events (e.g., dryness of the skin, lips, and eyes), hyperlipidemia, and decreased levels of freethyroxine and thyroid stimulating hormone.
• For most patients, the recommended starting dose is 30mg for up to 24 weeks, depending on response.¹⁰ A starting lower dose of 10mg daily may be tried in patients exhibiting unacceptable adverse reactions to the higher dose.¹¹
• Alitretinoin is an endogenous retinoid, with concentrations returning to normal range within 1-3 days after treatment cessation. It is rapidly eliminated and does not accumulate in the body.¹¹
• As with all systemic retinoids, alitretinoin is teratogenic and requires strict monitoring when used in women of childbearing potential. Pregnancy testing and the use of acceptable methods of contraception are required just prior to, during, and 1 month after therapy.

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Self-Care Tips for Patients

An essential part of HD management is to restore the normal skin barrier function by regularly moisturizing with emollients, both during and in between flares. Lifestyle modifications and patient self-care are critical components for successful ongoing management and minimizing adverse effects on quality of life (QoL).

• Use mild cleansers instead of harsh or perfumed soaps.
• Maintain the regimented use of bland moisturizers (e.g., petrolatum).
• Avoid products containing fragrances and preservatives.
• Bathe with warm water and limit the duration.
• If triggers are known, avoidance is a central HD management strategy.
• Reduce exposing hands to water, cleaning products, and aeroallergens by wearing gloves (wear cotton gloves under latex/rubber to absorb perspiration).
• Use barrier creams and practice glove hygiene to reduce antigen exposure and severity of skin reactions.
• Scratching can cause cracks to form, allowing bacteria to enter the damaged epidermis and result in infection.
• Antipruritic strategies include applying a cold compress to the affected area, keeping fingernails short, and using OTC products containing hydrocortisone.
• Avoid skin contact with fruits, vegetables, and raw meats.
• If possible, wear vinyl gloves to shampoo hair.
• Remove rings before wet-work or hand washing, as they can trap moisture and irritants.
• Efforts aimed at reducing stress are beneficial for controlling HD. Psychological stress may cause immunological changes that can aggravate HD.
• For education and social support, patients may benefit from interactions with national organizations or web-based social networks.

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Conclusion

Formulation of an effective treatment strategy will depend on many factors, including findings from diagnostic investigations, extent and severity of HD, treatment history, age, and patient preferences. Aside from achieving tangible improvements, the adopted therapeutic approach must also minimize QoL impairment from sleep interference, discomfort, disability, and heighten self-consciousness, which can lead to social avoidance behaviors. Consequently, early diagnosis and ongoing medical and adjunctive care are crucial for controlling chronicity and disease severity.

There is a significant unmet need for pharmacologic agents that are effective in the long-term management of severe CHD. Present treatment options are plagued with side-effects and unable to induce sustained periods of remission. However, the recent introduction of alitretinoin has broadened the therapeutic options and improved the outlook for patients who are unresponsive to conventional therapies. Within the framework of patient care, pharmacists play an integral role by counseling on adjunctive OTC medications, drug side-effects, proper usage, and tips for daily management. Such efforts directed at patient education convey practical advice and reinforce both the rationale and aims of prescribed therapies, which can help to optimize treatment outcomes.

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References

1. Ruzicka T, et al. Br J Dermatol 158(4):808-17 (2008 Apr).
2. Diepgen, et al. Contact Dermatitis 47:203-10 (2007).
3. Meding B, et al. Acta Derm Venereol 69(3):227-33 (1989).
4. Meding B, et al. J Invest Dermatol 124(5):893-7 (2005 May).
5. Cvetkovski RS, et al. Br J Dermatol 152(1):93-8 (2005 Jan).
6. Meding B. Acta Derm Venereol Suppl (Stockh) 153:1-43 (1990).
7. van Coevorden AM, et al. Br J Dermatol 151(2):446-51 (2004 Aug).
8. Robertson L. Skin Therapy Lett 14(3):1-5 (2009 Mar).
9. Ruzicka T, et al. Arch Dermatol 140(12):1453-9 (2004 Dec).
10. Health Canada. Notice of Decision for Toctino (2009 Nov 13). Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/phase1-decision/drug-med/nd_ad_2009_toctino_119010-eng.php. Accessed March 25, 2010.
11. 11. The electronic Medicines Compendium (eMC) on alitretinoin (Toctino®). Available at: http://emc.medicines.org.uk/ medicine/21177/SPC/Toctino+10mg+and+30mg+soft+capsules/. Accessed March 25, 2010.

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