Foot Eczema and Alitretinoin

When I first started working in a dermatology department many years ago, I remember  being told by one of the Consultants that “feet tend to be forgotten in skin disease” which certainly is true - reflected in the paucity of research in this area. Many years on, despite the great strides in drug treatment for chronic common skin disease, it seems the feet are still rarely a point of focus in this work. A recent publication focussing on foot eczema and treatment with a drug originally designated as a treatment for hand eczema caught my eye which I felt was worth looking at further.

Eczema and Quality of Life

Eczema is a common, global skin problem, covering a wide spectrum of presentations and manifestations including atopic dermatitis, allergy and chronic skin inflammation. Many studies have examined the effects of eczema and its impact on the quality of life for the patient and their close family [1, 2]. Involvement of the hands and feet technically represents a small proportion of total body surface area but functionally it can have a significant impact on work and activities in daily life. One study looking specifically at the foot, showed eczema in that the area has a very large impact on QOL with symptoms such as scaling, burning and oozing of the affected skin [3]. Similar results have been reported by another study including the impact of painful fissures arising on the foot [4].

Traditional management of eczema on the foot has relied on the use of emollients and topical steroids to manage flares and supress acute inflammation.  This has been the mainstay for many years and continues to be effective for some, but more recent drug developments have offered new avenues for patients.

Alitretinoin

In 2008, across Europe and the UK, a new class of oral retinoid was licenced for use in refractory hand eczema unresponsive to traditional topical steroids, under the brand name Toctino®. Alitretinoin (9-cis-retinoic acid) belongs to the family of drugs derived from vitamin A. Drugs of this group include tretinoin and acitretin which have been used for many years in dermatology as treatments for hyperkeratotic disorders affecting the skin.

Alitretinoin has demonstrated a double action in suppressing the inflammatory pathways observed in eczema affecting two receptors and reduction of downstream recruitment of activated T cells [5]. An early study demonstrated its efficacy versus placebo by showing 48% of patients with chronic hand eczema showed complete or near complete clearance versus only 17% of placebo treated patients with an effect that lasted on average 6 months after cessation of treatment [6]. Similar success was observed in another study of 680 patients with chronic hand eczema [7].

The drug is only prescribed by dermatologists when standard treatments fail to control the symptoms. As with all retinoids, the main drawbacks are the risk of teratogenic effects (risk of birth defects) and so it is contraindicated women of childbearing age unless specific conditions around pregnancy prevention are met. Other side effects include headache, drying of the skin and mucosa and alteration in thyroxine stimulating hormone and blood lipids which require careful monitoring during treatment.

 

Alitretinoin and Foot Eczema

Despite the focus on the drug for hand eczema, effects on foot eczema have not gone entirely unnoticed. In a review article published in the Australasian journal of Dermatology [8] it explicitly includes the foot in its recommended management of chronic hand and foot eczema recommending a 12-week course of the drug in eczema not responding to topical treatments or phototherapy.

Most recently a Korean paper has been published this month in the Journal of the European Academy of Dermatology focussing on the efficacy of alitretinoin in concomitant foot eczema [9]. In a small cohort of 20 adults with chronic foot and hand eczema, after ruling out other similar diagnoses such as allergies and fungal foot infection, they administered 10 - 30mgs of alitretinoin for the study period of 24 weeks.

The group consisted of middle-aged adults (mean age = 53.9 years) and various scoring systems were applied and measured for the duration of treatment for palmar and plantar involvement. Interestingly, at the start of the study foot lesions showed a higher symptom burden for patients than hand lesions. By week four, around 55% showed almost or complete clearance of hand lesions compared to only 25% in foot lesions. At the conclusion of the study though, 80% of hand lesions had almost or totally cleared, with 75% of foot lesions doing the same.

The slower response for the foot is possibly explained as it was more severe than hand involvement at the beginning of the study, whilst a slightly lower overall response could be due to external factors such as weight bearing, thickened plantar epidermis or friction lessening the effects of the drug. Overall, the safety profile was good in this small sample with no withdrawals of patients due to side effects.

Implications for Podiatrists

Foot eczema is not going to be uncommon in day-to-day practice. The key to managing the condition is identifying it as it arises. Eczema is one of the big three red rashes on the foot along with psoriasis and tinea pedis. Therefore, it is pertinent to make a sound diagnosis. With eczema particularly it is important to identify if there are any allergic or irritant triggering facets to the disease which can adversely affect management and treatment outcomes. For most, as the Australian and New Zealand guidelines state [8], there are a range of treatments available, and a stepwise approach is logical starting with topical and if there is little or no response consider the next steps including possible phototherapy or alitretinoin. For most, this will require a dermatology referral to facilitate this.

Along the line, newer drugs continue to emerge. Dupilumab is a monoclonal antibody which targets IL-4 and IL-13, key drivers of inflammation in eczema has shown to be effective in treating eczema. For many patients with disease restricted to the feet and hands, this has not been available to them. However, a study examining the effect of Dupilumab on hand and foot eczema demonstrated safety and effectiveness [10]. In the UK however, use of the drug is currently restricted  to those failing at least 1 systemic treatment. With time, we hope to see this available more widely.

References

1.            Birdi, G., R. Cooke, and R.C. Knibb, Impact of atopic dermatitis on quality of life in adults: a systematic review and meta-analysis. International Journal of Dermatology, 2020. 59(4): p. e75–e91.

2.            Ali, F., J. Vyas, and A.Y. Finlay, Counting the Burden: Atopic Dermatitis and Health-related Quality of Life. Acta Derm Venereol, 2020. 100(12): p. adv00161.

3.            Agrawal, P.V., et al., Assessment of Impairment of Quality of Life in Foot Eczema and Correlation thereof with Epidemiological Data of its Patients: A Cross-Sectional Study. Indian Dermatol Online J, 2020. 11(5): p. 766–770.

4.            Divya, P., et al., Clinicodemographic profile and assessment of quality of life in patients with palmoplantar psoriasis and Hyperkeratotic Eczema: A cross sectional study. IP Indian J Clin Exp Dermatol. , 2026. 12(1): p. 63–69.

5.            King, T., J. McKenna, and A.B. Alexandroff, Alitretinoin for the treatment of severe chronic hand eczema. Patient Prefer Adherence, 2014. 8: p. 1629–34.

6.            Ruzicka, T., et al., Efficacy and safety of oral alitretinoin (9‐cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double‐blind, placebo‐controlled, multicentre trial. British Journal of Dermatology, 2008. 158(4): p. 808–817.

7.            Diepgen, T.L., E. Pfarr, and T. Zimmermann, Efficacy and tolerability of alitretinoin for chronic hand eczema under daily practice conditions: results of the TOCCATA open study comprising 680 patients. Acta Derm Venereol, 2012. 92(3): p. 251–5.

8.            Rademaker, M., et al., Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative. Australas J Dermatol, 2021. 62(1): p. 17–26.

9.            Cha, S., et al., Efficacy of oral alitretinoin for concomitant foot eczema in chronic hand eczema. Journal of the European Academy of Dermatology and Venereology, 2026. n/a(n/a).

10.         Simpson, E.L., et al., Dupilumab treatment improves signs, symptoms, quality of life, and work productivity in patients with atopic hand and foot dermatitis: Results from a phase 3, randomized, double-blind, placebo-controlled trial. Journal of the American Academy of Dermatology, 2024. 90(6): p. 1190–1199.