Immunomodulation in Patients with Chronic Hand Eczema Treated with Oral Alitretinoin

Abstract

Background: Oral alitretinoin (9-cis-retinoic acid; 9-cis-RA) has shown clinical efficacy in patients with chronic hand eczema (CHE). Herein, we investigated the impact of oral 9-cis-RA on the local and systemic immune response in patients with CHE. Methods: Twenty patients with CHE were treated with oral alitretinoin (10 or 30 mg/day) for at least 24 weeks. Blood samples were taken for flow cytometry, and serum samples were assessed by ELISA to determine immunoglobulin (Ig) levels. Skin biopsies from lesional skin were evaluated immunohistochemically. Results: Upon 9-cis-RA treatment, improvement of the CHE was observed in all patients. A significant decrease in plasmablasts in the peripheral blood and a significant reduction of serum IgE levels were determined. Furthermore, we detected a significant reduction of CD4+ cells and regulatory T cells in the peripheral blood upon treatment. By contrast, these cell subsets were significantly increased in the affected skin. Cytokine analysis of activated CD154-positive T cells showed a reduction of interleukin (IL)-17 but not of IL-4 or IFN-γ production. Conclusions: Overall, our data indicate a disease-modifying effect of 9-cis-RA, including a systemic decrease in IL-17-positive cells, but decreased serum IgE and CD23 expression. The increased frequency of FoxP3-positive cells in the skin upon treatment may suggest a mechanism by which hand eczema is therapeutically targeted by 9-cis-RA, but this will need to be proven in the future studies.

Successful treatment of refractory chronic hand eczema with calcipotriol/betamethasone ointment: A report of three cases

“…Systemic treatments are indicated for refractory CHE, the majority of which have not been investigated in randomized clinical trials and are therefore prescribed off-label (2,3,8). At present, the only treatments approved are alitretinoin, which may be considered a second-line option as it has shown good response rates in clinical trials and observational studies (9)(10)(11)(12). In addition, cyclosporin, azathioprine, methotrexate and mycophenolate mofetil may all be considered third-line treatments (13,14).…”

Alitretinoin in treatment of chronic hand eczema – mechanism of action

“…Alitretynoina działa na linie niedojrzałych komó-rek (blasty) poprzez zmniejszenie ich procentowego udziału we krwi obwodowej. Zmniejsza też istotnie ilość całkowitego IgE we krwi, nie powodując jednocześnie odchylenia w liczbie wszystkich dojrzałych limfocytów B [22]. Podczas terapii alitretynoiną dochodzi do wyraźnej redukcji stężenia IL-17.…”

“…Podczas terapii alitretynoiną dochodzi do wyraźnej redukcji stężenia IL-17. Ponadto zmniejsza się liczba limfocytów CD4+ i Treg we krwi obwodowej, a wzrasta ich stężenie w obrębie skóry dotkniętej procesem zapalnym [22]. Przeciwzapalny efekt alitretynoiny potęgowany jest również przez hamowanie wydzielania tlenku azotu oraz m.in.…”

Retinoid Chemoprevention: Who Can Benefit?

“…In certain cases retinoids are useful in treating mycosis fungoides [92]. Chronic eczema is treated with 9-cis-RA, and one the mechanisms involved is an increase of FoxP3 cells in the skin [93]. In dissecting cellulitis, topical 13-cis-RA is the most effective drug to induce remission [94].…”