Impact of systemic alitretinoin treatment on skin barrier gene and protein expression in patients with chronic hand eczema

Kumari, Vandana; Timm, Katrin; Kühl, Anja A.; Heine, Guido; Worm, Margitta

doi:10.1111/bjd.14921

Cited by 22 publications

(17 citation statements)

References 41 publications

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“…The pathogenesis of HHE remains largely unclear. A previous study on the gene and protein expression of hand eczema, including 15 patients with chronic hyperkeratotic‐fissured hand eczema showed, among others, increased proliferative cell activity indicated by Ki‐67, and a decreased expression of the terminal differentiation marker loricrin in palmar lesional skin biopsies, which was normalised following alitretinoin treatment 8 . Another study showed an upregulation in keratinocyte host defence mechanism proteins (S100A7/S100A8/S100A9) in six patients with chronic hand eczema, including different subtypes, compared to healthy control skin 9 .…”

Section: Discussionmentioning

confidence: 91%

“…A previous study on the gene and protein expression of hand eczema, including 15 patients with chronic hyperkeratotic-fissured hand eczema showed, among others, increased proliferative cell activity indicated by Ki-67, and a decreased expression of the terminal differentiation marker loricrin in palmar lesional skin biopsies, which was normalised following alitretinoin treatment. 8 Another study showed an upregulation in keratinocyte host defence mechanism proteins (S100A7/S100A8/S100A9) in six patients with chronic hand eczema, including different subtypes, compared to healthy control skin. 9 A study on protein expression in seven patients with HHE, showed also increased proliferative cell activity indicated by Ki-67 and a strong upregulation of keratin (K)16 with, in addition, a decreased expression of loricrin in lesional palmar skin compared to perilesional skin and healthy control skin.…”

Section: Discussionmentioning

confidence: 97%

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Three cases of non‐atopic hyperkeratotic hand eczema treated with dupilumab

2020

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A unique point of this case is the development of anaphylactoid reactions several hours after exposure to the hair dyes, which gradually worsened over the following several days. PPD and its derivatives may cause delayed-type-as well as immediate-type-like reactions, although the related mechanism is not clearly understood. The current case might likely be due to combined immediate and delayed hypersensitivity to hair dye, 2,3 though the immediate hypersensitivity observed in this patient was atypical. The positive skin reactions to PPD and PTD-containing HD-A suggests that the patient might be allergic to both PPD and PTD. Unfortunately, as PTD was unavailable to us, we could not test it. The negative result of PPD-containing HD-B in the open test might be due to a lower PPD concentration in HD-B, as this was a "light hair colour" shade. Unexpectedly, the patient experienced systemic anaphylactoid reactions 16 hours after closed patch testing. As she had been hospitalized during the skin tests, we could respond promptly. Therefore, caution must be exercised, especially for patients with a history of anaphylactoid symptoms, to avoid possible systemic reactions during skin tests for hair dye.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Three cases of non‐atopic hyperkeratotic hand eczema treated with dupilumab

2020

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“…In fact, the skin endogenously produces substantial amounts of RA and its precursors (such as retinol) that contribute to the maintenance of skin homeostasis [16], while therapeutically applied retinoids represent approved (topical or oral) treatments for a wide range of skin disorders including psoriasis, acne, photoaging, non-melanoma skin cancer, cutaneous T-cell lymphomas, ichthyosis, as well as chronic hand eczema, and they even form part of cosmetic products [17,18,19,20,21,22,23,24]. …”

Section: Discussionmentioning

confidence: 99%

“…A tight association between the retinoid system and the skin is underscored by the amounts of RA and its precursors found in this organ and the abundance of proteins involved in RA metabolism and function [15,16], and further substantiated by the broad therapeutic use of retinoids for skin disorders; in fact, retinoid based therapies are inclined towards dermatological conditions [17,18,19,20,21,22,23,24]. …”

Section: Introductionmentioning

confidence: 99%

Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability

Babina

Artuc

Guhl

et al. 2017

IJMS

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The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, FcεRI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays. We found that while MC size and granularity remained unchanged, RA potently interfered with MC proliferation. Conversely, a modest survival-promoting effect from RA was noted. The granule constituents, histamine and tryptase, remained unaffected, while RA had a striking impact on MC chymase, whose expression dropped by gene and by peptidase activity. The newly uncovered MRGPRX2 performed similarly to chymase. Intriguingly, RA fostered allergic MC degranulation, in a way completely uncoupled from FcεRI expression, but it simultaneously restricted MRGPRX2-triggered histamine release in agreement with the reduced receptor expression. Vitamin-A-derived hormones thus re-shape skin-derived MCs numerically, phenotypically, and functionally. A general theme emerges, implying RA to skew MCs towards processes associated with (allergic) inflammation, while driving them away from the skin-imprinted MCTC (“MCs containing tryptase and chymase”) signature (chymase, MRGPRX2). Collectively, MCs are substantial targets of the skin retinoid network.

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“…Furthermore, Kumari et al ., 2016, provided immunohistological evidence that treatment with alitretinoin increased the expression of skin barrier proteins that correlated with clinical improvement of chronic hand eczema. They suggested that the improvement was via direct alitretinoin stimulation of keratinocyte proliferation and differentiation and indirectly through reducing inflammatory cytokines produced by infiltrating T cells …”

Section: Discussionmentioning

confidence: 99%

Expression of retinoid receptors in hand eczema

et al. 2020

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Background Hand eczema is the most common occupational skin disease. The etiology is multifactorial. Systemic alitretinoin, a pan-retinoic receptor agonist, has proven efficacy in the treatment of recalcitrant chronic hand eczema; however, its precise mechanism of action in hand eczema is not fully understood.Aims Assessment of the level of expression of retinoid receptors (RAR and RXR) in the skin of patients with hand eczema in an attempt to explain their possible role in the pathogenesis of the disease.Methods Thirty patients with hand eczema and 30 age-and sex-matched healthy controls were included. Full clinical examination was done, and tissue levels of retinoic acid receptor (RAR) and retinoid x receptor (RXR) were measured by quantitative real-time PCR (qRT-PCR). ResultsThe levels of RAR and RXR expression were significantly downregulated in the patient group compared to the control group; (P < 0.001) for both. In addition, there was a statistically significant negative correlation between Osnabr€ uck Hand Eczema Severity Index (OHSI) and the levels of RAR and RXR expression (P < 0.001).Conclusion Deficient retinoid receptor expression has a primary role in the pathogenesis, clinical phenotype, and severity of hand eczema and sheds light on the mechanism of action of retinoids in the treatment of chronic hand eczema.

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Impact of systemic alitretinoin treatment on skin barrier gene and protein expression in patients with chronic hand eczema

Cited by 22 publications

References 41 publications

Three cases of non‐atopic hyperkeratotic hand eczema treated with dupilumab

Three cases of non‐atopic hyperkeratotic hand eczema treated with dupilumab

Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability

Expression of retinoid receptors in hand eczema

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