Oral treatment of keratinizing disorders of skin and mucous membranes with etretinate. Comparative study of 113 patients

Mahrle, G.

doi:10.1001/archderm.118.2.97

Cited by 15 publications

(7 citation statements)

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“…In Darier disease oral retinoid treatment gives better results than any other treatment so far known [23,[45][46][47][48][49]. O ur own results are in agreement with those reported in the literature [9], In general, the most severely affected patients arc those who have most benefit from the treatment.…”

Section: Darier Diseasesupporting

confidence: 82%

Retinoids in Disorders of Keratinization: Their Use in Adults

Happle

Kerkhof²,

Traupe³

1987

Dermatology

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Hereditary disorders of keratinization may be a considerable handicap. Oral treatment with retinoids has been shown to be effective in many of these diseases. In the group of ichthyoses, the best results can be obtained in the various types of nonbullous congenital ichthyosis (erythrodermic autosomal recessive lamellar ichthyosis, nonerythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant lamellar ichthyosis). It should be borne in mind, however, that retinoid therapy alone cannot lead to a complete response of these forms of ichthyosis and that this treatment cannot replace an appropriate topical treatment. During continuous treatment with etretinate a reduction of the dosis to 0.5 mg/kg is often necessary. Etretinate treatment of bullous congenital ichthyosiform erythroderma is more difficult, and it is advisable to begin with a low dosis of 0.25–0.5 mg/kg. The epidermolytic form of palmoplantar keratoderma is in our opinion no indication for retinoid treatment which seems to result inevitably in large erosions. Good or excellent results have been seen in other forms of palmoplantar keratoderma including mal de Meleda, Papillon-Lefèvre syndrome, erythrokeratodermia variabilis, verrucous epidermal nevi, Darier disease and pityriasis rubra pilaris. In patients with Darier disease it is wise to begin with a relatively low dosage of 0.5 mg/kg and to adjust the dosage to the further course of the disease. The same is true for the ichthyosis seen in the Netherton syndrome, which may be either a diffuse hyperkeratosis or ichthyosis linearis circumflexa. In view of the fact that any inherited keratinization disorder requires long-term treatment, the risk of bone toxicity should be carefully weighed against the benefit of this therapy. The results so far obtained indicate that the effect of etretin is comparable to that of etretinate in the treatment of inherited keratinization disorders. Intermittent therapy should be tried whenever possible. A combination therapy seems reasonable in pityriasis rubra pilaris of the adult type. We have seen good results by combination with PUVA treatment. Autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis are inappropriate to treat with oral retinoid therapy because these diseases are too mild. Papillomatous epidermal nevi should also be excluded because they do not respond to the drug. Hailey-Hailey disease may even be worsened by this treatment. According to our experience, oral retinoid therapy has no effect in monilethrix.

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Section: Darier Diseasesupporting

confidence: 82%

Retinoids in Disorders of Keratinization: Their Use in Adults

Happle

Kerkhof²,

Traupe³

1987

Dermatology

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“…(1) Their importance as a dietary factor has been long recognized, (2) and more recently, the retinoids have been found to possess potent growth and differentiative activities on a variety of cell types. In the skin, retinoids have been useful in the treatm ent of a number of disorders, including acne, (3) psoriasis, (4) and disorders of keratinization, (5) and certain derm atologic malignancies, (6,7) including cutaneous T cell lymphoma (CTCL). (8±10) In CTCL, the mechanism responsible for the beneficial therapeutic effects of the retinoids remains unknown.…”

Section: Introduction T H E R Etin O Id S a R E A F A M Ily Of Compmentioning

confidence: 99%

Retinoids Synergize with Interleukin-2 to Augment IFN-gamma and Interleukin-12 Production by Human Peripheral Blood Mononuclear Cells

Fox¹,

Kubin²,

Cassin³

et al. 1999

Journal of Interferon & Cytokine Research

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We have demonstrated previously that cells from both the skin and peripheral blood from patients with cutaneous T cell lymphoma (CTCL) have elevated levels of protein and mRNA for Th2 cytokines, interleukin-4 (IL-4) and IL-5, and depressed levels of Thl cytokines, IL-2 and interferon-gamma (IFN-gamma). Furthermore, IL-12 in vitro can restore IFN-gamma production by these patients' cells to near normal levels. Because retinoids exert therapeutic activity in CTCL and are potent modulators of growth and differentiation of hematopoietic cells, we investigated the role of retinoids in modulating Thl cytokine production. Peripheral blood mononuclear cells (PBMC) from normal donors and patients with CTCL were cultured with medium, IL-2, 13-cis-retinoic acid, all-trans-retinoic acid, acetretin or etretinate alone, or IL-2 plus the retinoids for 24 h, and levels of IFN-gamma were determined using ELISA. IL-2 or retinoids alone could induce low but significant levels of IFN-gamma. However, when IL-2 was cultured with each retinoid, a synergistic augmentation of IFN-gamma levels (4-fold to 90-fold) was observed except in the case of etretinate. All-trans-retinoic acid (ATRA) was the most potent IFN-y inducer. Similar studies performed using PBMC from CTCL patients indicated the IFN-gamma augmentation occurred but in a blunted manner. The IFN-y-inducing effect of ATRA and 13-cis-retinoic acid could be abrogated by addition of anti-IL-12 antibodies, suggesting that IL-12 plays a role in the synergistic upregulation of IFN-gamma. Using an IL-12 p40-specific radioimmunoassay (RIA), we confirmed the presence of IL-12 in IL-2 plus retinoid-treated culture supernatants. Purified monocytes cultured with IL-2 plus ATRA did not secrete IL-12. Only when monocytes were cocultured with lymphocytes was there an increase in IL-12 production, suggesting the involvement of a paracrine feedback loop requiring both monocytes and lymphocytes. These data suggest that retinoids can induce Th1 cytokines from normal and CTCL PBMC and that this induction may be mediated through IL-12 production.

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“…Previous studies have shown that both oral etretinate and acitretin have been effective and well tolerated in children and adults affected by DOK. [1][2][3][5][6][7][8][9][10][11][12][13] However, the longest published duration of oral retinoids for adults is up to 10 years 2 and for children is up to 11 years. 3 The largest cohort of patients (956 psoriasis patients) on oral retinoids (etretinate) was described by Stern et al and this cohort was followed up prospectively for up to 4 years.…”

Section: Discussionmentioning

confidence: 99%