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Dermatology and Therapy May 2024Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous... (Review)
Review
Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.
PubMed: 38700645
DOI: 10.1007/s13555-024-01169-1 -
Dermatology (Basel, Switzerland) 2024Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive... (Review)
Review
BACKGROUND
Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive measures during 3 years after discontinuation. An alternative is needed for women of childbearing age. With alitretinoin, another retinoid, pregnancy is considered safe 1 month after discontinuation.
OBJECTIVES
The aim of this study was to provide evidence for alitretinoin as an alternative for acitretin for ichthyosis in women of childbearing age. Our experience is shared in a case series combined with an overview of the current literature.
METHODS
Nine women of childbearing age (19-31 years, median 21) with different subtypes of ichthyosis (autosomal recessive congenital ichthyosis, (superficial) epidermolytic ichthyosis, erythrokeratoderma variabilis, and epidermolytic epidermal nevi, a mosaic form of epidermolytic ichthyosis) were included and treated with 30 mg alitretinoin during 2-28 months. Severity was measured by Ichthyosis Area Severity Index (IASI) and Investigator Global Assessment (IGA). A literature search in Pubmed using the Mesh terms "alitretinoin," "skin diseases, genetic" and "ichthyosis" was performed.
RESULTS
Significant reduction in the mean scores of IGA, IASI-erythema, IASI-scaling, and IASI-total was seen. Seven patients are still being treated, 1 patient stopped to become pregnant, 1 patient discontinued due to financial reasons. Observed side effects were reversible headache (n = 6), asteatotic eczema (n = 1), "not feeling well" temporarily (n = 1), and easier blistering of the feet (n = 1). The literature search resulted in six case reports and case series about alitretinoin in ichthyosis and ichthyosis syndromes with in total 29 patients. The vast majority of articles (21/29) reported significant improvement or even complete remission of skin symptoms. However, validated outcome measures to support these results were lacking. Side effects (n = 16) were relatively mild, except for benign intracranial hypertension (n = 1) and autoimmune hypothyroidism (n = 1).
CONCLUSION
Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women of childbearing age and a suitable alternative to acitretin.
Topics: Pregnancy; Humans; Female; Young Adult; Adult; Alitretinoin; Acitretin; Hyperkeratosis, Epidermolytic; Ichthyosis; Immunoglobulin A
PubMed: 37666225
DOI: 10.1159/000533934 -
Frontiers in Pharmacology 2023In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their...
Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.
In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.
PubMed: 37663263
DOI: 10.3389/fphar.2023.1207976 -
Annals of Dermatology Nov 2023
PubMed: 38061756
DOI: 10.5021/ad.21.109 -
Acta Dermatovenerologica Alpina,... Dec 2023Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a...
Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a seborrheic and intertriginous distribution. The absence of specific targeted medications complicates the treatment process, and managing resistant cases can prove challenging due to recurrent exacerbations that may result in serious complications such as secondary bacterial and viral infections. Treatments of choice include antiseptics, topical corticosteroids, and systemic retinoids, mainly acitretin and isotretinoin. We report the case of a female patient with Darier disease that was unsuccessfully treated with acitretin and isotretinoin but showed significant improvement with alitretinoin. Previous reports on the efficacy of alitretinoin in Darier disease are reviewed.
Topics: Adolescent; Humans; Female; Darier Disease; Alitretinoin; Acitretin; Isotretinoin; Dermatologic Agents
PubMed: 38126103
DOI: No ID Found -
Rhode Island Medical Journal (2013) Aug 2023Kaposi sarcoma is a rare vascular malignancy associated with HHV-8 infection. Four variants of Kaposi sarcoma have been described: Classic, African, HIV-associated, and...
Kaposi sarcoma is a rare vascular malignancy associated with HHV-8 infection. Four variants of Kaposi sarcoma have been described: Classic, African, HIV-associated, and iatrogenic. Iatrogenic Kaposi sarcoma is typically associated with immunosuppression and organ transplantation. We present a case of iatrogenic Kaposi sarcoma associated with tofacitinib therapy. A 69-year-old woman with rheumatoid arthritis receiving tofacitinib presented with multiple firm, purple-red nodules and brown plaques on the left lower extremity and a single lesion on the right medial calf. Clinicopathologic correlation confirmed a diagnosis of Kaposi sarcoma. Tofacitinib was discontinued and she was started on Alitretinoin 0.1% gel bid. The purple-red Kaposi sarcoma nodules decreased 50% in size after 4 months and resolved at 1 year off the tofacitinib and initiation of alitretinoin gel. As the use of immunomodulators and biologics continues to expand, awareness of this association is important for prompt diagnosis and management.
Topics: Female; Humans; Aged; Sarcoma, Kaposi; Alitretinoin; Arthritis, Rheumatoid; Iatrogenic Disease
PubMed: 37494621
DOI: No ID Found -
The Journal of Biological Chemistry Oct 20239-cis-retinoic acid (9cRA) binds retinoic acid receptors (RAR) and retinoid X receptors (RXR) with nanomolar affinities, in contrast to all-trans-retinoic acid (atRA),...
9-cis-retinoic acid (9cRA) binds retinoic acid receptors (RAR) and retinoid X receptors (RXR) with nanomolar affinities, in contrast to all-trans-retinoic acid (atRA), which binds only RAR with nanomolar affinities. RXR heterodimerize with type II nuclear receptors, including RAR, to regulate a vast gene array. Despite much effort, 9cRA has not been identified as an endogenous retinoid, other than in pancreas. By revising tissue analysis methods, 9cRA quantification by liquid chromatography-tandem mass spectrometry becomes possible in all mouse tissues analyzed. 9cRA occurs in concentrations similar to or greater than atRA. Fasting increases 9cRA in white and brown adipose, brain and pancreas, while increasing atRA in white adipose, liver and pancreas. 9cRA supports FoxO1 actions in pancreas β-cells and counteracts glucose actions that lead to glucotoxicity; in part by inducing Atg7 mRNA, which encodes the key enzyme essential for autophagy. Glucose suppresses 9cRA biosynthesis in the β-cell lines 832/13 and MIN6. Glucose reduces 9cRA biosynthesis in 832/13 cells by inhibiting Rdh5 transcription, unconnected to insulin, through cAMP and Akt, and inhibiting FoxO1. Through adapting tissue specifically to fasting, 9cRA would act independent of atRA. Widespread occurrence of 9cRA in vivo, and its self-sufficient adaptation to energy status, provides new perspectives into regulation of energy balance, attenuation of insulin and glucose actions, regulation of type II nuclear receptors, and retinoid biology.
Topics: Animals; Mice; Alitretinoin; Glucose; Insulin; Tretinoin; Mice, Inbred C57BL; Rats; Cell Line; Gene Expression Regulation; Insulin-Secreting Cells; Energy Metabolism; Fasting; Proto-Oncogene Proteins c-akt
PubMed: 37714463
DOI: 10.1016/j.jbc.2023.105255 -
Pharmaceutics Mar 2024Vesicular hand eczema (VHE), a clinical subtype of hand eczema (HE), showed limited responsiveness to alitretinoin, the only approved systemic treatment for severe...
Vesicular hand eczema (VHE), a clinical subtype of hand eczema (HE), showed limited responsiveness to alitretinoin, the only approved systemic treatment for severe chronic HE. This emphasizes the need for alternative treatment approaches. Therefore, our study aimed to identify drug repurposing opportunities for VHE using transcriptomics and genomics data. We constructed a gene network by combining 52 differentially expressed genes (DEGs) from a VHE transcriptomics study with 3 quantitative trait locus (QTL) genes associated with HE. Through network analysis, clustering, and functional enrichment analyses, we investigated the underlying biological mechanisms of this network. Next, we leveraged drug-gene interactions and retrieved pharmaco-transcriptomics data from the DrugBank database to identify drug repurposing opportunities for (V)HE. We developed a drug ranking system, primarily based on efficacy, safety, and practical and pricing factors, to select the most promising drug repurposing candidates. Our results revealed that the (V)HE network comprised 78 genes that yielded several biological pathways underlying the disease. The drug-gene interaction search together with pharmaco-transcriptomics lookups revealed 123 unique drug repurposing opportunities. Based on our drug ranking system, our study identified the most promising drug repurposing opportunities (e.g., vitamin D analogues, retinoids, and immunomodulating drugs) that might be effective in treating (V)HE.
PubMed: 38675137
DOI: 10.3390/pharmaceutics16040476 -
Cureus Jan 2024A black male in his 60s diagnosed with classic Kaposi's sarcoma presented with multiple cutaneous nodules and edema of the right foot and lower leg. He was initially...
A black male in his 60s diagnosed with classic Kaposi's sarcoma presented with multiple cutaneous nodules and edema of the right foot and lower leg. He was initially treated with alitretinoin 1% topical treatment. However, 16 months after treatment with the alitretinoin, the skin lesions progressed, and he subsequently underwent a course of radiation therapy to a total dose of 2000 centigrays (cGy) in five fractions to his right foot and lower extremities. Approximately 1.5 years after the radiation therapy was completed, multiple new lesions developed on the right foot and distal lower leg. He then underwent a course of re-irradiation to this area using volumetric modulated arc therapy (VMAT) to a total dose of 3300 cGy in 11 fractions. At a four-week follow-up visit, the skin lesions had completely resolved; however, the patient experienced mild edema and tenderness of the right foot and lower leg. Although long-term outcomes need to be followed, re-irradiation showed positive short-term outcomes for classic Kaposi's sarcoma.
PubMed: 38322087
DOI: 10.7759/cureus.51782 -
Acta Dermato-venereologica Dec 2023
Topics: Humans; Alitretinoin; Mycosis Fungoides; Skin Neoplasms
PubMed: 38088788
DOI: 10.2340/actadv.v103.18472