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Annals of Dermatology Nov 2023
PubMed: 38061756
DOI: 10.5021/ad.21.109 -
Journal of Cutaneous Medicine and... Nov 2023Prurigo nodularis (PN) is a debilitating inflammatory skin disease characterized by red to violaceous pruritic lesions. The goal of therapy is to break the scratch-itch... (Review)
Review
IMPORTANCE
Prurigo nodularis (PN) is a debilitating inflammatory skin disease characterized by red to violaceous pruritic lesions. The goal of therapy is to break the scratch-itch cycle. Treatment varies and often requires a multimodal approach to target both immune and neural mediated aspects of disease.
OBJECTIVES
To review the efficacy of systemic treatment used to treat PN.
EVIDENCE REVIEW
A systematic search of keywords and Medical Subject Headings was performed in Ovid MEDLINE, Embase, Scopus, and ClinicalTrials.gov. The first 200 results of an abbreviated search in Google Scholar were also included. PRISMA guidelines were followed and the review was registered on PROSPERO (CRD42023412012). GRADE criteria were used to assess articles for quality of evidence.
FINDINGS
The search resulted in 1153 articles; 382 were duplicates, 643 were irrelevant, 19 were not retrieved, 21 were abstract only, and 88 are included in this review. There were 24 studies on dupilumab, 16 on thalidomide, 8 on cyclosporin, 7 on methotrexate, 3 each on lenalidomide and aprepitant, 2 each on alitretinoin, apremilast, baricitinib, gabapentin, intravenous (IV) immunoglobulins, pregabalin, tofacitinib, and 1 each on amitriptyline, azathioprine, butorphanol, isoquercitin, IV dexamethasone-cyclophosphamide/ oral cyclophosphamide, ketotifen, metronidazole, montelukast, nalbuphine, nemolizumab, serolopitant, tacrolimus, and herose derma zima capsule.
CONCLUSIONS AND RELEVANCE
Dupilumab reduces pruritus and appearance of lesions and is associated with the fewest number of side effects. Thalidomide and pregabalin are also effective, but their long-term use is limited by muscle and nerve pain. Janus Kinase inhibitors may be beneficial, but large population studies are lacking.
Topics: Humans; Thalidomide; Prurigo; Pregabalin; Cyclosporine; Pruritus; Cyclophosphamide
PubMed: 37987710
DOI: 10.1177/12034754231211797 -
Dermatitis : Contact, Atopic,... 2024Systemic remedies such as cyclosporine, methotrexate, and retinoids are off-license treatment options that are considered for severe chronic hand eczema (CHE) that is... (Comparative Study)
Comparative Study
Systemic remedies such as cyclosporine, methotrexate, and retinoids are off-license treatment options that are considered for severe chronic hand eczema (CHE) that is resistant to first-line treatment. The objective of this study was to determine the optimal treatment of CHE patients, including those with atopic Dermatitis®, and to compare the efficacy between cyclosporine and alitretinoin. This study was retrospective and included CHE patients who visited the Department of Dermatology at Hanyang University Seoul Hospital in Korea between March 2013 and February 2020. A total of 95 CHE patients was included in this study. In the cyclosporine treatment group, there were more patients with severe baseline Investigator Global Assessment (IGA) ( = 0.033) and higher immunoglobulin E (IgE) level ( = 0.019). The mean recurrence duration was 15.9 weeks in the alitretinoin group and 22.9 weeks in the cyclosporine group, the difference between which was not statistically significant. In a subgroup analysis according to treatment drug, only the low IgE group showed a better recurrence profile for alitretinoin treatment compared to cyclosporine treatment ( = 0.039). When comparing the cumulative recurrence rate during the treatment period and subsequent follow-up periods, the cyclosporine group showed a greater incidence of recurrence than the alitretinoin group in all follow-up periods. The results of our study are consistent with the previously reported efficacy of alitretinoin. Despite the rapid response in the cyclosporine group, 12 weeks of CHE treatment with alitretinoin showed superior efficacy compared to cyclosporine treatment. Both alitretinoin and cyclosporine groups showed efficacy in patients with CHE. Cyclosporine is an alternative treatment of CHE that is refractory to alitretinoin or relapses after its use, especially in the presence of atopic Dermatitis®.
Topics: Humans; Cyclosporine; Alitretinoin; Female; Male; Retrospective Studies; Hand Dermatoses; Eczema; Dermatologic Agents; Adult; Middle Aged; Chronic Disease; Dermatitis, Atopic; Recurrence; Tretinoin
PubMed: 37870578
DOI: 10.1089/derm.2023.0113 -
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 -
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 -
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 British Journal of Dermatology Sep 2023
Topics: Humans; Alitretinoin; Double-Blind Method; Eczema; Antibodies, Monoclonal, Humanized
PubMed: 37337439
DOI: 10.1093/bjd/ljad199 -
Journal of Molecular Graphics &... Nov 2023Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with... (Meta-Analysis)
Meta-Analysis
Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARβ). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.
Topics: Humans; Molecular Dynamics Simulation; Receptors, Histamine H1; HIV Infections; Receptors, Retinoic Acid; Histamine Antagonists; Histamine H1 Antagonists; Alitretinoin; Tretinoin
PubMed: 37331258
DOI: 10.1016/j.jmgm.2023.108539 -
International Journal of Molecular... Jun 2023Retinoids are a frequently used class of drugs in the treatment of inflammatory as well as malignant skin diseases. Retinoids have differential affinity for the retinoic...
Retinoids are a frequently used class of drugs in the treatment of inflammatory as well as malignant skin diseases. Retinoids have differential affinity for the retinoic acid receptor (RAR) and/or the retinoid X receptor (RXR). The endogenous dual RAR and RXR agonist alitretinoin (9- retinoic acid) demonstrated remarkable efficacy in the treatment of chronic hand eczema (CHE) patients; however, detailed information on the mechanisms of action remains elusive. Here, we used CHE as a model disease to unravel immunomodulatory pathways following retinoid receptor signaling. Transcriptome analyses of skin specimens from alitretinoin-responder CHE patients identified 231 significantly regulated genes. Bioinformatic analyses indicated keratinocytes as well as antigen presenting cells as cellular targets of alitretinoin. In keratinocytes, alitretinoin interfered with inflammation-associated barrier gene dysregulation as well as antimicrobial peptide induction while markedly inducing hyaluronan synthases without affecting hyaluronidase expression. In monocyte-derived dendritic cells, alitretinoin induced distinct morphological and phenotypic characteristics with low co-stimulatory molecule expression (CD80 and CD86), the increased secretion of IL-10 and the upregulation of the ecto-5'-nucleotidase CD73 mimicking immunomodulatory or tolerogenic dendritic cells. Indeed, alitretinoin-treated dendritic cells demonstrated a significantly reduced capacity to activate T cells in mixed leukocyte reactions. In a direct comparison, alitretinoin-mediated effects were significantly stronger than those observed for the RAR agonist acitretin. Moreover, longitudinal monitoring of alitretinoin-responder CHE patients could confirm in vitro findings. Taken together, we demonstrate that the dual RAR and RXR agonist alitretinoin targets epidermal dysregulation and demonstrates strong immunomodulatory effects on antigen presenting cell functions.
Topics: Humans; Alitretinoin; Retinoids; Tretinoin; Receptors, Retinoic Acid; Retinoid X Receptors; Antigen-Presenting Cells
PubMed: 37298605
DOI: 10.3390/ijms24119654