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International Journal of Molecular... Oct 2022Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a... (Review)
Review
Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.
Topics: Humans; Skin Neoplasms; Retinoids; Carcinoma, Squamous Cell; Vitamin A; Carcinoma, Basal Cell
PubMed: 36293471
DOI: 10.3390/ijms232012622 -
Health Technology Assessment... Sep 2019Pressure ulcers (PUs) are a burden to patients, carers and health-care providers. Specialist mattresses minimise the intensity and duration of pressure on vulnerable... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Pressure ulcers (PUs) are a burden to patients, carers and health-care providers. Specialist mattresses minimise the intensity and duration of pressure on vulnerable skin sites in at-risk patients.
PRIMARY OBJECTIVE
Time to developing a new PU of category ≥ 2 in patients using an alternating pressure mattress (APM) compared with a high-specification foam mattress (HSFM).
DESIGN
A multicentre, Phase III, open, prospective, planned as an adaptive double-triangular group sequential, parallel-group, randomised controlled trial with an a priori sample size of 2954 participants. Randomisation used minimisation (incorporating a random element).
SETTING
The trial was set in 42 secondary and community inpatient facilities in the UK.
PARTICIPANTS
Adult inpatients with evidence of acute illness and at a high risk of PU development.
INTERVENTIONS AND FOLLOW-UP
APM or HSFM - the treatment phase lasted a maximum of 60 days; the final 30 days were post-treatment follow-up.
MAIN OUTCOME MEASURES
Time to event.
RESULTS
From August 2013 to November 2016, 2029 participants were randomised to receive either APM ( = 1016) or HSFM ( = 1013). Primary end point - 30-day final follow-up: of the 2029 participants in the intention-to-treat population, 160 (7.9%) developed a new PU of category ≥ 2. There was insufficient evidence of a difference between groups for time to new PU of category ≥ 2 [Fine and Gray model HR 0.76, 95% confidence interval (CI) 0.56 to 1.04; exact -value of 0.0890 and 2% absolute difference]. Treatment phase sensitivity analysis: 132 (6.5%) participants developed a new PU of category ≥ 2 between randomisation and end of treatment phase. There was a statistically significant difference in the treatment phase time-to-event sensitivity analysis (Fine and Gray model HR 0.66, 95% CI 0.46 to 0.93; = 0.0176 and 2.6% absolute difference). Secondary end points - 30-day final follow-up: new PUs of category ≥ 1 developed in 350 (17.2%) participants, with no evidence of a difference between mattress groups in time to PU development, (Fine and Gray model HR 0.83, 95% CI 0.67 to 1.02; -value = 0.0733 and absolute difference 3.1%). New PUs of category ≥ 3 developed in 32 (1.6%) participants with insufficient evidence of a difference between mattress groups in time to PU development (Fine and Gray model HR 0.81, 95% CI 0.40 to 1.62; = 0.5530 and absolute difference 0.4%). Of the 145 pre-existing PUs of category 2, 89 (61.4%) healed - there was insufficient evidence of a difference in time to healing (Fine and Gray model HR 1.12, 95% CI 0.74 to 1.68; = 0.6122 and absolute difference 2.9%). Health economics - the within-trial and long-term analysis showed APM to be cost-effective compared with HSFM; however, the difference in costs models are small and the quality-adjusted life-year gains are very small. There were no safety concerns. Blinded photography substudy - the reliability of central blinded review compared with clinical assessment for PUs of category ≥ 2 was 'very good' (kappa statistic 0.82, prevalence- and bias-adjusted kappa 0.82). Quality-of-life substudy - the Pressure Ulcer Quality of Life - Prevention (PU-QoL-P) instrument meets the established criteria for reliability, construct validity and responsiveness.
LIMITATIONS
A lower than anticipated event rate.
CONCLUSIONS
In acutely ill inpatients who are bedfast/chairfast and/or have a category 1 PU and/or localised skin pain, APMs confer a small treatment phase benefit that is diminished over time. Overall, the APM patient compliance, very low PU incidence rate observed and small differences between mattresses indicate the need for improved indicators for targeting of APMs and individualised decision-making. Decisions should take into account skin status, patient preferences (movement ability and rehabilitation needs) and the presence of factors that may be potentially modifiable through APM allocation, including being completely immobile, having nutritional deficits, lacking capacity and/or having altered skin/category 1 PU.
FUTURE WORK
Explore the relationship between mental capacity, levels of independent movement, repositioning and PU development. Explore 'what works for whom and in what circumstances'.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN01151335.
FUNDING
This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 52. See the NIHR Journals Library website for further project information.
Topics: Adult; Aged; Aged, 80 and over; Beds; Female; Humans; Inpatients; Male; Middle Aged; Pressure Ulcer; Prospective Studies; United Kingdom; Young Adult
PubMed: 31559948
DOI: 10.3310/hta23520 -
Annals of Dermatology Feb 2021Oral alitretinoin is effective in the treatment of chronic hand eczema (CHE), and ≥12 weeks of alitretinoin treatment has been shown to be effective in Korean...
BACKGROUND
Oral alitretinoin is effective in the treatment of chronic hand eczema (CHE), and ≥12 weeks of alitretinoin treatment has been shown to be effective in Korean patients. However, in the real world, a considerable number of patients discontinue alitretinoin, which leads to treatment failure.
OBJECTIVE
To evaluate the compliance rate of alitretinoin treatment and explore common reasons for poor compliance in patients with CHE in the real world.
METHODS
We retrospectively reviewed the electronic medical records of CHE patients treated with alitretinoin. We defined 'poor-compliance' as subjects who were treated with alitretinoin for <12 weeks and 'good-compliance' as subjects who were treated with alitretinoin for ≥12 weeks. We reviewed the demographics, dose, and duration of alitretinoin usage, efficacy, and reasons for poor compliance.
RESULTS
A total of 137 subjects were enrolled, and 77 (56.2%) did not complete the 12-week treatment with alitretinoin. Among them, the non-improvement rate was significantly higher in the poor-compliance group than in the good-compliance group (<0.01). The main reasons for the alitretinoin cessation in the poor-compliance group were insufficient response (40.8%), followed by high cost (34.7%), and adverse events (24.5%).
CONCLUSION
Alitretinoin appears the preferred long-term treatment option for CHE. Although there are complaints about late efficacy, cost, and side effects, following proper explanation, these should not justify discontinuation. Physicians need to recognize the reasons for poor compliance with alitretinoin for each patient and suggest continuing alitretinoin for the successful treatment of CHE.
PubMed: 33911811
DOI: 10.5021/ad.2021.33.1.46 -
Clinical and Experimental Dermatology Dec 2022For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids...
For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids (acitretin, isotretinoin and alitretinoin) has been shown to be effective in reducing disease severity; however, potentially rare adverse effects (AEs) may occur, including hyperostotic skeletal changes. The true prevalence of this AE in adult patients administered life-long therapy is unknown. We identified 3 of 127 (2.4%) patients (with ichthyosis or Darier disease) who had been prescribed isotretinoin with or without acitretin, and who developed radiological signs and clinical symptoms of hyperostosis and ligamentous ossification. This clinical review highlights the significance of retinoid-induced skeletal hyperostosis in patients prescribed long-term, high-dose retinoid therapy for disorders of keratinization. Patients commencing systemic retinoid therapy, particularly women of childbearing age, should be counselled about this important and potentially serious AE, especially if long-term treatment is indicated.
Topics: Adult; Humans; Female; Acitretin; Isotretinoin; Alitretinoin; Hyperostosis; Ichthyosis
PubMed: 35988035
DOI: 10.1111/ced.15382 -
Medicina (Kaunas, Lithuania) Jul 2022Darier disease is an autosomal dominant disorder with dark crusty patches and is classified as hereditary acantholytic dermatosis. Keratotic papules and crust are often...
Darier disease is an autosomal dominant disorder with dark crusty patches and is classified as hereditary acantholytic dermatosis. Keratotic papules and crust are often present on the scalp, forehead, chest, back, upper arms, elbows, groin, and behind the ears, predominantly in seborrheic areas. A 48-year-old male patient presented skin lesions with pruritus on the trunk and both upper and lower extremities. He first noticed the lesion 15 years before. On physical examination, there were multiple erythematous papules with crust on the trunk and red-brown colored keratotic plaque on both extremities. The suspected histopathological diagnosis was psoriasis vulgaris. The patient's skin lesions and pruritus were significantly improved after the psoriasis treatment. While continuing psoriasis treatment, the patient showed sudden worsening of the skin lesions on the scalp, abdomen, and fingernails (V-shaped nicks) with pruritus. Punch biopsy was performed on the abdominal lesion again and the final diagnosis was Darier disease. The patient was then treated using alitretinoin while maintaining the use of guselkumab for psoriasis. There are only a few cases that we found in which patients with Darier disease also had psoriasis. We report this rare case of Darier disease with psoriasis and propose that an additional biopsy might be necessary for accurate diagnosis and proper treatment.
Topics: Biopsy; Darier Disease; Humans; Male; Middle Aged; Pruritus; Psoriasis; Skin
PubMed: 35888621
DOI: 10.3390/medicina58070902 -
Medicina (Kaunas, Lithuania) Nov 2020: prurigo is a chronic skin disorder associated with a history of chronic pruritus. The pathogenesis of prurigo is largely unknown and the treatment of prurigo is...
: prurigo is a chronic skin disorder associated with a history of chronic pruritus. The pathogenesis of prurigo is largely unknown and the treatment of prurigo is unsatisfactory and challenging. Conventional systemic treatments may be beneficial; however, their possible side effects and possible transient efficacy is still a problem. We aimed to present the clinical course and effect of treatment with alitretinoin on patients with prurigo nodularis initially treated with conventional treatments like oral antihistamine, cyclosporine, and phototherapy. : all the patients had prurigo nodularis refractory to conventional treatment. Their medical records included demographic features, past medical history, duration of disease, and treatment modalities; and the clinical courses of the patients were reviewed for this retrospective study. We evaluated patient pruritus and skin lesions for the duration. : we present reports involving 10 patients with refractory prurigo. All the patients in our cases were treated with oral alitretinoin after previous treatments and reported the improvement of skin lesions and pruritus within 2 weeks to 3 months. : we suggest that oral alitretinoin may be an effective and well tolerated treatment option for patients with intractable prurigo. Further clinical studies are warranted to confirm the long-lasting efficacy and safety of alitretinoin for treating patients with prurigo.
Topics: Alitretinoin; Cyclosporine; Humans; Prurigo; Pruritus; Retrospective Studies
PubMed: 33182351
DOI: 10.3390/medicina56110599 -
Dermatology (Basel, Switzerland) 2021Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is...
BACKGROUND
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management.
METHODS
A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies.
RESULTS
Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia.
CONCLUSIONS
This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.
Topics: Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Canada; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Retrospective Studies; Sezary Syndrome; Skin Neoplasms; Treatment Outcome; Young Adult
PubMed: 33429396
DOI: 10.1159/000512484 -
Journal of Cutaneous Medicine and... 2022Chronic hand dermatitis (CHD) is difficult to treat and has high individual and societal burdens. Phototherapy and oral alitretinoin are safe monotherapies for CHD, but...
BACKGROUND
Chronic hand dermatitis (CHD) is difficult to treat and has high individual and societal burdens. Phototherapy and oral alitretinoin are safe monotherapies for CHD, but their combination has not been assessed.
OBJECTIVE
To assess the effectiveness and safety of low dose oral alitretinoin combined with phototherapy versus high dose oral alitretinoin for CHD refractory to topical corticosteroids.
METHODS
This retrospective study of adult patients with CHD refractory to topical corticosteroid therapy compared low dose oral alitretinoin (10 mg three times weekly) combined with narrowband ultraviolet B therapy (three times weekly; LDA-UVB) to high dose oral alitretinoin (30 mg daily; HDA) for 16 weeks. Outcomes were improvement in disease severity measured by the Physician's Global Assessment and quality of life measured with the Dermatology Life Quality Index.
RESULTS
The mean age of the study population ( = 64) was 41.25 years and 57.8% were male. Both cohorts experienced improvements in disease severity and quality of life after 16 weeks, however, significantly more participants who received LDA-UVB ( = 21/33, 63.6%) achieved "clear" or "almost clear" assessments compared to those who received HDA ( = 12/31, 38.7%; < .05). Adverse effects were significantly more prevalent in the HDA group ( < .0001) and included headache, elevated cholesterol, and dry lips.
CONCLUSIONS
The combination of low dose oral alitretinoin with narrowband-UVB therapy was more effective and had fewer adverse effects compared to high dose oral alitretinoin for participants with CHD refractory to topical corticosteroid therapy.
Topics: Adrenal Cortex Hormones; Adult; Alitretinoin; Chronic Disease; Eczema; Female; Humans; Male; Quality of Life; Retrospective Studies; Treatment Outcome; Ultraviolet Therapy
PubMed: 35067082
DOI: 10.1177/12034754211071123 -
Skin Health and Disease Jun 2022While treatment options exist for solitary or disseminated Kaposi sarcoma (KS) disease, there are currently no standardized clinical treatment guidelines for cutaneous...
BACKGROUND
While treatment options exist for solitary or disseminated Kaposi sarcoma (KS) disease, there are currently no standardized clinical treatment guidelines for cutaneous KS.
OBJECTIVE
This systematic review seeks to identify safe and effective topical treatments for cutaneous KS lesions.
METHODS
We conducted a systematic review using peer-reviewed articles from January 1970 to September 2021 published in the PubMed/MEDLINE and EMBASE databases.
RESULTS
From the initial search that yielded 590 studies, 34 met the inclusion criteria and were selected. Of the 34 studies, seven were clinical trials, 26 were case reports/series and one was a multicentre study. A total of 634 patients were included in our review. The three most common topical treatments used for cutaneous KS were imiquimod, alitretinoin and timolol. Topical alitretinoin was used in three case reports and three clinical trials. Topical imiquimod was used in eight case reports, one prospective phase II cohort study and one comparative single-blinded non-controlled clinical study. Topical timolol was used in nine case reports/series. Our review also identified reports of less widely used topical treatments for cutaneous KS. These include topical diphencyprone (DPCP), all--retinoic-acid, rapamycin and bleomycin-dimethylsulfoxide (BLM-DMSO) which achieved variable response rates but have not been widely studied.
CONCLUSION
Topical alitretinoin, imiquimod and timolol demonstrated positive responses for cutaneous KS and the treatments were well tolerated. These three topical treatment modalities could be considered by clinicians when treating cutaneous KS.
PubMed: 35677916
DOI: 10.1002/ski2.107