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Indian Journal of Dermatology,... 2012Eczema, the commonest disorders afflicting the hands, is also the commonest occupational skin disease (OSD). In the dermatology outpatient departments, only the severe... (Review)
Review
Eczema, the commonest disorders afflicting the hands, is also the commonest occupational skin disease (OSD). In the dermatology outpatient departments, only the severe cases are diagnosed since patients rarely report with early hand dermatitis. Mild forms are picked up only during occupational screening. Hand eczema (HE) can evolve into a chronic condition with persistent disease even after avoiding contact with the incriminated allergen / irritant. The important risk factors for hand eczema are atopy (especially the presence of dermatitis), wet work, and contact allergy. The higher prevalence in women as compared to men in most studies is related to environmental factors and is mainly applicable to younger women in their twenties. Preventive measures play a very important role in therapy as they enable the affected individuals to retain their employment and livelihood. This article reviews established preventive and therapeutic options and newer drugs like alitretinoin in hand eczema with a mention on the etiology and morphology. Identifying the etiological factors is of paramount importance as avoiding or minimizing these factors play an important role in treatment.
Topics: Anti-Inflammatory Agents; Dermatitis, Occupational; Eczema; Emollients; Gloves, Protective; Hand Dermatoses; Humans; Immunosuppressive Agents; Retinoids; Skin Cream; Steroids
PubMed: 22960812
DOI: 10.4103/0378-6323.100547 -
Circulation Feb 2012
Topics: Alitretinoin; Animals; Lymphangiogenesis; Lymphatic Vessels; Lymphedema; Regeneration; Tretinoin
PubMed: 22275500
DOI: 10.1161/CIRCULATIONAHA.111.083477 -
AACE Clinical Case Reports 2022Although retinoid-associated central hypothyroidism has been reported on several occasions, there are very few studies on retinoid-associated central adrenal...
BACKGROUND/OBJECTIVE
Although retinoid-associated central hypothyroidism has been reported on several occasions, there are very few studies on retinoid-associated central adrenal insufficiency. Here, we present the case of a patient with alitretinoin-induced central hypothyroidism and adrenal insufficiency.
CASE REPORT
An 86-year-old man with a diagnosis of cutaneous T-cell lymphoma, treated with oral alitretinoin 30 mg po daily, topical steroids, and ultraviolet light therapy presented to the emergency department with generalized weakness, decreased energy, orthostasis, and unexplained falls. Thyroid-stimulating hormone (TSH) was 0.31 mIU/L (normal range: 0.4-4.4) from 1.93 before alitretinoin therapy, whereas free thyroxine was 5.7 pmol/L (normal range: 8-18) and the AM cortisol was 40 nmol/L (normal range: 120-535); these values were suggestive of central hypothyroidism and adrenal insufficiency. Adrenocorticotropic hormone (ACTH) was not measured because of a laboratory error. Alitretinoin was stopped, and one dose of hydrocortisone 100mg IV was initiated, followed by maintenance doses of oral hydrocortisone 20mg qam and 10mg qpm. Levothyroxine (50μg ) daily was started 24 hours later. After stopping hydrocortisone for 24 hours, the AM cortisol and ACTH levels were 406 nmol/L and 2.18 pmol/L (normal range:1.6-13.9), respectively. He was discharged on thyroid hormone replacement therapy and glucocorticoids. Repeat thyroid function tests 6 weeks later showed a TSH of 0.4 mIU/L, and free thyroxine of 9.7 pmol/L.
DISCUSSION
Alitretinoin activates nuclear receptors called retinoic acid receptors and retinoid X-receptors. Retinoic acid receptors and retinoid X-receptors are widely expressed in the anterior pituitary gland. RXR-selective ligands such as retinoids can suppress TSH secretion, resulting in central hypothyroidism. Retinoids have also been shown to decrease ACTH secretion, which can result in central adrenal insufficiency.
CONCLUSION
Although central adrenal insufficiency and hypothyroidism have not been commonly reported in patients taking retinoids, they should always be considered when caring for these patients.
PubMed: 36447824
DOI: 10.1016/j.aace.2022.08.004 -
Molecules (Basel, Switzerland) Sep 2022The heterodimeric complex between retinoic X receptor alpha (RXRα) and peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most important and...
The heterodimeric complex between retinoic X receptor alpha (RXRα) and peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most important and predominant regulatory systems, controlling lipid metabolism by binding to specific DNA promoter regions. X-ray and molecular dynamics (MD) simulations have revealed the average conformation adopted by the RXRα-PPARγ heterodimer bound to DNA, providing information about how multiple domains communicate to regulate receptor properties. However, knowledge of the energetic basis of the protein-ligand and protein-protein interactions is still lacking. Here we explore the structural and energetic mechanism of RXRα-PPARγ heterodimer bound or unbound to DNA and forming complex with co-crystallized ligands (rosiglitazone and 9--retinoic acid) through microsecond MD simulations, molecular mechanics generalized Born surface area binding free energy calculations, principal component analysis, the free energy landscape, and correlated motion analysis. Our results suggest that DNA binding alters correlated motions and conformational mobility within RXRα-PPARγ system that impact the dimerization and the binding affinity on both receptors. Intradomain correlated motions denotes a stronger correlation map for RXRα-PPARγ-DNA than RXRα-PPARγ, involving residues at the ligand binding site. In addition, our results also corroborated the greater role of PPARγ in regulation of the free and bound DNA state.
Topics: Alitretinoin; Carrier Proteins; DNA; Humans; Ligands; Molecular Dynamics Simulation; PPAR gamma; Rosiglitazone
PubMed: 36144514
DOI: 10.3390/molecules27185778 -
The Journal of Steroid Biochemistry and... Nov 2018Nuclear receptors are a superfamily of transcription factors restricted to animals. These transcription factors regulate a wide variety of genes with diverse roles in... (Review)
Review
Nuclear receptors are a superfamily of transcription factors restricted to animals. These transcription factors regulate a wide variety of genes with diverse roles in cellular homeostasis, development, and physiology. The origin and specificity of ligand binding within lineages of nuclear receptors (e.g., subfamilies) continues to be a focus of investigation geared toward understanding how the functions of these proteins were shaped over evolutionary history. Among early-diverging animal lineages, the retinoid X receptor (RXR) is first detected in the placozoan, Trichoplax adhaerens. To gain insight into RXR evolution, we characterized ligand- and DNA-binding activity of the RXR from T. adhaerens (TaRXR). Like bilaterian RXRs, TaRXR specifically bound 9-cis-retinoic acid, which is consistent with a recently published result and supports a conclusion that the ancestral RXR bound ligand. DNA binding site specificity of TaRXR was determined through protein binding microarrays (PBMs) and compared with human RXRɑ. The binding sites for these two RXR proteins were broadly conserved (∼85% shared high-affinity sequences within a targeted array), suggesting evolutionary constraint for the regulation of downstream genes. We searched for predicted binding motifs of the T. adhaerens genome within 1000 bases of annotated genes to identify potential regulatory targets. We identified 648 unique protein coding regions with predicted TaRXR binding sites that had diverse predicted functions, with enriched processes related to intracellular signal transduction and protein transport. Together, our data support hypotheses that the original RXR protein in animals bound a ligand with structural similarity to 9-cis-retinoic acid; the DNA motif recognized by RXR has changed little in more than 1 billion years of evolution; and the suite of processes regulated by this transcription factor diversified early in animal evolution.
Topics: Alitretinoin; Animals; Base Sequence; Binding Sites; DNA; Humans; Ligands; Placozoa; Protein Binding; Retinoid X Receptors; Signal Transduction
PubMed: 29510228
DOI: 10.1016/j.jsbmb.2018.02.010 -
Dermatology Online Journal May 2014Dissecting cellulitis (DC) also referred to as to as perifolliculitis capitis abscedens et suffodiens (Hoffman) manifests with perifollicular pustules, nodules,... (Review)
Review
Dissecting cellulitis (Perifolliculitis Capitis Abscedens et Suffodiens): a comprehensive review focusing on new treatments and findings of the last decade with commentary comparing the therapies and causes of dissecting cellulitis to hidradenitis suppurativa.
Dissecting cellulitis (DC) also referred to as to as perifolliculitis capitis abscedens et suffodiens (Hoffman) manifests with perifollicular pustules, nodules, abscesses and sinuses that evolve into scarring alopecia. In the U.S., it predominantly occurs in African American men between 20-40 years of age. DC also occurs in other races and women more rarely. DC has been reported worldwide. Older therapies reported effective include: low dose oral zinc, isotretinoin, minocycline, sulfa drugs, tetracycline, prednisone, intralesional triamcinolone, incision and drainage, dapsone, antiandrogens (in women), topical clindamycin, topical isotretinoin, X-ray epilation and ablation, ablative C02 lasers, hair removal lasers (800nm and 694nm), and surgical excision. Newer treatments reported include tumor necrosis factor blockers (TNFB), quinolones, macrolide antibiotics, rifampin, alitretinoin, metronidazole, and high dose zinc sulphate (135-220 mg TID). Isotretinoin seems to provide the best chance at remission, but the number of reports is small, dosing schedules variable, and the long term follow up beyond a year is negligible; treatment failures have been reported. TNFB can succeed when isotretinoin fails, either as monotherapy, or as a bridge to aggressive surgical treatment, but long term data is lacking. Non-medical therapies noted in the last decade include: the 1064 nm laser, ALA-PDT, and modern external beam radiation therapy. Studies that span more than 1 year are lacking. Newer pathologic hair findings include: pigmented casts, black dots, and "3D" yellow dots. Newer associations include: keratitis-ichthyosis-deafness syndrome, Crohn disease and pyoderma gangrenosum. Older associations include arthritis and keratitis. DC is likely a reaction pattern, as is shown by its varied therapeutic successes and failures. The etiology of DC remains enigmatic and DC is distinct from hidradenitis suppurativa, which is shown by their varied responses to therapies and their histologic differences. Like HS, DC likely involves both follicular dysfunction and an aberrant cutaneous immune response to commensal bacteria, such as coagulase negative staphylococci. The incidence of DC is likely under-reported. The literature suggests that now most cases of DC can be treated effectively. However, the lack of clinical studies regarding DC prevents full understanding of the disease and limits the ability to define a consensus treatment algorithm.
Topics: Acitretin; Alitretinoin; Anti-Bacterial Agents; Cellulitis; Dermatologic Agents; Diagnosis, Differential; Estrogens; Ethinyl Estradiol; Hidradenitis Suppurativa; History, 20th Century; Humans; Laser Therapy; Lymphotoxin-alpha; Phototherapy; Radiotherapy; Scalp Dermatoses; Skin Diseases, Genetic; Tretinoin; Zinc
PubMed: 24852785
DOI: No ID Found -
The Cochrane Database of Systematic... Aug 2014Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients.
OBJECTIVES
To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014.
SELECTION CRITERIA
Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens.
MAIN RESULTS
We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events.
AUTHORS' CONCLUSIONS
The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.
Topics: Alitretinoin; Antineoplastic Agents; Antiretroviral Therapy, Highly Active; Bleomycin; Doxorubicin; Drug Therapy, Combination; Etoposide; HIV Infections; Humans; Liposomes; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sarcoma, Kaposi; Skin Neoplasms; Tretinoin; Vincristine
PubMed: 25221796
DOI: 10.1002/14651858.CD003256.pub2 -
Dermatology (Basel, Switzerland) 2013Therapy-resistant lichen planus (LP) can be a challenging condition for dermatologists. There are some case reports about successful treatments with alitretinoin of... (Review)
Review
BACKGROUND
Therapy-resistant lichen planus (LP) can be a challenging condition for dermatologists. There are some case reports about successful treatments with alitretinoin of cutaneous and oral, but not of esophageal LP.
OBJECTIVE
We present the unique case of a patient with cutaneous, oral and esophageal LP which was refractory to classical treatment options (topical clobetasol propionate and pimecrolimus, intramuscular triamcinolone acetonide); because of systemic side effects the patient did not tolerate systemic acitretin dosed up to 25 mg daily.
METHODS
Oral alitretinoin was used at a dose of 30 mg daily.
RESULTS
Both oral and skin changes as well as dysphagia completely resolved within 4 weeks without any severe side effects and the drug was used for 6 months. No papules, intraoral striae or dysphagia recurred during the 6 months of treatment. After 4 months the patient relapsed with mucosal patches so that a second cycle was initiated for 6 months where oral LP lesions resolved after 4 weeks also (with sporadic mild headache).
CONCLUSION
Further studies are needed to better understand the impact of alitretinoin in LP. Our observation suggests alitretinoin as a new, well-tolerated treatment option for esophageal LP after failed response to conventional treatments.
Topics: Alitretinoin; Antineoplastic Agents; Deglutition Disorders; Esophageal Diseases; Female; Humans; Lichen Planus; Lichen Planus, Oral; Middle Aged; Tretinoin
PubMed: 23948733
DOI: 10.1159/000349980 -
Annals of Dermatology Dec 2019Chronic hand eczema (CHE) tends to be refractory to conventional therapy. Previous clinical trials have found that alitretinoin is an effective and well-tolerated...
BACKGROUND
Chronic hand eczema (CHE) tends to be refractory to conventional therapy. Previous clinical trials have found that alitretinoin is an effective and well-tolerated treatment for CHE. However, there is a relative lack of data on the effectiveness of alitretinoin in elderly patients.
OBJECTIVE
The aim of this study was to investigate the efficacy and safety of oral alitretinoin in elderly patients with moderate to severe CHE in Korea.
METHODS
We retrospectively investigated 46 CHE patients who were treated with either 10 mg or 30 mg of alitretinoin between June of 2016 and July of 2018. The physician's global assessment (PGA) was used to evaluate treatment efficacy. All adverse events were retrospectively evaluated with respect to laboratory testing, including complete blood cell count, fasting blood chemistry, lipid profile, and liver and thyroid function tests.
RESULTS
The mean patient age in this study was 71.0±5.1 years. The treatment period was over eight weeks. A total of 38 of 46 patients (82.6%) exhibited clinical improvement with PGA ratings of 'clear' or 'almost clear.' There were 13 patients (28.3%) who experienced an adverse effect, with the most common being headache (13.0%) and gastrointestinal symptoms (8.7%) followed by xerosis (6.5%). A total of 13 patients developed or exhibited worsening hypertriglyceridemia (28.3%).
CONCLUSION
Alitretinoin can be considered a safe and effective treatment option in elderly patients with moderate to severe CHE.
PubMed: 33911658
DOI: 10.5021/ad.2019.31.6.595 -
Annals of Dermatology Jun 2019
PubMed: 33911606
DOI: 10.5021/ad.2019.31.3.347