tretinoin and Chronic-Disease

All-trans retinoic acid (ATRA) application is a novel treatment approach for primary immune thrombocytopenia (ITP). This study aimed to evaluate the efficacy and safety of ATRA in the treatment of ITP. The databases of PubMed (MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Internet were searched on August 5, 2022, to find randomized controlled trials (RCTs) and observational studies. Five observational studies and four RCTs from China were included, and 760 Chinese patients were analyzed. In the five observational studies, the pooled overall response rate (ORR) and complete response rate (CRR) were 59.5% (95% confidence interval [CI], 52.4-66.4%) and 20.6% (95% CI, 14.3-27.6%), respectively. In the selected four RCTs, the pooled odds ratios for sustained response rate, ORR, and CRR were 3.00 (95% CI, 1.97-4.57; P < 0.01), 3.21 (95% CI, 2.15-4.78; P < 0.01), and 2.12 (95% CI, 1.17-3.86; P = 0.01), respectively. ATRA was associated with a reduction in relapse rate and salvage treatment rate (odds ratio, 0.30; 95% CI, 0.18-0.50; P < 0.01; 0.36; 95% CI, 0.23-0.56; P < 0.01, respectively). The pooled odds ratios for grade 1-2 dry skin, headache (or dizziness), and rash acneiform were 49.99 (95% CI, 16.05-155.67; P < 0.01), 1.75 (95% CI, 0.98-3.12; P = 0.06), and 0.37 (95% CI, 0.10-1.34; P = 0.13), respectively. This study suggests that ATRA may significantly improve the initial and long-term response of patients with ITP.

Topics: China; Chronic Disease; Humans; Purpura, Thrombocytopenic, Idiopathic; Remission Induction; Tretinoin

Alitretinoin is an endogenous vitamin A derivative, 9-cis-retinoic acid. Its anti-inflammatory and immunomodulatory efficacy results from controlling leukocyte activity and cytokine production in keratinocytes. We describe three patients with severe chronic hand eczema accompanied by nail dystrophy, which was treated with alitretinoin 30 mg. Clinical evaluation at 6 months showed complete or almost complete clearing of the nail lesions. We also briefly review the literature reporting on nail dystrophy and alitretinoin treatment. There is some evidence of the clinical effect of retinoids on nail formation, owing to the presence of retinoid receptors on the nail matrix. Further studies are required to better understand the impact of alitretinoin in nail diseases. Our observation supports alitretinoin as a treatment option in retinoid-responsive dermatoses associated with nail involvement.

Topics: Adult; Alitretinoin; Anti-Inflammatory Agents; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Male; Middle Aged; Nail Diseases; Treatment Outcome; Tretinoin

Management of hand eczema is complex because of the broad range of different pathogeneses, courses, and prognoses. Furthermore, the efficacy of most available treatments is not well established and the more severe forms can have a major impact on the patient's quality of life. Patient education, preventive measures, and the use of emollients are the mainstays in the management of hand eczema. High-potency topical corticosteroids are the treatment of choice, with calcineurin inhibitors used for maintenance. Phototherapy or systemic treatments are indicated in patients who do not respond to topical treatments. Switching from topical treatments should not be delayed to avoid sensitizations, time off work, and a negative impact on quality of life. Alitretinoin is the only oral treatment approved for use in chronic hand eczema.

Topics: Adrenal Cortex Hormones; Alitretinoin; Calcineurin Inhibitors; Chronic Disease; Combined Modality Therapy; Dermatitis, Contact; Dermatologic Agents; Disease Management; Eczema; Emollients; Gloves, Protective; Hand Dermatoses; Humans; Immunosuppressive Agents; Occupational Diseases; Phototherapy; Practice Guidelines as Topic; Quality of Life; Tretinoin

The poor prognosis for patients with hepatocellular carcinoma (HCC) is associated with its high rate of recurrence in the cirrhotic liver. Therefore, more effective strategies need to be urgently developed for the chemoprevention of this malignancy. The malfunction of retinoid X receptor α, a retinoid receptor, due to phosphorylation by Ras/mitogen-activated protein kinase is closely associated with liver carcinogenesis and may be a promising target for HCC chemoprevention. Acyclic retinoid (ACR), a synthetic retinoid, can prevent HCC development by inhibiting retinoid X receptor α phosphorylation and improve the prognosis for this malignancy. Supplementation with branched-chain amino acids (BCAA), which are used to improve protein malnutrition in patients with liver cirrhosis, can also reduce the risk of HCC in obese cirrhotic patients. In experimental studies, both ACR and BCAA exert suppressive effects on HCC development and the growth of HCC cells. In particular, combined treatment with ACR and BCAA cooperatively inhibits the growth of HCC cells. Furthermore, ACR and BCAA inhibit liver tumorigenesis associated with obesity and diabetes, both of which are critical risk factors for HCC development. These findings suggest that pharmaceutical and nutraceutical approaches using ACR and BCAA may be promising strategies for preventing HCC and improving the prognosis of this malignancy.

Topics: Amino Acids, Branched-Chain; Carcinoma, Hepatocellular; Chronic Disease; Clinical Trials as Topic; Dietary Supplements; Humans; Liver Diseases; Liver Neoplasms; Phosphorylation; Retinoid X Receptor alpha; Retinoid X Receptors; Retinoids; Tretinoin

In this review, we summarize recent advances in understanding vitamin A-dependent regulation of sex-specific differences in metabolic diseases, inflammation, and certain cancers. We focus on the characterization of the aldehyde dehydrogenase-1 family of enzymes (ALDH1A1, ALDH1A2, ALDH1A3) that catalyze conversion of retinaldehyde to retinoic acid. Additionally, we propose a "horizontal transfer of signaling" from estrogen to retinoids through the action of ALDH1A1. Although estrogen does not directly influence expression of Aldh1a1, it has the ability to suppress Aldh1a2 and Aldh1a3, thereby establishing a female-specific mechanism for retinoic acid generation in target tissues. ALDH1A1 regulates adipogenesis, abdominal fat formation, glucose tolerance, and suppression of thermogenesis in adipocytes; in B cells, ALDH1A1 plays a protective role by inducing oncogene suppressors Rara and Pparg. Considering the conflicting responses of Aldh1a1 in a multitude of physiological processes, only tissue-specific regulation of Aldh1a1 can result in therapeutic effects. We have shown through successful implantation of tissue-specific Aldh1a1-/- preadipocytes that thermogenesis can be induced in wild-type adipose tissues to resolve diet-induced visceral obesity in females. We will briefly discuss the emerging role of ALDH1A1 in multiple myeloma, the regulation of reproduction, and immune responses, and conclude by discussing the role of ALDH1A1 in future therapeutic applications.

Topics: Adipocytes; Adipogenesis; Adipose Tissue, White; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Animals; Body Fat Distribution; Chronic Disease; Cytokines; Diet; Disease Models, Animal; Estradiol; Female; Humans; Obesity; Polycystic Ovary Syndrome; Retinal Dehydrogenase; Retinaldehyde; Risk Factors; Sex Factors; Thermogenesis; Tretinoin

The management of hand eczema, more readily called chronic hand dermatitis, is complex. This heaviness is related not only to the disease itself by its different clinical forms but also the multiplicity and diversity of etiological factors, triggering / maintaining or aggravating factors. The repeated therapeutic failures are ransom of incorrect information about the disease and its environment, a lack of clarity in the prescription and duration of treatment in general too short. The reference treatment is high potency topical steroids with or without occlusion for 4-8 weeks followed by alitretinoin 30 mg / day for at least 3-6 months with a monthly lipid and liver monitoring and mandatory monthly pregnancy test in women of childbearing. Associated measures and patient education are the cornerstones of successful treatment. Other alternative treatments such as phototherapy, methotrexate, cyclosporin, mycophenolate mofetil etc. can be considered in case of resistance or for clearing followed by topical treatments.

Topics: Adrenal Cortex Hormones; Algorithms; Alitretinoin; Anti-Bacterial Agents; Chronic Disease; Dermatologic Agents; Disease Management; Drug Monitoring; Drug Therapy, Combination; Eczema; Emollients; Female; Hand Dermatoses; Histamine Antagonists; Humans; Immunosuppressive Agents; Male; Patient Education as Topic; Phototherapy; Pregnancy; Pregnancy Complications; Pregnancy Tests; Salicylic Acid; Tretinoin; Tumor Necrosis Factor-alpha

Oral alitretinoin (9-cis retinoic acid) is an endogenous retinoid related to vitamin A. Studies have shown that oral alitretinoin is effective and well-tolerated in the treatment of severe chronic hand eczema, so that it is approved for this indication. This review summarizes new studies and clinical experience on the off-label use of alitretinoin.

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Drug-Related Side Effects and Adverse Reactions; Eczema; Evidence-Based Medicine; Hand Dermatoses; Humans; Off-Label Use; Treatment Outcome; Tretinoin

Alitretinoin is an endogenous retinoid related to vitamin A. Studies have shown that oral alitretinoin is effective and well tolerated in the treatment of severe chronic hand eczema. This review summarizes the clinical pharmacokinetic and pharmacodynamic data from a number of studies involving alitretinoin. These include the effect of food on the pharmacokinetics of alitretinoin, interactions between alitretinoin and ketoconazole, simvastatin or cyclosporin A, the effect of alitretinoin on the pharmacokinetics of a combined oral contraceptive, alitretinoin in seminal fluid after repeated dosing, and the pharmacokinetics of alitretinoin and its metabolites in a clinical setting.

Topics: Administration, Oral; Alitretinoin; Animals; Chronic Disease; Dermatologic Agents; Drug Interactions; Eczema; Food-Drug Interactions; Hand Dermatoses; Humans; Tretinoin

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adrenal Cortex Hormones; Aged; Alitretinoin; Chronic Disease; Eczema; Evidence-Based Medicine; Female; Follow-Up Studies; Hand Dermatoses; Humans; Immunosuppressive Agents; Male; Middle Aged; Randomized Controlled Trials as Topic; Retinoids; Risk Assessment; Severity of Illness Index; Treatment Outcome; Tretinoin; Young Adult

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus sup

Topics: Algorithms; Alitretinoin; Azathioprine; Chronic Disease; Cyclosporine; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Immunosuppressive Agents; Psychometrics; PUVA Therapy; Quality of Life; Quality-Adjusted Life Years; Tretinoin

Topics: Administration, Oral; Alitretinoin; Chronic Disease; Drug Interactions; Eczema; Hand Dermatoses; Humans; Randomized Controlled Trials as Topic; Tretinoin

After an open preliminary study, two double-blind placebo-controlled randomized studies have confirmed the value of per os alitretinoin in the management of severe chronic hand eczema (CHE). The first showed dose-dependent efficacy and a response defined as "clear" or "almost clear" by 53% of the patients receiving 10-40 mg of alitretinoin per day for 12 weeks. In the second multicenter study (the Bach study), comparing the efficacy of a 12-week alitretinoin treatment (10 mg, 30 mg) to placebo for CHE, a "clear or almost clear" result was observed in 17% (placebo group), 28% (group alitretinoin 10 mg), and 48% (group alitretinoin 30 mg). The onset of action was also significantly shorter in the group treated with 30 mg of alitretinoin compared to the group treated with 10 mg. In a study of randomized retreatment versus placebo, 80% of the patients who were initially responders to alitretinoin and whose CHE had relapsed found "clear" or "almost clear" with alitretinoin 30 mg administered for 12-24 weeks compared to 48% with alitretinoin 10 mg. In all the studies, clinical tolerance was comparable and satisfactory, with the most frequent negative side effects being headache, flushing, and mucocutaneous signs identical to those compared with other retinoids. An increase in cholesterol and/or triglycerides was the most frequent biological side effect. Central hypothyroidism, with no clinical expression, was observed more rarely. These studies confirm that alitretinoin treatment can be envisaged as second-line therapy in adults with CHE that does not respond to well-observed treatment with class potent or very potent dermocorticoids.

Topics: Adult; Alitretinoin; Antineoplastic Agents; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Eczema; Hand Dermatoses; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Tretinoin

Alitretinoin is an endogenous retinoid and acts as a pan-agonist at retinoid receptors, binding with high affinity to both retinoic acid receptors and retinoid X receptors (RXR). Oral alitretinoin once daily is approved for use in patients with severe chronic hand eczema unresponsive to treatment with potent topical corticosteroids. In a large (n = 1032), randomized, double-blind, placebo-controlled, multicentre study (BACH) of up to 24 weeks' duration in adults with severe chronic hand eczema, significantly more patients in the alitretinoin 10 or 30 mg/day groups than in the placebo group responded to treatment with clear/almost clear hands, as assessed by the Physician Global Assessment (PGA) [primary endpoint]. In an extension phase of the BACH study, alitretinoin was effective in patients who relapsed after responding to initial treatment with the drug. Of patients who had responded to initial treatment with alitretinoin 30 mg/day, significantly more alitretinoin 30 mg/day than placebo recipients responded on the PGA with clear/almost clear hands during the extension phase (primary endpoint; 80% vs 8%). Of those who had responded to initial treatment with alitretinoin 10 mg/day, 48% of alitretinoin 10 mg/day and 10% of placebo recipients responded during the extension phase. Alitretinoin was generally well tolerated in clinical trials excluding pregnant women. The most common treatment-emergent adverse events and abnormal laboratory test results were consistent with those previously observed with other oral retinoids and RXR agonists.

Topics: Adult; Alitretinoin; Child; Chronic Disease; Eczema; Female; Hand; Humans; Pregnancy; Randomized Controlled Trials as Topic; Retinoid X Receptors; Skin; Tretinoin

Topics: Administration, Oral; Alitretinoin; Chronic Disease; Clinical Trials as Topic; Dermatologic Agents; Eczema; Glucocorticoids; Hand Dermatoses; Humans; Ointments; Phototherapy; Physical Therapy Modalities; PUVA Therapy; Time Factors; Tretinoin

About 10% of Germans have chronic hand eczema (CHE). Until recently only off-label use agents existed for the treatment of severe CHE cases refractory to topical steroids. In addition, data from controlled clinical trials confirming the efficacy of known treatment strategies was inadequate. With the availability of alitretinoin, 9-cis retinoic acid, this situation may change. In two large clinical trials alitretinoin showed high response rates and a favorable safety profile in the treatment of severe and refractory CHE. Alitretinoin has an anti-inflammatory and immunomodulatory mechanism of action. Acting as a panagonist it binds to retinoic acid receptors A (RAR) and X (RXR). It directly affects cytokine production in keratinocytes and down-regulates leukocyte activity. When used for CHE with detailed patient counseling and appropriate laboratory monitoring, alitretinoin is a promising new option for systemic treatment.

Topics: Alitretinoin; Anti-Infective Agents; Chronic Disease; Clinical Trials as Topic; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Recurrence; Treatment Outcome; Tretinoin

The outlook for patients with acute promyelocytic leukaemia has improved vastly with the use of all-trans retinoic acid. The development of this therapeutic agent stemmed from the finding that an abnormality of the retinoic acid receptor is involved in this disease. In the search for other molecular abnormalities in the acute leukaemias that might serve as therapeutic targets, the chromosomal translocations associated with this group of disorders have been helpful in indicating where to look for potential cancer genes. Some common signal-transduction pathways through which different such genes act have been identified, and compounds that interfere with these pathways are already being screened for.

Topics: Acute Disease; Chronic Disease; Humans; Leukemia; Leukemia, Promyelocytic, Acute; Molecular Biology; Protein-Tyrosine Kinases; Translocation, Genetic; Tretinoin

Given the many ways our culture promotes deeply tanned skin as a symbol of beauty, health, and even happiness, physicians face an uphill battle in promoting the healthy aspects of a pale complexion. Not only can excessive solar exposure accelerate and intensify aging in skin, it can also lead to serious health risks. Drs Browder and Beers tell why photoaging happens and how to prevent it.

Topics: Acute Disease; Biopsy; Chronic Disease; Family Practice; Humans; Patient Education as Topic; Protective Clothing; Skin Aging; Sunscreening Agents; Tretinoin; Ultraviolet Rays

Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases.

Topics: Antineoplastic Agents; Cholecalciferol; Chronic Disease; Hematopoietic Cell Growth Factors; Humans; Myelodysplastic Syndromes; Tretinoin

Topics: Biological Evolution; Carcinogens; Chronic Disease; DNA Repair; Environmental Pollutants; Genetic Diseases, Inborn; Humans; Mutation; Neoplasms; Tretinoin; Xeroderma Pigmentosum

Chronic rhinosinusitis with nasal polyps (CRSwNP) is usually treated with corticosteroids, given their anti-inflammatory effects. Unlike the nasal administration, the oral and ocular use of tretinoin, an immunoregulatory drug, is well established. Therefore, tretinoin was thought to act on nasal polyps, and possible adverse and/or therapeutic effects were investigated.. A first-in-human open-label trial was conducted enrolling patients with CRSwNP randomized into: a control group (CTR, n = 15), treated with budesonide for 24 weeks; and an intervention group (TRT, n = 15), who received budesonide and 0.1% tretinoin in the last 12 weeks. Primary endpoint included histopathological analysis and tissue immunoassay (Multiplex) for tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-4, IL-5, IL-13, and matrix metalloproteinase 9 (MMP-9) at 12 and 24 weeks. Secondary endpoints were: adverse events report, endoscopy (modified Lund-Kennedy scoring system [LKS]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), and olfactory test (Connecticut Chemosensory Clinical Research Center) at baseline, at 12 weeks, and at 24 weeks, in addition to serum biochemistry and tomographic findings (Lund-Mackay computed tomography [CT] staging system [LMS]) at baseline and 24 weeks.. TRT showed less microscopic edema (2/13 [15.4%] vs 8/13 [61.5%]; p = 0.044) as well as no increase in cytokines levels. All adverse events were categorized as "grade 1" (asymptomatic; mild). The most interesting part of this study was the improvement in smell between baseline (T0) and week 24 (T2) in TRT only (p = 0.041).. Transnasal tretinoin associated with budesonide was safe and well tolerated, and it should be investigated as a treatment option for some CRSwNP endotypes. ©2021 ARSAAOA, LLC.

Topics: Chronic Disease; Humans; Nasal Polyps; Quality of Life; Rhinitis; Sinusitis; Tretinoin

B-cell receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B-cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B-cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy because NOTCH has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from hematopoietic stem cell transplantation patients with and without cGVHD. Consistent with a molecular link between pathways, we found that BCR-NOTCH activation significantly increased the proximal BCR adapter protein BLNK. BCR-NOTCH activation also enabled persistent NOTCH2 surface expression, suggesting a positive feedback loop. Specific NOTCH2 blockade eliminated NOTCH-BCR activation and significantly altered NOTCH downstream targets and B-cell maturation/effector molecules. Examination of the molecular underpinnings of this "NOTCH2-BCR axis" in cGVHD revealed imbalanced expression of the transcription factors

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Allografts; B-Lymphocytes; Chronic Disease; Female; Gene Expression Regulation, Neoplastic; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Interferon Regulatory Factors; Male; Middle Aged; Neoplasm Proteins; Receptor, Notch2; Receptors, Antigen, B-Cell; Signal Transduction; Tretinoin

Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. In adults, ITP is more likely to be chronic, requiring individualised treatment and management. Corticosteroids and splenectomy are the most common therapy for ITP. However, these routine approaches failed in these patients with chronic ITP. The aim of this study was to evaluate the efficacy of immunomodulatory therapy with all-trans retinoid acid (ATRA) in adult patients with chronic ITP.. ATRA therapy was applied in a total of 35 patients with chronic ITP who failed with standard dose corticosteroids and/or splenectomy. The response ratio and the change of the T cell subsets including Th1, Th2, Th17 and Treg, were evaluated.. Complete response and overall response were observed in 10 (28.6%) and 19 patients (54.3%), respectively. Compared with the control group, a significant decreased level of Treg cells, IL-10 and Foxp3 expression were found in ITP patients. ATRA therapy could significantly increase the percentage of Treg cell, IL-10 level and Foxp3 expression.. Our findings indicate that ATRA therapy could induce significant changes of Treg cells to induce response in patients with chronic ITP.

Topics: Adult; Chronic Disease; Female; Humans; Immunologic Factors; Interleukin-10; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Tretinoin

We examined and evaluated the clinical characteristics of patients who had come to the Allergological and Occupational Dermatology unit in Florence with severe CHE refractory to potent topical corticosteroids. We evaluated the efficacy and safety of alitretinoin and we analyzed the response in the three months of follow-up in the group of patients who completed the cycle of therapy. Improvement in clinical signs and symptoms was assessed using mTLSS and PGA.. All patients were treated daily with single 30-mg doses of oral alitretinoin for 3 to 5 months. The study examined 15 patients with a clinical diagnosis of severe CHE. We found the treatment to be efficient in nine of 13 patients (69%) who were assessed as having "clear" or "almost clear" hands according to PGA.. Even if the number of patients we analyzed was limited and lacked a control group the study allowed us to confirm the efficacy of alitretinoin used in a "real life" clinical experience. In addition, thanks to the adoption of proper emollient therapy and avoidance of any relevant allergens or irritants, no recurrence of the condition was observed among the patients who completed therapy with a PGA value of "mild", "almost clear", or "clear" during three months after treatment.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Eczema; Emollients; Female; Follow-Up Studies; Hand Dermatoses; Humans; Male; Middle Aged; Risk Assessment; Severity of Illness Index; Treatment Outcome; Tretinoin

Oral alitretinoin (9-cis-retinoic acid; 9-cis-RA) has shown clinical efficacy in patients with chronic hand eczema (CHE). Herein, we investigated the impact of oral 9-cis-RA on the local and systemic immune response in patients with CHE.. Twenty patients with CHE were treated with oral alitretinoin (10 or 30 mg/day) for at least 24 weeks. Blood samples were taken for flow cytometry, and serum samples were assessed by ELISA to determine immunoglobulin (Ig) levels. Skin biopsies from lesional skin were evaluated immunohistochemically.. Upon 9-cis-RA treatment, improvement of the CHE was observed in all patients. A significant decrease in plasmablasts in the peripheral blood and a significant reduction of serum IgE levels were determined. Furthermore, we detected a significant reduction of CD4+ cells and regulatory T cells in the peripheral blood upon treatment. By contrast, these cell subsets were significantly increased in the affected skin. Cytokine analysis of activated CD154-positive T cells showed a reduction of interleukin (IL)-17 but not of IL-4 or IFN-γ production.. Overall, our data indicate a disease-modifying effect of 9-cis-RA, including a systemic decrease in IL-17-positive cells, but decreased serum IgE and CD23 expression. The increased frequency of FoxP3-positive cells in the skin upon treatment may suggest a mechanism by which hand eczema is therapeutically targeted by 9-cis-RA, but this will need to be proven in the future studies.

Topics: Adult; Aged; Alitretinoin; CD4-Positive T-Lymphocytes; Chronic Disease; Cytokines; Eczema; Female; Flow Cytometry; Hand; Humans; Immunoglobulin E; Immunohistochemistry; Immunologic Factors; Male; Middle Aged; T-Lymphocytes, Regulatory; Tretinoin

Severe chronic hand eczema (sCHE) is a persistent, disfiguring disease that responds poorly to conventional treatment and causes substantial physical and psychological disability. The objective of this study was to evaluate efficacy and safety of oral alitretinoin in sCHE in a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing alitretinoin with placebo. Efficacy was assessed every 4 weeks during treatment and 4 weeks after end of treatment (EOT, 24 weeks); responders were assessed every 4 weeks for a further 48 weeks after EOT. The study was conducted at academic and private dermatology centers. The participants were 596 patients with sCHE refractory to potent topical corticosteroids. Patients were treated with daily oral alitretinoin 30 mg or placebo for up to 24 weeks. Primary endpoint was proportion of responding patients based on Physician Global Assessment (PGA) of "clear" or "almost clear" at EOT. Key secondary endpoints: Patient Global Assessment (PaGA), change in modified Total Lesion Symptom Score (mTLSS), time to response (TTR), extent of disease at EOT, and duration of response (DOR). At EOT, 40% of alitretinoin-treated patients were responders vs 15% placebo-treated patients (odds ratio [OR] = 3.78; P < .001); a greater proportion of alitretinoin-treated patients achieved a PaGA of "cleared" or "almost cleared" (OR = 4.05; P< .001). A greater decrease in mTLSS occurred from baseline to EOT in alitretinoin- vs placebo-treated patients (treatment difference -24% P< .001). Median TTR for responders at EOT was shorter with alitretinoin vs placebo (65 vs 117 days; P< .001). Greater decreases in extent of disease at EOT were observed with alitretinoin vs placebo (treatment difference -22%; P< .001). The most common treatment-emergent adverse event was headache. Alitretinoin significantly improved signs/symptoms of sCHE, was well tolerated in patients refractory to potent topical corticosteroids, and may provide benefit to this population.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Double-Blind Method; Eczema; Female; Follow-Up Studies; Hand Dermatoses; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Tretinoin

Blinded, controlled studies have found that oral alitretinoin is well tolerated and effective in the treatment of severe chronic hand eczema (CHE).. To assess the safety and efficacy of oral alitretinoin in patients with severe CHE in an open-label study using flexible dosing and a new measurement of patient-relevant benefits.. In total, 249 patients aged 18-75 years with severe CHE unresponsive to treatment with topical corticosteroids received alitretinoin 30 mg once daily for up to 24 weeks. Safety assessments included adverse events (AEs) and laboratory tests. Efficacy assessments included Physician's Global Assessment (PGA), the Modified Total Lesion Symptom Score, Patient's Global Assessment and extent of disease, as well as intensity of pain and pruritus as determined by visual analogue scale (VAS) and a categorical scale for pruritus.. Alitretinoin was well tolerated when given for up to 24 weeks. Dose reduction occurred in 16.5% of patients. Dose interruption was required for 15.7% of patients, most commonly for headache. AEs and laboratory changes comprised effects typical of the retinoid class. A PGA response of 'clear' or 'almost clear' hands was reported for 46.6% of patients, similar to the response rate seen in blinded trials. Results of VAS and categorical assessments of pruritus provided supporting evidence of efficacy, and treatment was assessed as providing meaningful benefits to patients.. Oral alitretinoin 30 mg was well tolerated and effective, and provided distinct therapeutic benefits in severe CHE, as assessed by patients.

Topics: Administration, Oral; Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Drug Administration Schedule; Female; Glucocorticoids; Hand Dermatoses; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Failure; Treatment Outcome; Tretinoin; Young Adult

Alitretinoin (9-cis-retinoic acid) is an endogenous derivative of vitamin A and functions as an agonist of both families of nuclear receptors (retinoic acid receptor-α, -β, -γ; retinoid X receptor-α, -β, -γ). It has been investigated in the treatment of chronic hand eczema in many studies in recent years and the results have been promising.. To evaluate the efficacy and safety of oral alitretinoin in the treatment of chronic hand eczema that is refractory to treatment with potent topical corticosteroids and to analyze the long-term response to treatment.. A prospective, observational, descriptive study was undertaken in 15 patients with chronic hand eczema that was refractory to treatment with potent topical corticosteroids. Patients were administered oral alitretinoin 30 mg/d for 3 months followed by 6 months of follow-up.. A complete response, with "clear" hands was obtained in 7 patients (47%), 5 patients (33%) achieved a partial response (almost clear hands), 1 patient (7%) showed substantial improvement, 1 (7%) showed moderate improvement, and 1 patient (7%) did not respond to treatment. Relapse occurred within 6 months of treatment suspension in 54% of cases. The treatment was well tolerated. Side effects, observed in 50% of cases, were mild (headache, elevated lipid levels, slightly elevated transaminase levels, and epigastric pain), except in 1 patient, who had a substantial reduction in thyroid stimulating hormone levels.. The results of our study support the proposal of alitretinoin as an effective and safe short-term and medium-term treatment for chronic hand eczema in patients whose disease is refractory to treatment with potent topical corticosteroids.

Topics: Administration, Cutaneous; Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Alitretinoin; Child; Chronic Disease; Drug Resistance; Eczema; Female; Hand Dermatoses; Headache; Humans; Hypercholesterolemia; Middle Aged; Occupational Diseases; Prospective Studies; Thyrotropin; Treatment Outcome; Tretinoin

Recent studies have found that alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids.. To assess the pharmacokinetics (PK), efficacy and safety of alitretinoin 10 or 30 mg once daily.. This was a randomized, double-blind study, which enrolled 32 subjects aged 18-75 years with CHE unresponsive to potent topical corticosteroids. Subjects received alitretinoin 10 mg (n = 16) or 30 mg (n = 16) once daily for 12 or 24 weeks. Standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)), elimination half-life (t(1/2)), total systemic clearance (CL/F) and volume of distribution (Vd/F)] were determined for alitretinoin and metabolites. Efficacy was assessed using the Physician's Global Assessment (PGA) scale.. Chronic administration of alitretinoin for up to 24 weeks did not result in accumulation or time-dependent changes in the disposition of alitretinoin. Exposure was found to be proportional to dose. Systemic exposure (AUC) to alitretinoin was proportional to dose for 10 and 30 mg alitretinoin; 62.8% of subjects achieved clear/almost clear hands in the 30 mg group and 12.5% in the 10 mg group. Alitretinoin was well tolerated.. Chronic administration of alitretinoin for 12-24 weeks did not lead to accumulation or time-dependent changes in drug exposure. Alitretinoin was effective and well tolerated in the treatment of subjects with moderate or severe CHE unresponsive to potent topical corticosteroids.

Topics: Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Hand Dermatoses; Humans; Male; Middle Aged; Treatment Outcome; Tretinoin; Young Adult

Patients with severe chronic hand eczema (CHE) often respond to therapy with oral alitretinoin (9-cis retinoic acid). However, the efficacy of alitretinoin after disease relapse has not been demonstrated.. To assess the efficacy and safety of a second course of oral alitretinoin in patients with severe CHE who relapsed after achieving 'clear' or 'almost clear' hands following a previous course of alitretinoin.. The double-blind study included 117 patients with CHE who had responded to therapy in an earlier clinical trial and subsequently relapsed. Patients were randomized to receive their previous treatment or placebo. Treatment was alitretinoin 30 mg or 10 mg or placebo given once daily for 12-24 weeks. Response was defined as an overall Physician's Global Assessment rating of 'clear' or 'almost clear' hands at the end of therapy.. Response rates were 80% in patients retreated with 30 mg alitretinoin compared with 8% for placebo (P < 0.001). In patients retreated with 10 mg alitretinoin response rates were 48%, compared with 10% in the placebo group. Alitretinoin was well tolerated. Adverse reactions comprised typical retinoid class effects, and no late-arising side-effects were observed during this second course of treatment.. The majority of patients with CHE who previously achieved 'clear' or 'almost clear' hands following treatment with alitretinoin 30 mg per day also responded to a second course of treatment. Retreatment was well tolerated. Intermittent treatment with alitretinoin is suitable for the long-term management of CHE.

Topics: Administration, Oral; Alitretinoin; Chronic Disease; Dermatologic Agents; Double-Blind Method; Eczema; Female; Hand Dermatoses; Humans; Male; Middle Aged; Recurrence; Retreatment; Time Factors; Treatment Outcome; Tretinoin

Patients with severe chronic hand eczema (CHE) refractory to topical corticosteroids currently have limited treatment options suited for chronic use, and few controlled clinical studies have investigated new therapies in this setting.. To assess the efficacy and safety of oral alitretinoin (9-cis retinoic acid) taken at 10 mg or 30 mg once daily for up to 24 weeks, compared with placebo control, in the treatment of severe CHE refractory to topical corticosteroids.. A randomized, double-blind, placebo-controlled, prospective, multicentre trial was conducted in 111 dermatology outpatient clinics in Europe and Canada. A total of 1032 patients with severe refractory CHE were randomized in a 1 : 2 : 2 ratio to placebo, or 10 mg or 30 mg of oral alitretinoin once daily for up to 24 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for relapse for 24 weeks after the end of therapy. The primary efficacy parameter was Physician Global Assessment of overall CHE severity, with response defined as clear or almost clear hands.. Responses, defined as clear or almost clear hands, were achieved in up to 48% of patients treated with alitretinoin, compared with 17% for placebo (P < 0.001), with up to 75% median reduction in disease signs and symptoms. Treatment was well tolerated, with dose-dependent adverse effects comprising headache, mucocutaneous events, hyperlipidaemia, and decreased free thyroxine and thyroid-stimulating hormone. The median time to relapse, defined as recurrence of 75% of initial signs and symptoms, was 5.5-6.2 months in the absence of anti-eczema medication.. Alitretinoin given at well-tolerated doses induced clearing of CHE in a substantial proportion of patients with severe disease refractory to standard therapy.

Topics: Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Drug Administration Routes; Eczema; Epidemiologic Methods; Female; Hand Dermatoses; Humans; Male; Middle Aged; Tretinoin

To assess the efficacy and safety of oral alitretinoin (9-cis-retinoic acid), 10 mg/d, 20 mg/d, and 40 mg/d, compared with placebo control, in the treatment of chronic hand dermatitis.. Multicenter, randomized, double-blind, placebo-control, prospective trial.. A total of 43 outpatient clinics in 10 European countries.. Of 348 patients screened, 319 with moderate or severe refractory chronic hand dermatitis were randomized, in the ratio of 1:1:1:1, to 4 treatment groups and received allocated intervention. Of 75 patients who withdrew, 24 withdrew owing to adverse events.. Placebo or 10 mg, 20 mg, or 40 mg of oral alitretinoin (9-cis-retinoic acid) taken once daily for 12 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for a follow-up period of 3 months.. Physician's global assessment of overall chronic hand dermatitis severity.. Alitretinoin led to a significant and dose-dependent improvement in disease status, with responses in up to 53% of patients, and up to a 70% mean reduction in disease signs and symptoms. Treatment was generally well tolerated, with dose-dependent effects comprising headache, flushing, mucocutaneous events, hyperlipidemia, and decreased hemoglobin and decreased free thyroxin levels. Three months after discontinuation of treatment, the rate of relapse was 26%, independent of dose.. Alitretinoin given at well-tolerated doses induced substantial clearing of chronic hand dermatitis in patients refractory to conventional therapy.

Topics: Administration, Oral; Adrenal Cortex Hormones; Alitretinoin; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Female; Follow-Up Studies; Hand Dermatoses; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Treatment Outcome; Tretinoin

9-cis-Retinoic acid (9-cis-RA) has a particular pattern of binding and activating retinoid receptors. Treatment of chronic hand eczema is often refractory to conventional treatment.. Evaluation of oral 9-cis-RA therapy in chronic hand eczema in a pilot study.. Thirty-eight patients with refractory chronic hand eczema were treated in an exploratory open-label study with oral 9-cis-RA.. Twenty-one (55%) showed a very good response, 13 (34%) a good response, 2 (5.5%) a moderate response and 2 (5.5%) no response. Side effects were mild.. 9-cis-RA is a valuable drug when given at low doses to patients with chronic hand eczema.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Cheilitis; Chronic Disease; Eczema; Female; Flushing; Hand Dermatoses; Headache; Humans; Male; Middle Aged; Patient Satisfaction; Pilot Projects; Severity of Illness Index; Skin; Treatment Outcome; Tretinoin

Excessive exposure to sunlight results in drastic degradative changes in the constitutive cells of the epidermis. Among these is a profound abrogation of Langerhans cell number and function, leading to compromised immunologic competency. Retinoids have recently been shown to restore immunologic function in the setting of iatrogenic immunosuppresion. We asked whether topical tretinoin would reverse Langerhans cell depletion in chronically photodamaged skin. We examined the skin of 8 volunteers immunohistochemically before and after 6 months of daily applications of tretinoin. At baseline, there was a profound depletion of CD1a-positive Langerhans cells in the interfollicular epidermis, but not in the adjoining follicular epithelium. After tretinoin, all patients demonstrated replenishment of interfollicular epidermis by CD1a-positive Langerhans cells. This was associated with induction of HLA-DR expression on infundibular keratinocytes, as well as the appearance of CD1a dendritic cells in the papillary dermis. Thus, the enhancement of epidermal immunity in photodamaged skin may reflect restoration of antigen-presenting Langerhans cells. The source of this renewed dendritic cell population is likely to be follicular infundibulum and the papillary dermis.

Topics: Administration, Topical; Adult; Antigens, CD1; Cell Count; Chronic Disease; Dendritic Cells; Dermatitis, Phototoxic; Female; HLA-DR Antigens; Humans; Immunohistochemistry; Keratolytic Agents; Langerhans Cells; Male; Middle Aged; Skin; Tretinoin

Chronic exposure to a weak irritant leads to inflammatory changes which may be followed by pigmentary changes and accommodation. The inflammatory responses to acute exposure to an irritant have been extensively studied. This study investigated quantitatively the inflammatory reactions produced in photodamaged skin with chronic application of a weak chemical irritant (tretinoin cream 0.025%) over a period of 9 months (36 weeks). Forty-eight subjects with moderately to severely photodamaged skin were enrolled in a 36-week, double-blind placebo-controlled study. Tretinoin cream was applied nightly on the distal two thirds of one dorsal forearm and placebo on the other. The proximal third of each dorsal forearm received no treatment and served as control. Clinical assessments and diffuse reflectance measurements were made at 7 time points during treatment. Apparent concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and melanin were estimated by analysis of the diffuse reflectance spectra. No changes were observed in the apparent HbO2 or the Hb concentration of the placebo-treated or control sites, thus establishing a reliable baseline. The apparent HbO2 concentration of the tretinoin-treated sites increased significantly from baseline to a maximum at 12-18 weeks of treatment, then returned to baseline with continued applications. The changes in HbO2 concentration agreed closely with clinical assessments of erythema. The apparent melanin concentration, corresponding to diffuse hyperpigmentation, showed a large seasonal decrease in both the control and the treated sites, with an additional decrease in the treated sites between 12 and 18 weeks. Erythema appeared after repeated applications and eventually resolved under continuous treatment. The maximum decrease in hyperpigmentation occurred simultaneously with the maximum increase in erythema.

Topics: Administration, Oral; Adult; Aged; Chronic Disease; Dermatitis, Irritant; Double-Blind Method; Erythema; Hemoglobins; Humans; Keratolytic Agents; Melanins; Middle Aged; Oxyhemoglobins; Placebos; Skin Aging; Skin Pigmentation; Tretinoin; Ultraviolet Rays

Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were administered orally to 27 patients suffering from severe chronic generalized psoriasis. The clinical efficacy was evaluated by means of a new index, psoriasis area and severity index (PASI) based on severity and area of psoriatic lesions. At doses of 25 mg t.i.d. or 50 mg b.i.d. Ro 10--9359 proved to be an extremely potent antipsoriatic drug. A more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4-8 weeks of treatment. This good effect lasted about 5 weeks after treatment. Side effects were frequent, but mostly mild and completely reversible after termination of treatment.

Topics: Administration, Oral; Adult; Chemical Phenomena; Chemistry; Chronic Disease; Clinical Trials as Topic; Drug Evaluation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psoriasis; Tretinoin; Vitamin A

Topics: Alitretinoin; Chronic Disease; Eczema; Humans; Photosensitivity Disorders; Retinoids; Tretinoin

Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells.. This study sought to determine whether endogenous retinoids are involved in NP pathophysiology and disease severity in patients with CRSwNP and AERD.. NP tissue was collected from patients with AERD or CRSwNP, and concentrations of retinoids and fibrinolysis markers were measured using ELISA. Normal human bronchial epithelial cells were stimulated alone or in combination with RA and IL-13 for 24 hours.. This study observed lower retinoid levels in nasal polyps of patients with AERD than those with CRSwNP or healthy controls (P < .01). Levels of the fibrin-breakdown product d-dimer were the lowest in AERD polyps (P < .01), which is consistent with lower tPA expression (P < .01). In vitro, all-trans RA upregulated tPA levels in normal human bronchial epithelial cells by 15-fold and reversed the IL-13-induced attenuation of tPA expression in cultured cells (P < .01).. RA, a potent inducer of epithelial tPA in vitro, is reduced in tissue from patients with AERD, a finding that may potentially contribute to decreased levels of tPA and fibrinolysis in AERD. RA can induce tPA in epithelial cells and can reverse IL-13-induced tPA suppression in vitro, suggesting the potential utility of RA in treating patients with CRSwNP and/or AERD.

Topics: Asthma, Aspirin-Induced; Chronic Disease; Endothelial Cells; Fibrin; Fibrinolysis; Humans; Interleukin-13; Nasal Polyps; Rhinitis; Sinusitis; Tissue Plasminogen Activator; Tretinoin

Burning mouth syndrome is an intraoral chronic pain condition characterized by a moderate to severe sensation of burning from the oral mucosa. No clinical signs are found and there is no efficient treatment.. This pilot study included 10 women that were resistant to other previous treatments or noncompliant to systemic medications. Patients were asked to apply tretinoin gel 0.05% on their tongues twice daily for 14 days. Treatment effectiveness was assessed by completing a pre-study psychologic questionnaire and recording a daily wellbeing and pain log.. Significant pain-score decrease in 50% of the patients (delta numerical rating score -3.15 ± 3.02, P value = .005) was recorded. This finding was in concordance with the verbal statements including major quality-of-life improvement (P value = .05), without any treatment positive or negative predictive factors.. Topical tretinoin exhibits potential efficacy in patients with treatment resistant burning mouth syndrome and may also be used as a primary treatment modality.

Topics: Administration, Topical; Burning Mouth Syndrome; Chronic Disease; Chronic Pain; Female; Humans; Pilot Projects; Treatment Outcome; Tretinoin

Alitretinoin is the only systemic agent approved to treat moderate-severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. No nationwide Italian data regarding real-life efficacy, safety, and tolerability of treatment are available. The DECISA project (DErmatology Clinics in Italy: Survey on Alitretinoin) retrospectively examined data from a registry including 15 Dermatology Clinics authorized to prescription of alitretinoin for CHE patients. Disease severity was assessed at baseline, and after 3 and 6 months of treatment, using the 5-point Physician Global Assessment (PGA) and the modified Total Lesion-Symptoms-Severity (mTLSS) scores. Between November 2010 and July 2018, data of 248 male and 190 female patients (mean age 49.71 ± 13.20 years) treated with alitretinoin were collected. Of them, 43.2% had irritant contact dermatitis, 22.2% allergic contact dermatitis, 18.0% atopic dermatitis, 16.7% mixed (irritant/allergic) type of eczema. At 3 months, the 420 re-evaluated patients showed significantly reduced mTLSS and PGA (P < .0000001 vs baseline for both); PGA was clear/almost clear in 35.6% of cases. At 6 months, the 341 re-evaluated patients showed significant (P < .0000001) improvement of mTLSS and PGA vs baseline and 3 months (PGA clear/almost clear: 41.4%). Relapses occurred in 125 patients; 58 underwent an additional course of alitretinoin, with similarly good results. No relevant safety issues were reported; 86 patients experienced adverse effects, which forced 40 to prematurely stop treatment. The DECISA project results confirm the real-life efficacy, safety and tolerability of alitretinoin in the treatment of moderate to severe CHE refractory to standard topical therapies.

Topics: Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Dermatology; Eczema; Female; Hand Dermatoses; Humans; Italy; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Tretinoin

Alitretinoin is a systemic retinoid licensed for use in adult patients suffering from chronic hand eczema recalcitrant to potent topical steroids. Experience with its use in childhood is lacking.. To report on the efficacy and safety of alitretinoin treatment in a cohort of children and adolescents with chronic hand eczema (CHE) and other inflammatory skin diseases.. We performed a retrospective chart review of all consecutive patients under the age of 18 years treated with alitretinoin at our paediatric skin centre. Physician's Global Assessment (PGA) was used as the primary outcome measure.. Thirteen children (9 girls and 4 boys) were enrolled in this study. The median age at start of treatment with alitretinoin was 11.5 years (range 5.8-15.8 years). Nine children were diagnosed with CHE, two with severe atopic dermatitis (AD), and two with inherited ichthyosis [netherton syndrome (NS), autosomal recessive congenital ichthyosis (ARCI)]. Moderate to excellent response (PGA decrease of ≥1 point) was observed in 7 (78%) of the nine patients with CHE, one of the two patients with extensive AD and in the one patient with ARCI. In the remaining four subjects, no convincing effect was documented. Tolerability was overall very good. The most common adverse event was headache in 10 patients (77%) during the initiation of treatment, leading to interruption of therapy in one subject.. Alitretinoin seems to be highly effective and safe for the treatment of paediatric CHE and should thus be considered in children with refractory disease under topical therapy. Larger studies are required to corroborate these findings.

Topics: Adolescent; Adult; Alitretinoin; Child; Child, Preschool; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Male; Retrospective Studies; Treatment Outcome; Tretinoin

The prognosis of acute promyelocytic leukemia (APL) has been improved by the combination of all-trans retinoic acid (ATRA) with chemotherapy. Nonetheless, relapse occurs in a certain proportion of patients, mostly within three to four years after treatment. We herein report a patient treated with ATRA and chemotherapy achieving remission who relapsed approximately 17 years after the treatment. A literature review identified 5 additional reported cases of APL relapse after more than 10 years. None of them presented with generally established risk factors for relapse, such as a high leukocyte count. The potential for late relapse of APL occurring more than 10 years after treatment should be recognized.

Topics: Antineoplastic Agents; Chronic Disease; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Prognosis; Recurrence; Remission Induction; Risk Factors; Time Factors; Treatment Outcome; Tretinoin

Adoptively transferred regulatory T-cells represent a promising therapeutic approach for tolerance induction in autoimmunity and transplantation medicine. However, a major hurdle for clinical application is the manufacturing of sufficient Treg cell numbers with respect to the low frequency of naturally occurring Tregs in the peripheral blood. Therefore, ex vivo large-scale expansion is mandatory for most of the clinical conditions. Besides the Treg cell number other parameters of the cell product are of high relevance for safe and efficient clinical Treg cell application like Treg cell purity, suppressive capacity and genetic stability of the Treg cell phenotype. Moreover, migratory properties of ex vivo expanded Tregs should be defined very clearly in order to predict their migration to secondary lymphoid organs as sites of antigen-specific activation, in vivo proliferation and subsequent trafficking to affected target organs. Therefore, we studied different cell culture conditions for Treg large-cell expansion using all-trans retinoic acid (ATRA) and/or rapamycin (Rapa) with focus on their migratory properties. The tested culture conditions revealed comparable chemokine receptor expression profiles (CXCR3, CCR4, CCR6, CCR7) and functional migration capabilities (IP10 and CCL19) with respect to Th1 and Th2 inflammatory conditions. However, the most striking difference was detected for the expansion capacity, suppressive potency and genetic stability likely predisposing large-scale expansion with ATRA and/or Rapa for therapeutic intervention in acute GvHD and without supplementation for chronic GvHD.

Topics: Acute Disease; Cell Culture Techniques; Cell Movement; Cell Proliferation; Cells, Cultured; Chronic Disease; Graft vs Host Disease; Humans; Immune Tolerance; Immunotherapy, Adoptive; Receptors, Chemokine; Sirolimus; T-Lymphocytes, Regulatory; Th1 Cells; Th1-Th2 Balance; Th2 Cells; Transcriptome; Tretinoin

Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.

Topics: Administration, Oral; Adrenal Cortex Hormones; Alitretinoin; Chronic Disease; Dermatologists; Eczema; Hand Dermatoses; Health Care Surveys; Humans; Keratolytic Agents; Practice Patterns, Physicians'; PUVA Therapy; Tretinoin; United Kingdom

Alitretinoin is approved for the treatment of adults with severe chronic hand eczema (CHE) refractory to potent topical steroids. In the 6 years since launch, approximately 250 000 patients have been treated with alitretinoin.. To compare the postmarketing safety surveillance experience of alitretinoin with data from clinical trials and key safety issues with other retinoids.. An integrated safety analysis of the pivotal studies of alitretinoin and postmarketing adverse event (AE) reports received since approval for alitretinoin were analyzed.. In the pivotal trials, headache, erythema, nausea, increased blood triglycerides and increased blood creatinine phosphokinase were the most frequently reported AEs. Headache, hyperlipidemia and nausea were also frequently reported postmarketing AEs, but depression was relatively more frequently reported than in the pivotal trials. Inflammatory bowel disease and benign intracranial hypertension were rare, and very few cases have been reported in postmarketing surveillance. There have been no reports of teratogenicity in humans consequent to fetal exposure.. Safety data collected in pivotal trials and postmarketing surveillance suggest that alitretinoin is well tolerated by patients with CHE with a relatively low incidence of serious reactions. The adverse reaction profile is congruent with reported effects of other marketed oral retinoids.

Topics: Adult; Alitretinoin; Chronic Disease; Eczema; Female; Hand Dermatoses; Headache; Humans; Pregnancy; Tretinoin

Hand eczema affects nearly 10% of the population. The condition becomes severe and chronic in 5% to 7% of cases and is refractory to topical corticosteroids in 2% to 4%. This study aimed to describe the current use of oral alitretinoin in treating Spanish national health system patients with hand eczema that is refractory to potent topical corticosteroids.. Observational, descriptive, exploratory, cross-sectional study based on the retrospective analysis of records for patients with hand eczema treated with alitretinoin in the Spanish national health system.. We reviewed the records for 62 patients in 13 hospitals in 5 different administrative areas (autonomous communities) of Spain. Alitretinoin was usually used at a dosage of 30mg/d. In most cases the physician judged the clinical response to be satisfactory after a single cycle. The recorded adverse effects were foreseeable and of the type reported for systemic retinoids. The dermatologists agreed that the clinical benefits achieved with alitretinoin favored adherence to treatment and an early return to work.. The results show that oral alitretinoin is being used according to established recommendations and that response is good, with few adverse effects. The dermatologists agreed that the benefits favored adherence and improved the patients' health related quality of life.

Topics: Alitretinoin; Chronic Disease; Cross-Sectional Studies; Eczema; Hand Dermatoses; Humans; Retrospective Studies; Spain; Tretinoin

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoïne was approved. This study evaluates both retinoids in a daily practice cohort of patients with severe chronic hand eczema in terms of drug survival and reasons for discontinuation. Patients using alitretinoin or acitretin between 01-01-1994 and 01-08-2015 were included in this retrospective daily practice study and analyzed by Kaplan-Meier drug survival curves. Potential determinants were analyzed by Cox regression analyses. Ninety-five patients were treated with alitretinoin and 109 patients with acitretin. The main reasons for discontinuation were adverse events and cleared hand eczema, 29.5 and 27.4% in alitretinoin versus 43.1 and 23.9% in acitretin. Patients with hyperkeratotic hand eczema had most often a good effect of treatment: 68.3% in alitretinoin and 50.7% in acitretin treatment. The drug survival rates of alitretinoin and acitretin after 12, 24, 36, and 52 weeks were 69.3, 45.1, 19.6, 7.0% and 74.3, 45.5, 33.8, 23.2%, respectively. Alitretinoin and acitretin are effective treatment options for patients with hand eczema. However, both treatments were more effective in patients with hyperkeratotic hand eczema. Fewer patients discontinued alitretinoin compared with acitretin due to adverse events.

Topics: Acitretin; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Kaplan-Meier Estimate; Keratosis; Male; Middle Aged; Proportional Hazards Models; Remission Induction; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Tretinoin

Chronic hand eczema (CHE) is a common inflammatory skin disease that affects approximately 10% of the population. Systemic alitretinoin has been shown to be effective in patients with CHE who are refractory to topical corticosteroids.. To analyse the impact of alitretinoin on the skin barrier genes and protein expression in the skin lesions of patients with CHE.. Fifteen patients with CHE were treated with 30 mg daily of alitretinoin for up to 27 weeks. Disease severity was assessed using a clinical score. Skin biopsies from all the patients were evaluated before and after therapy for the expression of Ki-67, various skin barrier genes and thymic stromal lymphopoietin (TSLP) by real-time quantitative polymerase chain reaction and immunohistochemistry.. After alitretinoin application, an improvement in the clinical severity of CHE was observed in the majority of patients. Analysis of skin biopsies before treatment showed a significant increase in Ki-67-positive cells in the suprabasal layer and a dysregulated expression of various skin barrier genes, such as claudin 1, loricrin, filaggrin and cytokeratin 10, which were normalized after treatment. TSLP was significantly upregulated in patients with CHE and also normalized after alitretinoin treatment and negatively correlated with filaggrin.. Our data indicate that the expression of barrier genes and proteins was normalized following treatment with alitretinoin in patients with CHE. The change in expression levels of these genes correlated with the clinical efficacy, suggesting that alitretinoin exhibits a disease-modifying activity. TSLP is upregulated in CHE and seems to counteract filaggrin expression in the skin.

Topics: Administration, Cutaneous; Adult; Aged; Alitretinoin; Chronic Disease; Dermatologic Agents; Drug Administration Schedule; Eczema; Epidermis; Female; Filaggrin Proteins; Gene Expression; Hand Dermatoses; Humans; Ki-67 Antigen; Male; Middle Aged; Tight Junction Proteins; Tretinoin

Severe chronic hand eczema (CHE) has a debilitating effect on quality of life (QoL). PASSION evaluated the effectiveness of oral alitretinoin on QoL and work productivity in patients with severe CHE following prescribing guidelines.. A non-interventional, open-label, observational, multicentre study conducted in Germany in fulfilment of German guidelines. Patients (n = 631) were treated with once-daily alitretinoin for ≤24 weeks under standard daily practise conditions. Effectiveness was assessed by Physician Global Assessment (PGA), QoL Assessment (EQ-5D) and work impairment. Tolerability and safety were assessed by adverse event (AE) monitoring.. In total, 279 (44.2%) patients dropped out before Week 24. Of the 631 patients enrolled, 29.8% achieved a PGA rating of clear/almost clear at Week 24. Mean (standard deviation) EQ-5D utility and EQ-5D visual analogue scale scores at baseline were 0.76 (0.25) and 53.6 (23.55), respectively, and increased to 0.94 (0.12) and 80.8 (19.23) at Week 24, indicating improved QoL. At baseline, 49.4%/29.1% of patients reported strong/very strong workplace impairment, respectively, and decreased to 8.5%/1.4%, respectively, at Week 24. AEs were reported in 116 (18.4%) patients. No new safety signals were observed.. Alitretinoin produced marked improvement in the QoL and work productivity of patients with severe CHE.

Topics: Alitretinoin; Antineoplastic Agents; Chronic Disease; Dermatologic Agents; Eczema; Female; Hand Dermatoses; Humans; Male; Middle Aged; Quality of Life; Tretinoin

Alitretinoin is the only approved treatment for severe chronic hand eczema (CHE) refractory to potent topical corticosteroids. This study (FUGETTA) evaluated the effectiveness and impact on quality of life (QoL) of oral alitretinoin in patients with severe refractory CHE in accordance with prescription guidelines.. Open-label, multicenter, noninterventional, observational study conducted in Germany. Patients were treated at their physician's discretion with once-daily alitretinoin 10 mg or 30 mg for a maximum of 24 weeks. Effectiveness was assessed by Physician Global Assessment (PGA) and Dermatology Life Quality Index (DLQI). Adverse events (AEs) were assessed.. The study population included 658 patients (30 mg n = 581; 10 mg n = 77). At baseline, most patients had CHE characterized as severe by PGA (83 %). At last visit, 48 % of patients had a PGA response of clear/almost clear (30 mg: 49 %; 10 mg: 43 %). Mean improvement in DLQI scores at week 24 was 58 % (30 mg: mean [SD] change from baseline -10.4 [8.04]) and 70 % (10 mg: mean [SD] change from baseline -10.8 [7.29]). The overall incidence of AEs was low and similar in both groups.. Alitretinoin produced rapid, marked improvement in QoL of patients with severe CHE.

Topics: Administration, Cutaneous; Adolescent; Adult; Age Distribution; Alitretinoin; Chronic Disease; Dermatologic Agents; Dose-Response Relationship, Drug; Eczema; Female; Germany; Hand Dermatoses; Humans; Middle Aged; Patient Satisfaction; Prevalence; Quality of Life; Severity of Illness Index; Sex Distribution; Treatment Outcome; Tretinoin; Women's Health; Young Adult

Topics: Administration, Oral; Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Drug Resistance; Female; Humans; Pemphigus, Benign Familial; Tretinoin

The aim of the CARPE registry is to investigate characteristics and medical care in patients affected by chronic hand eczema. Patients are assessed by dermatological examination and patient questionnaire. Socio-economic and clinical data are collected, and quality of life is measured using the Dermatology Life Quality Index (DLQI). A total of 1,163 patients with chronic hand eczema were eligible for analysis (mean age 47.0 years; 54.6% female; mean disease duration 7.6 years). At inclusion, chronic hand eczema was very severe in 23.4%, severe in 47.0%, moderate in 20.1%, and clear or almost clear in 9.6% of patients. Median DLQI was 8.0. In all, 93.8% of patients reported use of topical corticosteroids, 25.6% systemic antihistamines, 28.3% topical calcineurin-inhibitors, 38.0% ultraviolet phototherapy, and 35.3% systemic treatment (19.7% alitretinoin) prior to inclusion in the registry. A significant proportion of patients may not receive adequate treatment according to the guideline on management of hand eczema.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Calcineurin Inhibitors; Chronic Disease; Eczema; Female; Germany; Glucocorticoids; Hand Dermatoses; Histamine Antagonists; Humans; Male; Middle Aged; Occupations; Pruritus; Quality of Life; Registries; Severity of Illness Index; Tretinoin; Ultraviolet Therapy; Young Adult

Chronic cholestasis results in liver injury and eventually liver failure. Although ursodeoxycholic acid (UDCA) showed limited benefits in primary biliary cirrhosis, there is an urgent need to develop alternative therapy for chronic cholestatic disorders. Previous studies from our laboratory demonstrated that all-trans-retinoic acid (atRA) is a potent suppressor of CYP7A1, the rate-limiting enzyme in bile acid synthesis. atRA also repressed the expression of tumor growth factor-β and collagen 1A1 in activated primary human stellate cells and LX2 cells. When administered together with UDCA to bile duct-ligated rats, this combined therapy significantly reduced the bile acid pool size and improved liver conditions. To further examine whether atRA alone or in combination with UDCA has greater beneficial effects than UDCA treatment alone, we assessed this treatment in two additional chronic cholestatic rodent models: α-naphthylisothiocyanate (ANIT)-treated rats and the Mdr2(-/-) (Abcb4(-/-)) knockout mouse. atRA alone significantly reduced bile duct proliferation, inflammation, and hydroxyproline levels in ANIT-treated rats, whereas the combination of atRA and UDCA significantly reduced plasma bile salt level compared with UDCA treatment. atRA alone or in combination with UDCA significantly reduced plasma levels of alkaline phosphatase and bile salts in 12-week-old Mdr2(-/-) mice. Reduced bile duct proliferation and inflammation were also observed in the livers of these mice. Together, atRA alone or in combination with UDCA significantly reduced the severity of liver injury in these two animal models, further supporting the combination treatment of atRA and UDCA as a potential new therapy for patients with chronic cholestatic liver disease who have not responded fully to UDCA.

Topics: 1-Naphthylisothiocyanate; Animals; ATP Binding Cassette Transporter, Subfamily B; ATP-Binding Cassette Sub-Family B Member 4; Bile Acids and Salts; Cell Proliferation; Cholagogues and Choleretics; Cholestasis; Chronic Disease; Disease Models, Animal; Drug Therapy, Combination; Liver; Male; Mice; Mice, Knockout; Rats; Rats, Sprague-Dawley; Tretinoin; Ursodeoxycholic Acid

Topics: Alitretinoin; Chronic Disease; Cyclosporine; Dermatologic Agents; Drug Substitution; Eczema; Foot Dermatoses; Hand Dermatoses; Humans; Male; Middle Aged; Nail Diseases; Nails, Malformed; Time Factors; Treatment Outcome; Tretinoin

The treatment of moderate to severe chronic hand dermatitis (CHD) has been advanced with the introduction of alitretinoin (9-cis-retinoic acid). Although clinical trial data demonstrated the efficacy and safety of alitretinoin, real-world experience is lacking in a more generalized patient population.. Patients with CHD often, and unsuccessfully, attempt several therapeutic options before seeing a dermatologist. This chart review study aimed to examine the experience of using alitretinoin for CHD in a dermatology office setting.. A retrospective chart review of electronic medical records was conducted of all patients prescribed alitretinoin in a community dermatology practice.. Alitretinoin was well tolerated in this patient population of 53 patients and showed a clinically significant reduction in disease symptoms.. Alitretinoin was a safe and well-tolerated treatment with significant clinical improvement in our patient population. Few clinically significant laboratory abnormalities were identified, and only one patient discontinued therapy due to adverse events.

Topics: Adult; Aged; Alitretinoin; Chronic Disease; Community Health Services; Dermatologic Agents; Dermatology; Female; Hand Dermatoses; Humans; Male; Middle Aged; Retreatment; Retrospective Studies; Treatment Outcome; Tretinoin

This non-interventional observational open study (TOCCATA, sponsored by Basilea Pharmaceutica Germany) investigated the use of alitretinoin to treat chronic hand eczema under daily "real life" medical practice conditions in Germany. A total of 349 dermatologists through-out Germany enrolled 680 adult patients with chronic hand eczema. Patients were prescribed and treated with alitretinoin in accordance with the summary of product characteristics. The maximum observation duration was 24 weeks, with efficacy and safety parameters evaluated every 4 weeks. Efficacy was primarily evaluated by assessing disease severity according to the Physician Global Assessment. In total, 56.7% of patients achieved a Physician Global Assessment rating of "clear" or "almost clear" hands, with only small differences in patients with different morphological forms: hyperkeratotic-rhagadiform (59.2%), fingertip (52.2%) and vesicular (47.9%). This observational study demonstrates the effectiveness and tolerability of alitretinoin in everyday clinical practice in addition to the known efficacy and safety obtain-ed by randomized controlled clinical trials.

Topics: Adult; Alitretinoin; Chronic Disease; Eczema; Female; Hand Dermatoses; Humans; Keratolytic Agents; Male; Middle Aged; Severity of Illness Index; Tretinoin

  In a previous large trial (Benefit of Alitretinoin in Chronic Hand Eczema; BACH), 47.7% of patients with severe chronic hand eczema (CHE) who received alitretinoin 30 mg achieved 'clear' or 'almost clear' hands during the initial 24-week treatment course..   The current open-label trial was designed to study extended treatment with a further 12- to 24-week course of oral alitretinoin 30 mg in patients who did not fully respond to initial treatment in the BACH study..   At the end of the BACH study, patients whose eczema was rated 'mild', 'moderate' or 'severe' according to the Physician's Global Assessment (PGA) were eligible for a 24-week, open-label, multicentre study. Patients (n=243) received 30 mg of alitretinoin once daily, irrespective of previous treatment in BACH; either alitretinoin 30 mg, alitretinoin 10 mg or placebo..   By the end of the follow-on study, the PGA response rate to the subsequent course of alitretinoin 30 mg was 50% and 39% in patients treated previously in BACH with 10 or 30 mg per day, respectively, and 51% in patients who previously received placebo in BACH. Alitretinoin was well tolerated, and no significant late-arising toxicities were seen.. For a considerable number of patients with CHE who did not fully respond after an initial 24-week treatment period, a switch from either placebo to the active compound at 30 mg or from the lower to the higher dose, or treatment prolongation at the higher dose could be beneficial. Alitretinoin remains well tolerated for overall treatment durations of up to 48 weeks.

Topics: Administration, Oral; Adult; Alitretinoin; Canada; Chronic Disease; Dermatologic Agents; Eczema; Europe; Female; Hand Dermatoses; Humans; Male; Middle Aged; Retreatment; Tretinoin

Topics: Alitretinoin; Chronic Disease; Eczema; Female; Foot Dermatoses; Humans; Middle Aged; Remission Induction; Tretinoin

Stem cell therapy is a potential strategy to treat patients with Parkinson's disease (PD); however, several practical limitations remain. As such, finding the appropriate stem cell remains the primary issue in regenerative medicine today. We isolated a pre-placental pluripotent stem cell from the chorionic villi of women with early tubal ectopic pregnancies. Our objectives in this study were (i) to identify the characteristics of hTS cells as a potential cell source for therapy; and (ii) to test if hTS cells can be used as a potential therapeutic strategy for PD.. hTS cells expressed gene markers of both the trophectoderm (TE) and the inner cell mass (ICM). hTS cells exhibited genetic and biological characteristics similar to that of hES cells, yet genetically distinct from placenta-derived mesenchymal stem cells. All-trans retinoic acid (RA) efficiently induced hTS cells into trophoblast neural stem cells (tNSCs) in 1-day. Overexpression of transcription factor Nanog was possibly achieved through a RA-induced non-genomic c-Src/Stat3/Nanog signaling pathway mediated by the subcellular c-Src mRNA localization for the maintenance of pluripotency in tNSCs. tNSC transplantation into the lesioned striatum of acute and chronic PD rats not only improved behavioral deficits but also regenerated dopaminergic neurons in the nigrostriatal pathway, evidenced by immunofluorescent and immunohistological analyses at 18-weeks. Furthermore, tNSCs showed immunological advantages for the application in regenerative medicine.. We successfully isolated and characterized the unique ectopic pregnancy-derived hTS cells. hTS cells are pluripotent stem cells that can be efficiently induced to tNSCs with positive results in PD rat models. Our data suggest that the hTS cell is a dynamic stem cell platform that is potentially suitable for use in disease models, drug discovery, and cell therapy such as PD.

Topics: Acute Disease; Animals; Behavior, Animal; Cell Proliferation; Chronic Disease; Dopamine; Female; Genome; Humans; Leukemia Inhibitory Factor; Neostriatum; Neural Stem Cells; Parkinson Disease; Pluripotent Stem Cells; Pregnancy; Pregnancy, Ectopic; Rats; Regeneration; Signal Transduction; Tretinoin; Trophoblasts

Chronic hand eczema (CHE) is a debilitating and distressing disease for patients, the physical symptoms of which are compounded by psychosocial problems. Alitretinoin is an endogenously occurring physiological vitamin A derivative (retinoid) that possesses strong anti-inflammatory and immunomodulatory activity. It is currently the only licensed product for severe CHE unresponsive to treatment with potent topical corticosteroids, and has been proven to be highly effective in clinical trials with two-thirds of patients who responded to treatment remaining in remission at 6 months. For those that did relapse, a second study showed they could be successfully retreated with a further 3-6 month course of alitretinoin. Seven case studies of alitretinoin have been provided by consultant dermatologists showing its use in normal UK clinical practice. The cases chosen demonstrate the efficacy of alitretinoin across several different subtypes of CHE, and the positive effects the treatment brought to patients' quality of life.

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Tretinoin

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Female; Foot Dermatoses; Hand Dermatoses; Humans; Middle Aged; Politics; Quality of Life; Tretinoin

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Engineering; Hand Dermatoses; Humans; Male; Middle Aged; Tretinoin

Topics: Adult; Alitretinoin; Chronic Disease; Dermatologic Agents; Hand Dermatoses; Humans; Information Science; Male; Tretinoin

Gaucher disease (GD) is associated with upregulation of CD1d and MHC-class II expression by monocytes. While the physiological impact of CD1d upregulation remains uncertain, it has been proposed that MHC-class II upregulation is associated with inflammation. Hereby, we show that the decrease in MHC-class II expression seen in GD patients under therapy correlates positively with chitotriosidase activity, a marker of inflamed macrophages. We also show that retinoic acid (RA) and the beta-glucocerebrosidase inhibitor conduritol-B-epoxide (CBE) lead to upregulation of CD1d expression by THP-1 cells, which correlated with an increase in mRNA expression. In vitro co-culture experiments showed that RA treated THP-1 cells were more stimulatory for CD4(+) than for CD8(+) T cells, as determined by CFSE loss, in comparison to untreated THP-1 cells. Interestingly, even though addition of exogenous isoglobotrihexosylceramide (iGb3), a physiological CD1d ligand, augmented the percentage of dividing CD4(+) T cells, we could not detect a significant expansion of CD4(+)Valpha24(+) invariant Natural Killer T (iNKT) cells. In contrast, addition of alpha-galactosylceramide (alpha-GC) induced expansion of Valpha24(+) iNKT cells as determined by using alpha-GC-loaded human CD1d dimers. These results strengthen the existence of a cross-talk between monocyte lipid accumulation, inflammation and changes in cell surface CD1d and MHC-class II in monocytes, which may result in inappropriate recognition events by immune cells and perpetuate chronic inflammation.

Topics: Antigens, CD1d; Antineoplastic Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Division; Cell Line; Chronic Disease; Coculture Techniques; Enzyme Inhibitors; Gaucher Disease; Globosides; Hexosaminidases; Histocompatibility Antigens Class II; Humans; Inflammation; Inositol; Monocytes; Natural Killer T-Cells; Protein Multimerization; RNA, Messenger; Tretinoin; Trihexosylceramides; Up-Regulation

Topics: Administration, Oral; Adult; Alitretinoin; Chronic Disease; Dermatitis, Atopic; Dermatologic Agents; Female; Hand Dermatoses; Humans; Male; Middle Aged; Treatment Outcome; Tretinoin; Young Adult

Cardiac disease is a significant complication of childhood oncologic therapy. We report the case of a 14-year-old female with acute promyelocytic leukemia who developed symptomatic cardiomyopathy only 4 months into treatment with a combination of daunomycin and all-trans retinoic acid (ATRA). Despite cessation of daunomycin, she demonstrated fluctuating systolic function in relation to ATRA administration. Improvement and deterioration in systolic function on echocardiogram and serum B-natriuretic peptide levels were seen while receiving ATRA 1 week on and 1 week off, respectively, during the maintenance phase of therapy.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Chronic Disease; Daunorubicin; Female; Humans; Leukemia, Promyelocytic, Acute; Natriuretic Peptide, Brain; Tretinoin

Topics: Alitretinoin; Chronic Disease; Eczema; Hand Dermatoses; Humans; Keratolytic Agents; Tretinoin

Alitretinoin is a new drug for systemic treatment of chronic hand eczema. Previous functional tests of skin topically treated with retinoids have indicated impaired skin barrier function, but no data are available on barrier parameters after systemic alitretinoin treatment. To investigate the effect of systemic alitretinoin on skin barrier function and response to irritants, a secondary objective was to determine if changes occur in the lipid profile of stratum corneum after treatment with systemic alitretinoin. We conducted an open clinical intervention study on eight people ascribed to systemic alitretinoin treatment. The criteria for being ascribed to alitretinoin were chronic hand eczema and insufficient therapeutic response to potent topical corticosteroids. Before initiation and after 2 months of systemic treatment with 30 mg alitretinoin, a challenge with sodium lauryl sulphate (SLS) was performed on the volar forearm and evaluated by trans-epidermal water loss (TEWL), erythema, and a cyanoacrylate skin sample was obtained for lipid analysis. We found no significant changes in response to SLS irritation as evaluated by TEWL and erythema, after treatment with alitretinoin for 2 months. No significant changes in stratum corneum lipids were found after 2 months of treatment. In conclusion, systemic alitretinoin does not influence skin susceptibility to irritants or the ceramide profile of stratum corneum.

Topics: Alitretinoin; Ceramides; Chronic Disease; Disease Progression; Eczema; Epidermis; Erythema; Humans; Irritants; Retinoids; Sodium Dodecyl Sulfate; Tretinoin; Water Loss, Insensible

The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland.. A long-term Markov cohort simulation model was used to estimate direct medical costs (euro) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions.. Annual costs of alitretinoin treatment accounted for 2'212 euro. After a time horizon of 22.4 years, average remaining long-term costs accounted for 42'208 euro or 38'795 euro in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in 14'816 euro/QALY gained. These results were robust to changes in key model assumptions.. The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland.

Topics: Administration, Oral; Adolescent; Adult; Aged; Alitretinoin; Chronic Disease; Cost of Illness; Cost-Benefit Analysis; Eczema; Humans; Longitudinal Studies; Markov Chains; Middle Aged; Quality-Adjusted Life Years; Severity of Illness Index; Switzerland; Treatment Outcome; Tretinoin; Young Adult

An earlier study showed that all-trans-retinoic acid (ATRA) prevents the development of monocrotalin-induced pulmonary hypertension (PH). The purpose of the present study was to determine the effect of ATRA on another model of chronic hypoxia-induced PH.. Male Sprague-Dawley rats were given 30 mg/kg ATRA or vehicle only by gavage once daily for 14 days during hypobaric hypoxic exposure. Chronic hypoxic exposure induced PH, right ventricular hypertrophy (RVH), and hypertensive pulmonary vascular changes. Quantitative morphometry of the pulmonary arteries showed that ATRA treatment significantly reduced the percentage of muscularized arteries in peripheral pulmonary arteries only with an external diameter between 15 and 50 microm. ATRA treatment also significantly reduced the medial wall thickness in small muscular arteries only with an external diameter between 50 and 100 microm. Unfortunately, these reductions did not accompany the lowering of pulmonary artery pressure nor decrease in RVH. Chronic hypoxia-induced PH rats with ATRA had a loss in body weight. Chronic hypoxia increased the expression of endothelial nitric oxide synthase in the lung on western blotting and immunohistochemistry, in which ATRA treatment had no effect.. The administration of ATRA might not have a therapeutic role in preventing the development of chronic hypoxia-induced PH, because of body weight loss and the subtle preventable effects of vascular changes.

Topics: Animals; Body Weight; Chronic Disease; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lung; Male; Nitric Oxide Synthase Type III; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Tretinoin; Weight Loss

Treg are endowed with immunosuppressive activities and have been proposed as promising targets for the therapy of autoimmune diseases. As the suppressive capacity of Treg depends on their migration into the affected tissues, we tested here whether modulation of Treg homing would enhance their capacity to suppress inflammation in mouse models of inflammatory bowel disease. Retinoic acid (RA) was used to induce the gut-specific homing receptor alpha(4)beta(7) efficiently and, to some extent, the chemokine receptor CCR9 on in vitro expanded Treg. Upon transfer, RA-treated Treg were indeed more potent suppressors in an acute, small intestinal inflammation model, compared with Treg stimulated without RA. By contrast, the efficacy of Treg to resolve an established, chronic inflammation of the colon in the transfer colitis model was not affected by RA-treatment. In the latter model, a rapid loss of RA-induced alpha(4)beta(7) expression and de novo induction of alpha(4)beta(7) on previously negative cells was observed on transferred Treg, which implies that Treg acquire gut-seeking properties in vivo under inflammatory and/or lymphopenic conditions. Together, our data show that the induction of appropriate homing properties prior to transfer increases the protective potential of adoptively transferred Treg in acute, but not in chronic, inflammatory disorders of the gut.

Topics: Acute Disease; Adoptive Transfer; Animals; Cells, Cultured; Chronic Disease; Colitis; Disease Models, Animal; Homeodomain Proteins; Humans; Immunosuppression Therapy; Inflammation; Inflammatory Bowel Diseases; Integrins; Intestine, Small; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, CCR; Receptors, Lymphocyte Homing; T-Lymphocytes, Regulatory; Tretinoin

The management of chronic hand eczema is often inadequate. There are currently no evidence-based guidelines specifically for the management of chronic hand eczema, and evidence for established treatments for hand eczema is not of sufficient quality to guide clinical practice. This consensus statement, based on a review of published data and clinical practice in both primary and secondary care, is intended to guide the management of chronic hand eczema. It describes the epidemiology and pathogenesis of hand eczema, its diagnosis and its effect on patients' quality of life. Management strategies include a skin education programme, lifestyle changes, and the use of emollients, barriers and soap substitutes. Topical drug therapy includes topical steroids and calcineurin inhibitors. Treatment with psoralen ultraviolet A and systemic therapies may then be appropriate, although there is no strong evidence of efficacy. Alitretinoin has been shown to be effective in a randomized controlled trial, and is currently the only treatment specifically licensed for the treatment of hand eczema. Recommendations for management are summarized in a treatment algorithm.

Topics: Alitretinoin; Chronic Disease; Dermatologic Agents; Emollients; Glucocorticoids; Hand Dermatoses; Humans; Quality of Life; Referral and Consultation; Tretinoin

The diversity of neuroblastoma and its clinical course depends on histology, biology and clinical features. We report a male presenting at 4 months of age with an abdominal mass and multiple subcutaneous nodules. The diagnosis was made by histological examination of a subcutaneous nodule and elevated urinary markers. The patient remained well during the subsequent 9 years. During that time no cytostatic treatment was given. Attempt to treat with cis-retinoic acid 10 years later did not result in any significant change of the clinical course. The patient has remained in good clinical condition for a 15-year observation period, having both progressing and regressing distant subcutaneous metastases. Skin nodules are the hallmarks of the indolent clinical course of the disease. We suggest the use of the "chronic neuroblastoma" as a term to describe patients with neuroblastoma showing indolent disease course over a very long period of time, but never achieving complete remission.

Topics: Abdominal Neoplasms; Adolescent; Adrenal Gland Neoplasms; Antineoplastic Agents; Child; Child, Preschool; Chronic Disease; Humans; Immunohistochemistry; Infant; Liver Neoplasms; Male; Neuroblastoma; Skin Neoplasms; Tretinoin

The death-associated protein kinase 2 (DAPK2) belongs to a family of Ca(2+)/calmodulin-regulated serine/threonine kinases involved in apoptosis. During investigation of candidate genes operative in granulopoiesis, we identified DAPK2 as highly expressed. Subsequent investigations demonstrated particularly high DAPK2 expression in normal granulocytes compared with monocytes/macrophages and CD34(+) progenitor cells. Moreover, significantly increased DAPK2 mRNA levels were seen when cord blood CD34(+) cells were induced to differentiate toward neutrophils in tissue culture. In addition, all-trans retinoic acid (ATRA)-induced neutrophil differentiation of two leukemic cell lines, NB4 and U937, revealed significantly higher DAPK2 mRNA expression paralleled by protein induction. In contrast, during differentiation of CD34(+) and U937 cells toward monocytes/macrophages, DAPK2 mRNA levels remained low. In primary leukemia, low expression of DAPK2 was seen in acute myeloid leukemia samples, whereas chronic myeloid leukemia samples in chronic phase showed intermediate expression levels. Lentiviral vector-mediated expression of DAPK2 in NB4 cells enhanced, whereas small interfering RNA-mediated DAPK2 knockdown reduced ATRA-induced granulocytic differentiation, as evidenced by morphology and neutrophil stage-specific maturation genes, such as CD11b, G-CSF receptor, C/EBPepsilon, and lactoferrin. In summary, our findings implicate a role for DAPK2 in granulocyte maturation.

Topics: Acute Disease; Antigens, CD34; Antigens, Differentiation; Apoptosis Regulatory Proteins; Calcium-Calmodulin-Dependent Protein Kinases; Cell Differentiation; Cell Line, Tumor; Chronic Disease; Death-Associated Protein Kinases; Gene Expression Profiling; Granulocytes; Hematopoietic Stem Cells; Humans; Leukemia, Myeloid; Myeloid Cells; Myelopoiesis; Neutrophils; RNA, Small Interfering; Tretinoin; Up-Regulation

Melasma is a symmetric progressive hyperpigmentation of facial skin that occurs in all races but has a predilection for darker skin phenotypes. Melasma has been associated with hormonal imbalances, sun damage, and genetic predisposition. Clinically, melasma can be divided into centrofacial, malar, and mandibular according to the pigment distribution on the skin. On Wood light examination, the pigment can be found within the epidermis, where it will enhance, or within the dermis, where it will not enhance. Melasma can be classified as mild, moderate, or severe for evaluation and treatment purposes. In this article, we will discuss the objective evaluation of the patient with melasma, as well as the treatments based on disease severity. Further recommendations for maintenance in these patients also will be addressed.

Topics: Chronic Disease; Dermatologic Agents; Drug Therapy, Combination; Estrogens; Humans; Melanosis; Neurocutaneous Syndromes; Progesterone; Skin; Treatment Outcome; Tretinoin; Vitamin A

To evaluate the effect and molecular mechanism of retinoic acid (RA) in preventing experimental pulmonary emphysema in rats.. Thirty-six Wistar rats were randomly divided into three groups, the normal group(A), the model group (B) and the RA treated group (C). Rats in group B group were exposed to cigarette smoke, and group C was treated with RA. Pulmonary function indices and histopathological changes were evaluated. The enzymatic activity of gelatinases was measured by ELISA, and the expression of gelatinases and the proliferating cell nuclear antigen (PCNA) was examined by immunohistochemical method.. Compared with group A, group B presented significant differences in FEV(0.3),FEV(0.3)/FVC and FRC [(5.1 +/- 0.4) ml vs (6.0 +/- 0.3) ml, (71 +/- 10) ml/s vs (87 +/- 3) ml/s, (7.2 +/- 2.2) ml vs (2.9 +/- 1.1) ml (P < 0.01)];the enzymatic activity [(1.06 +/- 0.23)ng/ml vs (0.53 +/- 0.17)ng/ml, (0.960 +/- 0.230)ng/ml vs (0.300 +/- 0.090)ng/ml] and the expression of gelatinases were also markedly elevated(P < 0.01). In comparison with group B, the pulmonary function indices in group C [(5.2 +/- 0.4)ml, (81 +/- 5) ml/s, (6.1 +/- 2.7)ml/s] were improved (P < 0.05); the enzymatic activity [(0.83 +/- 0.23)ng/ml, (0.570 +/- 0.010)ng/ml] and the expression of gelatinases were decreased, while the PCNA index staining (93 +/- 4 vs 53 +/- 6) was increased (P < 0.01).. RA can prevent the development of pulmonary emphysema in rats.

Topics: Animals; Chemoprevention; Chronic Disease; Disease Models, Animal; Keratolytic Agents; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Proliferating Cell Nuclear Antigen; Pulmonary Emphysema; Rats; Rats, Wistar; Respiratory Function Tests; Tretinoin

The use of retinoids in wound healing is increasing. It has been shown that retinoic acid reverses the inhibitory effects of glucocorticoids on wound healing and accelerates the formation of healthy granulation tissue. Pretreatment with tretinoin before epidermal injury such as chemical peeling and dermabrasion has shown accelerated wound healing. Enhanced healing of full-thickness skin wounds has also been demonstrated in early wound healing studies. However, tretinoin therapy can be quite irritating.. Our purpose was to observe the clinical and histologic effects of topical tretinoin solution 0.05% applied directly to the wound beds of chronic leg ulcerations.. We report on the cases of 5 patients with long-standing leg ulcerations. All were treated with topical tretinoin solution 0.05% applied directly to the wound bed. The tretinoin solution was left in contact with the ulcer bed for a maximum of 10 minutes daily and then rinsed with normal saline. Punch biopsy specimens were obtained from the wound beds at baseline and mid therapy. Standard wound care was continued throughout the study.. In this study we found that as early as 1 week after treatment with topical tretinoin solution 0.05%, there was increased granulation tissue first noted at the wound's edge. After 4 weeks of therapy with tretinoin, there was further stimulation of granulation tissue, new vascular tissue, and new collagen formation.. Short-contact tretinoin therapy is a novel modality in which to treat chronic ulcers and stimulate the formation of granulation tissue.

Topics: Administration, Cutaneous; Aged; Chronic Disease; Female; Granulation Tissue; Humans; Keratolytic Agents; Leg Ulcer; Male; Middle Aged; Tretinoin; Wound Healing

The alterations in the mucociliary unit in the course of chronic inflammation of the upper respiratory tract correspond to morphologic anomalies of the respiratory epithelium and induce cuboidal and squamous metaplasia. While the squamous pattern is most probably irreversible, it is still not clear whether it is possible to restore ciliogenesis in cuboidal metaplasia. In the present study, the action of different inductors of differentiation was evaluated in vitro in isolated cells and explants from human nasal metaplastic epithelium. Polar/apolar compounds induced secretory activity, whereas retinoic acid was able to induce ciliogenesis in some cases. Therefore, the cuboidal metaplastic condition appears to be reversible, and two distinct pathways of differentiation, secretory and ciliogenetic, are identifiable.

Topics: Acetamides; Cell Differentiation; Cells, Cultured; Chronic Disease; Cilia; Cryoprotective Agents; Dimethyl Sulfoxide; Epithelium; Hematinics; Humans; Keratolytic Agents; Metaplasia; Microscopy, Electron; Microscopy, Electron, Scanning; Nasal Cavity; Nasopharyngitis; Tretinoin

Topical retinoic acid has proved to be of variable benefit in a number of dry eye disorders of disparate aetiology, in which squamous metaplasia with keratinization of ocular epithelium is present. Its exact role in patients with dry eye however remains in dispute. We describe a case of severe dry eye due to chronic graft-versus-host disease, which was refractory to conventional therapy but which responded remarkably to topical retinoic acid with reversal of conjunctival keratinization and marked resolution of symptoms.

Topics: Administration, Topical; Bone Marrow Transplantation; Chronic Disease; Dry Eye Syndromes; Graft vs Host Disease; Humans; Male; Middle Aged; Tretinoin

We report an unusual hyperdiploid karyotype characterized by the simultaneous occurrence of tetrasomy 21 and trisomy 8 detected during early blastic evolution of a BCR-ABL-negative chronic myeloproliferative disorder. Blast cells from this patient showed a striking response to all-trans-retinoic acid (ATRA)-induced differentiation as evaluated by CD15 expression following in vitro exposure to this inducer. Our report represents the first description of such a composite karyotype in human hematologic malignancies.

Topics: Aged; Aneuploidy; Bone Marrow; Cell Differentiation; Cells, Cultured; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 8; Chronic Disease; Humans; Immunophenotyping; Karyotyping; Male; Myeloproliferative Disorders; Ploidies; Tretinoin; Trisomy

Cytosolic retinoic acid receptor in carcinoma, chronic pancreatitis, and normal pancreatic tissue were examined using sucrose density gradient centrifugation, isoelectric focussing on agarose gel and saturation analysis. Thirteen patients were studied. Cytosolic retinoic acid binding protein (cRABP) was detected in all the samples with chronic pancreatitis and pancreatic carcinoma, but not in the normal tissue. Using sucrose gradient centrifugation, the highest concentrations of cRABP were found in pancreatic carcinoma tissues, ranging from 5.5-23.9 pmol/mg protein. These concentrations were markedly different than in chronic pancreatitis tissue (0.7-2.7 pmol/mg protein). Saturation analysis of cRABP showed a mean dissociation constant of 21.5 nM and maximum binding sites of 5.2 pmol/mg protein. Cytosolic retinoic acid binding protein was separated at an isoelectric point of 4.5 on agarose gel. The presence of cRABP suggest that retinoic acid may have a role to play in the function of the pancreas.

Topics: Adult; Aged; Aged, 80 and over; Carrier Proteins; Chronic Disease; Cytosol; Humans; Middle Aged; Neoplasm Proteins; Pancreas; Pancreatic Neoplasms; Pancreatitis; Receptors, Retinoic Acid; Tretinoin

A 34-year-old female patient presented with the classical features of keratosis lichenoides chronica, a very rare dermatosis. Typical hyperkeratotic papules in a linear and reticular pattern were located on the upper extremities and the trunk. The nails and the perionychial areas showed marked vegetating lesions. After administration of a combined retinoid-PUVA therapy impressive remission was observed. The clinical picture, the differential diagnosis, in particular from lichen ruber planus, and the therapeutic aspects are discussed.

Topics: Administration, Oral; Administration, Topical; Adult; Chronic Disease; Combined Modality Therapy; Etretinate; Female; Humans; Lichen Planus; PUVA Therapy; Skin; Tretinoin

Eight of ten patients with chronic or subacute cutaneous lupus erythematosus completed 16 weeks of oral isotretinoin therapy (80 mg/day). All eight patients noted an excellent clinical response without significant side effects. (Two patients did not return to initial two-week follow-up.) Peripheral blood B- and T-cell counts were unaffected by therapy. Therapy was associated with resolution of routine histopathologic abnormalities, conversion of abnormal lesional direct immunofluorescence microscopy to normal, normalization of the epidermis on electron microscopy, and reduction of all T cells near the dermoepidermal junction without change in ratio of T-helper/inducer cells to T-suppressor/cytotoxic cells. Isotretinoin is a clinically effective short-term therapy for chronic or possibly for subacute cutaneous lupus erythematosus. The primary mechanism of action remains unestablished.

Topics: Administration, Oral; Adult; Basement Membrane; Chronic Disease; Complement C3; Drug Evaluation; Female; Fibrin; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Isotretinoin; Lupus Erythematosus, Discoid; Lymphocytes; Male; Middle Aged; Skin; Tretinoin

The clinical response to isotretinoin (13-cis-retinoic acid) in 11 patients with generalized pustular psoriasis was evaluated. Control of pustulation and systemic symptoms was achieved in ten cases, but additional therapy was required to produce complete clearing of all psoriatic lesions. Also, the efficacy of isotretinoin and etretinate in the treatment of chronic plaque psoriasis was compared in 29 patients. Isotretinoin was found to be less effective than etretinate in the treatment of chronic plaque psoriasis.

Topics: Adult; Aged; Biopsy; Chronic Disease; Etretinate; Female; Humans; Isotretinoin; Male; Middle Aged; Psoriasis; Tretinoin

Topics: Acne Vulgaris; Adolescent; Chronic Disease; Follow-Up Studies; Granuloma; Humans; Isotretinoin; Male; Skin Diseases; Tretinoin

Case report of a patient with keratosis lichenoides chronica and good response to a combined therapy with retinoids and photochemotherapy.

Topics: Chronic Disease; Humans; Keratosis; Male; Middle Aged; PUVA Therapy; Skin; Tretinoin

Severe forms of rosacea are a new indication for the treatment with 13-cis retinoic acid. Results of therapy and duration of remission were in five patients, treated in this way, much better than compared to standard therapeutic measurements.

Topics: Adult; Chronic Disease; Humans; Isotretinoin; Middle Aged; Rosacea; Tretinoin