Low-dose Isotretinoin Research Articles

Isotretinoin alleviates renal damage in rat chronic glomerulonephritis

Retinoids, derivatives of vitamin A, have strong anti-inflammatory and antiproliferative properties. We previously demonstrated that the pan-agonists all-transretinoic acid (RA) and isotretinoin (13-cis RA) alleviate renal damage in rat acute glomerulonephritis (GN) induced by anti-Thy-1.1 mAb OX-7. The present study examined the effects of low dose and high dose treatment with isotretinoin in the chronic glomerulonephritis model, Thy-GN. Thy-GN was induced by a single intravenous injection of monoclonal antibody (mAb) 1-22-3 in uninephrectomized Wistar rats (N = 7 to 10 per group). Control and nephritic groups were treated with vehicle (veh), low dose isotretinoin (2 mg/kg body wt), or high dose isotretinoin (10 mg/kg body wt). The experiment was terminated 60 days after induction of Thy-GN. In animals with Thy-GN, isotretinoin abrogated the increase in blood pressure and significantly reduced albuminuria. Glomerulosclerosis index, glomerular and interstitial cell counts, as well as the area of the interstitial space were significantly lower in nephritic rats treated with low and high dose isotretinoin compared to vehicle-treated nephritic controls. Treatment with isotretinoin also significantly reduced the number of glomerular and interstitial macrophages. The increase of transforming growth factor (TGF)-beta1, TGF receptor II and prepro-endothelin-1 gene expression in vehicle-treated nephritic rats was significantly attenuated by isotretinoin. Treatment with isotretinoin significantly reduces glomerular and interstitial damage in rats with chronic glomerulonephritis as indicated by different functional and histological markers. Retinoids may provide a novel therapeutic option for the treatment of glomerulonephritis.

Symptomatic DISH not seen with long-term, low-dose isotretinoin

Symptomatic DISH not seen with long-term, low-dose isotretinoin

Thrombocytosis induced by low-dose isotretinoin

International Journal of DermatologyVolume 39, Issue 12 p. 956-957 Thrombocytosis induced by low-dose isotretinoin Thomas Jansen MD, Thomas Jansen MD Bochum, GermanySearch for more papers by this authorPeter Altmeyer MD, Peter Altmeyer MD Bochum, GermanySearch for more papers by this author Thomas Jansen MD, Thomas Jansen MD Bochum, GermanySearch for more papers by this authorPeter Altmeyer MD, Peter Altmeyer MD Bochum, GermanySearch for more papers by this author First published: 07 July 2008 https://doi.org/10.1046/j.1365-4362.2000.00008-4.xCitations: 8Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume39, Issue12December 2000Pages 956-957 RelatedInformation

Long-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa

Background: Oral isotretinoin has been used to treat mild to severe hidradenitis suppurativa (HS). Objective: We reviewed the results of low-dose isotretinoin for 4 to 6 months in the treatment of 68 patients with HS. Methods: This is a retrospective study. Data are presented in terms of response rate, long-term follow-up, and the relation between response rate and severity. Results: In 16 patients (23.5%), the condition completely cleared during initial therapy and 11 patients (16.2%) maintained their improvement during the follow-up period. Treatment was more successful in the milder forms of HS. Conclusion: Monotherapy with isotretinoin for patients with HS usually has a limited therapeutic effect.(J Am Acad Dermatol 1999;40:73-6.)

Acne vulgaris in the elderly: the response to low-dose isotretinoin.

There is a very small number of patients who suffer from acne even in the sixth and seventh decades of life. These patients have suffered from acne for most of their lives, 30-60 years, and have often received multiple courses of antibiotics over many years. We saw 10 such patients over 4 years. One received oral isotretinoin 1 mg/kg per day, but was unable to tolerate the adverse effects of cheilitis and developed hyperlipidaemia. We subsequently treated nine others with oral isotretinoin, 0.25 mg/kg per day, for 6 months; in six the acne had virtually cleared by 3-4 months while the other three cleared by 6 months. Up to 36 months after therapy these patients have remained clear of acne except for one who relapsed after 11 months. Therefore, as these patients respond well with few side-effects both in the long- and short-term to low-dose isotretinoin, they should be treated with isotretinoin, although at the lower starting dose of 0.25 mg/kg per day compared with younger patients who are treated with 0.5-1 mg/kg per day, and the treatment maintained for 6 months.

Effect of isotretinoin therapy on natural killer cell activity in patients with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by sun sensitivity, defective DNA repair, markedly increased susceptibility to skin cancer, and a variety of immunological defects, including defective natural killer (NK) cell activity. Retinoid therapy has been demonstrated to protect effectively against the development of skin cancers in patients with XP, although its mechanism of action is unknown. We describe a series of eight XP patients, six of whom were given oral isotretinoin. The NK cell activity was not affected by low-dose isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK cell function, at the same time as producing a reduction in the frequency of development of skin cancers. Retinoid therapy may have a skin cancer preventing effect by enhancing other immune effector mechanisms or via epithelial cell differentiation.

Messages from completed randomized trials in head and neck cancer

During the last three decades numerous randomized trials have been conducted in head and neck squamous cell carcinoma. The issue of pre- vs post-operative radiotherapy in advanced cancers was settled in the late 70s in favour of the latter approach and new fractionation schemes are currently being investigated, with no definite answers as yet. There is no uniform policy regarding the problem of elective neck dissection in early stage anterior oral cavity carcinoma. Often some chemotherapeutic regimen is involved in clinical trials in an attempt to improve on the standard of surgery and radiotherapy. Neoadjuvant chemotherapy has never been proven to benefit patients with advanced squamous cell carcinoma of the head and neck despite being able to decrease the rate of distant metastases. Chemotherapy given prior to or simultaneously with definite radiotherapy seems to offer the best chances for preserving vital organs, such as the larynx. Methotrexate is still the least toxic and most potent drug in recurrent or metastatic disease. The chemoprotective effect of low-dose isotretinoin on multiple primaries in the head and neck has yet to be evaluated.

Micronuclei, a biomarker for chemoprevention trials: Results of a randomized study in oral pre‐malignancy

Biomarkers are being sought that could serve as surrogate end points for chemoprevention trials. Micronuclei, cytoplasmic fragments of DNA, have been proposed as a biomarker and studied in oral pre-malignancy. This study evaluated micronuclei frequency in a randomized chemoprevention trial of oral pre-malignancy. A recent clinical trial evaluated the responses of pre-malignant oral lesions to 3 months of therapy with isotretinoin followed by 9 months of either low-dose isotretinoin or beta-carotene. For 57 study participants, micronuclei were counted in mucosal scrapings of the lesion and in normal-appearing mucosa at baseline and following 3 months and 12 months of therapy. Micronuclei counts were higher in scrapings from the lesion than in the normal-appearing mucosa. Following 3 months of isotretinoin, the micronuclei counts in scrapings of the lesion were significantly reduced. With treatment, the mean micronuclei count declined at 3 months. In a randomized comparison, both isotretinoin and beta-carotene maintained the suppression of micronuclei. The change in micronuclei count was not associated with the clinical or histological response to treatment. Chemoprevention treatment with isotretinoin led to a reduction in frequency of micronuclei, a marker of recent DNA injury, which was then maintained by both isotretinoin and beta-carotene.

Comparison of Low-Dose Isotretinoin with Beta Carotene to Prevent Oral Carcinogenesis

High-dose isotretinoin therapy has been determined to be an effective treatment for leukoplakia. However, a high rate of relapses and toxic reactions led us to conduct a trial of a much lower dose of isotretinoin in the hope of maintaining a response and limiting toxicity. In the first phase of the study, 70 patients with leukoplakia underwent induction therapy with a high dose of isotretinoin (1.5 mg per kilogram of body weight per day) for three months; in the second phase, patients with responses or stable lesions were randomly assigned to maintenance therapy with either beta carotene (30 mg per day) or a low dose of isotretinoin (0.5 mg per kilogram per day) for nine months. In the first phase, the rate of response to high-dose induction therapy in the 66 patients who could be evaluated was 55 percent (36 patients). The lesions of seven patients progressed, and therefore they did not participate in the second phase of the trial. Of the 59 patients included in the second phase, 33 were assigned to beta carotene therapy and 26 to low-dose isotretinoin therapy; these two groups did not differ significantly in prognostic factors. Of the 53 patients who could be evaluated, 22 in the low-dose isotretinoin group and 13 in the beta carotene group responded to maintenance therapy or continued to have stable lesions (92 percent vs. 45 percent, P < 0.001). In situ carcinoma developed in one patient in each group, and invasive squamous-cell carcinoma in five patients in the beta carotene group. Toxicity was generally mild, though greater in the group given low-dose isotretinoin therapy. When preceded by high-dose induction therapy, low-dose isotretinoin therapy was significantly more active against leukoplakia than beta carotene and was easily tolerated.

Long-Term Therapy With Low-Dose Isotretinoin for Prevention of Basal Cell Carcinoma: A Multicenter Clinical Trial

High-dose isotretinoin has been reported to have a prophylactic effect on nonmelanoma skin cancer, although it is associated with significant toxicity. To test the effectiveness of the long-term administration of low-dose isotretinoin in reducing the occurrence of basal cell carcinoma at a new site in patients with previously treated basal cell carcinomas and to measure the toxicity associated with this regimen, we conducted a clinical trial at eight cancer centers. Nine hundred and eighty-one patients with two or more previously confirmed basal cell carcinomas were randomly assigned to receive either 10 mg of isotretinoin or a placebo daily. Patients were followed for 36 months and monitored at 6-month intervals for skin cancer and toxic effects. After 36 months of treatment, no statistically significant difference in either the cumulative percent of patients with an occurrence of basal cell carcinoma at a new site or the annual rate of basal cell carcinoma formation existed between patients receiving isotretinoin and those receiving the placebo. Elevated serum triglycerides, hyperostotic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P less than .001). This low-dose regimen of isotretinoin not only is ineffective in reducing the occurrence of basal cell carcinoma at new sites in patients with two or more previously treated basal cell carcinomas but also is associated with significant adverse systemic effects. The toxicity associated with the long-term administration of isotretinoin, even at the low dose used in this trial, must be weighted in planning future prevention trials.

Ocular Toxic Effects of Fenretinide

Ocular Toxic Effects of Fenretinide