-
1.
Scientific evidence for the use of current traditional systemic therapies in patients with hidradenitis suppurativa.
Alhusayen, R, Shear, NH
Journal of the American Academy of Dermatology. 2015;(5 Suppl 1):S42-6
Abstract
Traditional systemic therapies are frequently prescribed for the treatment of hidradenitis suppurativa (HS). Clinicians consider antibiotics, retinoids, antiandrogens, immunosuppressants, and less common treatment, such as fumarates, in the management of HS. Different classes of medications have been selected to treat HS based on their ability to target various pathways of the condition. Concerns about infection, such as infection with Clostridium difficile, necessitates switching therapy or shortening the course of therapy with specific antibiotics. This review explores the outcomes with the use of numerous medical therapies and postulates explanations for their efficacy or lack of response. Data on long-term safety and efficacy with traditional systemic therapies are lacking.
-
2.
A systematic review of clinical trials of treatments for the congenital ichthyoses, excluding ichthyosis vulgaris.
Hernández-Martin, A, Aranegui, B, Martin-Santiago, A, Garcia-Doval, I
Journal of the American Academy of Dermatology. 2013;(4):544-549.e8
Abstract
BACKGROUND The ichthyoses comprise a group of inherited disorders of keratinization. Because of the need for lifelong treatment, it is important that therapies are beneficial, safe, and well tolerated. OBJECTIVES We sought to review the evidence on existing treatments for the congenital ichthyoses, excluding ichthyosis vulgaris. METHOD We undertook a systematic review using the methodology of the Cochrane Collaboration. Articles published in MEDLINE, EMBASE, and CENTRAL and registered clinical trials were screened. Randomized controlled trials involving patients with the inherited ichthyoses, either syndromic or nonsyndromic but excluding ichthyosis vulgaris, were considered. RESULTS Six trials met the inclusion criteria. Topical treatments including 5% urea, 20% propylene glycol alone or in combination with 5% lactic acid, calcipotriol ointment, and liarozole 5% cream showed therapeutic benefit. Oral liarozole, a retinoic acid metabolism blocking agent, showed no advantage over oral acitretin. LIMITATIONS Most studies were performed on a small sample of patients and lacked methodological and reporting quality. The small number of trials and the nearly constant positive results make publication bias likely. The absence of standardization of outcome measures precluded the comparison of studies. CONCLUSIONS Topical treatments including emollients, calcipotriol ointment, and liarozole cream seem to have therapeutic benefit and a good safety profile, although the use of topical calcipotriol is limited by a maximum weekly dose of 100 g. The advantage of oral liarozole over acitretin is uncertain. Multicenter trials comparing oral and topical interventions and evaluation of long-term outcomes are needed.
-
3.
Efficacy and tolerability of topical 0.2% Myrtacine® and 4% vitamin PP for prevention and treatment of retinoid dermatitis in patients with mild to moderate acne.
Veraldi, S, Giovene, GL, Guerriero, C, Bettoli, V
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2012;(5):491-7
Abstract
AIM: The aim of the present study was to evaluate the efficacy and tolerability of an emulsion of 0.2% Myrtacine® and 4% vitamin PP, compared with a simple emollient cream, in the treatment of retinoid dermatitis in patients with mild-to-moderate acne. METHODS This was a prospective, multicenter, open-label, non-randomised, parallel-group study. Patients (age 12-49 years; skin phototype I-IV) with mild-to-moderate acne, who were treated with a topical retinoid for at least one month and had developed skin irritation were assigned to one of the two following treatments: 0.2% Myrtacine® and 4% vitamin PP (N.=116) or a simple emollient cream (N.=48). Both treatments were administered twice daily, 1-1.5 hours after the application of the topical retinoid. Study endpoints were improvement in signs and symptoms of retinoid dermatitis, global efficacy, reduction in acne severity, overall clinical outcome, patient satisfaction and tolerability. RESULTS At day 28, compared with the simple emollient cream, 0.2% Myrtacine® and 4% vitamin PP significantly decreased signs (erythema, dryness/scaling, oedema, and roughness) and symptoms (itching, stinging, burning sensation and discomfort) of retinoid dermatitis (P<0.01). In addition, compared with the simple emollient cream, 0.2% Myrtacine® and 4% vitamin PP decreased acne severity in a significantly greater proportion of patients (P=0.023) and was associated with a better clinical outcome (mild, intermediate, clinically relevant or global improvement; P<0.001). 0.2% Myrtacine® and 4% vitamin PP was also associated with greater patient satisfaction and was better tolerated than the simple emollient cream. CONCLUSION 0.2% Myrtacine® and 4% vitamin PP was effective and well tolerated in the treatment of retinoid dermatitis in patients with mild-to-moderate acne and significantly improved acne severity and overall clinical outcome.
-
4.
Chemoprevention of head and neck cancer with retinoids: a negative result.
Perry, CF, Stevens, M, Rabie, I, Yarker, ME, Cochrane, J, Perry, E, Traficante, R, Coman, W
Archives of otolaryngology--head & neck surgery. 2005;(3):198-203
Abstract
OBJECTIVE To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to enter appropriate patients into this trial. PATIENTS One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment. INTERVENTIONS Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for 1 year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years. MAIN OUTCOME MEASURES The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured. RESULTS There was no significant difference in the occurrence of second primary disease (P = .90), the recurrence of primary disease (P = .70), or disease-free time (P = .80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival. CONCLUSION With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.
-
5.
Physiopathology of acne vulgaris: recent data, new understanding of the treatments.
Pawin, H, Beylot, C, Chivot, M, Faure, M, Poli, F, Revuz, J, Dréno, B
European journal of dermatology : EJD. 2004;(1):4-12
Abstract
Acne is the most frequent reason for seeing a dermatologist, but its physiopathology is not completely well-known. Yet understanding of the mechanisms of action of the different acne treatments is very important to optimize their use. A lot of new data on the physiopathology have recently been published in the acne field. This paper summarizes the main points of these new facts.
-
6.
The use of retinoids in the prevention and treatment of skin cancer.
Niles, RM
Expert opinion on pharmacotherapy. 2002;(3):299-303
Abstract
There has been a significant increase in the number of cases of skin cancer diagnosed in the US in the past few years. Thus, it seems appropriate to review the available compounds that might be used in the chemoprevention of these lesions. This review focuses on the retinoids and details their results in clinical trials for treatment and prevention of skin cancer. Side effects of the various retinoid derivatives are also discussed. It is concluded that isotretinoin (13-cis-retinoic acid) is the most effective retinoid for the prevention of non-melanoma skin cancers in high-risk patients in clinical trials. Current basic research is focused on developing receptor-selective retinoids which would have a higher therapeutic index for the treatment and chemoprevention of skin cancer.
-
7.
Comparison of gene expression profiles in human keratinocyte mono-layer cultures, reconstituted epidermis and normal human skin; transcriptional effects of retinoid treatments in reconstituted human epidermis.
Bernard, FX, Pedretti, N, Rosdy, M, Deguercy, A
Experimental dermatology. 2002;(1):59-74
Abstract
In order to validate a model for predictive screening of dermatological drugs, we used a customized cDNA macro-array system containing 475 skin-related genes to analyze the gene expression patterns in human keratinocytes from different origins: (1) normal human epidermal keratinocyte mono-layer cultures, (2) the commercially available SkinEthic reconstituted human epidermis model, and (3) biopsies of normal human epidermis. Few markers of those that were detected significantly in keratinocyte mono-layers or in reconstituted epidermis were undetected or detected at very low level in the normal epidermis biopsies. A comparative expression of more than 100 markers could be evidenced in both normal epidermis and reconstituted epidermis samples; however, only 90% of these were detected in keratinocyte mono-layers: expression of several terminal differentiation markers, such as filaggrin, loricrin, and corneodesmosin were strongly detected in normal epidermis and reconstituted epidermis, but were not significantly expressed in keratinocyte mono-layers. Under the experimental conditions described herein, the reconstituted human epidermis model was found to significantly reproduce the gene expression profile of normal human epidermis. Using the same methodology, we then investigated the effects of all-trans retinoic acid, 9-cis retinoic acid, all-trans retinol and a commercialized tretinoin-containing cream (Retacnyl) on the gene expression profiles of reconstituted human epidermis. According to the nature and the length of the treatments, more than 40 genes were found significantly modified. Among the genes whose expression was decreased, we found cytokeratins 1, 10, 2E, and 6B, several cornified envelope precursors, integrins alpha 3, alpha 6, beta 1, beta 4, some components of desmosomes, of hemi-desmosomes and of the epidermal basement membrane. Transcriptional upregulation was observed for keratins 18 and 19, autocrine and paracrine growth factors such as HB-EGF, IGF 1, PDGF-A, calgranulins A and B, interleukin-1 alpha and the other IL-1-related markers, type II IL-1 receptor and type I IL-1-receptor antagonist. Our results confirm most of the known effects of retinoids on human epidermis, but also give new insights into their complex pharmacological activity on skin. The reconstituted human epidermis used proves to be a highly predictive model for efficacy evaluation of skin-targeted compounds, such as retinoids.
-
8.
Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer.
Sato, R, Helzlsouer, KJ, Alberg, AJ, Hoffman, SC, Norkus, EP, Comstock, GW
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002;(5):451-7
Abstract
Previous prospective studies have raised the possibility that the antioxidantproperties of carotenoids and vitamin E (alpha-tocopherol) and the role of vitamin A (retinol) in cellular differentiation may be associated with a reduced risk of subsequent breast cancer. To investigate the association between serum and plasma concentrations of retinol, retinyl palmitate, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, total-carotenoids, alpha-tocopherol, and gamma-tocopherol with subsequent development of breast cancer, a nested case control study was conducted among female residents of Washington County, Maryland, who had donated blood for a serum bank in 1974 or 1989. Cases (n = 295) and controls (n = 295) were matched on age, race, menopausal status, and date of blood donation, and the analyses were stratified by cohort participation. Median concentrations of beta-carotene, lycopene, and total carotene were significantly lower in cases compared with controls in the 1974 cohort (13.1, 12.5, and 7.9% difference; P = 0.01, 0.04, and 0.04, respectively) and for lutein in the 1989 cohort (6.7% difference; P = 0.02). The risk of developing breast cancer in the highest fifth was approximately half of that of women in the lowest fifth for beta-carotene [odds ratio (OR) = 0.41; 95% confidence interval (CI) 0.22-0.79; P trend = 0.007], lycopene (OR = 0.55; 95% CI 0.29-1.06; P trend = 0.04), and total carotene (OR = 0.55; 95% CI 0.29-1.03; P trend = 0.02) in the 1974 cohort. There was generally a protective association for other micronutrients in both cohorts, although none reached statistical significance. The results suggest that carotenoids may protect against the development of breast cancer.
-
9.
Management of guttate and generalized psoriasis vulgaris: prospective randomized study.
Caca-Biljanovska, NG, V'lckova-Laskoska, MT
Croatian medical journal. 2002;(6):707-12
Abstract
AIM: To assess the efficacy of betamethasone dipropionate 0.05% cream plus ultraviolet B (UVB) radiation with and without additional penicillin therapy in the treatment of guttate psoriasis, and to compare the efficacies of oral psoralen plus ultraviolet A (PUVA) therapy and systemic retinoids therapy for treatment of generalized psoriasis. METHODS Sixty patients with guttate (n = 20) and generalized psoriasis vulgaris (n = 40) of various intensity and duration treated at the Department of Dermatology, Medical School in Skopje, from February 2000 to January 2002, were included in this prospective, open-label, randomized, parallel group study. The clinical features of the patients were quantified according to the mean psoriasis area and severity index (PASI) values. Student s t-test for paired samples and two independent samples were used in statistical analysis. RESULTS The final PASI values were not significantly different for the patients receiving different treatments of guttate psoriasis or generalized psoriasis. The initial PASI values for guttate psoriasis patients treated with betamethasone dipropionate plus UVB with and without penicillin treatment (5.7 +/- 2.1 and 5.9 +/- 2.5, respectively) declined to 0.5 +/- 0.8 and 1.0 +/- 0.9, respectively, after the therapy. The initial PASI values in generalized psoriasis patients receiving PUVA dropped from 24.1 +/- 3.6 to 1.7 +/- 1.5 by the end of the therapy. Finally, pre-treatment PASI values in patients with generalized psoriasis receiving retinoids decreased from 24.6 +/- 3.5 to 0.9 +/- 1.1 after treatment. However, patients receiving systemic retinoids for generalized psoriasis had statistically higher incidence of side effects than patients receiving PUVA therapy (t = 6.458, df = 38, p < 0.001). CONCLUSION Penicillin should be applied in addition to local corticosteroids with UVB in the treatment of guttate psoriasis, since the disease may be triggered by a streptococcal infection. In cases of generalized psoriasis vulgaris, PUVA therapy caused fewer side effects than did systemic retinoids.
-
10.
CD 2394, a novel synthetic retinoid, initiates an embryonic type of differentiation in hyperproliferative skin.
Van Rossum, MM, Mommers, JM, Van Erp, PE, Leyninger, E, Clucas, A, Van de Kerkhof, PC
Acta dermato-venereologica. 2000;(2):98-101
Abstract
In human skin, there are 2 types of epidermal differentiation: normal differentiation, characterized by keratin 10 expression, and alternative differentiation. Alternative differentiation may be regeneration-associated differentiation (keratin 6 and 16) or re-induction of embryonic differentiation (expression of keratin 13, 15 and 19). The purpose of this study was to investigate the effect of the novel synthetic retinoid CD 2394 on hyperproliferative human skin, with respect to embryonic differentiation in particular. The effects of CD 2394 were compared with untreated and vehicle-treated skin 48 h after tape-stripping. In a multiparameter flow cytometric assay, parameters of proliferation, normal differentiation, embryonic differentiation and inflammation were assessed. With respect to proliferation, treatment with CD 2394 resulted in a decreased number of cells in the G2M-phase. Normal differentiation was decreased in CD 2394 treated skin. Furthermore, most of the CD 2394 treated samples showed expression of keratin 13, which was not seen in the otherwise treated skin. A correlation between keratin 10 and keratin 13 expression could not be demonstrated. This study showed that CD 2394 is capable of inducing an embryonic pathway of differentiation, which is distinct from normal differentiation or regeneration-associated differentiation.