Dapsone for the treatment of acne vulgaris: do the risks outweigh the benefits?

Dapsone is a "4,4'-diamino diphenyl sulfone" compound and an aniline derivative from synthetic sulphones. Sulphonamides were first used in humans as antimicrobial agents to treat streptococcal infections. Dapsone derived from sulphonamides was first used in the treatment of leprosy in 1940. Today, Dapsone treatment is among the treatment options for many dermatological diseases. Acne vulgaris is a chronic inflammatory disease, which causes scar formation and changed pigmentation. Acne affects 85% of teenagers, but can occur at any age and can last into adulthood and even lifelong. Through its antimicrobial, anti-inflammatory, and antioxidant effects, dapsone treatment (local or systemic) can also be used in the treatment of acne. Dapsone treatment can cause a variety of side effects that can be categorized as pharmacological, dose-related, allergic, or idiosyncratic reactions. In this review article, the risks and benefits of using dapsone treatment in acne vulgaris will be evaluated in light of the literature.

Update on the use of dapsone in dermatology.

Dapsone (4,4'-diaminodiphenylsulfone) is the only remaining sulfone used in anthropoid therapeutics and is commercially available as an oral formulation, an inhaled preparation, and a 5% or 7.5% cream. Dapsone has antimicrobial effects stemming from its sulfonamide-like ability to inhibit the synthesis of dihydrofolic acid. It also has anti-inflammatory properties such as inhibiting the production of reactive oxygen species, reducing the effect of eosinophil peroxidase on mast cells and down-regulating neutrophil-mediated inflammatory responses. This allows for its use in the treatment of a wide variety of inflammatory and infectious skin conditions. Currently in dermatology, the US Food and Drug Administration (FDA)-approved indications for dapsone are leprosy, dermatitis herpetiformis, and acne vulgaris. However, it proved itself as an adjunctive therapeutic agent to many other skin disorders. In this review, we discuss existing evidence on the mechanisms of action of dapsone, its FDA-approved indications, off-label uses, and side effects.

A randomized controlled trial of topical benzoyl peroxide 2.5% gel with a low glycemic load diet versus topical benzoyl peroxide 2.5% gel with a normal diet in acne (grades 1-3).

BACKGROUND: The improvement in insulin resistance and acne lesions on low glycemic load diets in various studies suggests that diet plays a significant role in acne pathogenesis. AIMS: To compare the efficacy of a low glycemic load diet plus topical benzoyl peroxide 2.5% gel with that of only topical benzoyl peroxide 2.5% gel in grades 1, 2 and 3 of acne vulgaris. METHODS: In a randomized controlled trial, 84 patients with grades 1, 2 and 3 acne vulgaris were divided into two groups, to receive a low glycemic load diet and no dietary intervention respectively. Acne lesions (face) were scored and graded at baseline and 4, 8 and 12 weeks. Homeostasis model assessment of insulin resistance and body mass index were measured during the first and last visits. Statistical analysis was done with Statistical Package for the Social Sciences, version 17.0. RESULTS: Both groups showed significant reduction in acne counts at 12 weeks (P = 0.931) with no statistically significant difference between the groups. The differences in body mass index and homeostasis model assessment of insulin resistance between the groups were statistically significant (P = 0.0001). Group 1 showed reductions in body mass index and homeostasis model assessment of insulin resistance values at the end of the study, whereas group 2 did not. LIMITATIONS: Application of mild topical cleanser in both the groups might have contributed to the improvement in epidermal barrier function, and topical application of 2.5% of benzoyl peroxide gel in both groups contributed to the improvement in acne counts. CONCLUSIONS: A low glycemic load diet did not result in any significant improvement in acne counts.

Update on etiopathogenesis and treatment of Acne.

Acne, the most common skin disease, is a disorder of pilosebaceous units that affects adolescents mainly and adults occasionally. The pathogenesis is multifactorial. Besides genetic predisposition, other major factors include the action of androgens, pro-inflammatory lipids acting as ligands of peroxisome proliferator-activated receptors in the sebocytes, toll-like receptor-2 acting on keratinocytes, recognition of pathogen-associated molecular patterns, cytokines, chemokines, inflammasomes, neuroendocrine regulatory mechanisms, diet and other pro-inflammatory targets implicated in the activation of immune detection and response. Most of these factors converge on mammalian target of rapamycin complex1 (mTORC1) activation which is further enhanced by the nutrient signaling of Western diet. This multitude of pathogenic factors has led to a new armamentarium of drugs for the treatment of acne. Topical anti-androgens, insulin-like growth factor-1 inhibitors, peroxisome proliferator-activated receptor-modulators, acetylcholine inhibitors, topical retinoic acid metabolism-blocking agents, vitamin D analogues, antimicrobial peptides, interleukin-1α and interleukin-1ß blockers and immunotherapy are some of the novel treatment options.

Effects of isotretinoin on the thyroid gland and thyroid function tests in acne patients: A preliminary study.

BACKGROUND: Isotretinoin is widely used in the treatment of acne. AIMS: We investigated the effects of isotretinoin on thyroid function tests and thyroid volume in acne patients. METHODS: In this prospective study, a total of 104 acne patients were included. Sixty-six patients were treated with isotretinoin for at least 4 months. Thirty eight patients were included in the control group. The levels of thyroid stimulating hormone, free triiodothyronine, free thyroxine, antithyroglobulin and antithyroid peroxidase antibodies were measured and a thyroid ultrasound was performed in all the subjects before treatment and 4 months after treatment. A "p" value of < 0.05 was considered significant. RESULTS: In the isotretinoin-treated group, thyroid stimulating hormone levels increased significantly during isotretinoin treatment (P = 0.018). Free triiodothyronine, free thyroxine, anti-thyroid peroxidase levels and thyroid volume decreased significantly during treatment (P = 0.016, P= 0.012, P= 0.006, P = 0.020 respectively). LIMITATIONS: The major limitation of this study is the lack of follow-up data after the cessation of isotretinoin therapy in acne patients. CONCLUSION: Patients treated with isotretinoin should be monitored with thyroid function tests.

Laser and light based treatments of acne.

Medical treatments for acne vulgaris include a variety of topical and oral medications. Poor compliance, lack of durable remission, and potential side effects are common drawbacks to these treatments. Therefore, there is a growing demand for a fast, safe, and side-effect-free novel therapy. Acne often improves after exposure to sunlight, and this has led to the development of laser and other light therapies resulting in the overall ease of treatment, with minimal adverse effects. A variety of light and laser devices has been used for the treatment of acne, including the potassium titanyl phosphate laser, the 585- and 595-nm pulsed dye lasers, the 1450-nm diode laser, radiofrequency devices, intense pulsed light sources, and photodynamic therapy using 5-aminolevulinic acid and indocyanine green. These devices are thought to target the underlying pathogenic factors such as propionibacterium acnes colonization, increased sebaceous gland activity, and the cutaneous inflammatory response. In this article, we review the current status of light- and laser-based treatment of acne.

Hormone therapy in acne.

Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

Efficacy of red light alone and methyl-aminolaevulinate-photodynamic therapy for the treatment of mild and moderate facial acne.

BACKGROUND: Photodynamic therapy (PDT) has been shown to be an effective alternative for acne. However, there is little information comparing the efficacy of red light alone and methyl aminolaevulinate (MAL)-PDT. AIMS: To compare the efficacy and tolerability of red light alone and MAL-PDT in patients with mild to moderate facial acne. METHODS: Thirty six patients with mild to moderate acne were enrolled. Eighteen patients recieved MAL-PDT and 18 received red light alone in two sessions, 2 weeks apart. Acne grade and lesion counts were assessed by blinded evaluators at baseline, 2, 4 and 10 weeks. RESULTS: At week 2, clinical improvement from acne grade II-IV to 0-I was observed in 82.3% of MAL-PDT group and 14.2% of red light alone group. Red light alone group had a gradual clinical improvement over time with a 77% response at week 10. In contrast, MAL-PDT group had a rapid clinical improvement with total response at week 10. Both treatments were significantly effective for improving acne lesions. However, MAL-PDT group had a greater response (P < 0.001). Histologically, decreased amounts of sebocytes and lipids along with atrophic sebaceous glands were observed after MAL-PDT. CONCLUSION: MAL-PDT has a quicker onset of action with a higher response than red light alone. MAL-PDT may induce a reduction in the size of the sebaceous glands and then long-term acne remission.

Erythema nodosum leprosum associated with minocycline.

Erythema nodosum leprosum is defined by the appearance of tender skin nodules, which can be accompanied by fever, joint pain, neuritis, edema, malaise and/or lymphadenopathy. The authors describe the case of a 19-year-old Angolan black woman, resident in Portugal for the last 10 years, diagnosed with Hansen's disease at the age of 12, irregular with follow-up and non-compliant with treatment. She was referred to our clinic with painful nodules and pustules on the upper limbs, diffuse facial infiltration with pustules and fever, after initiating minocycline with the intention of treating acne. Diagnosis of erythema nodosum leprosum was confirmed by the presence of acid-fast bacilli in the skin smear and also in skin biopsy. Minocycline was suspended and the patient was treated with systemic steroids, with prompt clinical improvement. Our case is reported to alert clinicians to this unusual presentation of erythema nodosum leprosum in a patient treated with highly bactericidal drugs that were not intended to treat Hansen's disease.

Efficacy and safety of a nano-emulsion gel formulation of adapalene 0.1% and clindamycin 1% combination in acne vulgaris: a randomized, open label, active-controlled, multicentric, phase IV clinical trial.

BACKGROUND: Acne vulgaris is a very common skin disease with a significant detrimental effect on the quality of life of the patients. AIMS: To assess the comparative efficacy and safety of a nano-emulsion gel formulation of adapalene and clindamycin combination with its conventional formulation in the treatment of acne vulgaris of the face. It was a prospective, randomized, open label, active-controlled, multicentric, clinical trial. METHODS: Eligible patients suffering from acne vulgaris of the face were randomized to receive once-daily treatment with a nano-emulsion gel or conventional gel formulation of adapalene 0.1% and clindamycin (as phosphate) 1% combination for 12 weeks. Total, inflammatory and noninflammatory lesion counts, with grading of acne severity were carried out on a monthly basis. Safety assessments were done to determine the comparative local and systemic tolerability. Two-tailed significance testing was carried out with appropriate statistical tests, and P-values < 0.05 were considered as significant. RESULTS: 209/212 patients enrolled in the study were eligible for efficacy and safety assessments in both nano-emulsion gel (118/119 patients) and conventional gel (91/93 patients) groups. Significantly better reductions in total (79.7% vs. 62.7%), inflammatory (88.7% vs. 71.4%) and noninflammatory (74.9% vs. 58.4%) lesions were reported with the nano-emulsion gel as compared to the conventional gel (P < 0.001 for all). Mean acne severity score also reduced significantly more with the nano-emulsion formulation (1.9 ± 0.9 vs. 1.4 ± 1.0; P < 0.001) than the comparator. Significantly lower incidence and lesser intensity of adverse events like local irritation (4.2% vs. 19.8%; P < 0.05) and erythema (0.8% vs. 9.9%; P < 0.05) were recorded with the nano-emulsion gel. CONCLUSIONS: The nano-emulsion gel formulation of adapalene and clindamycin combination appears to be more efficacious and better tolerated than the conventional formulation for the treatment of acne vulgaris in Indian patients. Further studies can elucidate the comparative treatment benefits of this nano-emulsion gel formulation.

Oral isotretinoin in different dose regimens for acne vulgaris: a randomized comparative trial.

BACKGROUND: Oral isotretinoin is recommended for severe nodulocystic acne in the doses of 1-2 mg/kg/day which is usually associated with higher incidence of adverse effects. To reduce the incidence of side-effects and to make it more cost-effective, the lower dose regimen of isotretinoin has been used. AIM: To compare the efficacy and tolerability of oral isotretinoin in daily, alternate, pulse and low-dose regimens in acne of all types and also to assess whether it can be used for mild and moderate acne also. METHODS: One hundred and twenty patients with acne were randomized into four different treatment regimens each consisting of 30 patients. Group A was prescribed isotretinoin 1 mg/kg/day, Group B 1 mg/kg alternate day, Group C 1 mg/kg/day for one week/four weeks and Group D 20 mg every alternate day for 16 weeks. Patients were further followed for eight weeks to see any relapse. Side-effects were also recorded. RESULTS: Though the daily high dose treatment Group A performed better initially at eight weeks, at the end of therapy at 16 weeks results were comparable in Group A , B and D. Patients with severe acne did better in Group A than in Group B, C and D. Patients with mild acne had almost similar results in all the groups while patients with moderate acne did better in Group A, B and D. Frequency and severity of treatment-related side-effects were significantly higher in treatment Group A as compared to Group B, C and D. CONCLUSION: We conclude that for severe acne either conventional high doses of isotretinoin may be used or we can give conventional high dose for initial eight weeks and later maintain on low doses. Use of isotretinoin should be considered in mild to moderate acne also, in low doses; 20 mg, alternate day seems to be an effective and safe treatment option in such cases.

Efficacy of low-dose isotretinoin in acne vulgaris.

Low-dose isotretinoin (0.5 mg/kg/day) is a mode of therapy for mild to moderate grades of acne. We analyzed the various trials of this mode of therapy with or without combination with topical agents. We also statistically analyzed the results, efficacy and relapse rates of standard therapy in comparison with the low-dose therapy. Our analysis of the data revealed that the efficacy and relapse rates of low-dose isotretinoin in mild to moderate grades of acne is comparable with the standard regimen (1 mg/kg/day), which is given in the severe grade of acne vulgaris. Thus, the grade of acne vulgaris should dictate the dose of administration of isotretinoin and the standard dose of 1 mg/kg/day is an unnecessary overtreatment for mild to moderate grades of acne.

An evaluation of dapsone gel 5% in the treatment of acne vulgaris.

BACKGROUND: Oral dapsone has been available for over 60 years. Its first clinical use was discovered in 1945, when it was found to be efficacious in inhibiting the progression of leprosy. The combined antibacterial and anti-inflammatory pharmacologic activities of dapsone have made it a widely investigated drug, particularly for use in refractory and unusual dermatologic conditions. However, the possibility of significant hematological side effects, even at low doses, has limited its use. Currently, oral dapsone has FDA approval for the treatment of leprosy and dermatitis herpetiformis. The potential of oral dapsone to treat acne vulgaris is well established, but the risks of serious side effects have made it an undesirable drug for use in the relatively healthy acne population. Recently, a topical formulation of dapsone (Aczone, Allergan, Inc., Irvine, CA, USA) has been approved by the FDA for the treatment of acne vulgaris. OBJECTIVE/METHODS: The aims of this study were to review the published literature on dapsone pharmacology and pharmacokinetics, and to evaluate the gel's efficacy and safety in treating acne vulgaris, and finally to provide personal insight into its future as a topical agent for acne vulgaris. RESULTS/CONCLUSIONS: Clinical studies indicate dapsone gel 5% is effective in treating mild to moderately severe acne. It is well tolerated, with pharmacokinetic evidence indicating topical dosing in comparison to oral administration significantly reduces systemic concentrations of the drug, and therefore risk of serious side effects. Data suggests that dapsone gel 5% has the potential to become an established topical drug for the treatment of acne vulgaris. However, studies comparing the clinical effectiveness of the dapsone gel 5% to other available topical antiacne drugs are needed as are studies accessing its usefulness and safety when combined with other acne pharmaceuticals.

Clindamycin lotion alone versus combination lotion of clindamycin phosphate plus tretinoin versus combination lotion of clindamycin phosphate plus salicylic acid in the topical treatment of mild to moderate acne vulgaris: a randomized control trial.

BACKGROUND: Acne vulgaris is a common skin disease that affects 85% to 100% of people at some time during their lives. It is characterized by noninflammatory follicular papules or comedones and by inflammatory papules, pustules, and nodules in its more severe forms. AIMS: To compare the efficacy of combination treatment of clindamycin+salicylic acid, versus clindamycin+tretinoin versus clindamycin alone in the treatment of the mild-to-moderate acne vulgaris. METHODS: This was a single-blinded, randomized clinical trial.Forty-two female patients (age range: 15-25 years) with mild-to-moderate acne vulgaris were selected randomly and subsequently randomized to 3 groups. Group A patients were treated with 1% clindamycin lotion (C lotion) twice daily. Group B patients were treated with 1% clindamycin+0.025% tretinoin lotion once nightly (CT lotion). Group C patients were treated with 1% clindamycin+2% salicylic acid lotion twice daily (CS lotion) for 12 weeks. For comparison of efficacy of these treatments, and regarding the skewed distribution of the data, Kruskal-Wallis Test and Mann-Whitney U test were used. SPSS software was used for statistical analysis. RESULTS: There was a significant difference between 3 types of treatment in the respect of the total lesion count (TLC) improvement (P = 0.039). The efficacy of treatment on Acne Severity Index (ASI) was maximum for CS lotion (81.80% reduction in ASI). CT lotion reduced ASI by as much as 73.73% during 12 weeks of treatment. The efficacy of C lotion was calculated to be 37.87% in the reduction of ASI. CONCLUSIONS: Our data suggested that the efficacy of CS lotion was significantly more than C lotion with respect to the TLC and ASI, although there was no significant difference between CS and CT lotion.