Low dose isotretinoin combined with tretinoin is effective to correct abnormalities of acne

Background: Isotretinoin is well known in the therapy of acne papulopustulosa and acne conglobata. No study has investigated the pathophysiological changes of the skin of acne patients, especially when low dose oral isotretinoin is given in combination with topical tretinoin. Patients and methods: 28 patients were treated for 6 months with oral isotretinoin. In the acne conglobata group (A – C) patients were treated with 10 mg (Group A) or 20 mg isotretinoin (Groups B, C) in combination with topical 0.05 % tretinoin cream. Group C was treated the first 2 weeks with 0.05 % betamethasone valerate cream instead of tretinoin cream. In the acne papulopustulosa group, the patients received 0.5 mg isotretinoin/kg bodyweight and 0.05 % tretinoin cream, either alone (Group E), or with oral methylprednisolone during induction (Group D). Results: Acne conglobata – A reduction of inflammatory lesion by 87 – 94 % and of non‐inflammatory lesions by 81 – 88 % was achieved (Groups A – C). A reduction of sebaceous gland size by 35 – 58 %, sebum production by 90 – 95 %, follicular keratinization by 55 – 70 % and Propionibacteria by 33 – 73 % was seen (Groups B and C better than Group A). In Group A the amount of lipids was only reduced by 6 %, in Group B by 35 % and in Group C by 40 %. Acne papulopustulosa – Sebum excretion rate and follicular keratinization were reduced in Group D by 89 % and 50 % respectively, with isotretinoin alone by 94 % and 53 %. The amount of lipids was reduced in Group D by 40 % and in Group E by 21 %. Conclusions: Because of the efficacy and cost‐benefit relationship of isotretinoin in the treatment of acne compared to other therapeutic approaches, further use low dose isotretinoin in the described settings seems to justified.     

Fractional carbon dioxide (CO2) laser combined with topical tretinoin for the treatment of different forms of cystic acne

Nodulocystic acne is prone to scarring and difficult to treat with treatments other than oral isotretinoin. The aim of this article is to discuss the role of a single session of a fractional carbon dioxide (CO₂) laser combined with a topical treatment with a tretinoin and antibiotic gel for a month as a successful treatment to improve nodulocystic acne and chronic microcystic acne. Two cases were involved: the first with nodulocystic acne lesions that persisted after oral retinoids and the second with chronic microcystic acne resistant to topical treatments. After only one session of treatment with the CO₂ laser and the topical treatment, a complete healing of the nodulocystic acne lesions was observed with minimal secondary effects. The microcystic acne showed great improvement. No other topical or oral treatment was needed. This treatment could be a safe and effective treatment for nodulocystic acne lesions and microcystic acne when other treatments fail. More studies should be performed to confirm our results.     

Pyogenic granulomas following topical application of tretinoin

Topical tretinoin is used in the treatment of acne and other dermatoses. The most common side-effects are itching, dryness and reddening of the skin. We report an additional cutaneous reaction, which occurred in patients using topical tretinoin. Pyogenic granulomas developed in two patients with acne and in one with dermatofibroma following application of tretinoin. The granulomas grew on the lesions after 2-3 weeks of therapy initiation. All patients were men and the granulomas developed in their trunk. The lesions resolved when topical tretinoin was ceased. Although the number of patients reported is too small to estimate the true incidence of this reaction, it is likely that dermatologists will encounter similar reactions in patients treated with topical tretinoin for acne or other reasons.     

Pyogenic granuloma-like lesions in a patient using topical tretinoin

A 16-year-old male developed numerous pyogenic granuloma like-lesions across his neck, chest and back after 6 weeks isotretinoin therapy for cystic acne. The isotretinoin was ceased and he was commenced on oral steroids. After 6 weeks, the lesions were almost completely healed. However, due to worsening comedonal acne, the patient was commenced on topical tretinoin cream 0.03% twice daily to his chest. He was reviewed 2 weeks later and, surprisingly, 2 new pyogenic granuloma-like lesions had developed on his chest. These lesions persisted until the topical tretinoin was ceased 3 months later.     

Topical treatment in acne: current status and future aspects

During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was adapalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance. Unfortunately, over the past years topical retinoids have been less used in inflammatory acne than they should be, taking the the mechanisms of action into account. Topical antimicrobials, in particular topical antibiotics, should be used less often than in the past and only for short periods to avoid the development of resistances. It seems better to combine those agents with topical retinoids, with BPO or with azelaic acid to enhance the efficacy and slow down the development of resistance. BPO is still the gold standard for papular-pustular acne of mild-to-moderate type in concentrations of 2-5%. Azelaic acid is an alternative with efficacy on the comedo and is antibacterial without development of resistances. Finally, the physical removal by electrocautery or CO(2) laser of multiple densely packed closed comedones, macrocomedones and microcysts is necessary to enhance the efficacy of topical comedolytic agents and to speed up the therapeutic results. Photodynamic therapy has not yet been proven efficacious in controlled studies. Blue and red light can probably be used in association with local agents but enhancement of the irritative potential of topical and systemic agents has to be considered.     

Combined topical treatment of acne with erythromycin and tretinoin

Vitamin A acid is the most effective comedolytic agent in the therapy of acne vulgaris. Antibiotics are suitable for the treatment of inflammatory lesions (papulo-pustules). Even topically applied, some antibiotics show a sufficient anti-inflammatory effect. Above all, erythromycin is reliable in the topical treatment of acne. Combined therapy with both topical tretinoin and erythromycin is more effective than either alone. During the first weeks of treatment, tretinoin leads to temporary deterioration of the disease, which can mostly be avoided by the anti-inflammatory effect of erythromycin simultaneously applied.     

Akne-Mycyna in the local treatment of acne

Akne-Mycyna, a new preparation for external treatment of acne containing 1% erythromycin, was used in 30 cases of acne: 12 cases of papulo-pustolous acne, 13 with pustulous acne, 5 with acne conglobata. The age of the patients ranged from 16 to 27 years, the mean duration of acne was 3.5 years. Selected lesions were smeared with Akne-Mycyna twice daily, mostly on one side of the face; symmetrical lesions were treated by conventional external methods. In the light of the study it is concluded that Akne-Mycyna is a very effective preparation for external treatment of papulo-pustulous acne and in milder cases of pustulous acne, with the duration of treatment at least 3 weeks. In deep forms of acne, particularly acne conglobata, Akne-Mycyna may be a valuable supplementation of systemic treatment.     

Scanning electron microscopic study of tretinoin (vitamin A acid) acne therapy.

Structural differences between untreated and tretinoin treated acne, uniquely evident with the scanning electron microscope, provide insight into the disease and its response to the drug. Early tretinoin therapy is characterized by the appearance of loosely adherent, parakeratotic cells which account for comedo expulsion and a disrupted skin surface. Persistence of the follicular and comedonal alterations account for the prophylactic value of long-term therapy. Meanwhile, the structure of the stratum corneum returns toward normal, with the clinical accommodation to the topical tretinoin.     

Topical management of acne scars: The uncharted terrain

Introduction

Scarring is a common but difficult to manage consequence of acne vulgaris. The intricate balance between the degradation of collagen and its inhibition is disturbed during the formation of acne scars. We mostly rely on invasive, non-topical modalities for the treatment of acne scars which may not be indicated in all patients. There is also a need for maintainence therapies after these procedures.

Review

The topical agents can be utilized as individual therapy, in combination with other modalities or delivered through assisted technology like iontophoresis. Retinoids have long been tried to prevent and treat acne scars. Tacrolimus and glycolic acid are among the newer sole agents that have been explored. Ablative lasers like Er:YAG, CO2 and Microneedling are being used in combination with topical agents like silicone gel, plasma gel, lyophilized growth factors, platelet rich plasma, insulin, and mesenchymal stem cells. These procedures not only increase the permeability of the topical agents but also concomitantly improve acne scars. Iontophoresis has proven beneficial in increasing the delivery of topical estriol and tretinoin.

Conclusion

There is lack of evidence to support the widespread use of these topical agents, and therefore, there is need for further well designed studies.     

Comparative study of ablative fractional photothermolysis versus topical retinoid cream in the treatment of idiopathic guttate hypomelanosis

Background: Despite various treatments attempts, no prospective studies have compared the different therapeutic modalities for treatment of idiopathic guttate hypomelanosis (IGH). This study aimed to compare the efficacy of CO₂ fractional laser (CO?FL), Er:YAG fractional laser (EYFL), and 0.025% topical tretinoin for treating IGH. Materials and Methods: A total of 122 lesions were analyzed from 18 patients (mean age, 70.00 ± 20.00 years). Treatment outcome evaluations included the visual analog scale (VAS) to assess lesion severity, investigator’s global assessment (IGA) to assess the extent of improvement, and patient’s satisfaction score (PSS). Results: Among the 122 lesions, 42, 40, and 40 were assigned to the CO?FL, EYFL, and topical tretinoin treatment groups, respectively. The VAS score was significantly improved after the second treatment. CO?FL and EYFL therapy had superior treatment efficacy compared to topical tretinoin (p < 0.01 in VAS, IGA, and PSS). There was no significant difference between the two types of fractional lasers. Conclusions: Ablative fractional laser (AFL) was an effective treatment with a relatively short treatment time without serious adverse events. We recommended AFL to treat IGH as an active treatment strategy.     

Management of acne vulgaris: an evidence‐based update

This review summarizes clinically important findings from 3 systematic reviews, 1 updated guideline and a selection from the 62 randomized controlled trials (RCTs) published between February 2007 and January 2009 on the topic of acne vulgaris. Low glycaemic‐load diets might reduce acne severity but this remains unproven. Written patient information leaflets have not been surpassed by other communication methods. New combination topical treatments have not shown convincing advantages over current combination products such as clindamycin/benzoyl peroxide. Topical dapsone is superior to placebo but has yet to be compared with standard topical treatments. Long‐term topical tretinoin to prevent nonmelanoma skin cancer in elderly men was associated with higher all‐cause mortality, but there is currently no evidence of increased mortality for topical retinoid use when treating acne. All oral tetracyclines have similar efficacy, yet minocycline is the most costly. Oral isotretinoin monotherapy remains the gold‐standard treatment for severe acne. Flutamide plus the oral contraceptive pill is beneficial for acne associated with polycystic ovary syndrome. Photodynamic therapy, phototherapy and laser therapy cannot be recommended universally for acne until minimal postinflammatory pigmentation and longer‐term benefit can be shown, especially with current high costs. Development of non‐antibiotic therapies is preferable to minimize the risk of community antibiotic resistance. Future trials should use active comparators at optimum doses and avoid noninferiority comparisons unless appropriately powered. Trials need to shift from using multiple, unvalidated outcome measures to including patient‐reported and quality‐of‐life outcomes, and all trials should be registered on a public clinical‐trials database.     

Comparison of the stability of topical isotretinoin and topical tretinoin and their efficacy in acne

After 4 hours of exposure to incandescent light, 80% of 0.05% topical isotretinoin and 60% of 0.05% topical tretinoin preparations remained in their original form. In contrast, after 2 hours of exposure to fluorescent light only 25% of topical tretinoin and possibly 60% of topical isotretinoin remained in their original forms. Longer exposure to fluorescent light did not result in further breakdown, and the final breakdown of both preparations was similar. A 12-week, double-blind clinical trial comparing isotretinoin (0.05%) with tretinoin (0.05%) applied topically to patients with moderate acne was carried out. Both preparations caused significant reductions in papules and pustules. However, neither treatment was significantly superior to the other in the reduction of acne lesions. This may be because both preparations are rapidly broken down to similar products when exposed to fluorescent light.     

13-cis-retinoic acid--an effective therapy for acne conglobata

46 patients suffering from severe forms of acne conglobata were treated with 13-cis-retinoic acid. The initial dosages of 40, 60 or 80 mg of 13-cis-retinoic acid per day were adapted according to the success of therapy or to severe side effects. Pustules and papules responded promptly followed by the reduction of nodes and cysts. The lesions of the face responded quicker than those of chest and back. After 6 months of therapy, the overall reduction of all acne lesions was 94.4% for the face and 85.8% for chest and back. Thus, the out-standing efficacy of 13-cis-retinoic acid in severe forms of acne conglobata has been documented once more.     

1450nm激光联合外用药物治疗中度寻常性痤疮疗效观察

目的:评价1450nm激光联合外用药物治疗中度寻常性痤疮的疗效和安全性。方法:采用随机对照的临床试验。A组采用1450nm激光治疗,同时外用1%克林霉素磷酸酯溶液剂和0.025%维A酸乳膏治疗,B组口服维胺酯联合外用药物治疗同A组,C组单纯使用外用药物治疗。治疗2、4和6周末观察疗效及不良反应。结果:A组疗效与B组疗效无显著差异,A、B组与C组疗效均有显著差异。结论:1450nm激光联合外用药治疗中度寻常性痤疮疗效较好,与口服维胺酯联合外用药治疗疗效相当,且无明显不良反应。     

Medikamentöse Therapie der Akne

Acne is treated according to the clinical picture and the pathophysiologically relevant mechanisms, such as seborrhea, follicular hyperkeratosis, P. acnes colonisation,and inflammation. In mild forms of acne, topical therapy is most appropriate. Comedonal acne can be treated with topical retinoids; papulopustular acne with a combination of retinoids and topical antimicrobial substances (benzoyl peroxide, antibiotics, or azelaic acid). Moderate forms or those with extrafacial involvement can be treated with oral antibiotics combined with topical retinoids or benzoyl peroxide. Acne conglobata and other severe manifestations are treated with oral isotretinoin. Women are also treated with oral contraceptives containing anti-androgenic progestins. If inflammation is prominent, initial short term treatment with oral glucocorticoids is helpful. Second-line agents include oral zinc or dapsone. Following successful treatment, topical retinoids are suitable for maintenance therapy.     

Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne.

BACKGROUND/AIMS: The primary aim of the study was to establish the clinical efficacy and safety of a combined treatment consisting of topical 20% azelaic acid (AA) cream and the oral antibiotic minocycline in the therapy of severe inflammatory acne (nodular papulopustular acne and acne conglobata) in a comparison with oral isotretinoin therapy. The secondary aim was to establish the value of AA cream as maintenance therapy in the prevention of recurrent acne. METHODS: This open-label but randomised study involved 85 patients with nodular papulopustular acne or acne conglobata (Leeds grading scale > 4) who were treated for 6 months. In an immediately subsequent 3-month second phase, eligible patients from the initial combination group used the AA cream as maintenance therapy, while the eligible patients from the isotretinoin group served as untreated control. RESULTS: A 6-month course of treatment with topical 20% AA cream plus oral minocycline in 50 patients proved to be effective in nodular forms of acne (median reduction of facial comedones: 70%; of papules and pustules: 88%; of deep inflammatory acne lesions: 100%). Overall, the combined treatment was not quite as effective as treatment with oral isotretinoin (35 patients; reduction of comedones: 83%; of papules and pustules: 97%; of deep inflammatory acne lesions: 100%). In the 3-month maintenance therapy phase, about half of the patients who received AA monotherapy maintained the very good facial result achieved by the end of phase I. A similar rate was found in the patients of the isotretinoin group, who received no further active acne treatment. In the other 50% of patients, differences existed between the groups as regards the degree of deterioration: Marked deterioration occurred more frequently under AA treatment, while only slight deterioration was more frequent in the isotretinoin group. The combination was tolerated much better than isotretinoin. The incidence of local side effects observed under the combination of AA and minocycline (36.5%, mainly transient burning and itching of mild or moderate intensity) was considerably lower than that seen with isotretinoin (65.7%). The rate of local side effects of marked intensity observed under the combination, i.e. 6%, was well within the range of 5-10% previously reported for AA. The incidence of systemic side effects was lower (8%, mainly gastrointestinal symptoms) under the combined therapy than under isotretinoin (14.3%). CONCLUSION: The combination of topical 20% AA cream and oral minocycline is an highly effective treatment in severe forms of acne. It is better tolerated and associated with fewer risks than oral isotretinoin - in particular, there is no risk of teratogenicity. The combination can be regarded as a valuable alternative in patients for whom isotretinoin is not indicated, who do not wish to use or can not tolerate isotretinoin therapy and particularly in female acne patients of child-bearing potential. Topical 20% AA cream can be used successfully as maintenance therapy to prolong the recurrence-free interval.     

Acne: systemic treatment

Acne vulgaris is a disease affecting mostly adolescents and young adults that, when severe, has the potential to result in scarring and permanent disfigurement. Systemic treatment is necessary to prevent significant psychological and social impairment in these patients.(1) Significant inflammatory and nodulocystic acne is usually recalcitrant to topical treatment, whereas uncommon acne variants, such as acne fulminans, pyoderma faciale, and acne conglobata, need to be promptly and effectively controlled. In all of these circumstances, systemic agents are indispensable. The choices include oral antibiotics, isotretinoin, and hormonal treatment (Table 1).     

Acne fulminans: investigation of acute febrile ulcerative acne.

Eight cases of acne fulminans (acute febrile ulcerative acne) are compared with 13 previously reported cases. This rare disorder of male teenage patients is characterized by the sudden appearance of highly inflammatory, tender, ulcerative and crusted lesions on the back, chest, and face: it is one of the most scarring acute dermatologic disorders of young patients. At the onset of the disease, all patients showed febrile temperatures and marked leukocytosis; other systemic symptoms occurred with varying frequency. Polyarthralgia was noted in half of our series. Investigations of potential trigger mechanisms (eg, septisemia due to Corynebacterium acnes, immunologic defects, altered polymorphonuclear leukocyte function, Shwartzman phenomenon) did not yield any clues regarding the pathogenesis of this disease. Clinical and laboratory findings suggest that acne fulminans is not directly related to acne conglobata.     

Topical retinoids in acne – an evidence‐based overview

Topical retinoids are important tools in the management of acne because they act against comedones and microcomedones and have direct anti‐inflammatory effects. The substances approved for acne treatment comprise tretinoin (all‐trans‐retinoic acid),isotretinoin (13‐cis retinoic acid) as well as the synthetic third‐generation polyaromatic retinoids adapalene and tazarotene,the latter being approved for acne treatment in the US only.Retinaldehyde is used in cosmetic preparations against acne. All topical retinoids are effective as single agents in mild to moderate acne but differ in efficacy and tolerability. Tazarotene 0.1% is more effective than tretinoin 0.025% or 0.1% microsphere gel or adapalene 0.1% gel or cream (EBM‐level 2c). Adapalene 0.1% is equally effective to tretinoin 0.025% or tretinoin microsphere 0.1% gel or tretinoin 0.05% cream or isotretinoin 0.05% gel (EBM‐level 2c). Adapalene 0.1% gel is significantly better tolerated than tazarotene 0.1% gel, tretinoin 0.025% and tretinoin 0.05% gel, tretinoin 0.05% cream,tretinoin microsphere 0.1% gel or isotretinoin 0.05% gel (EBM‐level 2c).The safety profile of topical retinoids differs from their systemic counterparts and is related mainly to local adverse effects, such as erythema, dry‐ness,itching and stinging.The currently available evidence justifies the use of topical retinoids in most types of acne and during maintenance treatment.     

Photodynamic therapy of acne vulgaris with topical delta-aminolaevulinic acid and incoherent light in Japanese patients

BACKGROUND: Photodynamic therapy (PDT) is useful for treatment of epidermal neoplasia but may also have a role in the treatment of inflammatory dermatoses. OBJECTIVES: To study the effect of PDT in patients with acne. METHODS: Three men and 10 women who suffered from intractable acne vulgaris were treated using PDT with topical delta-aminolaevulinic acid (ALA) and polychromatic visible light. Twenty per cent ALA in an oil-in-water emulsion was applied to the lesions for 4 h with a light-shielding dressing. The lesions were then exposed to polychromatic visible light at 600-700 nm using a halogen light source of energy intensity 17 mW cm-2 and a total energy dose of 13 J cm-2. RESULTS: All patients had apparent improvement of facial appearance and reduction of new acne lesions at 1, 3 and 6 months following PDT treatment. The adverse effects were discomfort, burning and stinging during irradiation, oedematous erythema for 3 days after PDT, epidermal exfoliation from the fourth to the 10th day, irritation and hypersensitivity to physical stimulation for 10 days after PDT, and pigmentation or erythema after epidermal exfoliation; the treated lesions returned to normal skin conditions within 1 month. CONCLUSIONS: PDT was beneficial in the treatment of acne. As a photoactivating light source, polychromatic visible light was thought to be better for use with acne patients than laser light because of its cost-effectiveness, uniform illumination and time-efficiency in treating large areas.