Systemic antibiotic therapy of acne vulgaris

Background: Inflammatory, medium to severe acne vulgaris is treated with systemic antibiotics worldwide. The rationale is an effect on Propionibacterium acnes as well as the intrinsic anti‐inflammatory properties of these antibiotics. Although there are no correlations between the number of P. acnes and the severity of the disease, associations between the degree of humoral and cellular immune responses towards P. acnes and the severity of acne have been reported. Exact data on practical use of these compounds, such as differential efficacy or side effects are unavailable.A summary of currently available studies is presented. Methods: The data of studies of systemic antibiotic therapy of acne vulgaris up to 1975, the summary of literature in English up to 1999, a systematic review of minocycline from 2002 as well as the data of randomized controlled studies published and listed in Medline thereafter were reviewed. Results: Tetracyclines [tetracycline 1 000 mg daily, doxycycline 100 (?200) mg daily, minocycline 100 (?200) mg daily, lymecycline 300 (?600) mg] and erythromycin 1 000 mg daily are significantly more effective than placebo in the systemic treatment of inflammatory acne.The data for tetracycline are best founded. Clindamycin is similarly effective. Co‐trimoxazole and trimethoprim are likely to be effective. Clear differences between the tetracyclines or between tetracycline and erythromycin cannot be ascertained. The data for the combination with topical treatments [topical benzoyl peroxide (BPO) or retinoids] suggest synergistic effects.Therefore systemic antibiotics should not be used as monotherapy. In case of similar efficacy, other criteria, such as pharmacokinetics (doxycycline, minocycline, lymecycline have longer half‐lives than tetracyclines), the rate of side‐effects (tetracycline: side effect‐rate ～4 % mild side effects; erythromycin: frequent gastrointestinal complaints; minocycline: rare, but potentially severe hypersensitivity reactions; doxycycline: dose‐dependent phototoxic reactions), the resistance rate [percentage of resistant bacteria higher with erythromycin (～ 50 %) than with tetracycline‐therapy (～ 20 %)], and the costs of therapy have to be taken into account. Conclusions: The systemic antibiotic therapy of widespread papulo‐pustular acne not amenable to a topical therapy is effective and well‐tolerated. In general therapy can be carried out for 3 months and should be combined with BPO to prevent resistance.     

Differences in phototoxic potency should be considered when tetracyclines are prescribed during summer-time. A study on doxycycline and lymecycline in human volunteers, using an objective method for recording erythema

Summary In order to test the phototoxic potency of the two tetracyclines most frequently prescribed in Sweden, a double-blind cross-over study using a double-dummy technique with doxycycline 0·1 g twice daily. lymecycline 0·6 g twice daily, and placebo, was performed in 15 healthy volunteers. Drugs were given for 3 consecutive days, and on the third day volunteers were tested with 25, 50, 75 and 100 J/cm² of artificial long-wave ultraviolet radiation (UVA), and assessed 6 h later for erythematous photoreactions. Objective readings were made using skin reflectance spectrophotometry. All three substances were tested in each individual at weekly intervals. Within 50, 75 and 100 J/cm² of UVA. lymecycline showed a slight increase in erythema compared with placebo, but this was not significant (50 and 100 J/cm²), or was of low significance (75 J/cm²). However, with the same doses, doxycycline showed a substantial increase in erythema compared with placebo, which was highly significant. We conclude that doxycycline has a higher phototoxic potency than lymecycline, and this is in agreement with earlier in vitro experimental data. We recommend that therapy with doxycycline is avoided during summer-time, and during holidays in a sunny climate.     

Association or lack of association between tetracycline class antibiotics used for acne vulgaris and lupus erythematosus

BACKGROUND: Previous studies have associated tetracyclines and, perhaps more specifically, minocycline use for the treatment of acne with onset of drug-induced lupus erythematosus (LE). OBJECTIVES: To determine the frequency of LE among those with acne who used antibiotics from the tetracycline class of antibiotics. METHODS: A retrospective cohort study of individuals aged 15-35 years with acne within the practices of the general practice physicians in the U.K. who participate in The Health Information Network (THIN). Our outcome measure was physician reports of LE. RESULTS: We identified 97 694 subjects with acne who were followed for about 520 000 person-years. They were on average about 22 years old and 57.5% were female. Minocycline exposure was noted in 24.8% of our subjects, doxycycline exposure in 15.6%, other tetracyclines in 42.3%, and 17.3% had not received a tetracycline antibiotic. The overall hazard ratio for the association of minocycline to LE was 2.64 (95% confidence interval 1.51-4.66) and when adjusted for age and gender was 3.11 (1.77-5.48). Those affected were often treated for LE. No association was noted for doxycycline and the other tetracyclines. CONCLUSIONS: The use of minocycline and not the other tetracyclines is associated with LE. LE as reported in THIN often required systemic therapy. Overall, the event is uncommon but the risk and benefit of minocycline therapy must be carefully considered.     

Second-generation tetracyclines, a dermatologic overview: clinical uses and pharmacology.

Tetracycline and its derivatives are frequently used in the treatment of acne, soft tissue bacterial infections, Lyme disease (borreliosis), chlamydial-infections, and respiratory tract infections. Several pharmacologic and microbiological properties of these antibiotics make them particularly suitable for such uses. First-generation tetracyclines have long been in use; however, the second-generation tetracyclines minocycline, doxycycline hyclate, and doxycycline monohydrate have also become widely prescribed, and can offer advantages to the dermatologist over tetracycline. This paper reviews the important pharmacologic and microbiological characteristics of these three commonly used second-generation tetracyclines, and their clinical applications in dermatology.     

Lymecycline in the treatment of acne: an efficacious,safe and cost-effective alternative to minocycline

A comparison of efficacy, safety and cost-effectiveness of lymecycline and minocycline in the treatment of acne vulgaris has been addressed. This was a multicenter, randomized, investigator-masked, parallel group trial involving patients with moderate to moderately severe acne vulgaris, receiving either lymecycline or minocycline for 12 weeks. Efficacy and safety evaluation was performed at baseline and at weeks 4, 8, and 12 and completed by a pharmacoeconomic analysis including week 12 data. One hundred and thirty-six patients were enrolled. At week 12, the mean percent reductions in inflammatory count were 63 % and 65 %, and for total lesions counts 58 % and 56 % for lymecycline and for minocycline respectively. Median percent reduction in non-inflammatory count were 54 % and 47 % for lymecycline and for minocycline respectively. Eighty-seven per cent of all patients tolerated the treatments well. Treatment with lymecycline was found to be 4 times more cost-effective than with minocycline. Results showed that lymecycline has a comparable efficacy and safety profile to minocycline while being 4 times more cost-effective.     

Tetracycline/doxycycline-induced cutaneous depressed pigmentation

Pigmentary disorders are recognized adverse effects of tetracyclines. Unlike minocycline, which occasionally causes black pigmentation of a variety of tissues, tetracycline itself or doxycycline is rarely attributed to the pigmentation of skin. Herein, we report the first case report of blue-black discoloration developed within depressed acne scars following tetracycline/doxycycline therapy for acne.     

Minocycline in Acne Vulgaris

Minocycline is a semi-synthetic, second-generation tetracycline. It was introduced in 1972 and has both antibacterial and anti-inflammatory properties. Minocycline is used for a variety of infectious diseases and in acne. Even today, new indications beyond the antibacterial indications are being investigated such as its use in neurologic diseases. Formerly, minocycline was thought to have a superior efficacy in the treatment of inflammatory acne, especially with respect to antibacterial-resistant Propionibacterium acnes. A thorough review of the literature, however, shows that minocycline is not more effective in acne than other tetracyclines. Compared with first-generation tetracyclines, minocycline has a better pharmacokinetic profile, and compared with doxycycline it is not phototoxic. However, minocycline has an increased risk of severe adverse effects compared with other tetracyclines. It may induce hypersensitivity reactions affecting the liver, lung, kidneys, or multiple organs (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS] syndrome) in the first weeks of treatment and, with long-term treatment, may cause autoimmune reactions (systemic lupus erythematosus, autoimmune hepatitis). In addition, CNS symptoms, such as dizziness, are more frequent compared with other tetracyclines. Long-term treatment may induce hyperpigmentation of the skin or other organs. Resistance of P. acnes to minocycline also occurs, dependent on the prescribing behavior. Considering the aspects of efficacy, its adverse effect profile, resistance, price, and alternatives, minocycline is no longer considered the first-line antibacterial in the treatment of acne.     

Cutaneous hyperpigmentation induced by doxycycline: histochemical and ultrastructural examination,laser microprobe mass analysis,and cathodoluminescence

Skin hyperpigmentation induced by minocycline is a well-recognized side effect of minocycline but has rarely been reported for other tetracyclines. Based on a previously reported unusual case of chronic doxycycline abuse in a psychotic patient, we have investigated the nature of the observed pigment changes in the same patient. Histopathologic investigation of lesional skin by light microscopy disclosed hyperpigmentation of the basal keratinocytes and pigment-laden histiocytes in the dermis and subcutaneous fat. Only the pigment in the histiocytes of the upper dermis was reactive for Fontana Masson stain and could be bleached by hydrogen peroxide. The other histiocytes contained iron and calcium deposits as shown by von Kossa and Perls staining as well as by laser microprobe mass analysis. Ultrastructurally, these histiocytes contained amorphous material within the cytoplasm and stored in lysosomal structures. Comparative cathodoluminescence disclosed the presence of doxycycline in affected skin by means of overlapping emission spectra between the patient's skin and pure doxycycline. Taken together, the histomorphologic and ultrastructural changes induced by doxycycline shared several features with cutaneous hyperpigmentation caused by minocycline. Our biophysical findings further suggest a direct deposition of doxycycline, probably chelated with iron and/or calcium, within the lesional skin. Based on the presented unique case and the reviewed literature, only suprapharmacologic doses of doxycycline may be sufficient to cause such pigment changes.     

Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy

BACKGROUND: Some antibiotics represent a mainstay in acne treatment. However, studies comparing their efficacies are rare. AIM: To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages. METHOD: Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks. Evaluations were made at the screening visit and at five on-treatment visits. They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings. RESULTS: Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules. By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments. There were less live and more dead bacteria. CONCLUSION: In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg.     

Prurigo pigmentosa: report of two cases in the United States and review of the literature

Prurigo pigmentosa is a rare inflammatory skin disease of unknown etiology presenting as a pruritic truncal eruption of reticulated and symmetric macules and papules with the predilection for young Japanese females. Although cases of PP are increasingly reported in the non-Japanese literature, dermatologists may be unfamiliar with this entity. Here we report a Caucasian American female and a Chinese American female with PP and a discussion of the literature. The treatments of choice for prurigo pigmentosa are tetracyclines such as doxycycline and minocycline, as well as dapsone. The prognosis is excellent.     

The use of lymecycline in the treatment of moderate to severe acne vulgaris: a comparison of the efficacy and safety of two dosing regimens

We compared the efficacy and safety of lymecycline 300 mg od vs lymecycline 150 mg bid or placebo in the treatment of moderate to severe acne. 271 patients received either oral lymecycline 300 mg od + placebo od, lymecycline 150 mg bid, or placebo bid, for 12 weeks. Reduction in inflammatory lesion counts at week 12 was the primary efficacy variable (global improvement was a primary efficacy parameter vs placebo) and safety was assessed by adverse events. Lymecycline 300 mg od was non-inferior to lymecycline 150 mg bid at all time points and superior to placebo throughout the study. Drug-related adverse events were similar for all treatment groups. Lymecycline 300 mg od is as effective and safe as lymecycline 150 mg bid in the treatment of moderate to severe acne. This new, once daily formulation could potentially contribute towards improved compliance rates with oral tetracyclines.     

The use of tetracyclines for the treatment of sarcoidosis

BACKGROUND: To evaluate the safety and efficacy of minocycline in the treatment of sarcoidosis, a nonrandomized, open study was performed in patients with cutaneous sarcoidosis. OBSERVATIONS: Twelve patients with cutaneous sarcoidosis were treated with minocycline, 200 mg/d, for a median duration of 12 months. Three patients had extracutaneous lesions at the time of the study. The median follow-up was 26 months. A clinical response was observed in 10 patients, consisting of complete responses in 8 patients and partial responses in 2 patients. A progression of skin lesions was observed in 1 patient, and lesions remained stable in another patient. Adverse effects were minimal, except in 1 patient, who developed hypersensitivity syndrome. A slight hyperpigmentation occurred in 2 patients at the site of previous lesions, which completely disappeared after minocycline use was discontinued. A relapse of skin symptoms occurred after minocycline withdrawal in 3 patients, who further received doxycycline, 200 mg/d, allowing a complete remission of lesions. CONCLUSIONS: These results support that minocycline and doxycycline may be beneficial for the treatment of cutaneous sarcoidosis. Randomized controlled studies are warranted for the evaluation of the true efficacy of tetracyclines in these patients.     

Variability in the clinical pattern of cutaneous side‐effects of drugs with systemic symptoms: does a DRESS syndrome really exist?

OBJECTIVE: To improve the definition of the various clinical patterns of patients with drug-induced cutaneous side-effects with systemic symptoms, and their possible relationships with the triggering medication, with the ultimate goal of helping in the identification of the causal drug in difficult situations when the patient is taking several drugs. METHODS: Cases of drug-induced cutaneous side-effects associated with various systemic syndromes related to anticonvulsants (carbamazepine, phenytoin and phenobarbitone), minocycline, allopurinol, abacavir and nevirapine were collected retrospectively from the French Pharmacovigilance database (FPD) over a period of 15 years (1985-2000). The clinical patterns typical of the causative drugs were described and compared with data from the literature. RESULTS: Two hundred and sixteen patients with symptoms and signs consistent with cutaneous drug reactions with systemic symptoms were reported to the FPD during this period of time. Their pattern was similar to published data for these drugs, with fever, cutaneous eruption, hepatic abnormalities and eosinophilia being the most prominent but inconstant symptoms. There are clues suggesting that some particular lesional patterns may exist for some drugs. CONCLUSIONS: Although some trends emerge from these retrospective data, they suggest that no clear, unified outline can currently be defined for these multi-organ drug-induced reactions. Instead, a constellation of various symptoms and signs were recorded, that might be sorted in different patterns according to the causal drug, a finding that might indeed improve accurate identification of the causative drug in patients receiving several principal medications at a time. A national prospective study systematically collecting standardized data is required better to define the outlines of these severe adverse drug reactions and to evaluate prognostic data.     

Tetracycline-resistant propionibacteria from acne patients are cross-resistant to doxycycline, but sensitive to minocycline

Antibiotic-resistant propionibacteria are being isolated with increasing frequency from antibiotictreated acne patients. Minimum inhibitory concentrations (MICs) of three tetracyclines, extensively used in acne therapy, were determined for 46 resistant and 19 sensitive propionibacterial isolates. Sensitive strains were inhibited by ≤1 μ/ml of all three tetracyclines. For every resistant strain tested, the MIC of tetracycline exceeded that of doxycycline which, in turn, exceeded that of minocycline. The mean MIC for resistant strains was 20.61±4.56 μ/ml of tetracycline, 9.70±2.03 μ/ml of doxycycline and 1.95±0.35 μ/ml of minocyciine. In order to determine whether these strains could be inhibited by concentrations of minocycline achievable in vivo, serum levels of minocycline were determined in acne patients receiving either the recommended dose of 50 mg b.d. (20 males, 14 females), or twice this dose (21 males, 12 females). Serum levels were significantly higher (P<0.001, Student's t-test) in patients receiving 100 mg b.d. Males on 50 mg h.d. had significantly lower serum levels than females on the same dose (P<0.05. Student's t-test). For all patients, the mean serum level on high-dose minocycline was 246±0.45 μ/ml, compared with 1.38±0.30 μ/ml on the smaller dose. These results indicate that tetracycline-resistant propionibacteria should be considered clinically minocycline sensitive, if patients who harbour such strains are prescribed 100 mg b.d. The recommended dose of minocycline for treating acne, especially in male patients, should be re-assessed.     

美他环素联合新癀片治疗寻常痤疮临床观察

目的评价美他环素联合新癀片治疗中、重度寻常痤疮的疗效与安全性。方法入选患者随机分为A组、B组和C组。A组口服盐酸美他环素胶囊0.2g,2次/d;新癀片1.28g,3次/d。B组口服盐酸美他环素胶囊0.2g,2次/d。C组口服盐酸米诺环素胶囊50mg,2次/d。三组患者同时外用维胺酯维E乳膏,每晚1次。疗程均为6周。于治疗前及治疗后第1、2、4和6周时分别计数皮损,观察疗效和不良反应。结果治疗2周和4周时,A组临床疗效均明显好于其他两组,差异有统计学意义(P<0.05);治疗结束时,各组均有75%以上的患者达到了基愈或显效,A组的有效率达到了90.1%。结论美他环素联合新癀片治疗寻常痤疮起效较快,疗效较好,耐受性良好。     

Cutaneous Adverse Effects of Ketoprofen for Topical Use

Background: Since its introduction in France, ketoprofen for topical use has been associated with a large number of cutaneous adverse effect reports. Therefore, the French Medicine Agency progressively introduced warnings and contraindications to its use. Despite this, serious adverse drug reactions (ADRs) still occur. Objective: To describe clinical patterns and estimate costs of spontaneously reported cutaneous ADRs of topical ketoprofen. Methods: All cases of cutaneous ADRs of topical ketoprofen reported to the Bordeaux regional pharmacovigilance center between January 1989 and December 2006 were included. Clinical patterns, in respect of adherence to recommendations, causality, seriousness, and direct costs incurred by the ADRs, were assessed. Results: A total of 136 cases were reported (median age: 42 years, 55.9% women). Proper use of topical ketoprofen regarding indications, warnings, and contraindications was not respected by one-third of the patients. Almost all cases occurred during sunny months. Symptoms consisted predominantly of bullous eruptions (29.4%) or contact dermatitis (27.2%). Generalized lesions were observed in 37.5% of patients. Causality was considered at least possible for most of the cases (92.6%). These ADRs induced hospital admission in 15 cases (11.0%). The total estimated cost was €42 962 ($US66 559), corresponding to €316 per case. This mean cost was nine times higher for serious ADRs. Conclusion: Topical ketoprofen is used to treat benign symptoms but can be associated with serious and costly cutaneous ADRs. Furthermore, the number of cases and the calculated costs may have been greatly under-estimated in the present study.     

In vitro antimicrobial susceptibility of Propionibacterium acnes isolated from acne patients in northern Mexico

Background Antimicrobials are essential in acne therapy. In the last decades, Propionibacterium acnes has become resistant to different antibiotics. Objective To determine antimicrobial susceptibility patterns of P. acnes to frequently used drugs. Materials and methods Cutaneous lesion samples were obtained from 50 patients with acne vulgaris, which were cultured in anaerobic media to demonstrate the presence of P. acnes. After that, antimicrobial susceptibility tests to tetracycline, minocycline, doxycycline, erythromycin, azithromycin, clindamycin, trimethoprim/sulfamethoxazole (SXT) and levofloxacin were performed. Results In the general study group, resistance to azithromycin was 82%, the most prevalent one (P < 0.05), followed by trimethoprim/sulfamethoxazole (68%) and erythromycin (46%). On the other hand, all strains isolated were susceptible to minocycline. Resistance bias were similar when subgroups with and without the previous antimicrobial therapy were performed, finding a low prevalence of resistance to tetracyclines and levofloxacin in both groups. Conclusions In our region, P. acnes is highly resistant to azithromycin, SXT, erythromycin and clindamycin; and being very susceptible to minocycline, levofloxacin and tetracycline, in vitro in both groups: with and without the previous antibiotic use. To our knowledge, high resistance prevalence to azithromycin and SXT has never been reported.     

寻常型银屑病患者171例阿维A治疗相关不良反应及停药原因分析

目的:分析寻常型银屑病患者阿维A治疗相关药物不良反应（ADR）及停药原因。方法:收集广西医科大学第一附属医院2014—2019年使用阿维A治疗的寻常型银屑病患者292例,回顾性分析其中符合纳入与排除标准且能够定期随访的193例患者的临床资料,统计用药期间出现的ADR及停药原因。结果:193例中171例出现519例次AD...     

Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris

BACKGROUND: In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne. OBJECTIVE: To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris. METHODS: Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules). RESULTS: This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline). CONCLUSION: Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.     

French people and skin diseases: results of a survey using a representative sample

OBJECTIVE: To evaluate, from the patients' viewpoint, the prevalence, management, and impact of main dermatologic disorders in France. DESIGN: Survey conducted from March 28 to May 6, 2002, with the Sofres Taylor Nelson Institute on 10,000 households using 1 questionnaire per household. SETTING: General community. PATIENTS: A total of 25,441 subjects from 10,000 households determined to be representative of the French population and regularly surveyed by the Taylor Nelson Sofres Institute. MAIN OUTCOME MEASURES: Estimation of the prevalence of skin disorders by the French population. RESULTS: Of the 10 000 households, 7466 (74.7%) returned the questionnaire, which was completed for 18,137 (71.3%) of the 25,441 subjects. Of those, 15,742 reported having had skin problems since birth, or, by extrapolation, 86.8% (47.29 million) of the French population; 7841 reported having had skin problems in the past 24 months, or, by extrapolation, 43.2% (23.53 million) of the French population; and 28.7% said that their skin problems impaired their daily life. However, 61% of the sample were satisfied with their dermatologist. CONCLUSION: This survey of perceived health status in France highlights both the prevalence of skin disorders and the underestimation of the effects of dermatologic disorders in public health. A majority of the French population is satisfied with the care supplied by dermatologists.