Practice and attitude of general practitioners towards initiating isotretinoin for acne vulgaris in Fars province, Iran: cross-sectional study.

BACKGROUND: Since general practitioners manage acne-related referrals, there needs to be more information in Iran about how drugs such as Isotretinoin are prescribed and the treatment plan. Thus, this study aimed to evaluate general practitioners s' practices and attitudes in prescribing Isotretinoin for acne vulgaris in primary care. METHODS: This web-based cross-sectional descriptive study was conducted using two questionnaires designed with the target population of GPs working in Fars province in 2021 regarding the prescription of Isotretinoin. Moreover, demographic information, questions about interest in dermatology, and participation in dermatology workshops were gathered. RESULTS: A total of 308 complete questionnaires were obtained. According to our results, 85 (27.6%) GPs prescribed Isotretinoin in primary care. Based on our results, higher age (OR: 1.042; CI95%: 1.013-1.072; P-value:0.004) and attending dermatological courses (OR: 3.280; CI95%: 1.592-6.755; P-value:0.001) were significantly correlated with more frequent Isotretinoin administration. Among GPs who do not prescribe Isotretinoin, the most common causes are concerns about liver dysfunction (54.7%), teratogenic concerns (37.2%), and lack of familiarity with the drug (31.4%) respectively. CONCLUSION: The results of this study depicted the reluctance of most physicians to prescribe Isotretinoin and factors such as taking part in supplementary courses under the supervision of dermatologists and following national guidelines that could encourage them to prescribe Isotretinoin.

Evaluation of the protective effects of curcumin-rich turmeric (Curcuma longa) extract against isotretinoin-induced liver damage in rats.

AIM: The aim of this study was to evaluate the protective effect of curcumin-rich turmeric (CRT) extract against isotretinoin (ISO)-induced liver damage through routine biochemical parameters and oxidative stress parameters that indicate liver damage. MATERIAL AND METHOD: 42 albino Wistar rats of 200 g were randomly grouped as Group I: Healthy control, Group II: Sunflower oil, Group III: Curcumin 200 mg/kg, Group IV: ISO control groups (7.5 mg/kg), Group V: Curcumin 50 mg/kg + ISO 7.5 mg/kg, Group VI: Curcumin 100 mg/kg + ISO 7.5 mg/kg, Group VII: Curcumin 200 mg/kg + ISO 7.5 mg/kg. At the end, after the rats were killed, their blood and liver tissues were collected. ALT and AST levels in serum; superoxide dismutase activity (SOD), GSH, and MDA levels in liver tissue were determined. RESULTS: Our results showed that ALT, AST, and MDA levels increased, and SOD and GSH levels decreased in the ISO-administered group compared to the healthy control group. CRT 50, 100, and 200 mg/kg groups were compared to ISO group. A dose-dependent increase in protective effect was observed. A decrease in ALT, AST, and MDA levels, and an increase in SOD and GSH levels were determined. A protective effect was found at all doses. The best protective effect was in the CRT 200 mg/kg group. CONCLUSION: CRT extract can be considered a candidate herbal medicine for the elimination of liver damage in individuals using ISO. However, further experimental and clinical validation should be studied.

Are antibiotics still relevant in acne? A review of the therapeutic conundrum.

Antibiotics have constituted the mainstay of acne therapy despite acne being classified as an inflammatory disorder. The indiscriminate usage of antibiotics over the years has thus fueled the issue of antimicrobial resistance. Cutibacterium acnes (C. acnes) can acquire resistance due to chromosomal mutation or genetic acquisition. C. acnes can transfer resistance to other resident flora, complicating the management of skin and soft tissue infections. It can also transfer resistant strains to other body sites and to immunocompromised and elderly patients thus putting them at risk of serious infections. Recent studies have highlighted the physiologic role of C. acnes in maintaining the normal homeostasis of the skin microbiome. The role of Malassezia in causation of acne has piqued interest in recent times. The efficacy of antibiotics in acne is attributed to their para-antibiotic, anti-inflammatory action rather than antimicrobial action. Thus, usage of low-dose antibiotics and alternatives to antibiotics has been advocated. Some alternative therapies showing efficacy in acne are probiotics, oral zinc, precision therapy using succinic acid, bacteriophages, and anti-biofilm therapy like myrtacin, topical azelaic acid, and salicylic acid. Using isotretinoin in early stages of acne can reduce the incidence of scarring and alleviate the need for antibiotics. Thus, a gradual shift from antibiotics to alternative therapies in acne is the need of the hour.

Analysis of the use of isotretinoin as an adjuvant in rhinoplasty.

BACKGROUND: Isotretinoin has been used in the treatment of acne for decades through the reduction of sebaceous secretion. There are reports in the literature that isotretinoin may be associated with decreased skin thickness, especially in patients with thick nasal skin for whom rhinoplasty can be more challenging. The objective of this study was to quantify, through ultrasonography, the effect of the use of oral isotretinoin in patients undergoing rhinoplasty, pre- and postoperatively. METHODS: Twenty-four patients participated in this randomized, single-blind controlled pilot clinical trial. The intervention group used oral isotretinoin (20 mg/day) for 2 months before rhinoplasty and for 4 months after. Both groups underwent rhinoplasty in the same plastic surgery department and were submitted to high-frequency (22 MHz) ultrasound evaluation of the epidermis and dermis on the nasal dorsum, nasal tip, and left nose wing at the beginning of the study and 6 months after rhinoplasty, with the aim of assessing changes in skin thickness. RESULTS: Six months after rhinoplasty, a statistically significant reduction was observed in the thickness of the epidermis and dermis of the nasal dorsum and left nose wing, as well as of the epidermis of the nasal tip, but only in the intervention group. The results of the satisfaction questionnaire were better after rhinoplasty in both groups, with no statistical difference between them regarding the specific questions; however, the intervention group had significantly higher satisfaction scores than the control group. CONCLUSIONS: Isotretinoin was effective in reducing the thickness of the skin covering the nose of the evaluated sites.

Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis.

Importance: Isotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear. Objective: To clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users. Data Sources: PubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023. Study Selection: Randomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users. Data Extraction and Synthesis: Relevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the I2 statistic, and meta-regression analyses were performed. Main Outcomes and Measures: Absolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users. Results: A total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants' average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; I2 = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; I2 = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide. Conclusions and Relevance: The findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.

Pityriasis Rubra Pilaris: An Updated Review of Clinical Presentation, Etiopathogenesis, and Treatment Options.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous reaction pattern with a significant impact on quality of life. Type I PRP is the most common PRP variant, presenting as erythematous papules emerging in a follicular distribution and later coalescing into plaques with characteristic islands of sparing; histologically, an alternating pattern of orthokeratosis and parakeratosis is considered the hallmark of PRP (checkerboard hyperkeratosis). Other PRP variants (types II-V) differ in their age of onset and clinical presentation. Type VI PRP is a rare PRP subtype associated with human immunodeficiency virus infection and is occasionally associated with diseases of the follicular occlusion tetrad. Caspase recruitment domain family, member 14 (CARD14)-associated papulosquamous eruption and facial discoid dermatitis are newly described disease states that have an important clinical overlap with PRP, creating shared conundrums with respect to diagnosis and treatment. The etiology inciting PRP often remains uncertain; PRP has been suggested to be associated with infection, malignancy, or drug/vaccine administration in some cases, although these are based on case reports and causality has not been established. Type V PRP is often due to inborn CARD14 mutations. Furthermore, recent literature has identified interleukin-23/T-helper-17 cell axis dysregulation to be a major mediator of PRP pathogenesis, paving the way for mechanism-directed therapy. At present, high-dose isotretinoin, ixekizumab, and secukinumab are systemic agents supported by single-arm prospective studies; numerous other agents have also been trialed for PRP, with variable success rates. Here, we discuss updates on clinical manifestations, present new insights into etiopathogenesis, and offer a survey of recently described therapeutic options.

Effects of oral isotretinoin treatment for acne vulgaris patients on anger responses and the relationship with temperament.

OBJECTIVE: Isotretinoin is the only medication against all the factors involved in acne vulgaris pathogenesis. The aim of our study was to verify whether patients with acne vulgaris receiving isotretinoin therapy exhibit elevated anger levels and to observe the correlation between age, temperament traits, and anger. METHODS: The study group comprised a sum of 100 cases, involving 50 individuals with acne vulgaris-required high-dose retinol therapy and 50 controls who did not start any medication. RESULTS: Our study showed that anger levels increased with drug use. A positive correlation between cyclothymic temperament, the anxiety-related behavior subdimension, and the introvert and passive-aggressive subdimension of interpersonal anger reactions has been recognized. In addition, a positive one was observed between hyperthymic temperament and the introvert subdimension, which is one of the anger-related thoughts and interpersonal anger reactions. CONCLUSION: This study elucidates anger dimensions such as anger-related thoughts, behaviors, and reactions in individuals who received retinol treatment for acne vulgaris. In addition to anger and its dimensions, temperament was also investigated. Although several studies have investigated the relationship between acne vulgaris and psychiatric symptoms, to the best of our knowledge, no research has been reported in the English-language literature regarding the relationship between anger dimensions and temperament after retinol treatment that might make our study an original and valuable contribution to the literature.

Does isotretinoin affect spermatogenesis in the long term? A rat model.

OBJECTIVES: Spermatogenesis, in which cell regeneration continues, can be affected by environmental, chemical, psychological factors or various diseases. There is conflicting information in the literature about the effect of isotretinoin, which is widely used in acne treatment, on testes and spermatogenesis. Therefore, we planned a rat study to evaluate the long-term efficacy of oral isotretinoin on testicular tissues and spermatogenesis. MATERIALS AND METHODS: The Group 1 (n = 6) 7.5 mg/kg/day and the Group 2 (n = 6) received isotretinoin at a dose of 30 mg/kg/day dissolved in sunflower oil, the Sham Group (n = 6) received only sunflower oil by gavage, and the control group (n = 6) received standard feed and water for four weeks. After the 4th week, all animals were fed with standard feed and water and followed for the next four weeks. At the end of the 8th week, all animals were sacrificed under deep anesthesia. Seminiferous tubule diameters, epithelial thickness, apoptotic index, sperm number and motility recorded Results: Sperm count, motility, vitality, diameter of seminiferous tubule and germinal epithelium thickness were decreased and apoptotic index increased in the groups received isotretinoin. There was no significant difference between the groups in terms of testosterone levels. CONCLUSIONS: We consider that further comprehensive studies, including human clinical trials, should be conducted to examine the negative effects of isotretinoin on spermatogenesis in the long term especially when there is a need using isotretinoin in men for various reasons and to eliminate the contradictions in the literature in this regard.

Clinical and histological features and treatment outcomes of patients with Morbihan disease: a systematic review.

Morbihan disease (MD) is considered a rare complication of rosacea, which is difficult to diagnose and challenging to treat. Here, we performed a systematic review of available case reports and case series to summarize key clinical and pathologic features of and successful treatment regimens for MD. We conducted a search of the PubMed/MEDLINE, EMBASE, and Cochrane electronic databases from their inception to the date of search on March 6, 2023. We found that MD affects patients in the fifth decade of life on average, more commonly reported in male than female (69% vs 31%). Clinically, MD affects the eyelids, cheeks, and forehead most commonly, presenting as non-pitting, erythematous edema or an edematous plaque. On biopsy, the pathologic features, such as dermal edema, sebaceous hyperplasia, perivascular and periadnexal inflammatory infiltrate, and granulomatous reaction, are frequently reported. Out of 55 patients who were able to achieve complete response without recurrence, 35% of patients were treated with isotretinoin and 22% were treated with tetracycline antibiotics with a daily dosage range of 20-80 mg and 40-200 mg, respectively. Out of those 55 patients, 22% and 7% were treated successfully with surgical intervention and intralesional injection of steroids, respectively. Additionally, lymphatic drainage has been shown to be an effective adjunctive therapeutic tool. More studies are necessary to understand the disease mechanism to improve the diagnosis of and develop evidence-based therapies for MD.

Effectiveness of the repurposed drug isotretinoin in an experimental murine model of Chagas disease.

Benznidazole and nifurtimox are the drugs currently used for the treatment of Chagas disease, however its side effects may affect patient adherence. In the search for new alternative therapies, we previously identified isotretinoin (ISO), an FDA-approved drug widely used for the treatment of severe acne through a drug repurposing strategy. ISO shows a strong activity against Trypanosoma cruzi parasites in the nanomolar range, and its mechanism of action is through the inhibition of T. cruzi polyamine and amino acid transporters from the Amino Acid/Auxin Permeases (AAAP) family. In this work, a murine model of chronic Chagas disease (C57BL/6 J mice), intraperitoneally infected with T. cruzi Nicaragua isolate (DTU TcI), were treated with different oral administrations of ISO: daily doses of 5 mg/kg/day for 30 days and weekly doses of 10 mg/kg during 13 weeks. The efficacy of the treatments was evaluated by monitoring blood parasitemia by qPCR, anti-T. cruzi antibodies by ELISA, and cardiac abnormalities by electrocardiography. No parasites were detected in blood after any of the ISO treatments. The electrocardiographic study of the untreated chronic mice showed a significant decrease in heart rate, while in the treated mice this negative chronotropic effect was not observed. Atrioventricular nodal conduction time in untreated mice was significantly longer than in treated animals. Mice treated even with ISO 10 mg/kg dose every 7 days, showed a significant reduction in anti-T. cruzi IgG levels. In conclusion, the intermittent administration of ISO 10 mg/kg would improve myocardial compromise during the chronic stage.

Oral Supplementation and Systemic Drugs for Skin Aging: A Narrative Review. / Tratamiento mediante suplementación oral o fármacos sistémicos del envejecimiento cutáneo. Revisión narrativa de la literatura.

Skin aging is influenced by intrinsic and extrinsic factors and involves multiple pathogenic mechanisms. The most widely used treatments are topical products and minimally invasive procedures. Evidence on the benefits of systemic therapy is limited for several reasons: Reliance on mostly small and predominantly female samples, short study durations, methodologic heterogeneity, and a lack of consensus on which outcome measures are clinically relevant. Furthermore, systemic drugs and oral supplements are not without adverse effects. Oral hydrolyzed collagen and oral hyaluronic acid are well tolerated, and numerous clinical trials show they can mitigate some signs of skin aging. Low-dose oral isotretinoin is another option, but it has a higher risk of adverse effects. Evidence is lacking on the effects of the many dietary supplements on offer, such as vitamins, flavonoids, plant extracts, and trace elements. The future of skin aging management would appear to lie in the use of senolytic and senomorphic agents targeting senescent cells in the skin.

Treatment of Resistant Acne Vulgaris in Adolescents Using Dietary Supplementation with Magnesium, Phosphate and Fatty Acids (Omega 6 and 7): Comparison with 13-Cis-Retinoic Acid.

The burden of disease associated with acne vulgaris has continued to increase over time in the world population. This continued growth suggests that there is an unmet dermatologic need for this condition worldwide. Potential sequelae of acne, such as scarring, depigmentation, and marked emotional and psychological problems (e.g., low self-esteem), can lead to significant morbidity. The purpose of this study was to investigate whether dietary supplementation with magnesium, phosphate, omega 6 (linoleic acid calcium salt - C18:2 fatty acid Ca salt), and omega 7 (palmitoleic acid calcium salt - C16:1 fatty acid Ca salt) would help patients with acne vulgaris, and to compare with isotretinoin (13-cis retinoic acid). Magnesium has anti-inflammatory properties. Linoleic and palmitoleic acids have bactericidal activity against Staphylococcus aureus and Cutibacterium acnes (formerly known as Propionibacterium acnes). A single-blind randomized study was conducted in which 257 patients were treated with the above dietary supplementation (group A) and 275 patients with isotretinoin (group B) for 6 months. All patients in group A (100%) reported complete regression of symptoms after 6 months of treatment. On the other hand, 187 subjects (68%) in group B reported complete resolution of symptoms during the same period. The difference between the groups (p < 0.05) was statistically significant. The study was approved by the CEP/CONEP. This natural formulation promotes regression and/or cure of acne vulgaris symptoms and has better results than drugs (such as isotretinoin), without significant side effects.

Isotretinoin-induced arthritis: A rare but feasible diagnosis. Case report

Many medications and vaccines have had implications in the development of musculoskeletal and joint symptoms, and among them the use of retinoids has been associated with the development of musculoskeletal symptoms, as well as axial symptoms suggestive of spondyloarthritis, with sacroiliitis, and to a lesser extent the development of peripheral symptoms. We describe the debut of peripheral inflammatory symptoms with the use of isotretinoin, in a previously healthy patient.

Muchos medicamentos y vacunas han tenido implicaciones en el desarrollo de síntomas osteomusculares y articulares. Entre ellos, el uso de retinoides se ha asociado con el desarrollo de síntomas musculoesqueléticos, así como síntomas axiales sugestivos de espondiloartritis con sacroileítis, y en menor proporción el desarrollo de síntomas periféricos. Describimos el inicio de síntomas inflamatorios periféricos con el uso de isotretinoína en una paciente previamente sana.

High versus low dose oral isotretinoin in the treatment of cutaneous and genital warts.

Although oral isotretinoin has been considered as a potential therapeutic option for the treatment of different types of warts, the optimum dosage regimen is not yet well-established. To evaluate the efficacy and adverse effects of high versus low doses of oral isotretinoin in the treatment of cutaneous and genital warts. The study included 100 patients who were randomly assigned to two groups, 50 patients in each. Group 1 received 0.6 mg/kg/day (high dose isotretinoin) and Group 2 received 0.3 mg/kg/day (low dose isotretinoin). In both groups, therapy was given daily until resolution was achieved or for a maximum of 3 months. Complete clearance of warts was observed in 76% of the high dose isotretinoin group and in 46% of the low dose isotretinoin group. There was a statistically significant difference in the therapeutic response between the two groups. Recurrence was higher in the low dose group (26%) than the high dose group (7.8%). Adverse effects were mild and tolerable. High dose of systemic isotretinoin is more effective than low dose and seems to be a promising well-tolerated and effective therapeutic option for the treatment of cutaneous and genital warts.

Cost-effectiveness of topical pharmacological, oral pharmacological, physical and combined treatments for acne vulgaris.

BACKGROUND: Acne vulgaris is a common skin condition that may cause psychosocial distress. There is evidence that topical treatment combinations, chemical peels and photochemical therapy (combined blue/red light) are effective for mild-to-moderate acne, while topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy are most effective for moderate-to-severe acne. Effective treatments have varying costs. The National Institute for Health and Care Excellence (NICE) in England considers cost-effectiveness when producing national clinical, public health and social care guidance. AIM: To assess the cost-effectiveness of treatments for mild-to-moderate and moderate-to-severe acne to inform relevant NICE guidance. METHODS: A decision-analytical model compared costs and quality-adjusted life-years (QALYs) of effective topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, from the perspective of the National Health Service in England. Effectiveness data were derived from a network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion. RESULTS: All of the assessed treatments were more cost-effective than treatment with placebo (general practitioner visits without active treatment). For mild-to-moderate acne, topical treatment combinations and photochemical therapy (combined blue/red light) were most cost-effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, and oral isotretinoin were the most cost-effective. Results showed uncertainty, as reflected in the wide confidence intervals around mean treatment rankings. CONCLUSION: A range of treatments are cost-effective for the management of acne. Well-conducted studies are needed to examine the long-term clinical efficacy and cost-effectiveness of the full range of acne treatments.

Effect of isotretinoin (Netlook) on the testis of adult male albino rats and the role of omega 3 supplementation: A histological and biochemical study.

Isotretinoin is an oral retinoid which used across the world in the treatment of patients especially adolescents complaining of acne. In spite of the prevalent clinical use of isotretinoin, the generation of oxidative stress with the affection of several organs leads to the limitation and restriction of its use. Omega-3 (N-3) is an essential polyunsaturated fatty acid (PUFAs) with powerful antioxidant properties. The aim of this study was to investigate the histological and biochemical changes occurring in the rat testis following isotretinoin intake and to evaluate the role of omega 3 supplementation in ameliorating testicular damage. Thirty adult male albino rats were divided equally into three groups. Group I is the control group, group II received isotretinoin (1.0 mg/kg/day) dissolved in distilled water and group III received isotretinoin (1.0 mg/kg/day) and omega 3 (400 mg/kg/day). Testis samples were collected and processed for light and electron microscopic examination. The blood samples were collected for biochemical assessments. Results indicated that isotretinoin caused histological changes in all stages of spermatogenesis and alterations of the hormonal assay. These changes in the rat testis which were corrected by omega 3 use.

Scrotal calcinosis in a patient treated with isotretinoin: a rare entity.

Scrotal calcinosis is a rare disorder characterized by multiple papules or nodules of calcification in the scrotal skin. The pathogenesis of this disease is poorly understood. The condition presents as several brown to yellowish asymptomatic nodules on the scrotum. Excision followed by scrotal reconstruction is the treatment of choice. It leaves a good cosmetic result with low chances of recurrence. Newer treatments, such as ablative lasers, have been proposed with very good results. We describe the case of a 28-year-old patient with a history of severe acne treated with oral isotretinoin that presented for scrotal nodules. On laboratory examination, hypercalcemia was found with normal phosphorus, parathyroid hormone, and vitamin D hormone levels. Hypercalcemia was linked to his isotretinoin therapy. Serum calcium concentrations normalized after cessation of isotretinoin and hydration. Because the patient refused surgery, a biopsy of the lesion confirmed the diagnosis of scrotal calcinosis. Then the patient was referred to a cosmetic laser center to treat his condition.

Is routine laboratory testing in healthy young patients taking isotretinoin necessary: a critically appraised topic.

CLINICAL QUESTION: Is monitoring of liver function, lipids and full blood count necessary in healthy people taking isotretinoin? BACKGROUND: Routine blood testing was recommended in the original licence for Roaccutane™ (isotretinoin) in 1983. In recent years, less frequent monitoring has been suggested by various authors. DATA SOURCES: We performed four individual systematic searches of the MEDLINE database, via PubMed, from origin to 2 May 2021, supplemented by a hand search of all references in the identified papers. STUDY SELECTION: Inclusion criteria were any description of clinical symptoms, laboratory abnormalities and/or physical findings, and any paper that explicitly described the patients as asymptomatic, during treatment with oral isotretinoin. DATA EXTRACTION: Two independent reviewers (J.A. and D.J.) assessed articles for eligibility of inclusion. Evaluation of the data was done also by two of the authors (A.A., D.J. and J.A.) for each section, with the aim to use the presented evidence including guidelines, databases, case series, case reports, cohort studies and randomized clinical trials to delineate the clinical presentation and frequency of adverse events that might be amenable to laboratory monitoring. RESULTS: We identified 407 papers in our searches and reviewed 125 papers in four sections. Overall, reported adverse events were very rare (< 1 in 10 000) and were either idiosyncratic or not preventable by monitoring, accompanied by symptoms, or seen in identifiable predisposed individuals who might benefit from monitoring because of pre-existing conditions. RECOMMENDATION FOR CLINICAL CARE: We could not find evidence to support the benefit of monitoring to detect adverse events. We suggest that in healthy young people laboratory monitoring for oral isotretinoin is unnecessary and risks detecting nonserious biochemical abnormalities. However, we recognize that new information about adverse events may change that recommendation.

Voriconazole is superior to combined itraconazole/isotretinoin therapy and itraconazole monotherapy in recalcitrant dermatophytosis.

BACKGROUND: There has been an emergence of recalcitrant, recurrent, and difficult-to-treat tinea. Monotherapy with oral antifungals leads to partial clearance or high recurrence of lesions. Isotretinoin is a good adjuvant to systemic antifungals in chronic dermatophytosis. Voriconazole could be a future alternative due to its efficacy against dermatophytes and little resistance. OBJECTIVE: To evaluate the efficacy and safety of oral itraconazole, combined itraconazole/isotretinoin therapy, and voriconazole for recalcitrant tinea. PATIENTS AND METHODS: This study included 90 patients with chronic, recurrent and/or recalcitrant tinea. They were equally divided into three groups: itraconazole monotherapy, combined itraconazole/isotretinoin therapy, and voriconazole monotherapy. All patients received treatments for 6 weeks. The clinical response was classified as either a complete or incomplete clinical cure. Potassium hydroxide microscopy and culture were performed to identify mycological cure. Patients with complete cure were followed up for another 6 months to detect any recurrence. RESULTS: Complete clinical cure was observed in 53.3% of the itraconazole group, 70% of the itraconazole/isotretinoin group, and 83.3% of the voriconazole group. Mycological cure was detected in 56.7% of the itraconazole group, 83.3% of the itraconazole/isotretinoin group, and 86.7% of the voriconazole group. There was a statistically significant difference between the three groups in favour of voriconazole, then the combined group. No significant adverse effects were observed. The recurrence rate was significantly lower in the voriconazole group compared with the other two groups. CONCLUSIONS: Voriconazole could be a future alternative for the treatment of recalcitrant dermatophytosis.