Omalizumab in the treatment of Morbihan syndrome in an adolescent girl - case report and literature review.

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.

Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

The impact of oral isotretinoin on ovarian functions of acne patients complaining of polycystic ovarian syndrome: a prospective study.

BACKGROUND: Women have polycystic ovarian syndrome (PCOS) at higher rates than any other endocrine condition with an average incidence rate of 6 to 8%. Acne is an immune mediate common condition frequently affecting adolescents and adults and is often associated with PCOS. The objective of the study was to assess the impact of oral isotretinoin on ovarian functions of acne patients suffering from PCOS. Forty women with a clinical diagnosis of acne as well as PCOS participated in this prospective clinical trial. Participants were given oral doses of isotretinoin ranging from 0.5 to 1 milligram per kilogram (mg/kg), for a total of 120 to 150 mg/kg. To establish baseline values of hormone levels, on days 2-5 of the menstrual cycle, venous blood samples were obtained. Moreover, global acne grading system (GAGS), follicle count, and bilateral ovarian volumes were evaluated both before and after isotretinoin treatment. RESULTS: A significant reduction in global acne score from pre-treatment levels to post-treatment levels was observed (11.58 ± 5.857 vs. 1.65 ± 1.369). Ovarian volume was significantly reduced from 10.26 ± 1.539 before treatment to 8.74 ± 1.436 after treatment on the right side (P < 0.001) and from 11.08 ± 1.564 before treatment to 9.36 ± 1.479 after treatment on the left side (P < 0.001). A significant reduction in free testosterone level and hirsutism scores were observed after treatment (P < 0.001; P < 0.01 respectively. CONCLUSION: Isotretinoin may exert beneficial effects in hyperandrogenic women with PCOS and needs to be further evaluated by large multicentre controlled trials.

Fractional ablative CO2 laser and oral isotretinoin-A prospective randomized controlled split-face trial comparing concurrent versus delayed laser treatment for acne scars.

BACKGROUND: Therapeutic dogma has been to treat acne scars with ablative fractional laser no less than 6 months after isotretinoin (ITN) cessation. OBJECTIVE: To evaluate the safety and efficacy of fractional ablative CO2 laser (FACL) in patients treated concurrently with ITN. METHODS: We conducted a prospective split-face randomized control trial in patients treated with FACL concurrently with ITN versus patients treated with FACL 6 months post-ITN treatment. Patients received 3 monthly sessions of FACL with concurrent ITN treatment on half of the face; the other side of the face received the same FACL treatment regimen 6 months post-ITN cessation. Patients were followed for adverse effects up to 6 months post-FACL treatment. Final cosmesis was scored using the Quantitative Global Acne Scarring Grading System (GASGS) by three independent dermatologists. RESULTS: The GASGS of the concurrent ITN-FACL treated side of the face was significantly lower than the side treated with delayed laser therapy (4.7 ± 2.5 vs. 7.7 ± 2.9, respectively, p < 0.001). LIMITATIONS: The laser's settings were standardized, and not adjusted per patient skin type. CONCLUSION: Per our prospective trial, concurrent treatment of FACL -ITN is superior to delayed FACL treatment 6 months post-ITN cessation. Fractional ablative laser treatment is effective in improving acne scars, which persist despite isotretinoin therapy.

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.

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.

Tumor necrosis factor-α inhibitor treatment of acne fulminans - a clinical and literature review.

Acne fulminans (AF) is a rare, serious, sudden-onset and long-lasting skin disease that causes scarring of face and body. Standard treatment with combined long-term isotretinoin and prednisolone is not always sufficient and has a well-known propensity for adverse effects leaving an unmet need for improved therapy. Case reports suggest that tumor necrosis factor (TNF)-α inhibitors may play a role in the management of AF. In a 3-year retrospective data collection from two dermatology centers and literature review of clinical cases of acne fulminans treated with anti-TNF-α therapy, three clinical cases and twelve literature cases were identified. A total of five different TNF-α inhibitors have been tested, with adalimumab being the most commonly used. Clinical response was seen after 1 month in 2/3 (67%) clinical cases and 5/12 (42%) literature cases, respectively, and treatment was successful in 2/3 (67%) and 11/12 (92%) after a median 3-7 months. All reported adverse effects were mild and reversible. Anti-TNF-α treatment may provide rapid improvement in patients with AF when initial treatment with isotretinoin and prednisolone fails. However, randomized controlled trials are lacking, and exact dosage and timing need to be explored before clinical implementation.

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.

Efficacy of alitretinoin in the treatment of Darier disease: a case report.

Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a seborrheic and intertriginous distribution. The absence of specific targeted medications complicates the treatment process, and managing resistant cases can prove challenging due to recurrent exacerbations that may result in serious complications such as secondary bacterial and viral infections. Treatments of choice include antiseptics, topical corticosteroids, and systemic retinoids, mainly acitretin and isotretinoin. We report the case of a female patient with Darier disease that was unsuccessfully treated with acitretin and isotretinoin but showed significant improvement with alitretinoin. Previous reports on the efficacy of alitretinoin in Darier disease are reviewed.

Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment.

This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne and isotretinoin's mode of action. Puberty-induced insulin-like growth factor 1 (IGF-1), insulin and androgen signaling activate the kinase AKT and mechanistic target of rapamycin complex 1 (mTORC1). A Western diet (hyperglycemic carbohydrates and milk/dairy products) also co-stimulates AKT/mTORC1 signaling. The AKT-mediated phosphorylation of nuclear FoxO1 and FoxO3 results in their extrusion into the cytoplasm, a critical switch which enhances the transactivation of lipogenic and proinflammatory transcription factors, including androgen receptor (AR), sterol regulatory element-binding transcription factor 1 (SREBF1), peroxisome proliferator-activated receptor γ (PPARγ) and signal transducer and activator of transcription 3 (STAT3), but reduces the FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor for infundibular keratinocyte homeostasis. The AKT-mediated phosphorylation of the p53-binding protein MDM2 promotes the degradation of p53. In contrast, isotretinoin enhances the expression of p53, FoxO1 and FoxO3 in the sebaceous glands of acne patients. The overexpression of these proapoptotic transcription factors explains isotretinoin's desirable sebum-suppressive effect via the induction of sebocyte apoptosis and the depletion of BLIMP1(+) sebocyte progenitor cells; it also explains its adverse effects, including teratogenicity (neural crest cell apoptosis), a reduced ovarian reserve (granulosa cell apoptosis), the risk of depression (the apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin.

PAPA Syndrome: Challenges in Achieving Long-Term Remission.

For over two decades, the acronym PAPA syndrome has been used to describe an autoinflammatory condition caused by missense mutations in the PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1) gene and clinically characterized by the presence of pyogenic arthritis, pyoderma gangrenosum (PG), and acne (1,2). Due to the involvement of the PSTPIP1 gene in the regulation of innate immunity, mutations of this gene cause abnormal activation of inflammasomes, complexes of NLRP3/ASC/caspase-1 proteins. As a result, production of interleukin-1ß, a key molecule that triggers synthesis of cytokines necessary for the recruitment of neutrophils, is significantly increased (2,3). Additionally, the levels of other pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ) and interleukin 17 (IL-7) are also elevated, which further disrupts inflammatory mechanisms in the microenvironment (4). Since hyperproduction of IL-1 and other involved cytokines is the predominant event in the pathogenesis, these molecules are promising targets in the treatment of PAPA syndrome. Corticosteroids and biologics are currently the most commonly used agents for inducing and hastening remission of symptoms (5). A substantial step forward in the treatment of PAPA syndrome has been the introduction of medications blocking the cytokines crucial in the pathogenesis of this disorder, with TNF-α and IL-1 inhibitors being the most frequent choice of such biological therapy (6). We report the case of a 22-year-old male patient with PAPA syndrome who was referred to our department 18 months ago due to exacerbation of skin changes. Initial presentation and subsequent evolution of disease in this patient matched the typical clinical pattern of PAPA syndrome. The first symptoms occurred at the age of two in the form of unspecific joint disease that was diagnosed as juvenile idiopathic arthritis. Subsequently, in the early adolescence the patient presented with new skin changes manifesting as severe acne and persistent pyoderma gangrenosum-like ulcers. At the same time, severity of joint involvement gradually decreased. After the characteristic phenotype of the disease had fully developed, suspicion of possible syndromic origin of symptoms arose. For this reason, genetic analysis was performed as requested by attending pediatricians at the University Clinical Center in Sarajevo, and E250Q mutation of the PSTPIP1 gene was detected. Thus, the diagnosis of PAPA syndrome was confirmed. Throughout the duration of the disease, several types of medication had been introduced in the treatment with varying success. Earliest joint symptoms were alleviated with non-steroidal anti-inflammatory drugs, while repeated courses of corticosteroids were the mainstay of the therapy during a decade-long period. As a consequence of prolonged steroid therapy, growth disorder, among various other side-effects, had been especially pronounced. Acting as a classic steroid-sparing immunosuppressive agent, methotrexate had also been part of the patient's treatment regimen. Lastly, biologics, including both TNF-α and IL-a inhibitors, had been separately administered as the remaining treatment options. However, adalimumab expressed a predominant effect on joint symptoms, whereas re-activation of previously undetected Hepatitis-B infection occurred during the subsequent therapy with anakinra. Due to this adverse reaction, anakinra treatment was discontinued. At the initial examination, the patient presented with multiple erythematous, partially excoriated papules and nodules, along with residual post-inflammatory hyperpigmented patches and scars on the skin of the whole back, chest, shoulders, and upper arms (Figure 1, Figure 2). The presence of postoperative scars on the elbows, resulting from previously performed surgical procedures of persistently affected joints with the goal of achieving pain relief and functional improvement, was also observed. Several smaller ulcers with undermined edges (Figure 3), as well as residual hyperpigmentation and cicatrices (Figure 4) were visible on the lower extremities. Additionally, the patient reported appearance of pustules and non-healing ulcers after minor trauma, which corresponds to the pathergy phenomenon, a common feature of PAPA syndrome. In contrast to the severity of cutaneous changes, the joint symptoms were mild. After thorough assessment of the patient's medical history and current condition, a multi-agent regimen was initiated, consisting of adalimumab, isotretinoin, and prednisone. Regular check-ups during the 12 months of treatment showed that the applied agents stabilized the patient's condition, alleviated more severe and acute skin changes, and slowed down further exacerbation of symptoms. Due to the rarity of PAPA syndrome, data on its treatment is scarce. Official guidelines are non-existing, and available information is based on case reports, case series, and a few smaller retrospective studies (5,7). In general, response to therapy remains inconsistent between patients, despite introduction of novel drugs. Furthermore, single treatment regimens are often not equally effective for all manifestations of the disease, which in a number of cases results in the administration of multi-agent treatment (2). As described in our case report, we opted for a multi-agent regimen not only due to specific individual role of each drug in the treatment of PAPA syndrome but also because of the possible augmented effect of combined therapy. Initially, a short course of systemic corticosteroid (prednisone 30 mg/day for 3 weeks) was introduced in order to alleviate acute symptoms until other agents started showing their effects. The initial dose of administered corticosteroid was gradually tapered by 5 mg every week and soon discontinued. Adalimumab (40 mg every 2 weeks for 12 months) was chosen since its previous administration was without significant adverse effects and with more acceptable end results, unlike therapy with anakinra (8). In addition, TNF-α inhibitors, such as adalimumab, etanercept, and infliximab, have been generally regarded as a more effective treatment option for cutaneous changes, while anakinra, an anti-IL-1 agent, has been more beneficial in alleviating joint symptoms (9-11). Since the skin of our patient was significantly more affected than the joints, adalimumab was a preferred option for biological treatment. Finally, isotretinoin (0.5 mg/kg/day for 6 months) also found a place in our multi-agent therapy plan as a specific, supportive treatment agent for acne (12). Due to the fact that our national health insurance system covered the costs of treatment with TNF-α inhibitors for only 12 months, adalimumab had to be discontinued after the end of this period. Episodes of acute exacerbation that the patient experienced after the cessation of multi-agent regimen were addressed with systemic corticosteroids and symptomatic therapy. Based on case reports, corticosteroids are usually one of the first agents to be administered in patients diagnosed with PAPA syndrome. They are frequently effective in alleviating joint symptoms, but, on the other hand, high doses of corticosteroids can worsen acne lesions (6). Moreover, due to the multiple side-effects of corticosteroids, such as electrolyte abnormalities, hypertension, hyperglycemia, osteoporosis, growth suppression, and adrenal insufficiency (13), a steroid-sparing agent is typically introduced into treatment together with or after corticosteroid therapy. A substantial step forward in the treatment of PAPA syndrome has been achieved with the introduction of medications targeting cytokines crucial in the pathogenesis of this disorder. The two most commonly used groups of such biological drugs have been those that block TNF-α and IL-1. A longer lasting improvement of symptoms has been achieved in a number of cases with both types of agents. Since other medications have often failed to establish long-term control of PAPA syndrome, such effects can be seen as a valuable accomplishment (6,14). Regardless of this observation, the response to treatment still differs between patients. More variable effects have been documented for IL-1 inhibitors, such as anakinra, while TNF-α inhibitors, such as adalimumab, infliximab, and etanercept, have been associated with more steady responses (4,6,10). The inconsistent effect of biologic therapies could be explained by the fact that PSTPIP1 protein is involved in various biochemical processes in different cells of the immune system. Thuse, none of the medications has an adequate spectrum of activity to control all involved immunological pathways (5,15). Overall, due to scarcity of valid information and guidelines, there is an increasing need for multicentric randomized controlled trials that would provide evidence-based data on effective treatment options for PAPA syndrome. Despite the rarity of this disorder, extensive research should be performed in order to discover therapies that could successfully manage all different manifestations of PAPA syndrome. Consequently, such efforts and breakthroughs would lead to decreased mortality and improved quality of life for patients suffering from this debilitating disease. The case described herein shows that PAPA syndrome can remain undiagnosed for longer periods of time, resulting in delayed treatment. Furthermore, the available therapeutic options are not sufficient to achieve long-term remission in many patients. Thus, continuous and comprehensive research is vital for ensuring adequate care of patients with PAPA syndrome.

Durability of the improvement of collagen I and collagen III with the use of oral isotretinoin in the treatment of photoaging.

BACKGROUND: Oral isotretinoin (ISO) is the drug of choice for the treatment of severe acne. For photoaging treatment, ISO has been proved to be effective in some controlled and noncontrolled trials and is an alternative to topical retinoic acid (RA) therapy, which causes an expected skin irritation. OBJECTIVE: To evaluate and compare the skin remodeling in patients taking ISO 20 mg 3 times a week for 12 weeks and 12 weeks after the end of the treatment to quantify collagen I and collagen III augmentation. MATERIAL AND METHODS: Immunohistochemical studies were performed to evaluate the expression of collagen I and collagen III, metalloproteinases (MMPs) -1, -3, -7, -9, -12, and the tissue inhibitor of MMP type-1 (TIMP-1) of the skin of 20 45 to 50-year-old women through morphometry in a semiquantitative method. The inclusion criteria were facial aging 2 and 3 of Glogau's classification, with phototypes between II and V who had not entered menopause. Biopsies of the skin of the left preauricular region were performed at three different times: pre-treatment (T0), end of 12-week treatment (T1), and 12 weeks posttreatment (T2). RESULTS: Collagen fibers I and III increased with statistical significance in T1 (50.7%; P = 0.012) but not in T2 (49.7%), which in turn was higher than in T0 (47.2%) for collagen I and T1 (33.3%; P = 0.002) but not in T2 (32.7%), and also was higher than T0 (32.0%) for collagen III. MMP-9 presented a decreased activity with statistical significance in T1 (P = 0.047) and T2 (P = 0.058). MMP-1 showed a reduction in T2 only (P = 0.015). MMPs -3, -7, -12, and TIMP-1 did not present significant modification in their expressions during or after the treatment. CONCLUSIONS: Low-dose ISO is effective in remodeling the extracellular matrix (ECM). This study found that the increase of collagen occurs through the augmentation of both collagen I and collagen III fibers. With originality, it was possible to verify the durability of these fibers for at least 12 weeks. This may be related to the decrease in MMP-9 expression verified at the end of the treatment and 12 weeks posttreatment.

Evaluation of recovery time of tear film function and ocular surface after discontinuing oral isotretinoin treatment for acne vulgaris : Correlation between oral isotretinoin and tear film function.

PURPOSE: This study aimed to evaluate the recovery time of tear film function and ocular surface after discontinuing systemic isotretinoin treatment. METHODS: This was a prospective, cross-sectional study. 34 eyes of 17 patients treated with low- dose oral isotretinoin (< 0.5 mg/kg/day) were enrolled. The modified OSDI score, tear break-up time, Schirmer test, and corneal staining were performed in all patients at baseline, during the course of treatment and after withdrawing treatment every two weeks until the result returned to baseline. RESULTS: Tear breakup time appeared to be the most sensitive and changed significantly at 2 weeks after starting treatment (p < 0.001) and returned to baseline at 4 weeks after withdrawal from treatment (p < 0.001). The Schirmer test results significantly decreased at 6 weeks and returned to baseline at 4 weeks after withdrawal from treatment (p < 0.001). OSDI scores were significantly changed at 6 weeks after treatment (81.8%) and returned to baseline at 2 weeks (54.5%) after withdrawal from treatment. No significant change was found in the MGD. Corneal staining was significantly positive 90.9% 6 weeks after starting treatment and returned to baseline 6 weeks after withdrawal from treatment (p < 0.001). CONCLUSION: Dry eye disease can return to baseline levels after treatment withdrawal. At least 6 weeks later, they could wear contact lenses again, and it was useful to prepare all patients requiring further ocular surgery.

Oral Isotretinoin and Its Uses in Dermatology: A Review.

In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some "off-label" use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.

Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials.

PURPOSE: Acne is an extremely common skin disease with an estimated global prevalence of 9.4%. We aim to provide comprehensive comparisons of the common pharmacological treatments for acne. METHODS: Randomized controlled trials comparing the efficacy of pharmacological therapies for acne vulgaris in patients of any age and sex and with a treatment duration of >2 weeks were included. PubMed and Embase databases were searched from inception until February 2022. Our prespecified primary end points were mean percentage reduction in total, inflammatory, and noninflammatory lesions. Treatment ranking was determined by P values. RESULTS: There were 210 articles describing 221 trials and 37 interventions included in the analysis. Our primary analysis of percentage reduction in total lesion count had 65,601 patients enrolled. Across all trials, the mean age was 20.4 years. The median duration of treatment was 12 weeks. The median total, inflammatory, and noninflammatory lesion counts were 72, 27, and 44, respectively. The most effective treatment was oral isotretinoin (mean difference [MD] = 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (BPO) (MD = 38.15; P = .95) and by triple therapy containing an oral antibiotic, a topical retinoid, and BPO (MD = 34.83; P = .90). For monotherapies, oral or topical antibiotics or topical retinoids have comparable efficacy for inflammatory lesions, while oral or topical antibiotics have less effect on noninflammatory lesions. CONCLUSION: The most effective treatment for acne is oral isotretinoin, followed by triple therapies containing a topical retinoid, BPO, and an antibiotic. We present detailed comparisons of each intervention to serve as a practical database.