Report of successful treatment of follicular occlusion triad with adalimumab and research progress on biologic therapy for follicular occlusion triad.

Purpose: This article aims to present a case report of a patient with Follicular occlusion triad (FOT) who achieved successful disease control with adalimumab combined with isotretinoin and provide a comprehensive review of the current research progress on biologic therapies for FOT.Methods: We report a case of a 22-year-old female patient diagnosed with FOT, who was treated with adalimumab combined with isotretinoin after failing to respond to conventional therapies. A systematic literature review was conducted to summarize the current research progress on biologic therapies for FOT, including TNF-α inhibitors, IL-17 inhibitors, IL-12/IL-23 inhibitors, IL-23 inhibitors, IL-1 inhibitors, and other novel biologic agents.Results: The patient achieved significant improvement in skin lesions, pain, and quality of life after three months of treatment with adalimumab combined with isotretinoin, without experiencing severe adverse reactions. The literature review revealed that adalimumab and secukinumab are the two FDA-approved biologics for FOT, while others, such as bimekizumab, infliximab, anakinra, and bermekimab, have shown promise in clinical studies.Conclusions: Biologic therapies have revolutionized FOT management, providing effective options for patients unresponsive to conventional treatments. As our understanding of FOT pathogenesis and the mechanisms of action of biologics grows, further advancements in biologic therapies for FOT are expected.

The effect of family history of atherosclerosis and other risk factors on changes in serum lipid levels in acne patients treated with isotretinoin.

BACKGROUND: Oral isotretinoin causes changes in serum lipid values. These changes are not seen in every patient, regardless of dose. It is unclear what causes these changes and how often serum lipid values should be followed up. AIMS: We aimed to evaluate the relationship between the change in serum lipid values and personal and familial risk factors. METHODS: Serum lipid values at baseline (0th), 1st, 3rd, and 6th months of isotretinoin treatment of acne patients aged 16 years and over using oral isotretinoin at a dose of 0.5-1 mg/kg/day between January 2017 and December 2019 were recorded retrospectively. The relationship between personal and familial risk factors and changes in serum lipid values were evaluated statistically. RESULTS: In pairwise comparison, a significant difference was detected between the 0th and 1st month, 0th and 3rd month, 0th and 6th month, and 1st and 6th month in the average serum lipid (Low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), total cholesterol, triglyceride) levels. However, no significant difference was detected between 3rd and 6th month. The change in LDL levels between the 0th and the 3rd month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.034). The change in VLDL levels between the 0th and 6th month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.022). It was observed that the changes in total cholesterol and VLDL levels between the 0th and 3rd month increased as body mass index (BMI) increased (p = 0.03, p = 0.014, respectively). Similarly, the changes in triglyceride and VLDL levels between 0th and 6th month and between 1st and 6th month increased by an increase in BMI (respectively; p = 0.006, p = 0.019; p = 0.016, p = 0.022). The increase in the levels of VLDL between the 1st and the 6th month was found to be significantly higher in smokers than in non-smokers (p = 0,032). CONCLUSION: We recommend evaluation of serum lipids values in the 0th, 1st, and 3rd month in all acne patients using oral isotretinoin and that these values have to be checked monthly in the following months for smokers, those with a history of atherosclerosis, and those with a BMI above normal.

Untargeted Lipidomics Analysis to Discover Lipid Profiles and Biomarkers of Rabbit Acne Model and Reveal Action Mechanism of Isotretinoin.

Background: Acne vulgaris (AV), a chronic inflammatory pilosebaceous disorder, affects 80-90% of teenagers. This study aimed to discover lipid profiles and biomarkers of the rabbit ear acne model, and investigate the mechanism of isotretinoin in treating acne at the lipid level. Methods: Untargeted lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was performed to identify skin lipid metabolites in blank control (groups C), model group (group M) and isotretinoin group (group T). Multivariate statistical analysis was used to process the lipidomics data. Results: A total of 43 lipid classes comprising 6989 lipid species were identified from the mass spectrometry data. The orthogonal partial least squares discriminant analysis (OPLS-DA) model demonstrated significant separation in skin lipidomic profiles between group M and group C. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 299 significantly different lipid metabolites were identified. These lipid metabolites consisted mainly of ceramides (Cer) (53.85%), phosphatidylethanolamines (PE) (9.03%), phosphatidylcholines (PC)(5.35%), and sphingomyelin (SM)(4.01%). Combining with AUC ≥ 0.9 as the elected criteria, Cer (d18;1_24:0), zymosterol (ZyE)(33:5), Cer (t43:1), ZyE (33:6), ZyE (24:7), and ZyE (35:6) have "high" accuracy. Isotretinoin treatment normalized 25 lipid metabolites in the acne model. Conclusion: Our findings provide new insights into the role of lipid metabolism in the pathogenesis of acne and the action mechanism of isotretinoin.

Meibography health score: a simple grading system for isotretinoin-induced meibography alterations on patients with acne vulgaris.

PURPOSE: To develop a simple, subjective, and reliable grading scale for isotretinoin-induced meibography changes. METHODS: After analyzing meibography images obtained from systemic isotretinoin users, a grading scale was proposed and named "meibography health score." The score ranged from 1 to 3, with decreasing gland reflectivity and identifiable margins. A total of 11 medical professionals were asked to grade 10 meibography images obtained from isotretinoin users using the proposed scale and were divided into three groups: (A) ophthalmologists with experience with meibography, (B) ophthalmologists with no experience with meibography, and (C) radiologists. The kappa statistic was determined to test interrater reliability. RESULTS: The overall kappa was approximately 0.64. The kappa scores for Groups A, B, and C were 0.78, 0.59, and 0.90, respectively. Grade 2 had the lowest kappa scores (0.62, 0.35, and 0.82 for A, B, and C, respectively) and grade 3 the highest (0.78, 0.90, and 1.0 for A, B and C, respectively). Furthermore, Group C had the highest kappa scores and Group B the lowest. CONCLUSION: The meibography health score exhibited good interrater reliability, particularly in severe cases.

Increased femoral cartilage thickness in acne patients using isotretinoin: could it be a sign of early osteoarthritis?

Vitamin A derivatives have inhibitory effects on cartilage tissue, such as decreasing chondrocyte proliferation and collagen synthesis, and increasing the loss of glycosaminoglycans and proteoglycans. Therefore, isotretinoin (a vitamin A derivative) may play a role in the pathogenesis of cartilage-related diseases like osteoarthritis by affecting the balance of cartilage tissue. The aim of this study was to evaluate the distal femoral cartilage thickness in acne patients under the systemic isotretinoin therapy and to determine whether it constitutes a risk factor for the development of osteoarthritis. The study included 52 patients (42 female, 10 male, mean age 23.31 ± 3.89 years) who were prescribed systemic isotretinoin for acne and completed at least 3 months of treatment, along with 45 healthy controls ((35 female, 10 male, mean age 23.85 ± 4.77 years). Bilateral distal femoral cartilage thickness was measured by ultrasonography before isotretinoin treatment and after the completion of the third month of treatment. After treatment, a statistically significant increase was found in the thickness of the right medial, right lateral, left medial, left lateral, and left intercondylar cartilage (p = 0.014, 0.012, 0.019, 0.027, 0.002, respectively). There was also an increase in the right intercondylar cartilage thickness, but this was not statistically significant (p = 0.1). Systemic isotretinoin seems to make cartilage thicker. The increase in femoral cartilage thickness observed after short-term isotretinoin treatment might be an indicator of very early-stage osteoarthritis. Extended follow-up studies with larger participant pools are necessary to substantiate this result.

Laboratory Monitoring in Isotretinoin Therapy for Acne: How Long and How Often Must We Test Our Patients?

The optimal frequency and timing of laboratory monitoring during isotretinoin treatment remains controversial. We aimed to investigate the frequency, timing, and severity of abnormal results during isotretinoin for acne. We conducted a retrospective cohort study comprising 444 acne patients prescribed isotretinoin at Boston Medical Center from 2004 to 2017; these patients had at least one available baseline laboratory result. We categorized patients into two groups: group A (normal values at baseline and during the first 2 months of isotretinoin therapy) and group B (abnormal values at baseline or during the first 2 months of isotretinoin therapy) and assessed the laboratory values after 2 months. The frequency of abnormal results for triglycerides, cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) after 2 months for patients in group A was 21.1%, 13.6%, 8.8%, and 6.0%, respectively, with very rare grade 2 (moderate) or higher abnormalities. In contrast, the frequency of abnormal results for patients in group B for triglycerides, cholesterol, AST, and ALT was higher at 67.9%, 88.0%, 40.0%, and 25.0%, respectively (P < 0.05, except for ALT). No patient developed higher than grade 1 (mild) complete blood count (CBC) abnormality. This study proposed that healthy patients with normal results at baseline and during the first 2 months of isotretinoin therapy might not need routine monitoring after month 2 of medication. Routine monitoring of CBC is not necessary.

Isotretinoin-Induced Skin Fragility in an Aerialist.

Isotretinoin is widely used for treatment of severe cystic acne; however, its use is accompanied by mucocutaneous adverse effects. The established protocol for conducting cutaneous procedures on patients undergoing current or recent treatment with isotretinoin recommends a cessation period of at least 6 months to mitigate risks for delayed wound healing and hypertrophic scarring due to medication-induced skin fragility. We present a unique case of isotretinoin-induced skin fragility resulting in blistering and erosions on the palms of a 25-year-old competitive aerial trapeze artist. This case highlights the underrecognized risk for skin vulnerability in athletes undergoing isotretinoin treatment and the importance of guiding athletes on heightened skin vulnerability during isotretinoin treatment.

Isotretinoin-Induced Hypersomnia: A Cross-sectional Study and Literature Review.

BACKGROUND: Isotretinoin is an oral retinoic drug for severe resistant acne cases that has controversially been associated with multiple psychiatric adverse effects. Research has primarily focused on depression and suicidality; however, a few case studies reported hypersomnia and sleep changes after isotretinoin initiation. OBJECTIVE: To assess sleep quality and measure rates of hypersomnia, depression, and anxiety in patients undergoing isotretinoin therapy. METHODS: This cross-sectional study was conducted at outpatient clinics of the university hospital. The rate of self-reported oversleeping was measured. In addition, researchers used the Pittsburgh Sleep Quality Index to assess sleep quality and conducted semistructured clinical interviews to detect depression and anxiety. RESULTS: Of 123 patients with acne on isotretinoin, 77 (62.6%) reported oversleeping. Nearly half (60 patients, 48.8%) were categorized as poor sleepers according to the Pittsburgh Sleep Quality Index. The interviews revealed anxiety and depression percentages among 9.8% and 4.9% of participants, respectively. CONCLUSIONS: Hypersomnia was noticeably high in this study sample; thus, it may cautiously suggest a possible link between isotretinoin and hypersomnia. However, more research is needed to investigate this potential relationship.

Pityriasis Rubra Pilaris - a difficult path to optimal treatment. Case report.

Pityriasis Rubra Pilaris is a rare, chronic inflammatory dermatosis of unknown etiology, presenting with erythema and papular eruptions. Treatment is difficult due to the lack of causal therapy, guidelines and requires an individualized approach. The most common treatments are systemic retinoids, immunosuppressants, phototherapy and biological therapy. This article presents the case of a 73-year-old man suffering from type 1 pityriasis rubra pilaris. The patient was initially treated with acitretin, which was discontinued due to hypogammaglobulinemia. This rare side effect of acitretin has not been previously published. As a second-line treatment, the patient received methotrexate, but with no clinical improvement after 3 months and an increase in skin pruritus. Finally, the use of isotretinoin resulted in significant clinical improvement and was well tolerated.

Prevalence and factors associated with olfactory impairment among patients with acne treated with oral isotretinoin: a cross-sectional study.

OBJECTIVE: This study aimed to investigate the prevalence and factors associated with olfactory dysfunction in individuals exposed to Isotretinoin (ISO) for the treatment of acne, using the University of Pennsylvania Smell Identification Test (UPSIT®). METHODS: This cross-sectional study enrolled age and sex-matched patients with acne who were current users of oral ISO and unexposed controls without olfactory complaints. UPSIT® and a validated questionnaire (Nasal Obstruction Symptom Evaluation) were administered to evaluate nasal obstruction in patients exposed to ISO. RESULTS: A total of seventy patients were recruited, with 35 in the exposed group and 35 in the unexposed group, consisting of 18 males and 17 females in each group, aged from 17 to 47 years. The prevalence of olfactory dysfunction was higher in the exposed group compared to the non-exposed group (62.9% vs. 17.1%), yielding a Prevalence Ratio (PR) of 3.7 (95% CI 1.9-7.1). However, no participants were categorized as anosmia or severe hyposmia and the majority of dysfunction was mild hyposmia compared to moderate hyposmia (51.5% vs. 11.4%). Among the exposed individuals, gasoline, orange, coffee, and wood exhibited the highest rates of identification errors (≥54%). Olfactory function demonstrated a negative correlation with treatment duration (p = 0.01), cumulative dose (p = 0.02), and nasal obstruction (p = 0.02). CONCLUSIONS: Olfactory dysfunction was more prevalent among ISO users, despite the patients being unaware of the disorder. Olfactory changes were correlated with treatment duration, cumulative dose, and nasal obstruction. LEVEL OF EVIDENCE: Level 4.

Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study.

BACKGROUND: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. CONCLUSION: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

Efficacy and Safety of Micronized Isotretinoin Administered Once Daily Without Food in Patients With Recalcitrant Nodular Acne.

INTRODUCTION: Micronized isotretinoin 0.4 to 0.8 mg/kg/day administered in 2 divided doses with or without meals is approved for the treatment of severe nodular acne in patients aged 12 years or older. Although practitioners may suggest once-daily dosing to increase patient compliance, supporting data are limited. METHODS: In this pilot study, patients aged 12 years or older with severe nodular acne (Investigator's Global Assessment [IGA] =>4 and >5 facial nodules) received once-daily micronized isotretinoin 0.4 to 0.8 mg/kg/day without food for 20 weeks. The coprimary efficacy endpoints were changes from baseline in nodular lesion count (NLC) and percentage of patients with a =>90% reduction in NLC at week 24. Secondary endpoints included percentage of patients achieving IGA 0/1; reductions in inflammatory lesion count (ILC) and noninflammatory lesion count (NILC); adverse events (AEs); and severity of erythema, dryness, peeling, oiliness, burning, and pruritus. Analyses included all enrolled patients with the last observation carried forward. RESULTS: Twenty-two of 24 patients completed the study. From baseline to week 24, NLC decreased by a median (quartile [Q]1, Q3) of 6 (5, 7), all patients experienced complete clearance of nodules, 23/24 (96%) patients achieved IGA 0/1, and ILC and NILC decreased by a mean +/- standard deviation of 97.8% +/- 5.7% and 98.4% +/- 6.2%, respectively (all P<0.0001). There were small, significant, early increases in the severity of erythema, dryness, and peeling; 2 patients experienced 3 AEs considered unrelated to treatment. CONCLUSIONS: Once-daily micronized isotretinoin administered without food was efficacious and well tolerated in patients with severe nodular acne.  J Drugs Dermatol. 2024;23(6):423-428.     doi:10.36849/JDD.7863.

Consensus Statements on the Use of Novel Formulations of Isotretinoin: A Modified Delphi Process.

Oral isotretinoin remains a mainstay of treatment for severe, recalcitrant nodular acne. Novel formulations of isotretinoin have been developed over the past decade, including lidose isotretinoin and micronized isotretinoin. It is important to understand the differences between isotretinoin formulations to help guide clinical decision-making and selection of isotretinoin therapy. This study aims to provide evidence-based consensus statements regarding the use of novel formulations of isotretinoin for the treatment of moderate-to-severe acne. The Expert Consensus Group consisted of dermatologists with expertise in the treatment of acne. Voting members met in person to conduct a modified Delphi process; a maximum of 2 rounds of voting were conducted for each consensus statement. A total of 5 statements were generated regarding the use of novel formulations of isotretinoin, addressing the efficacy, tolerability, and side effects of novel isotretinoin formulations. All 5 statements achieved agreement with high consensus. The Expert Consensus Group agrees that individualized selection of isotretinoin therapy is important to maximize efficacy and minimize side effects. Compared to generic isotretinoin, micronized isotretinoin may require lower doses to achieve sufficient plasma concentrations. With the increased bioavailability of micronized formulation, there is no need to calculate cumulative dose; instead, the general recommendation with micronized isotretinoin is to treat for at least 5 months, or longer if needed to achieve clearance. Micronized isotretinoin can be taken in the fed or fasted state and has an acceptable safety profile. J Drugs Dermatol. 2024;23(6):429-432.     doi:10.36849/JDD.7971.