Isotretinoin's Effect on Fasting Lipid Profile in Acne Patients.

OBJECTIVE: To determine the isotretinoin's effect on fasting lipid profile in patients with acne. STUDY DESIGN: Observational study. Place and Duration of the Study: Outpatient Department of Dermatology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan, from 22nd June to 21st December 2022. METHODOLOGY: Patients of clinically moderate and severe acne were selected and prescribed a dose of 0.5mg /kg cap isotretinoin for 6 months. They were advised to get a fasting lipid profile at the baseline and then after two months of isotretinoin therapy. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grading system and Adult Treatment Panel III were used for the grading of abnormalities. McNemar Bowker test was used to assess the difference in variables [serum triglycerides (TGs), cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL)] at the baseline and after 2 months follow-up. RESULTS: A total of 214 patients were evaluated. After 2 months of isotretinoin therapy, TGs and cholesterol levels were elevated to higher grade in 2% of the patients. Likewise in 1% of patients, LDL levels rised to higher grade. Moreover, HDL levels declined to lower grade in 2% of the patients taking isotretinoin. CONCLUSION: Insignificant alterations in the various serum lipid parameters were observed in acne patients during isotretinoin therapy. It is advisable to obtain a baseline fasting lipid profile in all acne patients on isotretinoin and repeated in those with baseline abnormal levels and in patients with a clinical sign of metabolic syndrome and a family history of dyslipidemias. KEY WORDS: Acne, Hyperlipidemias, Isotretinoin, Laboratory monitoring.

Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

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.

Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: Cases of inflammatory bowel disease (IBD) following isotretinoin use have been reported previously, but whether isotretinoin exposure is associated with IBD has been unclear. OBJECTIVE: The aim was to evaluate whether isotretinoin use is associated with IBD. METHODS: We performed a systematic review and searched MEDLINE, Embase, and CENTRAL databases from inception to January 27, 2023 for relevant case-control and cohort studies. Our outcome was the pooled odds ratio (OR) for IBD and its two subtypes (Crohn disease and ulcerative colitis) in relation to isotretinoin exposure. We conducted a random-effects model meta-analysis and a sensitivity analysis by excluding low-quality studies. A subgroup analysis was undertaken by including studies considering antibiotic use. A trial sequential analysis (TSA) was performed to test the robustness of the conclusiveness of our results. RESULTS: We included eight studies (four case-control and four cohort studies) with a total of 2,522,422 participants. The meta-analysis found no increased odds for IBD among patients receiving isotretinoin (OR 1.01; 95% confidence interval [CI] 0.80-1.27). Nor did the meta-analysis find increased odds for either Crohn disease (OR 0.87; 95% CI 0.65-1.15) or ulcerative colitis (OR 1.27; 95% CI 0.94-1.73) associated with isotretinoin exposure. The sensitivity and subgroup analyses produced similar results. In TSA, the Z-curve reached the futility boundaries when using relative risk reduction thresholds ranging from 5% to 15%. CONCLUSION: This meta-analysis with TSA found no evidence of an association of isotretinoin use with IBD. Isotretinoin should not be withheld because of unnecessary concerns for the development of IBD. PROSPERO REGISTRATION NO: CRD42022298886.

Isotretinoin and the risk of inflammatory bowel disease and irritable bowel syndrome: A large-scale global study.

INTRODUCTION: Risk of inflammatory bowel disease under isotretinoin is a scope of a long-standing controversy. The burden of isotretinoin-related irritable bowel syndrome has not been investigated. OBJECTIVE: To evaluate the risk of Crohn's disease, ulcerative colitis (UC), and irritable bowel syndrome in patients with acne starting isotretinoin vs oral antibiotics treatment. METHODS: A global population-based retrospective cohort study assigned 2 groups of patients with acne initiating isotretinoin (n = 77,005) and oral antibiotics (n = 77,005). Comprehensive propensity-score matching was conducted. RESULTS: The lifetime risk of Crohn's disease (hazard ratio [HR], 1.05; 95% CI, 0.89-1.24; P = .583) and UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) was comparable between study groups, whereas the lifetime risk of irritable bowel syndrome was lower in isotretinoin-prescribed patients (HR, 0.82; 95% CI, 0.76-0.89; P < .001). In time-stratified analysis, isotretinoin-related risk of UC was significantly increased during the first 6 months following drug initiation (HR, 1.93; 95% CI, 1.29-2.88; P = .001), but decreased afterward to level the risk of the comparator group. The absolute risk difference within the first 6 months was clinically marginal (5.0 additional UC cases/10,000 patients starting isotretinoin; 95% CI, 2.5-7.7). LIMITATIONS: Retrospective data collection. CONCLUSION: Isotretinoin does not confer an elevated risk of Crohn's disease, whilst it might be associated with a slight and transient increase in UC risk.

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.

Effect of Evening Primrose Oil Supplementation on Selected Parameters of Skin Condition in a Group of Patients Treated with Isotretinoin-A Randomized Double-Blind Trial.

Background: Retinoids, which include isotretinoin, reduce sebum levels, the degree of epidermal wetness (CORN) and cause an increase in transepidermal water loss (TEWL). Weight gain has also been observed in isotretinoin-treated patients. An agent that can reduce the severity of isotretinoin side effects is evening primrose oil (Oenothera paradoxa). The purpose of this study was to evaluate the effect of evening primrose oil supplementation in patients with acne vulgaris treated with isotretinoin on skin hydration status (CORN), transepidermal water loss (TEWL), skin oiliness (sebum) and changes in body weight and BMI. Methods: Patients diagnosed with acne were assigned to the isotretinoin-treated group (n = 25) or the isotretinoin and evening primrose oil-treated group (n = 25). The intervention lasted 9 months. CORN (with a corneometer), TEWL (with a tewameter) and sebum (with a sebumeter) were assessed twice, as well as body weight and BMI (Tanita MC-780). Results: The isotretinoin-treated group showed statistically significant reductions in CORN (p = 0.015), TEWL (p = 0.004) and sebum (p < 0.001) after the intervention. In the group treated with isotretinoin and evening primrose oil, TEWL and sebum levels also decreased significantly (p < 0.05), while CORN levels increased from 42.0 ± 9.70 to 50.9 ± 10.4 (p = 0.017). A significant decrease in body weight (p < 0.001) and BMI (p < 0.001) was observed in both groups after 9 months of intervention. Conclusions: During isotretinoin treatment, supplementation with evening primrose oil increased skin hydration. However, there were no differences between groups in transepidermal water loss, skin oiliness, weight loss and BMI.

The utility of laboratory testing for pediatric patients undergoing isotretinoin treatment.

Isotretinoin, the most effective treatment for severe cystic acne, involves laboratory monitoring. In this retrospective case series of 130 pediatric patients taking isotretinoin, there were significant increases in cholesterol (143.9 mg/dl to 155.3 mg/dl), triglycerides (81.8 mg/dl to 115.2 mg/dl), and low-density lipoprotein (82.0 mg/dl to 98.1 mg/dl), and a decrease in high-density lipoprotein (50.0 mg/dl to 44.7 mg/dl) from baseline to follow-up (p < .05); there were no significant changes in liver enzymes. None of the patients had clinical sequelae (triglyceride-induced pancreatitis, retinoid-induced hepatotoxicity) related to their abnormal lab values. These findings question the utility of laboratory monitoring for prevention of severe clinical sequelae in pediatric patients, and suggest testing based on individualized risk factors may be more appropriate.

Effect of Evening Primrose Oil Supplementation on Biochemical Parameters and Nutrition of Patients Treated with Isotretinoin for Acne Vulgaris: A Randomized Double-Blind Trial.

Background: Acne vulgaris is one of the most common skin diseases. One of the therapeutic options recommended for severe acne or acne that has not responded to previous therapies is isotretinoin. However, its use may lead to adverse changes in the serum lipid profile and increased levels of transaminases. In this study, we evaluated the effect of supplementation with evening primrose oil in acne vulgaris patients treated with isotretinoin on blood lipid parameters and transaminase activity. Methods: Study participants were randomly assigned to two treatments: conventional with isotretinoin (25 patients) and novel with isotretinoin combined with evening primrose oil (4 × 510 mg/day; 25 patients) for 9 months. Results: Compared to isotretinoin treatment, isotretinoin treatment combined with evening primrose oil had a positive effect on TCH concentrations (mean: 198 vs. 161, p < 0.001), LDL (95.9 vs. 60.2, p < 0.001), HDL (51.0 vs. 48.0, p < 0.001), TG (114 vs. 95.0, p < 0.001), ALT (24.0 vs. 22.0, p < 0.001), and AST (28.0 vs. 22.0, p < 0.001), but had no effect on the energy and ingredient content of the diets (p > 0.05) after treatment. Conclusion: Evening primrose oil was found to have beneficial effects on lipid profiles and transaminase activity during isotretinoin treatment. However, longer studies are needed to make more reliable decisions regarding the use of evening primrose oil and its safety in clinical practice. The evening primrose oil treatment group also showed a reduction in dietary energy due to a reduction in dietary protein and carbohydrates.

Comparative efficacy of using a combination of intralesional purified protein derivative with low dose isotretinoin in the treatment of recalcitrant common warts.

Intralesional immunotherapy with purified protein derivative (PPD) is an effective and tolerable therapeutic modality for the treatment of common warts. However, the complete clearance rates are still unsatisfactory. We thought to evaluate the efficacy and safety of adding low dose isotretinoin to intralesional PPD versus PPD monotherapy for viral warts. The study included two groups: Group (A) was treated by intralesional PPD at 2-week intervals until complete clearance or for a maximum of six sessions in addition to an oral placebo. Group (B): was treated with both intralesional PPD and low dose isotretinoin for a 3-month course. There was no statistically significant difference between both groups regarding the therapeutic response. In common warts, the low dose of isotretinoin did not add a true therapeutic value in the studied groups. Perhaps higher doses of isotretinoin could provide a better response, which warrants further investigation.

Isotretinoin-induced inflammatory back pain and sacroiliitis in patients with moderate-to-severe acne vulgaris.

INTRODUCTION: Isotretinoin has been reported to induce inflammatory back pain (IBP) and sacroiliitis in the patients with acne vulgaris. The aim of this study is to investigate the incidence of IBP and sacroiliitis in patients receiving isotretinoin treatment compared with oral antibiotics for acne vulgaris. MATERIALS AND METHODS: A total of 201 patients with moderate-to-severe acne vulgaris who received isotretinoin (n = 100) or oral antibiotics (n = 101) were included in the study. All patients were monthly questioned for IBP symptoms during their treatment. Patients described IBP were also evaluated for sacroiliitis by c-reactive protein, sedimentation rate, HLAB27, and sacroiliac magnetic resonance imaging (MRI). Isotretinoin was discontinued in all patients diagnosed as sacroiliitis, and these patients were reevaluated after 3 months. RESULTS: IBP was observed in 21 (10.4%), and sacroiliitis was detected in 11 (11%) patients on isotretinoin treatment; in oral antibiotic group, we did not observe IBP or sacroiliitis. The incidence of IBP and sacroiliitis differed significantly between the isotretinoin and oral antibiotic groups (p < 0.0001, p = 0.02). Complete regression was observed in the great majority of patients following cessation of isotretinoin. CONCLUSIONS: Our study is the largest prospective controlled study that investigated the incidence of sacroiliitis in patients receiving isotretinoin and compared with patients using oral antibiotics.

Therapeutic agents affecting the immune system and drug-induced inflammatory bowel disease (IBD): A review on etiological and pathogenetic aspects.

In recent years, therapeutic agents affecting the immune system have been largely implemented in the treatment of various hematological, rheumatological and dermatological disorders. Their clinical use has offered important benefits for affected patients and has also ameliorated clinical outcome and prognosis in many cases. Nonetheless, as any treatment, the use of these drugs may be associated with side effects. One of the target organs in such cases is the gastrointestinal tract. In particular, the exacerbation or the onset of inflammatory bowel disease (IBD) in treated patients is not infrequent, although the mechanism of action of these agents may be different. In this review we will focus on the use of therapeutic agents affecting the immune system and the development or exacerbation of IBD, with a mention on the possible underlying pathogenetic mechanisms.