Isotretinoin and timing of procedural interventions: Clinical implications and practical points.

BACKGROUND: For decades, the notion that elective surgeries and cutaneous procedures should be postponed for 6-12 months in patients on, or recently administered with isotretinoin, has been widely accepted. However, some recent studies showed the need for a change in this regard. METHOD: Here, we reviewed the existing data in this regard through searching on PubMed, Google Scholar, and Scopus. All of the relevant papers published in English, until October, 2022, which we could access to their full-texts, were included. RESULTS: We found some recommendations made by plastic surgeons, dermatologists, ENT surgeons, ophthalmologists, orthopedic surgeons, and dentists regarding the correct timing of procedural interventions in patients on, or recently administered with isotretinoin and tried to summarize them to provide a practical guide for clinicians. CONCLUSION: Physicians may discuss with patients regarding the known risk of abnormal wound healing in the setting of systemic isotretinoin treatment and suggest that, when possible, surgical procedures be postponed until the activity of the retinoids has time to subside. It is even more important regarding patients with darker skin phototypes to follow an even more strict guideline.

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

El envejecimiento cutáneo está influido por factores intrínsecos y extrínsecos y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son sobre todo tópicos o son procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen a mujeres de manera mayoritaria, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos o fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos, como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos, presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo parece ser el tratamiento con agentes senolíticos o senomórficos dirigidos específicamente contra células cutáneas senescentes. (AU)

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. (AU)

[Translated article] 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. (AU)

El envejecimiento cutáneo está influido por factores intrínsecos y extrínsecos y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son sobre todo tópicos o son procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen a mujeres de manera mayoritaria, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos o fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos, como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo parece ser el tratamiento con agentes senolíticos o senomórficos dirigidos específicamente contra células cutáneas senescentes. (AU)

A detailed regimen of isotretinoin for the successful treatment of severe keratosis pilaris.

Although a well-known recommended treatment option, there are currently no studies that describe the detailed regimen of isotretinoin for the treatment of primary keratosis pilaris. Based on previous studies involving other hyperkeratotic disorders, this report describes a safe and effective treatment course of isotretinoin for severe keratosis pilaris.

Embryonal Tumor With Multilayered Rosettes of the Parietooccipital Region: A Case Report.

Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.

How safe and effective is prescribing oral isotretinoin to treat acne in patients on renal dialysis? A systematic review.

BACKGROUND: Patients on renal dialysis often develop severe acne. In spite of this, the literature remains scarce about the use of isotretinoin for the treatment of acne in this group of patients, and many clinicians remain apprehensive and hesitant to use it. AIM: To systematically review the literature surrounding the safety and efficacy of isotretinoin for the treatment of acne in patients on renal dialysis. METHODS: Four electronic databases (MEDLINE, Embase, CINAHL, Emcare) were systematically searched in March 2021. The search strategy incorporated the terms 'isotretinoin', 'renal', 'kidney', 'dialysis' and 'acne', along with terms closely related to these. Studies were considered eligible if they reported the use of isotretinoin for treatment of acne in patients with renal impairment or on renal dialysis, and if they had relevant implications to this topic. RESULTS: The search resulted in a total of 63 results. Using the PRISMA approach, 11 articles were deemed relevant to this review: 1 randomized single-blinded placebo-controlled trial, 2 case series, 2 retrospective studies and 6 case reports. Hence the level of evidence was mostly low (Grading of Recommendations, Assessment, Development and Evaluations level 3). CONCLUSION: This review of the literature suggests that low-dose isotretinoin (10-20 mg) can safely and successfully be used to treat severe acne in patients on renal dialysis, leading to a significant improvement in their quality of life. As the current literature on this topic is scarce, more studies would be beneficial to further establish the safe use of isotretinoin in patients on renal dialysis.

Oral isotretinoin: 29 years of medical malpractice cases in the United States.

BACKGROUND: Reviews of malpractice claims in the United States show trends of increasing payments with statistically higher payouts for more debilitating and permanent injuries. OBJECTIVES: To examine lawsuits involving notable associated adverse reactions of isotretinoin. METHODS: Court records of US legal trials from 1985 to 2014 were obtained from a major computerized database: LexisNexis. Data were compiled on the demographics of the defendant and plaintiff, litigation over adverse drug reaction, legal allegations, verdicts, and ruling decisions. RESULTS: Seventy unique cases met inclusion criteria and were selected for review. Forty-four cases cited physicians, and 26 cited a pharmaceutical company. When data from physician and pharmaceutical company litigations were combined, individuals 17 years or younger were more likely to be granted litigation outcomes in their favor compared with adults (P = .0016). Cases alleging failure to monitor were associated with an outcome in favor of the plaintiff (P = .0379). LIMITATIONS: Cases settled or terminated before going to court could not be reviewed. CONCLUSIONS: Familiarity with malpractice trends through precedent-setting cases will increase physician awareness of common pitfalls, potentially mitigating litigation risk and improving patient care.

ARTICLE: Advances in Oral Isotretinoin Therapy.

Since its approval in 1982, oral isotretinoin has revolutionized acne therapy. However, oral isotretinoin use has long been associated with challenges of variable bioavailability and food dependence. It is recommended to ingest oral isotretinoin with a high-fat meal in order to maximize absorption, but many patients fail to adhere to this recommendation. This may lead to inadequate isotretinoin absorption levels. Patients who fail to achieve isotretinoin target cumulative dose are more likely to experience symptom relapse. To address the challenge of traditional isotretinoin variable bioavailability, subsequent isotretinoin formulations have attempted to improve its absorption abilities. In 2014, an isotretinoin formulation utilizing Lidose technology, known as Absorica, showed significant improvements in absorption levels compared to traditional oral isotretinoin in the fasted state. In 2019, isotretinoin absorption levels were further advanced in a new formulation approved by the FDA known as Absorica LD. Utilizing advanced micronization technology that physically reduces the size of the drug molecule, Absorica LD exhibits twice the absorption levels of Absorica under fasting conditions. In the fed state, Absorica LD achieves similar plasma levels to Absorica with a 20 percent lower dose. Absorica LD also produces consistent serum isotretinoin levels irrespective of gastrointestinal contents. By eliminating the “food effect” seen in traditional oral isotretinoin, Absorica LD has the potential to improve patient adherence and long-term patient outcomes. J Drugs Dermatol. 20:5(Suppl):s5-11.

Effectiveness Of Oral Omega 3 In Reducing Mucocutaneous Side Effects Of Oral Isotretinoin In Patients With Acne Vulgaris.

BACKGROUND: Acne vulgaris has been a common clinical condition. Due to. high prevalence and unclear etio-pathogenesis of acne vulgaris, large number of treatment options have been available across the globe. Limited work has been done to explore the options which may manage or prevent these adverse effects and improve the adherence to the prescribed medications. We therefore conducted this trial to look for effectiveness of oral omega 3 in reducing mucocutaneous side effects of oral isotretinoin in patients with acne vulgaris. OBJECTIVE: To look for effectiveness of oral omega 3 in reducing mucocutaneous side effects of oral isotretinoin in patients with acne vulgaris. It was a randomized control trial conducted at Department of Dermatology Pak Emirates Military Hospital Rawalpindi. Ten months, June 2019 to May 2020. METHODS: A total of 60 patients of acne vulgaris put on oral isotretinoin by consultant dermatologist were included in the study. Patients were randomized into groups by lottery method. Group A received the placebo along with oral isotretinoin while Group B received oral omega 3 in standard dose in addition to oral isotretinoin. Comparison was made in both the groups regarding common mucocutaneous side effects. RESULTS: Out of 60patients with acne vulgaris and put on isotretinoin included in the study, 26 (43.3%) received placebo in addition to isotretinoin while 34 (56.7%) received omega 3 in addition to isotretinoin. Forty (66.7%) patients were female while 20 (33.3%) were male. Cheilitis 35 (58.3%) was the commonest side effect followed by lip dryness 33 (55%). Application of chi-square test revealed that cheilitis, lip dryness and xerosis were significantly found in more patients who received placebo as compared to those who received omega 3 along with isotretinoin. CONCLUSION: Mucocutaneous side effects were a very common finding among patients of acne vulgaris managed with isotretinoin. Cheilitis was the most reported mucocutaneous side effects among the target population. This RCT demonstrated that omega 3 was superior to placebo in order to prevent or manage cheilitis, xerosis or dry lips.

Does Systemic Isotretinoin Treatment Constitute a Predisposition to Allergic Sensitization?

13-cis-retinoic acid (13-cRA) is a safe treatment for severe acne, as it has immunomodulatory effects such as enhancing the antigen-presenting activity of epidermal Langerhans cells (LCs) and T-cell activity. The aim of this study was to prospectively show the alteration of sensitization and irritation reactions in acne patients undergoing 13-cRA therapy. This cross-sectional descriptive study consisted of 65 severe to refractory acne patients. The standard thin-layer rapid-use epicutaneous test (T.R.U.E. test) was used to screen sensitization and irritation reactions before and after 3-month 13-cRA treatment. Patch test results after 13-cRA therapy revealed an increase in newly formed sensitization and irritation reactions. Sensitization rate was significantly higher (43.1%) in the second patch test, when compared with the first patch test results (27.7%; P = 0.002). No statistical difference was found in irritation rates. In this study, the sensitization rate was higher after treatment, which could be attributed to the greater antigen penetration due to the disrupted barrier and/or the upregulation of antigen-presenting activity in LC. This would cause a more prominent immune reaction to antigens. Based on these findings, we suggest that 13-cRA may have a sensitization effect, and physicians should be aware of this complication due to 13-cRA treatment. (SKINmed. 2021;19:-0).

Lupus miliaris disseminatus faciei with complete response to isotretinoin.

Lupus miliaris disseminatus faciei is an uncommon type of granulomatous rosacea characterized by a papular eruption in the central regions of the face. A 43-year-old woman presented with an asymptomatic papular eruption on the face that had developed over a period of five months. Physical examination revealed multiple, small, reddish-brown papules, distributed symmetrically on the central area of the face. A biopsy was taken, showing dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells. No foreign bodies were found in granulomas and no mycobacterial or fungal components were detected. On the basis of these findings, the diagnosis of lupus miliaris disseminatus faciei was made. The patient was given oral isotretinoin 20mg/day with initial slow response. After 6 months' treatment the lesions completely disappeared. Many authors consider this entity to be a variant of granulomatous rosacea. It is a chronic condition that primarily affects young adults. Treatment is usually unsatisfactory. Therapies with corticosterois, tetracyclines, retinoids, clofazimine or topical tacrolimus have been described but there is a lack of controlled studies and convincing results. Our success with a 6-month course of low dose isotretinoin suggests consideration of a longer trial prior to abandoning this as treatment.

Differences in Depression and Distress Between Acne Patients on Isotretinoin vs Oral Antibiotics.

BACKGROUND: Little is known regarding differential effects of systemic anti-acne treatments on mental health. OBJECTIVE: To determine whether differences exist in mental health outcomes between acne patients treated with isotretinoin versus oral antibiotics (doxycycline, minocycline, or tetracycline). METHODS: Population study utilizing the 2004-2017 Medical Expenditure Panel Survey. Depressive symptoms were assessed using Patient Health Questionnaire 2 (PHQ-2); psychological distress was measured by the Kessler 6-Item Psychological Distress Scale (K6). Acne patients completed both the PHQ-2 and K6 during treatment with isotretinoin or oral antibiotics. Lower scores on both measures indicate better mental health outcomes. RESULTS: After adjusting for socio-demographic characteristics, patients on isotretinoin had fewer depressive symptoms than patients on oral antibiotics, as measured by mean PHQ-2 scores (isotretinoin 0.280 vs oral antibiotics 0.656, difference=0.337, P<0.01). The adjusted comparison also showed patients on isotretinoin had less psychological distress than patients on oral antibiotics, as measured by K6 scores (isotretinoin 2.494 vs oral antibiotics 3.433, difference=0.759, P=0.043). LIMITATIONS: No direct assessment of acne severity. CONCLUSION: Acne patients on isotretinoin experienced less depressive symptoms and psychological distress as compared to oral antibiotics. J Drugs Dermatol. 2021;20(2):172-177. doi:10.36849/JDD.5559.

Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032.

PURPOSE: Previously our randomized phase III trial demonstrated that immunotherapy including dinutuximab, a chimeric anti-GD2 mAb, GM-CSF, and IL2 improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers. PATIENTS AND METHODS: Patients recieved six cycles of isotretinoin with or without five cycles of immunotherapy which consists of dinutuximab with GM-CSF alternating with IL2. Accrual was discontinued early due to meeting the protocol-defined stopping rule for efficacy, as assessed by 2-year event-free survival (EFS). Plasma levels of dinutuximab, soluble IL2 receptor (sIL2R), and human anti-chimeric antibody (HACA) were assessed by ELISA. Fcγ receptor 2A and 3A genotypes were determined by PCR and direct sequencing. RESULTS: For 226 eligible randomized patients, 5-year EFS was 56.6 ± 4.7% for patients randomized to immunotherapy (n = 114) versus 46.1 ± 5.1% for those randomized to isotretinoin only (n = 112; P = 0.042). Five-year overall survival (OS) was 73.2 ± 4.2% versus 56.6 ± 5.1% for immunotherapy and isotretinoin only patients, respectively (P = 0.045). Thirteen of 122 patients receiving dinutuximab developed HACA. Plasma levels of dinutuximab, HACA, and sIL2R did not correlate with EFS/OS, or clinically significant toxicity. Fcγ receptor 2A and 3A genotypes did not correlate with EFS/OS. CONCLUSIONS: Immunotherapy with dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample size than originally planned, yet clinically significant long-term differences in survival were observed.

Cryotherapy plus low-dose oral isotretinoin vs cryotherapy only for the treatment of anogenital warts: a randomized clinical trial.

BACKGROUND: Anogenital warts are a common human papillomavirus infection. They cause emotional distress, especially when they are in the anogenital region. Cryotherapy is a first-line treatment. Previous clinical trials and case series have reported variable results with retinoids (isotretinoin) as adjuvant therapy. OBJECTIVE: To determine the safety and efficacy of low-dose oral isotretinoin as adjuvant treatment of anogenital warts. METHODS: Forty-six patients with anogenital warts were randomly assigned to isotretinoin + cryotherapy (n = 23) or only cryotherapy (n = 23). Patients were allocated via an interactive web-based randomization system. Evaluators were blinded to treatments. Isotretinoin 20 mg/daily + cryotherapy or cryotherapy were prescribed for 6 weeks. Patients were followed for 4 months. Genotyping of lesions was performed before treatment started. Dermatology Life Quality Index (DLQI) and Columbia-Suicide Severity Rating Scale (C-SSRS) were measured at the beginning and end of therapy. All patients completed the study. RESULTS: Both Groups had 50% clearance at the end of treatment. Recurrence in the combined group was not significantly lower than in the cryotherapy group (P = 0.59). Improvement was observed in the DLQI of all patients in both groups (P = 0.001). No suicidal intention was detected with the C-SSRS. Two patients (one in each group) had liver function test abnormalities after treatment. CONCLUSION: Combined therapy showed a slight not significant efficacy for anogenital warts in Hispanic patients. Low-dose isotretinoin seems to be safe even when it is used with cryotherapy on anogenital warts. TRIAL REGISTRATION: On April 25, 2019 with registration number DE19-00004, CONBIOÉTICA-19-CEI-001-20160404. Prospectively registered.

Prescribing Isotretinoin for Transgender Patients: A Call to Action and Recommendations.

Case Scenerio: A 26-year-old patient presents to the dermatology clinic with severe nodulocystic scarring acne. The patient identifies as a transgender male and notes that he has been receiving hormone replacement therapy for the past 4 years with weekly intramuscular testosterone injections.

Isotretinoin in the treatment of hidradenitis suppurativa: a retrospective study.

OBJECTIVE: Isotretinoin has been used off-label in hidradenitis suppurativa (HS) patients with variable results, making it difficult to predict which patients with HS are likely to benefit. MATERIAL AND METHODS: We conducted a retrospective review of HS patients who presented to UCLA HS clinic between August 2009 and March 2018 and collected data on their demographics, reported history of isotretinoin treatment for HS, and treatment response. A number of patient variables were analyzed between the responders and non-responders to see if any were associated with a higher likelihood of a beneficial response. RESULTS: Of the 209 patients, 39 (18.7%) reported prior treatment with isotretinoin. A beneficial response to isotretinoin was reported by 14 (35.9%) patients, while 25 (64.1%) patients reported no response. When comparing responders to non-responders, responders were more likely to have a history of pilonidal cyst (p = .024). Having a concomitant history of regular or cystic acne did not appear to enhance HS treatment response to isotretinoin. CONCLUSIONS: Our data suggest that for HS patients, having a history of pilonidal cyst is associated with a beneficial response to isotretinoin.

Acne in the first three decades of life: An update of a disorder with profound implications for all decades of life.

Acne vulgaris is a chronic, inflammatory, skin condition that involves the pilosebaceous follicles and is influenced by a variety of factors including genetics, androgen-stimulation of sebaceous glands with abnormal keratinization, colonization with Cutibacterium acnes (previously called Propionibacterium acnes), and pathological immune response to inflammation. Acne can occur at all ages and this discussion focuses on the first three decades of life. Conditions that are part of the differential diagnosis and/or are co-morbid with acne vulgaris are also considered. Acne in the first year of life includes neonatal acne (acne neonatorum) that presents in the first four weeks of life and infantile acne that usually presents between 3 and 6 months of the first year of life with a range of 3 to 16 months after birth. Acne rosacea is a chronic, inflammatory, skin condition that is distinct from acne vulgaris, typically presents in adults, and has four main types: erythemato-telangiectatic, papulopustular, phymatous and ocular. Treatment options for acne vulgaris include topical retinoids, topical benzoyl peroxide, antibiotics (topical, oral), oral contraceptive pills, isotretinoin, and others. Management must consider the increasing impact of antibiotic resistance in the 21st century. Psychological impact of acne can be quite severe and treatment of acne includes awareness of the potential emotional toll this disease may bring to the person with acne as well as assiduous attention to known side effects of various anti-acne medications (topical and systemic). Efforts should be directed at preventing acne-caused scars and depigmentation on the skin as well as emotional scars within the person suffering from acne.