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Background: A potential link between isotretinoin and sexual dysfunction has been reported in various studies. However, such an association has not been explored within the context of a literature review until now., Objectives: To evaluate the methodology and quality of studies investigating this association, and to examine the definitions of sexual dysfunction used., Methods: A scoping review approach was used to identify peer-reviewed research articles. The search terms used were 'isotretinoin', 'sexual dysfunction', 'erectile dysfunction', 'ejaculatory disorders', 'decreased libido', 'female sexual interest', 'female arousal disorder', 'libido', 'pelvic pain', 'dyspareunia', 'orgasmic disorder', 'impotence', 'ovaries', 'fertility' and 'menstrual irregularity'., Results: In total, 55 peer-reviewed manuscripts were included, consisting of 8 animal studies and 46 human studies with 2420 patients. Of the studies in humans, there were 18 case reports or case series, 2 case-control studies, 4 cross-sectional studies, 6 longitudinal studies, 3 pharmacovigilance reports and 13 cohort studies. The most frequently observed dose range of isotretinoin was 0.5-1.0 mg kg-1 per day, usually for a duration of 1-6 months. More than half of the studies (54%, n = 25) reported a beneficial or neutral effect of isotretinoin on sexual function. The majority of studies (89%, n = 41) were categorized as Oxford Evidenced-Based Medicine level 4., Conclusions: This scoping review revealed very weak evidence supporting a link between isotretinoin and sexual dysfunction. Notably, the diverse definitions of sexual dysfunction pose a significant challenge for comparative analysis. The authors advocate for a standardized definition of sexual dysfunction and a framework for determining causality in order to contribute to a more comprehensive understanding of the relationship between isotretinoin and sexual dysfunction., Competing Interests: Conflicts of interest MR has been an investigator for Douglas Pharmaceuticals, NZ and has published a number of articles on low-dose isotretinoin., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflicts of interest M.R. has been an investigator for Douglas Pharmaceuticals, NZ and has published a number of articles on low-dose isotretinoin.

Discoid (nummular) eczema is a common and distinctive eczema variant, which has not been studied in depth. Although the principles of management are similar to that of classic atopic dermatitis, distinctions are made due to its unique presentation and persistent clinical course in children. Australian and New Zealand dermatologists with an interest in paediatric eczema developed a consensus narrative to assist clinicians in diagnosing and treating this subtype of eczema. Identifying triggers, potent topical corticosteroids under occlusion, skin barrier support and management of pruritus are first-line therapies, however, many eventually require systemic immunomodulatory agents., (© 2022 Australasian College of Dermatologists.)

A significant barrier to the usage of isotretinoin has been concerns regarding its adverse effect profile. The dose-dependent mucocutaneous side effects of isotretinoin are well recognized and easily managed, particularly if a lower dose is used. A possible association with depression has gained widespread media attention and is a source of concern for many patients and their carers, but data from prospective studies and recent meta-analyses have been reassuring. Furthermore, there has been much confusion amongst both patients and physicians regarding a possible association with inflammatory bowel disease, as well the ocular and rheumatological adverse effects of isotretinoin. We provide an update on the evidence surrounding the adverse effects of isotretinoin and discuss practical strategies to prevent and manage these adverse effects. We also discuss appropriate laboratory monitoring for patients taking isotretinoin.

Since it was first approved for use in 1982, isotretinoin has revolutionized the management of acne vulgaris. Despite almost four decades of widespread use, uncertainty still exists regarding the manner in which it is best prescribed. In this review, we provide an update on the pharmacokinetics, mechanism of action, contraindications, interactions, and appropriate dosing schedule of isotretinoin in the treatment of acne. We also discuss the safety of performing concurrent dermatological procedures in patients taking isotretinoin., (© 2020 the International Society of Dermatology.)

The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus., (© 2017 The Australasian College of Dermatologists.)

Background/objectives: Rosacea is a chronic inflammatory disorder that affects up to 10% of the population. Standard treatments include topical azelaic acid and metronidazole or systemic tetracyclines. Isotretinoin has generally been restricted to severe disease, often at a dose of 0.5-1.0 mg/kg/day., Method: Retrospective review of open-label isotretinoin (initial dose 20 mg/day, with dose adjustments according to response), in patients with mild to moderate papulopustular rosacea., Results: Altogether 52 patients (33 women), mean age 48 years (range 18-86) were treated with isotretinoin over a 5-year period. All patients were commenced on 20-mg isotretinoin/day which was reduced to 10-20 mg once to five times a week (equivalent to 5 mg/day) in 67%, but increased in 15% (who all had additional acne) to 30-40 mg/day. In terms of dose/kg/day, 29% received ≤ 0.1 mg/kg/day, 46% received 0.11-0.25 mg/kg/day and 10% received > 0.5 mg/kg/day. Treatment was continued for 57 weeks (range 9-223). Six patients (12%) did not attend follow up. Of the remainder, in 91% (42/46) the rosacea had cleared or was excellent. One patient stopped isotretinoin because of its adverse effects. Two-fifths (44%) suffered no adverse effect. The most common side-effect was cheilitis in half (52%), which was mild in all but one patient., Conclusion: Very low-dose isotretinoin (e.g., 10-20 mg once to five times a week, equivalent to 5 mg/day) is an effective treatment for mild to moderate papulopustular rosacea and is well tolerated., (© 2016 The Australasian College of Dermatologists.)

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti-inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4 weeks, then every 3-6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre-conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti-tumour necrosis factor biologics., (© 2016 The Australasian College of Dermatologists.)

Background: The importance of the cumulative dose of isotretinoin with respect to relapse of acne vulgaris remains controversial. Although guidelines recommend 0.5-1.0 mg/kg/d to a minimum cumulative dose of 120 mg/kg, there has been a trend toward the use of lower daily dosages with no reference to cumulative dose., Objectives: This study aimed to determine the influence of daily and cumulative dosage on relapse in acne., Methods: Charts of patients with acne treated with isotretinoin were reviewed. Demographic details and daily cumulative doses and duration were compared between patients who received one course and two or more courses, respectively., Results: Of 1453 patients, 326 (22.4%) received a second course of treatment (study population). The remainder served as controls (n = 1127). Dosage varied from 10 mg/week to 1.1 mg/kg/d, cumulative dosage from 1 to >300 mg/kg, and duration of treatment from 8 weeks to 5 years. Compared with controls, patients who received a second course were more likely to be women (61 vs. 47%; P < 0.001) and received higher daily (0.71 vs. 0.58 mg/kg/d; P < 0.001) and cumulative (126 vs. 101 mg/kg; P < 0.001) doses. Patients treated with very low doses (e.g. 10 mg three times per week) and/or low cumulative doses (e.g. 25-50 mg/kg) did not relapse more often than controls., Conclusions: Neither daily nor cumulative dosages influenced relapse of acne vulgaris in patients treated with varying doses of isotretinoin as long as treatment was continued for ≥2 months after the acne had completely resolved., (© 2015 The International Society of Dermatology.)

Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian and New Zealand children. Severe eczema costs over AUD 6000/year per child in direct medical, hospital and treatment costs as well as time off work for caregivers and untold distress for the family unit. In addition, it has a negative impact on a child's sleep, education, development and self-esteem. The treatment of atopic eczema is complex and multifaceted but a core component of therapy is to manage the inflammation with topical corticosteroids (TCS). Despite this, TCS are often underutilised by many parents due to corticosteroid phobia and unfounded concerns about their adverse effects. This has led to extended and unnecessary exacerbations of eczema for children. Contrary to popular perceptions, (TCS) use in paediatric eczema does not cause atrophy, hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when used appropriately as per guidelines. In rare cases, prolonged and excessive use of potent TCS has contributed to striae, short-term hypothalamic-pituitary-adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate periorificial rosacea. TCS are very effective treatments for eczema. When they are used to treat active eczema and stopped once the active inflammation has resolved, adverse effects are minimal. TCS should be the cornerstone treatment of atopic eczema in children., (© 2015 The Australasian College of Dermatologists.)

Background: Despite acne persisting into adulthood in up to 50% of the population, very few therapeutic studies have been performed in this age group., Objectives: To assess the efficacy of 5 mg/day isotretinoin in adult acne., Methods: An investigator initiated, industry-sponsored, randomized, double-blind, placebo-controlled, parallel-group clinical study of isotretinoin 5 mg/day in the treatment of low-grade adult acne for 16 weeks followed by an open-label phase of 16 weeks. Group 1 received 32 weeks of 5 mg isotretinoin/day; Group 2 first received 16 weeks of placebo, followed by 16 weeks open-label 5 mg isotretinoin/day. Patients were followed for a further 10 weeks off treatment. The primary end-point was the difference in acne lesion count and disability score after 16 weeks isotretinoin compared to placebo. Secondary end-points included differences in these counts/scores after 32 weeks of isotretinoin compared to baseline, and after 10 weeks off treatment, compared to end of treatment (week 32)., Results: There were highly significant differences (P < 0.0001) in acne lesion count, Dermatology Life Quality Index and self-assessment after 16 weeks of isotretinoin, compared to placebo (both per protocol and intention to treat). Acne lesions fell significantly, within 4 weeks of 5 mg isotretinoin/day (Group 1) and continued to fall during 32 weeks of treatment [acne lesion count (mean ± SD): 11.3 ± 8.1 (baseline), 3.6 ± 5.5 (week 16), 1.3 ± 3.1 (week 32), P < 0.0001)]. There was a similar significant reduction in acne lesion count in Group 2, but only from week 20, 4 weeks after starting open-label 5 mg isotretinoin. Adverse effects were minimal., Conclusions: Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects., (© 2013 The Authors Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.)

With 30 years of clinical use, it is appropriate to review the use of isotretinoin. We now understand that retinoids influence cellular growth, differentiation, morphogenesis and apoptosis, inhibit tumour promotion and malignant cell growth, exert immuno-modulatory actions and alter cellular cohesiveness. This has expanded the indications of isotretinoin from just acne and rosacea to a wide range of inflammatory and malignant skin disorders. While the standard dose of 0.5 to 1 mg/kg per day for 4 months to a cumulative dose of 120-140 mg/kg per day has served us well in the management of acne vulgaris, there is emerging evidence that much lower dosages (as low as 5 mg/day) are just as effective but have significantly fewer adverse effects. Relapse of acne vulgaris continues to be a problem but we are beginning to recognise that this is related less to the cumulative dose and more to the length of sebaceous gland suppression. Other factors important for relapse include a macrocomedonal pattern of acne, smoking and age, both younger (under 14 years) and older (over 25 years). After 30 years of use, we now understand why isotretinoin is such an effective drug. Not only does it clear acne in almost all patients, long-term remission can be achieved in 70-80% of patients with a single course. Important changes in the use of isotretinoin include using a lower daily dose for a longer period of time. New indications continue to emerge, particularly as a potential treatment for both intrinsic and extrinsic (photo) aging. Teratogenicity however, remains a very significant concern., (© 2012 The Author Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.)

Background/objectives: Isotretinoin has revolutionized the management of acne vulgaris. However, concerns continue regarding the adverse effect profile of isotretinoin. This study aims to review the adverse effects experienced by patients started on isotretinoin by a single dermatologist., Methods: Retrospective chart review of 1743 patients started on isotretinoin for various dermatological conditions over a 6-year period. Details of the dose of isotretinoin used, concomitant medications, adverse effects and outcome were recorded., Results: One-fifth (18.5%) of patients reported no adverse effects during the study period. Cheilitis was the most commonly reported adverse effect, affecting 78% of users, followed by eczema and tiredness, seen in 12% each. However, these were clearly dose-dependent, as the group treated with doses of isotretinoin under 0.25 mg/kg/day only reported cheilitis in 47%, eczema in 7% and tiredness in 5%, compared with 96%, 16% and 18%, respectively, in those treated with more than 0.75 mg/gm/day. Twenty-four patients (1.4%) stopped isotretinoin because of adverse effects; a further three patients complained of severe adverse effects on at least one occasion, but continued taking the medication. The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2). There were no reported instances of suicidal ideation or attempted suicide., Conclusions: Other than the two oral contraceptive failures, there were no serious adverse events recorded during this review period. Isotretinoin is a very effective medication with a low adverse-effect profile when used at lower doses., (© 2010 The Author. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.)

Background: Fumaric acid esters (FAE) are effective against psoriasis vulgaris and monomethylfumarate (MMF) is believed to be the most bioactive metabolite of this medication. Earlier we found that the beneficial effects of FAE medication are accompanied by a downregulation of type 1 cytokine production by T-helper (Th) lymphocytes, which are important as they maintain a type 1 cytokine [interferon (IFN)-gamma, interleukin (IL)-2] environment in the skin lesions of psoriasis vulgaris patients and once maximal beneficial effects are obtained type 2 cytokine production is also decreased. In vitro MMF selectively induced type 2 cytokine production by primed Th lymphocytes, whereas type 1 cytokine production by and profileration of T lymphocytes were unaffected., Objectives: As dendritic cells (DCs) present in these skin lesions play a key role in the activation of Th lymphocytes, we investigated the effects of MMF on monocyte-derived DC differentiation., Methods: Monocytes were differentiated into immature (i) DCs by cytokines with or without MMF. To establish whether these cells were differentiated into iDCs, we analysed the expression of cell surface molecules on these cells and the capacity to capture antigens using flow cytometry. Next, we determined whether these MMF-incubated (MMF-)iDCs could be matured by lipopolysaccharide (LPS) and whether MMF affected this responsiveness as well. For this purpose we measured cytokine production by these LPS-stimulated cells (MMF-DCs) using enzyme-linked immunosorbent assays as well as their ability to activate naive Th lymphocytes., Results: The presence of MMF during the differentiation of monocytes into iDCs resulted in cells that retained low levels of CD14 and hardly expressed CD1a. Upon maturation, these MMF-iDCs upregulated CD83 and costimulatory molecules and HLA-DR on their surface, indicating that these cells respond to LPS, albeit less than control iDCs. In addition, in response to LPS, MMF-iDCs did not decrease the capacity to capture antigens when compared with control iDCs. MMF-DCs hardly produced IL-12p70 and IL-10 and low levels of tumour necrosis factor (TNF)-alpha, whereas IL-8 produced by MMF-DCs and control DCs did not differ. Moreover, MMF-DCs were less able to induce IFN-gamma production by naive Th lymphocytes compared with control DCs. The production of IL-4 and IL-10 by naive Th lymphocytes cocultured with MMF-DCs did not differ from that by T cells cocultured with control DCs., Conclusions: MMF inhibited the monocyte-derived DC differentiation resulting in cells that cannot be appropriately matured to DCs. Consequently, these MMF-DCs are less effective than control DCs in stimulating type 1 cytokine, but not type 2 cytokine production, in Th lymphocytes. This general immunomodulatory effect may in part explain the beneficial effects of FAE therapy in psoriasis.

A 55-year-old woman with severe, chronic, treatment-resistant ulcerating necrobiosis lipoidica of the shins was commenced on oral cyclosporin at a dose of 2.5 mg/kg/day. Improvement started within 1 week of commencing treatment, and the lesions healed completely over 8 months. Further ulceration occurred 3 months after discontinuing cyclosporin, with improvement on reintroduction of cyclosporin. There have been four previous case reports of healing of treatment-resistant ulcerating necrobiosis lipoidica with cyclosporin.

Atopic dermatitis is an increasingly prevalent common childhood disease. While the majority of patients have mild disease, atopic dermatitis can cause considerable distress to patients and their caregivers, with significant social and financial cost to families. With a prevalence of 15 - 20% in Western countries, atopic dermatitis also has a considerable health and societal cost to the community. Many new treatments have been shown to be therapeutically effective, particularly in severe disease, including cyclosporin A (Neoral, Novartis AG), interferon, tacrolimus (Fujisawa Pharmaceutical Co. Ltd.) and iv. immunoglobulin. These are expensive when compared to standard treatments like emollients and topical corticosteroids and have significant adverse effects that limit their use. Additional costs related to monitoring are incurred and the long-term safety of these treatments is yet to be determined. However, an advantage over more traditional therapies is their ability to produce benefits even after treatment ceases. Treatments that produce long-term remissions have a greater likelihood of being cost-effective. With monetary constraints on healthcare and the importance governments place on reducing drug costs, economic evaluations are becoming an increasingly important factor for drug acceptance. Those evaluating cost-effectiveness should pay particular attention to the potential reduction in indirect and intangible costs. Unfortunately, there is a dearth of cost-effectiveness studies in atopic eczema and this needs to be addressed with some urgency.

Medicament allergies in patients with chronic leg ulcers is well recognized. In the past, topical antibiotics, rubber additives and wool alcohols have been the most common reported allergens. Allergy to topical corticosteroids has been reported. We document two cases of multiple corticosteroid allergy in patients with chronic leg ulceration.