Marius Rademaker Hot Spots 2018 Very Low-Dose Isotretinoin

Very low-dose isotretinoin in mild to moderate papulopustular rosacea; a retrospective review of 52 patients.



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.


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.


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.


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.

As a hill walker I have climbed a number of hills including Popocatepetl (5452m), Kilimanjaro (5895m), Machupuchare (to 5105m) and various Munro’s in Scotland and New Zealand. I now keep to lower but longer distance walks such as the Camino de Santiago (Spain), the Lycian Way (Turkey) and the te Araroa Trail of New Zealand (3000 km). Unsuccessful ventures include the infamous 1979 Fastnet race (fortunately retired due to gear failure), singing  and the clarinet.

Making sense of the effects of the cumulative dose of isotretinoinin acne vulgaris



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.


This study aimed to determine the influence of daily and cumulative dosage on relapse in acne.


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.


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.


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.

Adverse effects of topical corticosteroids in paediatric eczema: Australasian consensus statement


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.

Isotretinoin: dose, duration and relapse. What does 30 years of usage tell us?


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 isotretinoinfrom 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.
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