Journal of Dermatological Treatment ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: https://www.tandfonline.com/loi/ijdt20 Dermatological indications for the use of isotretinoin beyond acne Emily Forbat, Faisal R. Ali & Firas Al-Niaimi To cite this article: Emily Forbat, Faisal R. Ali & Firas Al-Niaimi (2018) Dermatological indications for the use of isotretinoin beyond acne, Journal of Dermatological Treatment, 29:7, 698-705, DOI: 10.1080/09546634.2018.1445194 To link to this article: https://doi.org/10.1080/09546634.2018.1445194 Accepted author version posted online: 26 Feb 2018. Published online: 14 Mar 2018. Submit your article to this journal Article views: 503 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ijdt20 JOURNAL OF DERMATOLOGICAL TREATMENT 2018, VOL. 29, NO. 7, 698–705 https://doi.org/10.1080/09546634.2018.1445194 REVIEW ARTICLE Dermatological indications for the use of isotretinoin beyond acne Emily Forbata, Faisal R. Alib and Firas Al-Niaimib aChelsea and Westminster Hospital, London, UK; bDermatological Surgery & Laser Unit, St John’s Institute of Dermatology, Guy’s Cancer Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK ABSTRACT ARTICLE HISTORY While the use of isotretinoin has revolutionized the treatment of acne vulgaris, isotretinoin is increasingly Received 3 February 2018 recognized as a useful therapeutic option for many other cutaneous conditions. We review the evidence Accepted 14 February 2018 underlying the use of isotretinoin for a variety of dermatological indications including hidradenitis suppu- KEYWORDS rativa, sebaceous gland pathology, rosacea, scarring alopecia, cosmetic dermatology, and non-melanoma skin cancer prophylaxis amongst other uses, and thus consider alternative uses within dermatology prac- Isotretinoin; retinoids; rosacea; cosmetic tice. The studies found benefit of isotretinoin, however most trials lacked statistical power and in many dermatology; hidradenitis cases the use was limited to case series. Isotretinoin, if used within the correct cohort with appropriate suppurativa pretreatment counseling regarding side-effects, is a well-tolerated medication with potential as either an adjunctive treatment or a second-line agent in those recalcitrant cases unresponsive to first-line therapy. Introduction 33 case studies/case series (6,7,9–39), two retrospective reviews (8,40), six randomized control trials (RCTs) (41–46), two random- Isotretinoin, also known as 13-cis-retinoic acid, is a synthetic drug ized comparative trials (47,48), one open-label non-randomized best known for its treatment of acne (1). The mechanism of action prospective pilot study (49), one retrospective comparison study results from isotretinoin-induced expression of apoptotic protein (50), one single-blind randomized study (51), two case-controlled necrosis factor, and a recent review suggests that apoptosis is the randomized clinical studies (52,53), and one cohort study (54). culprit for the multitude of well-known side-effects of isotretinoin (2). Isotretinoin regulates cell proliferation by binding to nuclear Within these studies, 2996 patients were treated between 1985 retinoic acid receptors. Furthermore, it is said to decrease poly- and 2017 (Table 1). amine synthesis and keratinization which contributes to its anti- inflammatory and anti-prolific properties (3). Isotretinoin was first Hidradenitis suppurativa approved for the treatment of acne in 1982 (4). The UK license for isotretinoin was first established in 2001, and the European direct- A retrospective review has been carried out assessing the use of ive advises the treatment of acne to start at a dose of 0.5 mg/kg isotretinoin for the treatment of hidradenitis suppurativa (HS) (39). and be avoided in children under 12 years old, with strict preg- There have been a multitude of papers which refute the benefit nancy prevention strategies. Furthermore, liver function and lipid of isotretinoin in patients with concomitant HS and acne (56,57). monitoring are required to be checked prior to treatment, Treatment with isotretinoin in these cases of dual pathology often 1 month post-initiation of treatment, and 3 months thereafter (5). demonstrated a minimal response of HS, despite both HS and The longest duration of use of isotretinoin from our review was 7 acne both being associated with ductal abnormalities (58). Huang years, in which low-dose isotretinoin was used intermittently to and Kirchhof argue that isotretinoin should not be dismissed, as treat erythema dyschromicum perstans (6). The age range of careful literature evaluation in fact demonstrates that in the cor- patients reviewed in this article varied from just under 7 months rect cohort – i.e. those with mild/moderate HS, females, or con- of age to 64 years old (7,8). comitant acne – complete remission has been achieved (8). Further research is required, as the use of isotretinoin in HS is Method sparse. We conducted a literature search in October 2017, to review the Sebaceous gland pathology current uses of isotretinoin in dermatology beyond the treatment of acne. A PubMed, search was carried out, with the search criteria A randomized comparative trial comparing alternate daily use of ‘Isotretinoin’ & ‘Dermatology’. Only articles published in English 10 mg isotretinoin versus topical anti-seborrheic treatment in were included. Review articles were omitted, unless they specific- moderate to severe seborrhea and seborrheic dermatitis (N ¼ 45) ally analyzed studies within them. Articles on the use of isotreti- over 6 months, demonstrated a significantly greater reduction in noin and acne were also excluded. scalp sebum secretion (p ¼ .004) in the isotretinoin arm after 3 months (47). Patients were not followed-up beyond 3 months and Results the dosage was not weight-dependent. Tagliolatto et al. treated 20 patients with sebaceous hyperplasia with isotretinoin (1 mg/kg Our search identified 1125 studies, of which 49 met the criteria of per day) for 2 months; the average number of skin lesions assessing the use of isotretinoin beyond acne. In total, there were decreased from 24 to 2 per patient (p < .05) (59). Isotretinoin is CONTACT Dr Emily Forbat [email protected] Chelsea and Westminster Hospital, 369 Fulham Rd, London SW10 9NH, UK ß 2018 Informa UK Limited, trading as Taylor & Francis Group Table 1. Studies on the use of isotretinoin beyond acne. Study Indication Aim Patient number Dose Findings Part 1: Inflammatory dermatoses and infectious disorders Inflammatory dermatoses Huang and Kirchhof (8) Hidradenitis A retrospective N ¼ 25 0.45 ± 0.20 mg/kg/day for 6.8 ± 4.3 32% no response, suppurativa chart review months 32% partial response, 36% complete response Rademaker (40) Papulopustular A retrospective N ¼ 52 20 mg isotretinoin/day 12% did not attend follow up. rosacea review reduced to 10–20 mg once to five Those that did attend, 91% (42/46): rosacea cleared or times a week in 67%, was excellent. or One patient stopped due to SE. increased in 15% (who all had add- 44% no SE. itional acne) to 30–40 mg/day The most common SE was cheilitis in 52%, which was mild in all but one patient Sbidian et al. (41) Papulopustular A RCT N ¼ 156 0.25 mg/kg/day Post 4-month treatment at least 90% reduction of pap- rosacea versus ules/papules in comparison to pre-treatment. placebo for 4 months Significantly higher skindex score in treated group versus placebo group. 58.3% of 51 patients who agreed to 4 month FU, demon- strated relapse Rallis and Korfitis (20) Granulomatous A case study N ¼ 1 0.7 mg/kg/day for 24 weeks. 3-month FU: satisfactory rosacea 5-month FU: total remission 6-month post-cessation of treatment: no recurrence. Uslu et al. (22) Rosacea A case series N ¼ 25 20 mg/day for 4 months, tapering the Papule and pustule, erythema index, sebum level, dose within the following 6 months. dermatologist’s and patient’s erythema scores, and dermatologist’s sebum scores: significantly lower, one- month post-therapy versus pre-therapy (p < .05). 45% relapse within median FU of 11 months Gollnick et al. (52) Rosacea Doxycycline- and placebo- N ¼ 573 One of three different dosages of iso- Isotretinoin 0.3 mg/kg most effective dose versus placebo. controlled, randomized tretinoin With IST: clinical study 0.1 mg Complete remission in 24% (14%) 0.3 mg Marked improvement 57% (55%) versus the bracketed fig- 0.5 mg ures for doxycycline (per kg body weight) SE: increase incidence of dermatitis facialis with 0.5 mg/kg þ doxycycline (100 mg daily for 14 days, then 50 mg daily) or placebo JOURNAL OF DERMATOLOGICAL TREATMENT for 12 weeks. Mortazavi et al. (51) Psoriasis vulgaris A single blind N ¼ 37 Intervention group: narrow band ultra- Psoriasis Area Severity Index (PASI) scores demonstrated randomized violet B (NBUVB) þ isotretinoin no significant difference between efficacies of two clinical study (0.5 mg/kg/day) treatments Control group: narrow band ultraviolet But B (NBUVB) þ isotretinoin Isotretinoin þ NBUVB can reduce phototherapy sessions (0.5 mg/kg/day) and cumulative NBUVB dose required. Al-Shobaili and Al- Pustular psoriasis A case study N ¼ 1 Initially started on methotrexate No relapse after methotrexate stopped after the isotreti- Khenaizan (30) 15 mg/week for 6 weeks, (relapsed noin was commenced. when methotrexate was reduced.) Excellent control when isotretinoin continued at 40 mg/ Therefore, day in conjunction with topical steroids. 40 mg/day per oral (0.75 mg/kg/day) isotretinoin was added, and 3 weeks later methotrexate was stopped. Infectious disorders Al-Hamamy, Salman and Plane Warts A case series N ¼ 26 Mean of 0.5 mg/kg/day for 2 months. 73.07% complete response Abdulsattar (19) 26.92% no response at the end of treatment. 78.94% who had complete response, no recurrence at 4- month follow up 699 (continued) Table 1. Continued 700 Study Indication Aim Patient number Dose Findings Georgala et al (44) Condylomata acumi- A randomized Placebo- N ¼ 60 Randomly assignment to receive Group 1: nata of the cervix controlled trial Group 1: isotretinoin, 0.5 mg/kg daily 32.1% responded completely E.