586 Commentaries
Light on fumaric acid esters therapy for psoriasis
(DMF) and three salts of monoethylfumarate.1,3,7 DMF can also be used as monotherapy and is not inferior compared with Fumadermâ.3,8 An important disadvantage of the use of FAEs is the relatively slow onset of action. As psoriasis is a chronic disease with a well-known significant impact on health-related quality of life, accelerating response to treatment is worth achieving. Weisenseel et al. suggested in the conclusion of their study that the combination of FAE plus UVB might induce a faster therapeutic response, which would be useful, particularly in the first 3 months of FAE therapy.9 This concept has now been confirmed by the results of the present RCT.1 The most frequent adverse events of FAEs are usually not severe, occur during the first months of treatment and consist of gastrointestinal disorders, flushing, transient eosinophilia and lymphopenia.4 In our university hospital in Leiden we have the clinical experience that FAE therapy is effective in about 50% of patients. In these responders FAE therapy can be continued with high efficacy and minor side-effects for many years.3,7 Once remission has been achieved the dose may be reduced to a lower dose to maintain clinical response while minimizing the risk of side-effects.5 Although severe side-effects of FAE therapy are rare, these can be life threatening. Progressive multifocal leukoencephalopathy (PML), which is caused by a brain infection with JC polyomavirus, is a potentially fatal condition.5,10 PML appears to be related to FAE-induced CD4 and CD8 cell cytopenia and older age of the patients.10 Renal impairment has been described as another potential, more severe side-effect of FAE therapy, but may be the result of an initial overdose of FAEs.5 Slow titration of the dose and careful monitoring of renal function should be able to prevent renal impairment. In conclusion, FAE therapy is a relatively safe treatment for patients with moderate-to-severe psoriasis. Combination with UVB significantly accelerates the improvement of clinical symptoms during the first 3 months of treatment as has been demonstrated by Tzaneva et al.1 In responders, FAE therapy can be continued with high efficacy and few side-effects for many years, but the treating physician should always be aware of possible severe side-effects.
DOI: 10.1111/bjd.16272
Conflicts of interest
Conflicts of interest None to declare. Division of Dermatology, University of Toronto, Sunnybrook Health Sciences Centre (M1-722), 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5 E-mail:
[email protected]
P . F L E M I N G iD
References 1 Gulliver W. Long-term prognosis in patients with psoriasis. Br J Dermatol 2008; 159(Suppl. 2):2–9. 2 Lynde CW, Poulin Y, Vender R et al. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol 2014; 71:141–50. 3 Papp KA, Leonardi CL, Blauvelt A et al. Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3). Br J Dermatol 2018; 178:674–81. 4 Gordon KB, Blauvelt A, Papp KA et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med 2016; 375:345–56. 5 Langley RG, Elewski BE, Lebwohl M et al. Secukinumab in plaque psoriasis – results of two phase 3 trials. N Engl J Med 2014; 371:326–38. 6 Kagami D, Rizzo HL, Kurtz SE et al. IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J Immunol 2010; 185:5453–62. 7 Girolomoni G, Mrowietz U, Paul C. Psoriasis: rationale for targeting interleukin-17. Br J Dermatol 2012; 167:717–24. 8 Wu JJ, Poon KT, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol 2012; 148:1244–50. 9 Strober B, Leonardi C, Papp KA et al. Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: etanercept comparisons and integrated data. J Am Acad Dermatol 2017; 76:432–40.e17.
None to declare. Linked Article: Tzaneva et al. Br J Dermatol 2018; 178:682–688. The current issue of the British Journal of Dermatology features a randomized controlled trial (RCT) showing a faster therapeutic response in patients with psoriasis when fumaric acid esters (FAEs) are combined with narrowband ultraviolet (UV) B therapy.1 FAEs have been used as systemic therapy for psoriasis since their introduction by the German chemist Schweckendiek in 1959.2–4 Limited evidence suggests that FAEs are superior to placebo and equally effective as methotrexate.2,5 However, FAEs are less effective than secukinumab during the first 6 months of treatment.6 Fumadermâ (Biogen Idec GmbH, Germany), which was used in the study by Tzaneva et al.,1 is a mixture of dimethylfumarate
Department of Dermatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands E-mail:
[email protected]
J.N. BOUWES BAVINCK E.J. VAN ZUUREN
References 1 Tzaneva S, Geroldinger A, Trattner H, Tanew A. Fumaric acid esters in combination with a 6-week course of narrowband ultraviolet B provides an accelerated response compared with fumaric acid esters monotherapy in patients with moderate-to-severe plaque psoriasis: a randomized prospective clinical study. Br J Dermatol 2018; 178:682–88.
Ó 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
British Journal of Dermatology (2018) 178, pp583–594
Commentaries 2 Atwan A, Ingram JR, Abbott R et al. Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol 2016; 175:873–81. 3 Lijnen R, Otters E, Balak D et al. Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study. J Dermatolog Treat 2016; 27:31–6. 4 Walker F, Adamczyk A, Kellerer C et al.; Study group. Fumadermâ in daily practice for psoriasis: dosing, efficacy and quality of life. Br J Dermatol 2014; 171:1197–205. 5 Smith D. Fumaric acid esters for psoriasis: a systematic review. Ir J Med Sci 2017; 186:161–77. 6 Sticherling M, Mrowietz U, Augustin M et al. Secukinumab is superior to fumaric acid esters in treating patients with moderate-to-severe plaque psoriasis who are naive to systemic treatments: results from the randomized controlled PRIME trial. Br J Dermatol 2017; 177:1024–32. 7 Hoefnagel JJ, Thio HB, Willemze R et al. Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis. Br J Dermatol 2003; 149:363–9. 8 Mrowietz U, Szepietowski JC, Loewe R et al. Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumadermâand placebo-controlled trial (BRIDGE). Br J Dermatol 2017; 176:615–23. 9 Weisenseel P, Reich K, Griemberg W et al. Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST). J Dtsch Dermatol Ges 2017; 15:180–6. 10 Gieselbach RJ, Muller-Hansma AH, Wijburg MT et al. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases. J Neurol 2017; 264:1155–64.
Tobacco smoking and hidradenitis suppurativa: associated disease and an important modifiable risk factor DOI: 10.1111/bjd.16261 Linked Article: Garg et al. Br J Dermatol 2018; 178:709–714. Tobacco smoking is exceedingly common among patients with hidradenitis suppurativa (HS), with a reported prevalence as high as 70–90%.1–3 Prior studies have shown that smoking is not only a commonly reported comorbidity among patients with HS but also a potential risk factor for more severe or treatment-refractory disease.3–5 However, these prior studies have been relatively small and homogeneous, and the conclusions drawn have not been entirely uniform. They also have not clearly established the temporal relationship between smoking and HS. The question of whether smoking increases the risk of developing HS de novo or is instead a consequence of the disease (perhaps stemming from the high rates of anxiety and depression among such patients6) has remained unanswered. In this month’s issue of the British Journal of Dermatology, Garg et al. report their analysis of HS incidence among tobacco smokers in a large and diverse cohort of patients from across the U.S.7 © 2018 British Association of Dermatologists
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The study utilizes a multi-health system data analytics and research platform that includes 50 million patients. While the study design is retrospective, the methodology enabled the authors to measure the incidence of new HS diagnoses among nearly 4 million tobacco smokers during a 3-year period. Adjusting for age, sex, race and obesity, the odds of a new diagnosis of HS were increased by 90% among those who smoked tobacco (odds ratio 190, 95% confidence interval 184–196). This increase remained consistent across all demographic subgroups. While there are inherent limitations in a retrospective study of this nature – including the ability to diagnose and classify smokers and patients with HS accurately from administrative data, or to establish true causality – the present study supplies more complete epidemiological information regarding the link between smoking and HS onset. For the practising clinician, the results of this analysis provide further reason to query patients about smoking status and counsel them about smoking cessation. This approach should apply not only to those diagnosed with HS but also those perceived to be at risk, including (potentially) those with early HS-spectrum disease, a positive family history of HS, or other follicular occlusion disorders (e.g. dissecting cellulitis, acne or pilonidal cyst). These results add to a growing body of literature establishing this connection and raising awareness of tobacco smoking as a modifiable risk factor affecting HS incidence, severity and treatment response. At the same time, recent literature has associated HS with a significantly increased risk of adverse cardiovascular outcomes and all-cause mortality, independent of confounding factors.8 Engagement in dermatological care may therefore represent a crucial opportunity to address modifiable cardiovascular risk factors, of which tobacco smoking is among the most important. By better defining the association between tobacco smoking and HS, the work by Garg et al. should help to empower dermatologists to engage their patients on this important topic and will improve their ability to provide patient education and counselling that is evidence-based.
Acknowledgments The author would like to acknowledge Joslyn Sciacca-Kirby for her critical revision of this commentary.
Conflicts of interest None to declare. Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104-4211, U.S.A. E-mail:
[email protected]
R. MICHELETTI
References 1 Canoui-Poitrine F, Revuz JE, Wolkenstein P et al. Clinical characteristics of a series of French patients with hidradenitis suppurativa,
British Journal of Dermatology (2018) 178, pp583–594
