Complementary alternative medicine (CAM) has been described by the National Center for Complementary and Integrative Medicine as “health care approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice.”1 Although this definition is broad, CAM encompasses therapies such as traditional Chinese medicine, herbal therapies, dietary supplements, and mind/body interventions. The use of CAM has grown, and according to a 2012 National Center for Complementary and Integrative Health survey, more than 30% of US adults and 12% of US children use health care approaches that are considered outside of conventional medical practice. In a survey study of US adults, at least 17.7% of respondents said they had taken a dietary supplement other than a vitamin or mineral in the last year.1 Data from the 2007 National Health Interview Survey showed that the prevalence of adults with skin conditions using CAM was 84.5% compared to 38.3% in the general population.2 In addition, 8.15 million US patients with dermatologic conditions reported using CAM over a 5-year period.3 Complementary alternative medicine has emerged as an alternative or adjunct to standard treatments, making it important for dermatologists to understand the existing literature on these therapies. Herein, we review the current evidence-based literature that exists on CAM for the treatment of atopic dermatitis (AD), psoriasis, and alopecia areata (AA).
Atopic Dermatitis
Atopic dermatitis is a chronic, pruritic, inflammatory skin condition with considerable morbidity.4,5 The pathophysiology of AD is multifactorial and includes aspects of barrier dysfunction, IgE hypersensitivity, abnormal cell-mediated immune response, and environmental factors.6 Atopic dermatitis also is one of the most common inflammatory skin conditions in adults, affecting more than 7% of the US population and up to 20% of the total population in developed countries. Of those affected, 40% have moderate or severe symptoms that result in a substantial impact on quality of life.7 Despite advances in understanding disease pathology and treatment, a subset of patients opt to defer conventional treatments such as topical and systemic corticosteroids, antibiotics, nonsteroidal immunomodulators, and biologics. Patients may seek alternative therapies when typical treatments fail or when the perceived side effects outweigh the benefits.5,8 The use of CAM has been well described in patients with AD; however, the existing evidence supporting its use along with its safety profile have not been thoroughly explored. Herein, we will discuss some of the most well-studied supplements for treatment of AD, including evening primrose oil (EPO), fish oil, and probiotics.5
Oral supplementation with polyunsaturated fatty acids commonly is reported in patients with AD.5,8 The idea that a fatty acid deficiency could lead to atopic skin conditions has been around since 1937, when it was suggested that patients with AD had lower levels of blood unsaturated fatty acids.9 Conflicting evidence regarding oral fatty acid ingestion and AD disease severity has emerged.10,11 One unsaturated fatty acid, γ-linolenic acid (GLA), has demonstrated anti-inflammatory properties and involvement in barrier repair.12 It is converted to dihomo-GLA in the body, which acts on cyclooxygenase enzymes to produce the inflammatory mediator prostaglandin E1. The production of GLA is mediated by the enzyme delta-6 desaturase in the metabolization of linoleic acid.12 However, it has been reported that in a subset of patients with AD, a malfunction of delta-6 desaturase may play a role in disease progression and result in lower baseline levels of GLA.10,12 Evening primrose oil and borage oil contain high amounts of GLA (8%–10% and 23%, respectively); thus, supplementation with these oils has been studied in AD.13
EPO for AD Studies investigating EPO (Oenothera biennis) and its association with AD severity have shown mixed results. A Cochrane review reported that oral borage oil and EPO were not effective treatments for AD,14 while another larger randomized controlled trial (RCT) found no statistically significant improvement in AD symptoms.15 However, multiple smaller studies have found that clinical symptoms of AD, such as erythema, xerosis, pruritus, and total body surface area involved, did improve with oral EPO supplementation when compared to placebo, and the results were statistically significant (P=.04).16,17 One study looked at different dosages of EPO and found that groups ingesting both 160 mg and 320 mg daily experienced reductions in eczema area and severity index score, with greater improvement noted with the higher dosage.17 Side effects associated with oral EPO include an anticoagulant effect and transient gastrointestinal tract upset.8,14 There currently is not enough evidence or safety data to recommend this supplement to AD patients.
Although topical use of fatty acids with high concentrations of GLA, such as EPO and borage oil, have demonstrated improvement in subjective symptom severity, most studies have not reached statistical significance.10,11 One study used a 10% EPO cream for 2 weeks compared to placebo and found statistically significant improvement in patient-reported AD symptoms (P=.045). However, this study only included 10 participants, and therefore larger studies are necessary to confirm this result.18 Some RCTs have shown that topical coconut oil, sunflower seed oil, and sandalwood album oil improve AD symptom severity, but again, large controlled trials are needed.5 Unfortunately, many essential oils, including EPO, can cause a secondary allergic contact dermatitis and potentially worsen AD.19
Fish Oil for AD Fish oil is a commonly used supplement for AD due to its high content of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids exert anti-inflammatory effects by displacing arachidonic acid, a proinflammatory omega-6 fatty acid thought to increase IgE, as well as helper T cell (TH2) cytokines and prostaglandin E2.8,20 A 2012 Cochrane review found that, while some studies revealed mild improvement in AD symptoms with oral fish oil supplementation, these RCTs were of poor methodological quality.21 Multiple smaller studies have shown a decrease in pruritus, severity, and physician-rated clinical scores with fish oil use.5,8,20,22 One study with 145 participants reported that 6 g of fish oil once daily compared to isoenergetic corn oil for 16 weeks identified no statistically significant differences between the treatment groups.20 No adverse events were identified in any of the reported trials. Further studies should be conducted to assess the utility and dosing of fish oil supplements in AD patients.
Probiotics for AD Probiotics consist of live microorganisms that enhance the microflora of the gastrointestinal tract.8,20 They have been shown to influence food digestion and also have demonstrated potential influence on the skin-gut axis.23 The theory that intestinal dysbiosis plays a role in AD pathogenesis has been investigated in multiple studies.23-25 The central premise is that low-fiber and high-fat Western diets lead to fundamental changes in the gut microbiome, resulting in fewer anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).23-25 These SCFAs are produced by microbes during the fermentation of dietary fiber and are known for their effect on epithelial barrier integrity and anti-inflammatory properties mediated through G protein–coupled receptor 43.25 Multiple studies have shown that the gut microbiome in patients with AD have higher proportions of Clostridium difficile, Escherichia coli, and Staphylococcus aureus and lower levels of Bifidobacterium, Bacteroidetes, and Bacteroides species compared to healthy controls.26,27 Metagenomic analysis of fecal samples from patients with AD have shown a reduction of Faecalibacterium prausnitzii species when compared to controls, along with a decreased SCFA production, leading to the hypothesis that the gut microbiome may play a role in epithelial barrier disruption.28,29 Systematic reviews and smaller studies have found that oral probiotic use does lead to AD symptom improvement.8,30,31 A systematic review of 25 RCTs with 1599 participants found that supplementation with oral probiotics significantly decreased the SCORAD (SCORing Atopic Dermatitis) index in adults and children older than 1 year with AD but had no effect on infants younger than 1 year (P<.001). They also found that supplementation with diverse microbes or Lactobacillus species showed greater benefit than Bifidobacterium species alone.30 Another study analyzed the effect of oral Lactobacillus fermentum (1×109 CFU twice daily) in 53 children with AD vs placebo for 16 weeks. This study found a statically significant decrease in SCORAD index between oral probiotics and placebo, with 92% (n=24) of participants supplementing with probiotics having a lower SCORAD index than baseline compared to 63% (n=17) in the placebo group (P=.01).31 However, the use of probiotics for AD treatment has remained controversial. Two recent systematic reviews, including 39 RCTs of 2599 randomized patients, found that the use of currently available oral probiotics made little or no difference in patient-rated AD symptoms, investigator-rated AD symptoms, or quality of life.32,33 No adverse effects were observed in the included studies. Unfortunately, the individual RCTs included were heterogeneous, and future studies with standardized probiotic supplementation should be undertaken before probiotics can be routinely recommended.
The use of topical probiotics in AD also has recently emerged. Multiple studies have shown that patients with AD have higher levels of colonization with S aureus, which is associated with T-cell dysfunction, more severe allergic skin reactions, and disruptions in barrier function.34,35 Therefore, altering the skin microbiota through topical probiotics could theoretically reduce AD symptoms and flares. Multiple RCTs and smaller studies have shown that topical probiotics can alter the skin microbiota, improve erythema, and decrease scaling and pruritus in AD patients.35-38 One study used a heat-treated Lactobacillus johnsonii 0.3% lotion twice daily for 3 weeks vs placebo in patients with AD with positive S aureus skin cultures. The S aureus load decreased in patients using the topical probiotic lotion, which correlated with lower SCORAD index that was statistically significant compared to placebo (P=.012).36 More robust studies are needed to determine if topical probiotics should routinely be recommended in AD.
Psoriasis
Psoriasis vulgaris is a chronic inflammatory skin condition characterized by pruritic, hyperkeratotic, scaly plaques.39,40 Keratinocyte hyperproliferation is central to psoriasis pathogenesis and is thought to be a T-cell–driven reaction to antigens or trauma in genetically predisposed individuals. Standard treatments for psoriasis currently include topical corticosteroids and anti-inflammatories, oral immunomodulatory therapy, biologic agents, and phototherapy.40 The use of CAM is highly prevalent among patients with psoriasis, with one study reporting that 51% (n=162) of psoriatic patients interviewed had used CAM.41 The most common reasons for CAM use included dissatisfaction with current treatment, adverse side effects of standard therapy, and patient-reported attempts at “trying everything to heal disease.”42 Herein, we will discuss some of the most frequently used supplements for treatment of psoriatic disease.39
Fish Oil for Psoriasis One of the most common supplements used by patients with psoriasis is fish oil due to its purported anti-inflammatory qualities.20,39 The consensus on fish oil supplementation for psoriasis is mixed.43-45 Multiple RCTs have reported reductions in psoriasis area and severity index (PASI) scores or symptomatic improvement with variable doses of fish oil.44,46 One RCT found that using EPA 1.8 g once daily and DHA 1.2 g once daily for 12 weeks resulted in significant improvement in pruritus, scaling, and erythema (P<.05).44 Another study reported a significant decrease in erythema (P=.02) and total body surface area affected (P=.0001) with EPA 3.6 g once daily and DHA 2.4 g once daily supplementation compared to olive oil supplementation for 15 weeks.46 Alternatively, multiple studies have failed to show statistically significant improvement in psoriatic symptoms with fish oil supplementation at variable doses and time frames (14–216 mg daily EPA, 9–80 mg daily DHA, from 2 weeks to 9 months).40,47,48 Fish oil may impart anticoagulant properties and should not be started without the guidance of a physician. Currently, there are no data to make specific recommendations on the use of fish oil as an adjunct psoriatic treatment.
Curcumin for Psoriasis Another supplement routinely utilized in patients with psoriasis is curcumin,40,49,50 a yellow phytochemical that is a major component of the spice turmeric. Curcumin has been shown to inhibit certain proinflammatory cytokines including IL-17, IL-6, IFN-γ, and tumor necrosis factor α and has been regarded as having immune-modulating, anti-inflammatory, and antibacterial properties.40,50 Curcumin also has been reported to suppress phosphorylase kinase, an enzyme that has increased activity in psoriatic plaques that correlates with markers of psoriatic hyperproliferation.50,51 When applied topically, turmeric microgel 0.5% has been reported to decrease scaling, erythema, and psoriatic plaque thickness over the course of 9 weeks.50 In a nonrandomized trial with 10 participants, researchers found that phosphorylase kinase activity levels in psoriatic skin biopsies of patients applying topical curcumin 1% were lower than placebo and topical calcipotriol applied in combination. The lower phosphorylase kinase levels correlated with level of disease severity, and topical curcumin 1% showed a superior outcome when compared to topical calcipotriol.40,49 Although these preliminary results are interesting, there still are not enough data at this time to recommend topical curcumin as a treatment of psoriasis. No known adverse events have been reported with the use of topical curcumin to date.
Oral curcumin has poor oral bioavailability, and 40% to 90% of oral doses are excreted, making supplementation a challenge.40 In one RCT, oral curcumin 2 g daily (using a lecithin-based delivery system to increase bioavailability) was administered in combination with topical methylprednisolone aceponate 0.1%, resulting in significant improvement in psoriatic symptoms and lower IL-22 compared to placebo and topical methylprednisolone aceponate (P<.05).52 Other studies also have reported decreased PASI scores with oral curcumin supplementation.53,54 Adverse effects reported with oral curcumin included gastrointestinal tract upset and hot flashes.53 Although there is early evidence that may support the use of oral curcumin supplementation for psoriasis, more data are needed before recommending this therapy.
Indigo Naturalis for Psoriasis Topical indigo naturalis (IN) also has been reported to improve psoriasis symptoms.39,53,55 The antipsoriatic effects are thought to occur through the active ingredient in IN (indirubin), which is responsible for inhibition of keratinocyte proliferation.40 One study reported that topical IN 1.4% containing indirubin 0.16% with a petroleum ointment vehicle applied to psoriatic plaques over 12 weeks resulted in a significant decrease in PASI scores from 18.9 at baseline to 6.3 after IN treatment (P<.001).56 Another study found that over 8 weeks, topical application of IN 2.83% containing indirubin 0.24% to psoriatic plaques vs petroleum jelly resulted in 56.3% (n=9) of the treatment group achieving PASI 75 compared to 0% in the placebo group (n=24).55 One deterrent in topical IN treatment is the dark blue pigment it contains; however, no other adverse outcomes were found with topical IN treatment.56 Larger clinical trials are necessary to further explore IN as a potential adjunct treatment in patients with mild psoriatic disease. When taken orally, IN has caused gastrointestinal tract disturbance and elevated liver enzyme levels.57
Herbal Toxicities It is important to consider that oral supplements including curcumin and IN are widely available over-the-counter and online without oversight by the US Food and Drug Administration.40 Herbal supplements typically are compounded with other ingredients and have been associated with hepatotoxicity as well as drug-supplement interactions, including abnormal bleeding and clotting.58 There exists a lack of general surveillance data, making the true burden of herbal toxicities more difficult to accurately discern. Although some supplements have been associated with anti-inflammatory qualities and disease improvement, other herbal supplements have been shown to possess immunostimulatory characteristics. Herbal supplements such as spirulina, chlorella, Aphanizomenon flos-aquae, and echinacea have been shown to upregulate inflammatory pathways in a variety of autoimmune skin conditions.59
Probiotics for Psoriasis Data on probiotic use in patients with psoriasis are limited.23 A distinct pattern of dysbiosis has been identified in psoriatic patients, as there is thought to be depletion of beneficial bacteria such as Bifidobacterium, lactobacilli, and F prausnitzii and increased colonization with pathogenic organisms such as Salmonella, E coli, Heliobacter, Campylobacter, and Alcaligenes in psoriasis patients.23,59,60 Early mouse studies have supported this hypothesis, as mice fed with Lactobacillus pentosus have developed milder forms of imiquimod-induced psoriasis compared to placebo,55 and mice receiving probiotic supplementation have lower levels of psoriasis-related proinflammatory markers such as TH17-associated cytokines.61 Another study in humans found that daily oral Bifidobacterium infantis supplementation for 8 weeks in psoriatic patients resulted in lower C-reactive protein and tumor necrosis factor α levels compared to placebo.62 Studies on the use of topical probiotics in psoriasis have been limited, and more research is needed to explore this relationship.38 At this time, no specific recommendations can be made on the use of probiotics in psoriatic patients.
Alopecia Areata
Alopecia areata is nonscarring hair loss that can affect the scalp, face, or body.63,64 The pathophysiology of AA involves the attack of the hair follicle matrix epithelium by inflammatory cells without hair follicle stem cell destruction. The precise events that precipitate these episodes are unknown, but triggers such as emotional or physical stress, vaccines, or viral infections have been reported.65 There is no cure for AA, and current treatments such as topical minoxidil and corticosteroids (topical, intralesional, or oral) vary widely in efficacy.64 Although Janus kinase inhibitors recently have shown promising results in the treatment of AA, the need for prolonged therapy may be frustrating to patients.66 Severity of AA also can vary, with 30% of patients experiencing extensive hair loss.67 The use of CAM has been widely reported in AA due to high levels of dissatisfaction with existing therapies.68 Herein, we discuss the most studied alternative treatments used in AA
Garlic and Onion for Alopecia One alternative treatment that has shown promising initial results is application of topical garlic and onion extracts to affected areas.64,69,70 Both garlic and onion belong to the Allium genus and are high in sulfur and phenolic compounds.70 They have been reported to possess bactericidal and vasodilatory activity,71 and it has been hypothesized that onion and garlic extracts may induce therapeutic effects through induction of a mild contact dermatitis.70 One single-blinded, controlled trial using topical crude onion juice reported that 86.9% (n=20) of patients had full regrowth of hair compared to 13.3% (n=2) of patients treated with a tap water placebo at 8 weeks (P<.0001). This study also noted that patients using onion juice had a higher rate of erythema at application site; unfortunately, the study was small with only 38 patients.70 Another double-blind RCT using garlic gel 5% with betamethasone valerate cream 0.1% compared to betamethasone valerate cream alone found that after 3 months, patients in the garlic gel group had increased terminal hairs and smaller patch sizes compared to the betamethasone valerate cream group.69 More studies are needed to confirm these results.
Aromatherapy With Essential Oils for Alopecia Another alternative treatment in AA that has demonstrated positive results is aromatherapy skin massage with essential oils to patches of alopecia.72 Although certain essential oils, such as tea tree oil, have been reported to have specific antibacterial or anti-inflammatory properties, essential oils have been reported to cause allergic contact dermatitis and should be used with caution.73,74 For example, tea tree oil is a well-known cause of allergic contact dermatitis, and positive patch testing has ranged from 0.1% to 3.5% in studies assessing topical tea tree oil 5% application.75 Overall, there have been nearly 80 essential oils implicated in contact dermatitis, with high-concentration products being one of the highest risk factors for an allergic contact reaction.76 One RCT compared daily scalp massage with essential oils (rosemary, lavender, thyme, and cedarwood in a carrier oil) to daily scalp massage with a placebo carrier oil in AA patients. The results showed that at 7 months of treatment, 44% (n=19) of the aromatherapy group showed improvement compared to 15% (n=6) in the control group.77 Another study used a similar group of essential oils (thyme, rosemary, atlas cedar, lavender, and EPO in a carrier oil) with daily scalp massage and reported similar improvement of AA symptoms compared to control; the investigators also reported irritation at application site in 1 patient.78 There currently are not enough data to recommend aromatherapy skin massage for the treatment of AA, and this practice may cause harm to the patient by induction of allergic contact dermatitis.
There have been a few studies to suggest that the use of total glucosides of peony with compound glycyrrhizin and oral Korean red ginseng may have beneficial effects on AA treatment, but efficacy and safety data are lacking, and these therapies should not be recommended without more information.64,79,80
Final Thoughts
Dermatologic patients frequently are opting for CAM,2 and although some therapies may show promising initial results, alternative medicines also can drive adverse events.19,30 The lack of oversight from the US Food and Drug Administration on the products leads to many unknowns for true health risks with over-the-counter CAM supplements.40 As the use of CAM becomes increasingly common among dermatologic patients, it is important for dermatologists to understand the benefits and risks, especially for commonly treated conditions. More data is needed before CAM can be routinely recommended.
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Hosking A-M, Juhasz M, Atanaskova Mesinkovska N. Complementary and alternative treatments for alopecia: a comprehensive review. Skin Appendage Disord. 2019;5:72-89.
Tkachenko E, Okhovat J-P, Manjaly P, et al. Complementary & alternative medicine for alopecia areata: a systematic review [published online December 20, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.12.027
Ismail FF, Sinclair R. JAK inhibition in the treatment of alopecia areata—a promising new dawn? Expert Rev Clin Pharmacol. 2020;13:43-51. doi:10.1080/17512433.2020.1702878
van den Biggelaar FJHM, Smolders J, Jansen JFA. Complementary and alternative medicine in alopecia areata. AM J Clin Dermatol. 2010;11:11-20.
Hussain ST, Mostaghimi A, Barr PJ, et al. Utilization of mental health resources and complementary and alternative therapies for alopecia areata: a U.S. survey. Int J Trichology. 2017;9:160-164.
Hajheydari Z, Jamshidi M, Akbari J, et al. Combination of topical garlic gel and betamethasone valerate cream in the treatment of localized alopecia areata: a double-blind randomized controlled study. Indian J Dermatol Venereol Leprol. 2007;73:29-32.
Sharquie KE, Al-Obaidi HK. Onion juice (Allium cepa L.), a new topical treatment for alopecia areata. J Dermatol. 2002;29:343-346.
Burian JP, Sacramento LVS, Carlos IZ. Fungal infection control by garlic extracts (Allium sativum L.) and modulation of peritoneal macrophages activity in murine model of sporotrichosis. Braz J Biol. 2017;77:848-855.
Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy. successful treatment for alopecia areata. Arch Dermatol. 1998;134:1349-1352.
Lakshmi C, Srinivas CR. Allergic contact dermatitis following aromatherapy with valiya narayana thailam—an ayurvedic oil presenting as exfoliative dermatitis. Contact Dermatitis. 2009;61:297-298.
Carson CF, Hammer KA, Riley TV. Melaleuca alternifolia (tea tree) oil: a review of antimicrobial and other medicinal properties. Clin Microbiol Rev. 2006;19:50-62.
Groot AC de, Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis. 2016;75:129-143.
de Groot AC, Schmidt E. Essential oils, part I: introduction. dermatitis. 2016;27:39-42.
Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy. successful treatment for alopecia areata. Arch Dermatol. 1998;134:1349-1352.
Ozmen I, Caliskan E, Arca E, et al. Efficacy of aromatherapy in the treatment of localized alopecia areata: a double-blind placebo controlled study. Gulhane Med J. 2015;57:233.
Oh GN, Son SW. Efficacy of Korean red ginseng in the treatment of alopecia areata. J Ginseng Res. 2012;36:391-395.
Yang D-Q, You L-P, Song P-H, et al. A randomized controlled trial comparing total glucosides of paeony capsule and compound glycyrrhizin tablet for alopecia areata. Chin J Integr Med. 2012;18:621-625.
From the University of Wisconsin School of Medicine and Public Health, Madison. Dr. Shields is from the Department of Dermatology.
The authors report no conflict of interest.
Correspondence: Bridget E. Shields, MD, 1 S Park St, University of Wisconsin School of Medicine and Public Health, Department of Dermatology, Madison, WI 53711 ([email protected]).
From the University of Wisconsin School of Medicine and Public Health, Madison. Dr. Shields is from the Department of Dermatology.
The authors report no conflict of interest.
Correspondence: Bridget E. Shields, MD, 1 S Park St, University of Wisconsin School of Medicine and Public Health, Department of Dermatology, Madison, WI 53711 ([email protected]).
Author and Disclosure Information
From the University of Wisconsin School of Medicine and Public Health, Madison. Dr. Shields is from the Department of Dermatology.
The authors report no conflict of interest.
Correspondence: Bridget E. Shields, MD, 1 S Park St, University of Wisconsin School of Medicine and Public Health, Department of Dermatology, Madison, WI 53711 ([email protected]).
Complementary alternative medicine (CAM) has been described by the National Center for Complementary and Integrative Medicine as “health care approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice.”1 Although this definition is broad, CAM encompasses therapies such as traditional Chinese medicine, herbal therapies, dietary supplements, and mind/body interventions. The use of CAM has grown, and according to a 2012 National Center for Complementary and Integrative Health survey, more than 30% of US adults and 12% of US children use health care approaches that are considered outside of conventional medical practice. In a survey study of US adults, at least 17.7% of respondents said they had taken a dietary supplement other than a vitamin or mineral in the last year.1 Data from the 2007 National Health Interview Survey showed that the prevalence of adults with skin conditions using CAM was 84.5% compared to 38.3% in the general population.2 In addition, 8.15 million US patients with dermatologic conditions reported using CAM over a 5-year period.3 Complementary alternative medicine has emerged as an alternative or adjunct to standard treatments, making it important for dermatologists to understand the existing literature on these therapies. Herein, we review the current evidence-based literature that exists on CAM for the treatment of atopic dermatitis (AD), psoriasis, and alopecia areata (AA).
Atopic Dermatitis
Atopic dermatitis is a chronic, pruritic, inflammatory skin condition with considerable morbidity.4,5 The pathophysiology of AD is multifactorial and includes aspects of barrier dysfunction, IgE hypersensitivity, abnormal cell-mediated immune response, and environmental factors.6 Atopic dermatitis also is one of the most common inflammatory skin conditions in adults, affecting more than 7% of the US population and up to 20% of the total population in developed countries. Of those affected, 40% have moderate or severe symptoms that result in a substantial impact on quality of life.7 Despite advances in understanding disease pathology and treatment, a subset of patients opt to defer conventional treatments such as topical and systemic corticosteroids, antibiotics, nonsteroidal immunomodulators, and biologics. Patients may seek alternative therapies when typical treatments fail or when the perceived side effects outweigh the benefits.5,8 The use of CAM has been well described in patients with AD; however, the existing evidence supporting its use along with its safety profile have not been thoroughly explored. Herein, we will discuss some of the most well-studied supplements for treatment of AD, including evening primrose oil (EPO), fish oil, and probiotics.5
Oral supplementation with polyunsaturated fatty acids commonly is reported in patients with AD.5,8 The idea that a fatty acid deficiency could lead to atopic skin conditions has been around since 1937, when it was suggested that patients with AD had lower levels of blood unsaturated fatty acids.9 Conflicting evidence regarding oral fatty acid ingestion and AD disease severity has emerged.10,11 One unsaturated fatty acid, γ-linolenic acid (GLA), has demonstrated anti-inflammatory properties and involvement in barrier repair.12 It is converted to dihomo-GLA in the body, which acts on cyclooxygenase enzymes to produce the inflammatory mediator prostaglandin E1. The production of GLA is mediated by the enzyme delta-6 desaturase in the metabolization of linoleic acid.12 However, it has been reported that in a subset of patients with AD, a malfunction of delta-6 desaturase may play a role in disease progression and result in lower baseline levels of GLA.10,12 Evening primrose oil and borage oil contain high amounts of GLA (8%–10% and 23%, respectively); thus, supplementation with these oils has been studied in AD.13
EPO for AD Studies investigating EPO (Oenothera biennis) and its association with AD severity have shown mixed results. A Cochrane review reported that oral borage oil and EPO were not effective treatments for AD,14 while another larger randomized controlled trial (RCT) found no statistically significant improvement in AD symptoms.15 However, multiple smaller studies have found that clinical symptoms of AD, such as erythema, xerosis, pruritus, and total body surface area involved, did improve with oral EPO supplementation when compared to placebo, and the results were statistically significant (P=.04).16,17 One study looked at different dosages of EPO and found that groups ingesting both 160 mg and 320 mg daily experienced reductions in eczema area and severity index score, with greater improvement noted with the higher dosage.17 Side effects associated with oral EPO include an anticoagulant effect and transient gastrointestinal tract upset.8,14 There currently is not enough evidence or safety data to recommend this supplement to AD patients.
Although topical use of fatty acids with high concentrations of GLA, such as EPO and borage oil, have demonstrated improvement in subjective symptom severity, most studies have not reached statistical significance.10,11 One study used a 10% EPO cream for 2 weeks compared to placebo and found statistically significant improvement in patient-reported AD symptoms (P=.045). However, this study only included 10 participants, and therefore larger studies are necessary to confirm this result.18 Some RCTs have shown that topical coconut oil, sunflower seed oil, and sandalwood album oil improve AD symptom severity, but again, large controlled trials are needed.5 Unfortunately, many essential oils, including EPO, can cause a secondary allergic contact dermatitis and potentially worsen AD.19
Fish Oil for AD Fish oil is a commonly used supplement for AD due to its high content of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids exert anti-inflammatory effects by displacing arachidonic acid, a proinflammatory omega-6 fatty acid thought to increase IgE, as well as helper T cell (TH2) cytokines and prostaglandin E2.8,20 A 2012 Cochrane review found that, while some studies revealed mild improvement in AD symptoms with oral fish oil supplementation, these RCTs were of poor methodological quality.21 Multiple smaller studies have shown a decrease in pruritus, severity, and physician-rated clinical scores with fish oil use.5,8,20,22 One study with 145 participants reported that 6 g of fish oil once daily compared to isoenergetic corn oil for 16 weeks identified no statistically significant differences between the treatment groups.20 No adverse events were identified in any of the reported trials. Further studies should be conducted to assess the utility and dosing of fish oil supplements in AD patients.
Probiotics for AD Probiotics consist of live microorganisms that enhance the microflora of the gastrointestinal tract.8,20 They have been shown to influence food digestion and also have demonstrated potential influence on the skin-gut axis.23 The theory that intestinal dysbiosis plays a role in AD pathogenesis has been investigated in multiple studies.23-25 The central premise is that low-fiber and high-fat Western diets lead to fundamental changes in the gut microbiome, resulting in fewer anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).23-25 These SCFAs are produced by microbes during the fermentation of dietary fiber and are known for their effect on epithelial barrier integrity and anti-inflammatory properties mediated through G protein–coupled receptor 43.25 Multiple studies have shown that the gut microbiome in patients with AD have higher proportions of Clostridium difficile, Escherichia coli, and Staphylococcus aureus and lower levels of Bifidobacterium, Bacteroidetes, and Bacteroides species compared to healthy controls.26,27 Metagenomic analysis of fecal samples from patients with AD have shown a reduction of Faecalibacterium prausnitzii species when compared to controls, along with a decreased SCFA production, leading to the hypothesis that the gut microbiome may play a role in epithelial barrier disruption.28,29 Systematic reviews and smaller studies have found that oral probiotic use does lead to AD symptom improvement.8,30,31 A systematic review of 25 RCTs with 1599 participants found that supplementation with oral probiotics significantly decreased the SCORAD (SCORing Atopic Dermatitis) index in adults and children older than 1 year with AD but had no effect on infants younger than 1 year (P<.001). They also found that supplementation with diverse microbes or Lactobacillus species showed greater benefit than Bifidobacterium species alone.30 Another study analyzed the effect of oral Lactobacillus fermentum (1×109 CFU twice daily) in 53 children with AD vs placebo for 16 weeks. This study found a statically significant decrease in SCORAD index between oral probiotics and placebo, with 92% (n=24) of participants supplementing with probiotics having a lower SCORAD index than baseline compared to 63% (n=17) in the placebo group (P=.01).31 However, the use of probiotics for AD treatment has remained controversial. Two recent systematic reviews, including 39 RCTs of 2599 randomized patients, found that the use of currently available oral probiotics made little or no difference in patient-rated AD symptoms, investigator-rated AD symptoms, or quality of life.32,33 No adverse effects were observed in the included studies. Unfortunately, the individual RCTs included were heterogeneous, and future studies with standardized probiotic supplementation should be undertaken before probiotics can be routinely recommended.
The use of topical probiotics in AD also has recently emerged. Multiple studies have shown that patients with AD have higher levels of colonization with S aureus, which is associated with T-cell dysfunction, more severe allergic skin reactions, and disruptions in barrier function.34,35 Therefore, altering the skin microbiota through topical probiotics could theoretically reduce AD symptoms and flares. Multiple RCTs and smaller studies have shown that topical probiotics can alter the skin microbiota, improve erythema, and decrease scaling and pruritus in AD patients.35-38 One study used a heat-treated Lactobacillus johnsonii 0.3% lotion twice daily for 3 weeks vs placebo in patients with AD with positive S aureus skin cultures. The S aureus load decreased in patients using the topical probiotic lotion, which correlated with lower SCORAD index that was statistically significant compared to placebo (P=.012).36 More robust studies are needed to determine if topical probiotics should routinely be recommended in AD.
Psoriasis
Psoriasis vulgaris is a chronic inflammatory skin condition characterized by pruritic, hyperkeratotic, scaly plaques.39,40 Keratinocyte hyperproliferation is central to psoriasis pathogenesis and is thought to be a T-cell–driven reaction to antigens or trauma in genetically predisposed individuals. Standard treatments for psoriasis currently include topical corticosteroids and anti-inflammatories, oral immunomodulatory therapy, biologic agents, and phototherapy.40 The use of CAM is highly prevalent among patients with psoriasis, with one study reporting that 51% (n=162) of psoriatic patients interviewed had used CAM.41 The most common reasons for CAM use included dissatisfaction with current treatment, adverse side effects of standard therapy, and patient-reported attempts at “trying everything to heal disease.”42 Herein, we will discuss some of the most frequently used supplements for treatment of psoriatic disease.39
Fish Oil for Psoriasis One of the most common supplements used by patients with psoriasis is fish oil due to its purported anti-inflammatory qualities.20,39 The consensus on fish oil supplementation for psoriasis is mixed.43-45 Multiple RCTs have reported reductions in psoriasis area and severity index (PASI) scores or symptomatic improvement with variable doses of fish oil.44,46 One RCT found that using EPA 1.8 g once daily and DHA 1.2 g once daily for 12 weeks resulted in significant improvement in pruritus, scaling, and erythema (P<.05).44 Another study reported a significant decrease in erythema (P=.02) and total body surface area affected (P=.0001) with EPA 3.6 g once daily and DHA 2.4 g once daily supplementation compared to olive oil supplementation for 15 weeks.46 Alternatively, multiple studies have failed to show statistically significant improvement in psoriatic symptoms with fish oil supplementation at variable doses and time frames (14–216 mg daily EPA, 9–80 mg daily DHA, from 2 weeks to 9 months).40,47,48 Fish oil may impart anticoagulant properties and should not be started without the guidance of a physician. Currently, there are no data to make specific recommendations on the use of fish oil as an adjunct psoriatic treatment.
Curcumin for Psoriasis Another supplement routinely utilized in patients with psoriasis is curcumin,40,49,50 a yellow phytochemical that is a major component of the spice turmeric. Curcumin has been shown to inhibit certain proinflammatory cytokines including IL-17, IL-6, IFN-γ, and tumor necrosis factor α and has been regarded as having immune-modulating, anti-inflammatory, and antibacterial properties.40,50 Curcumin also has been reported to suppress phosphorylase kinase, an enzyme that has increased activity in psoriatic plaques that correlates with markers of psoriatic hyperproliferation.50,51 When applied topically, turmeric microgel 0.5% has been reported to decrease scaling, erythema, and psoriatic plaque thickness over the course of 9 weeks.50 In a nonrandomized trial with 10 participants, researchers found that phosphorylase kinase activity levels in psoriatic skin biopsies of patients applying topical curcumin 1% were lower than placebo and topical calcipotriol applied in combination. The lower phosphorylase kinase levels correlated with level of disease severity, and topical curcumin 1% showed a superior outcome when compared to topical calcipotriol.40,49 Although these preliminary results are interesting, there still are not enough data at this time to recommend topical curcumin as a treatment of psoriasis. No known adverse events have been reported with the use of topical curcumin to date.
Oral curcumin has poor oral bioavailability, and 40% to 90% of oral doses are excreted, making supplementation a challenge.40 In one RCT, oral curcumin 2 g daily (using a lecithin-based delivery system to increase bioavailability) was administered in combination with topical methylprednisolone aceponate 0.1%, resulting in significant improvement in psoriatic symptoms and lower IL-22 compared to placebo and topical methylprednisolone aceponate (P<.05).52 Other studies also have reported decreased PASI scores with oral curcumin supplementation.53,54 Adverse effects reported with oral curcumin included gastrointestinal tract upset and hot flashes.53 Although there is early evidence that may support the use of oral curcumin supplementation for psoriasis, more data are needed before recommending this therapy.
Indigo Naturalis for Psoriasis Topical indigo naturalis (IN) also has been reported to improve psoriasis symptoms.39,53,55 The antipsoriatic effects are thought to occur through the active ingredient in IN (indirubin), which is responsible for inhibition of keratinocyte proliferation.40 One study reported that topical IN 1.4% containing indirubin 0.16% with a petroleum ointment vehicle applied to psoriatic plaques over 12 weeks resulted in a significant decrease in PASI scores from 18.9 at baseline to 6.3 after IN treatment (P<.001).56 Another study found that over 8 weeks, topical application of IN 2.83% containing indirubin 0.24% to psoriatic plaques vs petroleum jelly resulted in 56.3% (n=9) of the treatment group achieving PASI 75 compared to 0% in the placebo group (n=24).55 One deterrent in topical IN treatment is the dark blue pigment it contains; however, no other adverse outcomes were found with topical IN treatment.56 Larger clinical trials are necessary to further explore IN as a potential adjunct treatment in patients with mild psoriatic disease. When taken orally, IN has caused gastrointestinal tract disturbance and elevated liver enzyme levels.57
Herbal Toxicities It is important to consider that oral supplements including curcumin and IN are widely available over-the-counter and online without oversight by the US Food and Drug Administration.40 Herbal supplements typically are compounded with other ingredients and have been associated with hepatotoxicity as well as drug-supplement interactions, including abnormal bleeding and clotting.58 There exists a lack of general surveillance data, making the true burden of herbal toxicities more difficult to accurately discern. Although some supplements have been associated with anti-inflammatory qualities and disease improvement, other herbal supplements have been shown to possess immunostimulatory characteristics. Herbal supplements such as spirulina, chlorella, Aphanizomenon flos-aquae, and echinacea have been shown to upregulate inflammatory pathways in a variety of autoimmune skin conditions.59
Probiotics for Psoriasis Data on probiotic use in patients with psoriasis are limited.23 A distinct pattern of dysbiosis has been identified in psoriatic patients, as there is thought to be depletion of beneficial bacteria such as Bifidobacterium, lactobacilli, and F prausnitzii and increased colonization with pathogenic organisms such as Salmonella, E coli, Heliobacter, Campylobacter, and Alcaligenes in psoriasis patients.23,59,60 Early mouse studies have supported this hypothesis, as mice fed with Lactobacillus pentosus have developed milder forms of imiquimod-induced psoriasis compared to placebo,55 and mice receiving probiotic supplementation have lower levels of psoriasis-related proinflammatory markers such as TH17-associated cytokines.61 Another study in humans found that daily oral Bifidobacterium infantis supplementation for 8 weeks in psoriatic patients resulted in lower C-reactive protein and tumor necrosis factor α levels compared to placebo.62 Studies on the use of topical probiotics in psoriasis have been limited, and more research is needed to explore this relationship.38 At this time, no specific recommendations can be made on the use of probiotics in psoriatic patients.
Alopecia Areata
Alopecia areata is nonscarring hair loss that can affect the scalp, face, or body.63,64 The pathophysiology of AA involves the attack of the hair follicle matrix epithelium by inflammatory cells without hair follicle stem cell destruction. The precise events that precipitate these episodes are unknown, but triggers such as emotional or physical stress, vaccines, or viral infections have been reported.65 There is no cure for AA, and current treatments such as topical minoxidil and corticosteroids (topical, intralesional, or oral) vary widely in efficacy.64 Although Janus kinase inhibitors recently have shown promising results in the treatment of AA, the need for prolonged therapy may be frustrating to patients.66 Severity of AA also can vary, with 30% of patients experiencing extensive hair loss.67 The use of CAM has been widely reported in AA due to high levels of dissatisfaction with existing therapies.68 Herein, we discuss the most studied alternative treatments used in AA
Garlic and Onion for Alopecia One alternative treatment that has shown promising initial results is application of topical garlic and onion extracts to affected areas.64,69,70 Both garlic and onion belong to the Allium genus and are high in sulfur and phenolic compounds.70 They have been reported to possess bactericidal and vasodilatory activity,71 and it has been hypothesized that onion and garlic extracts may induce therapeutic effects through induction of a mild contact dermatitis.70 One single-blinded, controlled trial using topical crude onion juice reported that 86.9% (n=20) of patients had full regrowth of hair compared to 13.3% (n=2) of patients treated with a tap water placebo at 8 weeks (P<.0001). This study also noted that patients using onion juice had a higher rate of erythema at application site; unfortunately, the study was small with only 38 patients.70 Another double-blind RCT using garlic gel 5% with betamethasone valerate cream 0.1% compared to betamethasone valerate cream alone found that after 3 months, patients in the garlic gel group had increased terminal hairs and smaller patch sizes compared to the betamethasone valerate cream group.69 More studies are needed to confirm these results.
Aromatherapy With Essential Oils for Alopecia Another alternative treatment in AA that has demonstrated positive results is aromatherapy skin massage with essential oils to patches of alopecia.72 Although certain essential oils, such as tea tree oil, have been reported to have specific antibacterial or anti-inflammatory properties, essential oils have been reported to cause allergic contact dermatitis and should be used with caution.73,74 For example, tea tree oil is a well-known cause of allergic contact dermatitis, and positive patch testing has ranged from 0.1% to 3.5% in studies assessing topical tea tree oil 5% application.75 Overall, there have been nearly 80 essential oils implicated in contact dermatitis, with high-concentration products being one of the highest risk factors for an allergic contact reaction.76 One RCT compared daily scalp massage with essential oils (rosemary, lavender, thyme, and cedarwood in a carrier oil) to daily scalp massage with a placebo carrier oil in AA patients. The results showed that at 7 months of treatment, 44% (n=19) of the aromatherapy group showed improvement compared to 15% (n=6) in the control group.77 Another study used a similar group of essential oils (thyme, rosemary, atlas cedar, lavender, and EPO in a carrier oil) with daily scalp massage and reported similar improvement of AA symptoms compared to control; the investigators also reported irritation at application site in 1 patient.78 There currently are not enough data to recommend aromatherapy skin massage for the treatment of AA, and this practice may cause harm to the patient by induction of allergic contact dermatitis.
There have been a few studies to suggest that the use of total glucosides of peony with compound glycyrrhizin and oral Korean red ginseng may have beneficial effects on AA treatment, but efficacy and safety data are lacking, and these therapies should not be recommended without more information.64,79,80
Final Thoughts
Dermatologic patients frequently are opting for CAM,2 and although some therapies may show promising initial results, alternative medicines also can drive adverse events.19,30 The lack of oversight from the US Food and Drug Administration on the products leads to many unknowns for true health risks with over-the-counter CAM supplements.40 As the use of CAM becomes increasingly common among dermatologic patients, it is important for dermatologists to understand the benefits and risks, especially for commonly treated conditions. More data is needed before CAM can be routinely recommended.
Complementary alternative medicine (CAM) has been described by the National Center for Complementary and Integrative Medicine as “health care approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice.”1 Although this definition is broad, CAM encompasses therapies such as traditional Chinese medicine, herbal therapies, dietary supplements, and mind/body interventions. The use of CAM has grown, and according to a 2012 National Center for Complementary and Integrative Health survey, more than 30% of US adults and 12% of US children use health care approaches that are considered outside of conventional medical practice. In a survey study of US adults, at least 17.7% of respondents said they had taken a dietary supplement other than a vitamin or mineral in the last year.1 Data from the 2007 National Health Interview Survey showed that the prevalence of adults with skin conditions using CAM was 84.5% compared to 38.3% in the general population.2 In addition, 8.15 million US patients with dermatologic conditions reported using CAM over a 5-year period.3 Complementary alternative medicine has emerged as an alternative or adjunct to standard treatments, making it important for dermatologists to understand the existing literature on these therapies. Herein, we review the current evidence-based literature that exists on CAM for the treatment of atopic dermatitis (AD), psoriasis, and alopecia areata (AA).
Atopic Dermatitis
Atopic dermatitis is a chronic, pruritic, inflammatory skin condition with considerable morbidity.4,5 The pathophysiology of AD is multifactorial and includes aspects of barrier dysfunction, IgE hypersensitivity, abnormal cell-mediated immune response, and environmental factors.6 Atopic dermatitis also is one of the most common inflammatory skin conditions in adults, affecting more than 7% of the US population and up to 20% of the total population in developed countries. Of those affected, 40% have moderate or severe symptoms that result in a substantial impact on quality of life.7 Despite advances in understanding disease pathology and treatment, a subset of patients opt to defer conventional treatments such as topical and systemic corticosteroids, antibiotics, nonsteroidal immunomodulators, and biologics. Patients may seek alternative therapies when typical treatments fail or when the perceived side effects outweigh the benefits.5,8 The use of CAM has been well described in patients with AD; however, the existing evidence supporting its use along with its safety profile have not been thoroughly explored. Herein, we will discuss some of the most well-studied supplements for treatment of AD, including evening primrose oil (EPO), fish oil, and probiotics.5
Oral supplementation with polyunsaturated fatty acids commonly is reported in patients with AD.5,8 The idea that a fatty acid deficiency could lead to atopic skin conditions has been around since 1937, when it was suggested that patients with AD had lower levels of blood unsaturated fatty acids.9 Conflicting evidence regarding oral fatty acid ingestion and AD disease severity has emerged.10,11 One unsaturated fatty acid, γ-linolenic acid (GLA), has demonstrated anti-inflammatory properties and involvement in barrier repair.12 It is converted to dihomo-GLA in the body, which acts on cyclooxygenase enzymes to produce the inflammatory mediator prostaglandin E1. The production of GLA is mediated by the enzyme delta-6 desaturase in the metabolization of linoleic acid.12 However, it has been reported that in a subset of patients with AD, a malfunction of delta-6 desaturase may play a role in disease progression and result in lower baseline levels of GLA.10,12 Evening primrose oil and borage oil contain high amounts of GLA (8%–10% and 23%, respectively); thus, supplementation with these oils has been studied in AD.13
EPO for AD Studies investigating EPO (Oenothera biennis) and its association with AD severity have shown mixed results. A Cochrane review reported that oral borage oil and EPO were not effective treatments for AD,14 while another larger randomized controlled trial (RCT) found no statistically significant improvement in AD symptoms.15 However, multiple smaller studies have found that clinical symptoms of AD, such as erythema, xerosis, pruritus, and total body surface area involved, did improve with oral EPO supplementation when compared to placebo, and the results were statistically significant (P=.04).16,17 One study looked at different dosages of EPO and found that groups ingesting both 160 mg and 320 mg daily experienced reductions in eczema area and severity index score, with greater improvement noted with the higher dosage.17 Side effects associated with oral EPO include an anticoagulant effect and transient gastrointestinal tract upset.8,14 There currently is not enough evidence or safety data to recommend this supplement to AD patients.
Although topical use of fatty acids with high concentrations of GLA, such as EPO and borage oil, have demonstrated improvement in subjective symptom severity, most studies have not reached statistical significance.10,11 One study used a 10% EPO cream for 2 weeks compared to placebo and found statistically significant improvement in patient-reported AD symptoms (P=.045). However, this study only included 10 participants, and therefore larger studies are necessary to confirm this result.18 Some RCTs have shown that topical coconut oil, sunflower seed oil, and sandalwood album oil improve AD symptom severity, but again, large controlled trials are needed.5 Unfortunately, many essential oils, including EPO, can cause a secondary allergic contact dermatitis and potentially worsen AD.19
Fish Oil for AD Fish oil is a commonly used supplement for AD due to its high content of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids exert anti-inflammatory effects by displacing arachidonic acid, a proinflammatory omega-6 fatty acid thought to increase IgE, as well as helper T cell (TH2) cytokines and prostaglandin E2.8,20 A 2012 Cochrane review found that, while some studies revealed mild improvement in AD symptoms with oral fish oil supplementation, these RCTs were of poor methodological quality.21 Multiple smaller studies have shown a decrease in pruritus, severity, and physician-rated clinical scores with fish oil use.5,8,20,22 One study with 145 participants reported that 6 g of fish oil once daily compared to isoenergetic corn oil for 16 weeks identified no statistically significant differences between the treatment groups.20 No adverse events were identified in any of the reported trials. Further studies should be conducted to assess the utility and dosing of fish oil supplements in AD patients.
Probiotics for AD Probiotics consist of live microorganisms that enhance the microflora of the gastrointestinal tract.8,20 They have been shown to influence food digestion and also have demonstrated potential influence on the skin-gut axis.23 The theory that intestinal dysbiosis plays a role in AD pathogenesis has been investigated in multiple studies.23-25 The central premise is that low-fiber and high-fat Western diets lead to fundamental changes in the gut microbiome, resulting in fewer anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).23-25 These SCFAs are produced by microbes during the fermentation of dietary fiber and are known for their effect on epithelial barrier integrity and anti-inflammatory properties mediated through G protein–coupled receptor 43.25 Multiple studies have shown that the gut microbiome in patients with AD have higher proportions of Clostridium difficile, Escherichia coli, and Staphylococcus aureus and lower levels of Bifidobacterium, Bacteroidetes, and Bacteroides species compared to healthy controls.26,27 Metagenomic analysis of fecal samples from patients with AD have shown a reduction of Faecalibacterium prausnitzii species when compared to controls, along with a decreased SCFA production, leading to the hypothesis that the gut microbiome may play a role in epithelial barrier disruption.28,29 Systematic reviews and smaller studies have found that oral probiotic use does lead to AD symptom improvement.8,30,31 A systematic review of 25 RCTs with 1599 participants found that supplementation with oral probiotics significantly decreased the SCORAD (SCORing Atopic Dermatitis) index in adults and children older than 1 year with AD but had no effect on infants younger than 1 year (P<.001). They also found that supplementation with diverse microbes or Lactobacillus species showed greater benefit than Bifidobacterium species alone.30 Another study analyzed the effect of oral Lactobacillus fermentum (1×109 CFU twice daily) in 53 children with AD vs placebo for 16 weeks. This study found a statically significant decrease in SCORAD index between oral probiotics and placebo, with 92% (n=24) of participants supplementing with probiotics having a lower SCORAD index than baseline compared to 63% (n=17) in the placebo group (P=.01).31 However, the use of probiotics for AD treatment has remained controversial. Two recent systematic reviews, including 39 RCTs of 2599 randomized patients, found that the use of currently available oral probiotics made little or no difference in patient-rated AD symptoms, investigator-rated AD symptoms, or quality of life.32,33 No adverse effects were observed in the included studies. Unfortunately, the individual RCTs included were heterogeneous, and future studies with standardized probiotic supplementation should be undertaken before probiotics can be routinely recommended.
The use of topical probiotics in AD also has recently emerged. Multiple studies have shown that patients with AD have higher levels of colonization with S aureus, which is associated with T-cell dysfunction, more severe allergic skin reactions, and disruptions in barrier function.34,35 Therefore, altering the skin microbiota through topical probiotics could theoretically reduce AD symptoms and flares. Multiple RCTs and smaller studies have shown that topical probiotics can alter the skin microbiota, improve erythema, and decrease scaling and pruritus in AD patients.35-38 One study used a heat-treated Lactobacillus johnsonii 0.3% lotion twice daily for 3 weeks vs placebo in patients with AD with positive S aureus skin cultures. The S aureus load decreased in patients using the topical probiotic lotion, which correlated with lower SCORAD index that was statistically significant compared to placebo (P=.012).36 More robust studies are needed to determine if topical probiotics should routinely be recommended in AD.
Psoriasis
Psoriasis vulgaris is a chronic inflammatory skin condition characterized by pruritic, hyperkeratotic, scaly plaques.39,40 Keratinocyte hyperproliferation is central to psoriasis pathogenesis and is thought to be a T-cell–driven reaction to antigens or trauma in genetically predisposed individuals. Standard treatments for psoriasis currently include topical corticosteroids and anti-inflammatories, oral immunomodulatory therapy, biologic agents, and phototherapy.40 The use of CAM is highly prevalent among patients with psoriasis, with one study reporting that 51% (n=162) of psoriatic patients interviewed had used CAM.41 The most common reasons for CAM use included dissatisfaction with current treatment, adverse side effects of standard therapy, and patient-reported attempts at “trying everything to heal disease.”42 Herein, we will discuss some of the most frequently used supplements for treatment of psoriatic disease.39
Fish Oil for Psoriasis One of the most common supplements used by patients with psoriasis is fish oil due to its purported anti-inflammatory qualities.20,39 The consensus on fish oil supplementation for psoriasis is mixed.43-45 Multiple RCTs have reported reductions in psoriasis area and severity index (PASI) scores or symptomatic improvement with variable doses of fish oil.44,46 One RCT found that using EPA 1.8 g once daily and DHA 1.2 g once daily for 12 weeks resulted in significant improvement in pruritus, scaling, and erythema (P<.05).44 Another study reported a significant decrease in erythema (P=.02) and total body surface area affected (P=.0001) with EPA 3.6 g once daily and DHA 2.4 g once daily supplementation compared to olive oil supplementation for 15 weeks.46 Alternatively, multiple studies have failed to show statistically significant improvement in psoriatic symptoms with fish oil supplementation at variable doses and time frames (14–216 mg daily EPA, 9–80 mg daily DHA, from 2 weeks to 9 months).40,47,48 Fish oil may impart anticoagulant properties and should not be started without the guidance of a physician. Currently, there are no data to make specific recommendations on the use of fish oil as an adjunct psoriatic treatment.
Curcumin for Psoriasis Another supplement routinely utilized in patients with psoriasis is curcumin,40,49,50 a yellow phytochemical that is a major component of the spice turmeric. Curcumin has been shown to inhibit certain proinflammatory cytokines including IL-17, IL-6, IFN-γ, and tumor necrosis factor α and has been regarded as having immune-modulating, anti-inflammatory, and antibacterial properties.40,50 Curcumin also has been reported to suppress phosphorylase kinase, an enzyme that has increased activity in psoriatic plaques that correlates with markers of psoriatic hyperproliferation.50,51 When applied topically, turmeric microgel 0.5% has been reported to decrease scaling, erythema, and psoriatic plaque thickness over the course of 9 weeks.50 In a nonrandomized trial with 10 participants, researchers found that phosphorylase kinase activity levels in psoriatic skin biopsies of patients applying topical curcumin 1% were lower than placebo and topical calcipotriol applied in combination. The lower phosphorylase kinase levels correlated with level of disease severity, and topical curcumin 1% showed a superior outcome when compared to topical calcipotriol.40,49 Although these preliminary results are interesting, there still are not enough data at this time to recommend topical curcumin as a treatment of psoriasis. No known adverse events have been reported with the use of topical curcumin to date.
Oral curcumin has poor oral bioavailability, and 40% to 90% of oral doses are excreted, making supplementation a challenge.40 In one RCT, oral curcumin 2 g daily (using a lecithin-based delivery system to increase bioavailability) was administered in combination with topical methylprednisolone aceponate 0.1%, resulting in significant improvement in psoriatic symptoms and lower IL-22 compared to placebo and topical methylprednisolone aceponate (P<.05).52 Other studies also have reported decreased PASI scores with oral curcumin supplementation.53,54 Adverse effects reported with oral curcumin included gastrointestinal tract upset and hot flashes.53 Although there is early evidence that may support the use of oral curcumin supplementation for psoriasis, more data are needed before recommending this therapy.
Indigo Naturalis for Psoriasis Topical indigo naturalis (IN) also has been reported to improve psoriasis symptoms.39,53,55 The antipsoriatic effects are thought to occur through the active ingredient in IN (indirubin), which is responsible for inhibition of keratinocyte proliferation.40 One study reported that topical IN 1.4% containing indirubin 0.16% with a petroleum ointment vehicle applied to psoriatic plaques over 12 weeks resulted in a significant decrease in PASI scores from 18.9 at baseline to 6.3 after IN treatment (P<.001).56 Another study found that over 8 weeks, topical application of IN 2.83% containing indirubin 0.24% to psoriatic plaques vs petroleum jelly resulted in 56.3% (n=9) of the treatment group achieving PASI 75 compared to 0% in the placebo group (n=24).55 One deterrent in topical IN treatment is the dark blue pigment it contains; however, no other adverse outcomes were found with topical IN treatment.56 Larger clinical trials are necessary to further explore IN as a potential adjunct treatment in patients with mild psoriatic disease. When taken orally, IN has caused gastrointestinal tract disturbance and elevated liver enzyme levels.57
Herbal Toxicities It is important to consider that oral supplements including curcumin and IN are widely available over-the-counter and online without oversight by the US Food and Drug Administration.40 Herbal supplements typically are compounded with other ingredients and have been associated with hepatotoxicity as well as drug-supplement interactions, including abnormal bleeding and clotting.58 There exists a lack of general surveillance data, making the true burden of herbal toxicities more difficult to accurately discern. Although some supplements have been associated with anti-inflammatory qualities and disease improvement, other herbal supplements have been shown to possess immunostimulatory characteristics. Herbal supplements such as spirulina, chlorella, Aphanizomenon flos-aquae, and echinacea have been shown to upregulate inflammatory pathways in a variety of autoimmune skin conditions.59
Probiotics for Psoriasis Data on probiotic use in patients with psoriasis are limited.23 A distinct pattern of dysbiosis has been identified in psoriatic patients, as there is thought to be depletion of beneficial bacteria such as Bifidobacterium, lactobacilli, and F prausnitzii and increased colonization with pathogenic organisms such as Salmonella, E coli, Heliobacter, Campylobacter, and Alcaligenes in psoriasis patients.23,59,60 Early mouse studies have supported this hypothesis, as mice fed with Lactobacillus pentosus have developed milder forms of imiquimod-induced psoriasis compared to placebo,55 and mice receiving probiotic supplementation have lower levels of psoriasis-related proinflammatory markers such as TH17-associated cytokines.61 Another study in humans found that daily oral Bifidobacterium infantis supplementation for 8 weeks in psoriatic patients resulted in lower C-reactive protein and tumor necrosis factor α levels compared to placebo.62 Studies on the use of topical probiotics in psoriasis have been limited, and more research is needed to explore this relationship.38 At this time, no specific recommendations can be made on the use of probiotics in psoriatic patients.
Alopecia Areata
Alopecia areata is nonscarring hair loss that can affect the scalp, face, or body.63,64 The pathophysiology of AA involves the attack of the hair follicle matrix epithelium by inflammatory cells without hair follicle stem cell destruction. The precise events that precipitate these episodes are unknown, but triggers such as emotional or physical stress, vaccines, or viral infections have been reported.65 There is no cure for AA, and current treatments such as topical minoxidil and corticosteroids (topical, intralesional, or oral) vary widely in efficacy.64 Although Janus kinase inhibitors recently have shown promising results in the treatment of AA, the need for prolonged therapy may be frustrating to patients.66 Severity of AA also can vary, with 30% of patients experiencing extensive hair loss.67 The use of CAM has been widely reported in AA due to high levels of dissatisfaction with existing therapies.68 Herein, we discuss the most studied alternative treatments used in AA
Garlic and Onion for Alopecia One alternative treatment that has shown promising initial results is application of topical garlic and onion extracts to affected areas.64,69,70 Both garlic and onion belong to the Allium genus and are high in sulfur and phenolic compounds.70 They have been reported to possess bactericidal and vasodilatory activity,71 and it has been hypothesized that onion and garlic extracts may induce therapeutic effects through induction of a mild contact dermatitis.70 One single-blinded, controlled trial using topical crude onion juice reported that 86.9% (n=20) of patients had full regrowth of hair compared to 13.3% (n=2) of patients treated with a tap water placebo at 8 weeks (P<.0001). This study also noted that patients using onion juice had a higher rate of erythema at application site; unfortunately, the study was small with only 38 patients.70 Another double-blind RCT using garlic gel 5% with betamethasone valerate cream 0.1% compared to betamethasone valerate cream alone found that after 3 months, patients in the garlic gel group had increased terminal hairs and smaller patch sizes compared to the betamethasone valerate cream group.69 More studies are needed to confirm these results.
Aromatherapy With Essential Oils for Alopecia Another alternative treatment in AA that has demonstrated positive results is aromatherapy skin massage with essential oils to patches of alopecia.72 Although certain essential oils, such as tea tree oil, have been reported to have specific antibacterial or anti-inflammatory properties, essential oils have been reported to cause allergic contact dermatitis and should be used with caution.73,74 For example, tea tree oil is a well-known cause of allergic contact dermatitis, and positive patch testing has ranged from 0.1% to 3.5% in studies assessing topical tea tree oil 5% application.75 Overall, there have been nearly 80 essential oils implicated in contact dermatitis, with high-concentration products being one of the highest risk factors for an allergic contact reaction.76 One RCT compared daily scalp massage with essential oils (rosemary, lavender, thyme, and cedarwood in a carrier oil) to daily scalp massage with a placebo carrier oil in AA patients. The results showed that at 7 months of treatment, 44% (n=19) of the aromatherapy group showed improvement compared to 15% (n=6) in the control group.77 Another study used a similar group of essential oils (thyme, rosemary, atlas cedar, lavender, and EPO in a carrier oil) with daily scalp massage and reported similar improvement of AA symptoms compared to control; the investigators also reported irritation at application site in 1 patient.78 There currently are not enough data to recommend aromatherapy skin massage for the treatment of AA, and this practice may cause harm to the patient by induction of allergic contact dermatitis.
There have been a few studies to suggest that the use of total glucosides of peony with compound glycyrrhizin and oral Korean red ginseng may have beneficial effects on AA treatment, but efficacy and safety data are lacking, and these therapies should not be recommended without more information.64,79,80
Final Thoughts
Dermatologic patients frequently are opting for CAM,2 and although some therapies may show promising initial results, alternative medicines also can drive adverse events.19,30 The lack of oversight from the US Food and Drug Administration on the products leads to many unknowns for true health risks with over-the-counter CAM supplements.40 As the use of CAM becomes increasingly common among dermatologic patients, it is important for dermatologists to understand the benefits and risks, especially for commonly treated conditions. More data is needed before CAM can be routinely recommended.
References
Complementary, alternative, or integrative health: what’s in a name? National Center for Complementary and Integrative Health website. Updated April 2021. Accessed April 25, 2021. https://www.nccih.nih.gov/health/complementary-alternative-or-integrative-health-whats-in-a-name
Fuhrmann T, Smith N, Tausk F. Use of complementary and alternative medicine among adults with skin disease: updated results from a national survey. J Am Acad Dermatol. 2010;63:1000-1005.
Landis ET, Davis SA, Feldman SR, et al. Complementary and alternative medicine use in dermatology in the United States. J Altern Complement Med. 2014;20:392-398.
Solman L, Lloyd‐Lavery A, Grindlay DJC, et al. What’s new in atopic eczema? an analysis of systematic reviews published in 2016. part 1: treatment and prevention. Clin Exp Dermatol. 2019;44:363-369.
Vieira BL, Lim NR, Lohman ME, et al. Complementary and alternative medicine for atopic dermatitis: an evidence-based review. Am J Clin Dermatol. 2016;17:557-581.
David Boothe W, Tarbox JA, Tarbox MB. Atopic dermatitis: pathophysiology. In: Fortson EA, Feldman SR, Strowd LC, eds. Management of Atopic Dermatitis: Methods and Challenges. Springer International Publishing; 2017:21-37.
Atopic dermatitis in America. Asthma and Allergy Foundation of America website. Accessed July 30, 2021. https://www.aafa.org/atopic-dermatitis-in-america
Schlichte MJ, Vandersall A, Katta R. Diet and eczema: a review of dietary supplements for the treatment of atopic dermatitis. Dermatol Pract Concept. 2016;6:23-29.
Brown WR, Hansen AE. Arachidonic and linolic acid of the serum in normal and eczematous human subjects. Proc Soc Exp Bio Med. 1937;36:113-117.
Lee J, Bielory L. Complementary and alternative interventions in atopic dermatitis. Immunol Allergy Clin North Am. 2010;30:411-424.
Ferreira MJ, Fiadeiro T, Silva M, et al. Topical γ-linolenic acid therapy in atopic dermatitis. Allergo J. 1998;7:213-216.
Simon D, Eng PA, Borelli S, et al. Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis. Adv Ther. 2014;31:180-188.
Fan Y-Y, Chapkin RS. Importance of dietary γ-linolenic acid in human health and nutrition. J Nutr. 1998;128:1411-1414.
Bamford JTM, Ray S, Musekiwa A, et al. Oral evening primrose oil and borage oil for eczema. Cochrane Database Syst Rev. 2013;4:CD004416.
Williams H. Evening primrose oil for atopic dermatitis. BMJ. 2003;327:2.
Schalin-Karrila M, Mattila L, Jansen CT, et al. Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol. 1987;117:11-19.
Chung BY, Park SY, Jung MJ, et al. Effect of evening primrose oil on Korean patients with mild atopic dermatitis: a randomized, double-blinded, placebo-controlled clinical study. Ann Dermatol. 2018;30:409-416.
Anstey A, Quigley M, Wilkinson JD. Topical evening primrose oil as treatment for atopic eczema. J Dermatolog Treat. 1990;1:199-201.
de Groot AC, Schmidt E. Essential oils, part I: introduction. Dermatitis. 2016;27:39-42.
Reynolds KA, Juhasz MLW, Mesinkovska NA. The role of oral vitamins and supplements in the management of atopic dermatitis: a systematic review. Int J Dermatol. 2019;58:1371-1376.
Bath-Hextall FJ, Jenkinson C, Humphreys R, et al. Dietary supplements for established atopic eczema [published online February 15, 2012]. Cochrane Database Syst Rev. Accessed July 22, 2021. doi:10.1002/14651858.CD005205.pub3
Balic´ A, Vlašic´ D, Žužul K, et al. Omega-3 versus omega-6 polyunsaturated fatty acids in the prevention and treatment of inflammatory skin diseases. Int J Mol Sci. 2020;21:741.
Salem I, Ramser A, Isham N, et al. The gut microbiome as a major regulator of the gut-skin axis. Front Microbiol. 2018;9:1459.
Agrawal R, Wisniewski JA, Woodfolk JA. The role of regulatory T cells in atopic dermatitis. Pathogenesis Manage Atopic Dermatitis. 2011;41:112-124.
Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282-1286.
Lee E, Lee S-Y, Kang M-J, et al. Clostridia in the gut and onset of atopic dermatitis via eosinophilic inflammation. Ann Allergy Asthma Immunol. 2016;117:91-92.e1.
Nylund L, Nermes M, Isolauri E, et al. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria. Allergy. 2015;70:241-244.
Kim H-J, Kim HY, Lee S-Y, et al. Clinical efficacy and mechanism of probiotics in allergic diseases. Korean J Pediatr. 2013;56:369-376.
Song H, Yoo Y, Hwang J, et al. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol. 2016;137:852-860.
Kim S-O, Ah Y-M, Yu YM, et al. Effects of probiotics for the treatment of atopic dermatitis: a meta-analysis of randomized controlled trials. Ann Allergy Asthma Immunol. 2014;113:217-226.
Weston S, Halbert A, Richmond P, et al. Effects of probiotics on atopic dermatitis: a randomised controlled trial. Arch Dis Child. 2005;90:892-897.
Huang R, Ning H, Shen M, et al. Probiotics for the treatment of atopic dermatitis in children: a systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol. 2017;7:392.
Makrgeorgou A, Leonardi-Bee J, Bath-Hextall FJ, et al. Probiotics for treating eczema. Cochrane Database Syst Rev. 2018;11:CD006135.
Knackstedt R, Knackstedt T, Gatherwright J. The role of topical probiotics in skin conditions: a systematic review of animal and human studies and implications for future therapies. Exp Dermatol. 2020;29:15-21.
Woo TE, Sibley CD. The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis. J Am Acad Dermatol. 2020;82:222-228.
Blanchet-Réthoré S, Bourdès V, Mercenier A, et al. Effect of a lotion containing the heat-treated probiotic strain Lactobacillus johnsonii NCC 533 on Staphylococcus aureus colonization in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017;10:249-257.
Nakatsuji T, Hata TR, Tong Y, et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nature Medicine. 2021;27:700-709.
França K. Topical probiotics in dermatological therapy and skincare: a concise review. Dermatol Ther (Heidelb). 2020;11:71-77.
Talbott W, Duffy N. Complementary and alternative medicine for psoriasis: what the dermatologist needs to know. Am J Clin Dermatol. 2015;16:147-165.
Gamret AC, Price A, Fertig RM, et al. Complementary and alternative medicine therapies for psoriasis: a systematic review. JAMA Dermatol. 2018;154:1330-1337.
Fleischer AB, Feldman SR, Rapp SR, et al. Alternative therapies commonly used within a population of patients with psoriasis. Cutis. 1996;58:216-220.
Ben-Arye E, Ziv M, Frenkel M, et al. Complementary medicine and psoriasis: linking the patient’s outlook with evidence-based medicine. Dermatology. 2003;207:302-307.
Millsop JW, Bhatia BK, Debbaneh M, et al. Diet and psoriasis: part 3. role of nutritional supplements. J Am Acad Dermatol. 2014;71:561-569.
Bittiner SB, Tucker WF, Cartwright I, et al. A double-blind, randomised, placebo-controlled trial of fish oil in psoriasis. Lancet. 1988;1:378-380.
Ford AR, Siegel M, Bagel J, et al. Dietary recommendations for adults with psoriasis or psoriatic arthritis from the medical board of the National Psoriasis Foundation: a Systematic review. JAMA Dermatol. 2018;154:934-950.
Gupta AK, Ellis CN, Tellner DC, et al. Double-blind, placebo-controlled study to evaluate the efficacy of fish oil and low-dose UVB in the treatment of psoriasis. Br J Dermatol. 1989;120:801-807.
Kristensen S, Schmidt EB, Schlemmer A, et al. Beneficial effect of n-3 polyunsaturated fatty acids on inflammation and analgesic use in psoriatic arthritis: a randomized, double blind, placebo-controlled trial. Scand J Rheumatol. 2018;47:27-36.
Søyland E, Funk J, Rajka G, et al. Effect of dietary supplementation with very-long-chain n-3 fatty acids in patients with psoriasis. N Engl J Med. 1993;328:1812-1816.
Heng MCY, Song MK, Harker J, et al. Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters. Br J Dermatol. 2000;143:937-949.
Sarafian G, Afshar M, Mansouri P, et al. Topical turmeric microemulgel in the management of plaque psoriasis; a clinical evaluation. Iran J Pharm Res. 2015;14:865-876.
Reddy S, Aggarwal BB. Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. FEBS Letters. 1994;341:19-22.
Antiga E, Bonciolini V, Volpi W, et al. Oral curcumin (meriva) is effective as an adjuvant treatment and is able to reduce IL-22 serum levels in patients with psoriasis vulgaris. Biomed Res Int. 2015;2015:283634.
Kurd SK, Smith N, VanVoorhees A, et al. Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: a prospective clinical trial. J Am Acad Dermatol. 2008;58:625-631.
Carrion-Gutierrez M, Ramirez-Bosca A, Navarro-Lopez V, et al. Effects of Curcuma extract and visible light on adults with plaque psoriasis. Eur J Dermatol. 2015;25:240-246.
Cheng H-M, Wu Y-C, Wang Q, et al. Clinical efficacy and IL-17 targeting mechanism of indigo naturalis as a topical agent in moderate psoriasis. BMC Complement Altern Med. 2017;17:439.
Lin Y-K, Chang C-J, Chang Y-C, et al. Clinical assessment of patients with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using indigo naturalis. Arch Dermatol. 2008;144:1457-1464.
Naganuma M, Sugimoto S, Suzuki H, et al. Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey. J Gastroenterol. 2019;54:891-896.
Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Alimentary Pharmacol Ther. 2013;37:3-17.
Bax CE, Chakka S, Concha JSS, et al. The effects of immunostimulatory herbal supplements on autoimmune skin diseases. J Am Acad Dermatol. 2021;84:1051-1058.
Scher JU, Ubeda C, Artacho A, et al. Decreased bacterial diversity characterizes an altered gut microbiota in psoriatic arthritis and resembles dysbiosis of inflammatory bowel disease. Arthritis Rheumatol. 2015;67:128-139.
Chen Y-H, Wu C-S, Chao Y-H, et al. Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasis-like mice. J Food Drug Anal. 2017;25:559-566.
Groeger D, O’Mahony L, Murphy EF, et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013;4:325-339.
Hosking A-M, Juhasz M, Atanaskova Mesinkovska N. Complementary and alternative treatments for alopecia: a comprehensive review. Skin Appendage Disord. 2019;5:72-89.
Tkachenko E, Okhovat J-P, Manjaly P, et al. Complementary & alternative medicine for alopecia areata: a systematic review [published online December 20, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.12.027
Ismail FF, Sinclair R. JAK inhibition in the treatment of alopecia areata—a promising new dawn? Expert Rev Clin Pharmacol. 2020;13:43-51. doi:10.1080/17512433.2020.1702878
van den Biggelaar FJHM, Smolders J, Jansen JFA. Complementary and alternative medicine in alopecia areata. AM J Clin Dermatol. 2010;11:11-20.
Hussain ST, Mostaghimi A, Barr PJ, et al. Utilization of mental health resources and complementary and alternative therapies for alopecia areata: a U.S. survey. Int J Trichology. 2017;9:160-164.
Hajheydari Z, Jamshidi M, Akbari J, et al. Combination of topical garlic gel and betamethasone valerate cream in the treatment of localized alopecia areata: a double-blind randomized controlled study. Indian J Dermatol Venereol Leprol. 2007;73:29-32.
Sharquie KE, Al-Obaidi HK. Onion juice (Allium cepa L.), a new topical treatment for alopecia areata. J Dermatol. 2002;29:343-346.
Burian JP, Sacramento LVS, Carlos IZ. Fungal infection control by garlic extracts (Allium sativum L.) and modulation of peritoneal macrophages activity in murine model of sporotrichosis. Braz J Biol. 2017;77:848-855.
Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy. successful treatment for alopecia areata. Arch Dermatol. 1998;134:1349-1352.
Lakshmi C, Srinivas CR. Allergic contact dermatitis following aromatherapy with valiya narayana thailam—an ayurvedic oil presenting as exfoliative dermatitis. Contact Dermatitis. 2009;61:297-298.
Carson CF, Hammer KA, Riley TV. Melaleuca alternifolia (tea tree) oil: a review of antimicrobial and other medicinal properties. Clin Microbiol Rev. 2006;19:50-62.
Groot AC de, Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis. 2016;75:129-143.
de Groot AC, Schmidt E. Essential oils, part I: introduction. dermatitis. 2016;27:39-42.
Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy. successful treatment for alopecia areata. Arch Dermatol. 1998;134:1349-1352.
Ozmen I, Caliskan E, Arca E, et al. Efficacy of aromatherapy in the treatment of localized alopecia areata: a double-blind placebo controlled study. Gulhane Med J. 2015;57:233.
Oh GN, Son SW. Efficacy of Korean red ginseng in the treatment of alopecia areata. J Ginseng Res. 2012;36:391-395.
Yang D-Q, You L-P, Song P-H, et al. A randomized controlled trial comparing total glucosides of paeony capsule and compound glycyrrhizin tablet for alopecia areata. Chin J Integr Med. 2012;18:621-625.
References
Complementary, alternative, or integrative health: what’s in a name? National Center for Complementary and Integrative Health website. Updated April 2021. Accessed April 25, 2021. https://www.nccih.nih.gov/health/complementary-alternative-or-integrative-health-whats-in-a-name
Fuhrmann T, Smith N, Tausk F. Use of complementary and alternative medicine among adults with skin disease: updated results from a national survey. J Am Acad Dermatol. 2010;63:1000-1005.
Landis ET, Davis SA, Feldman SR, et al. Complementary and alternative medicine use in dermatology in the United States. J Altern Complement Med. 2014;20:392-398.
Solman L, Lloyd‐Lavery A, Grindlay DJC, et al. What’s new in atopic eczema? an analysis of systematic reviews published in 2016. part 1: treatment and prevention. Clin Exp Dermatol. 2019;44:363-369.
Vieira BL, Lim NR, Lohman ME, et al. Complementary and alternative medicine for atopic dermatitis: an evidence-based review. Am J Clin Dermatol. 2016;17:557-581.
David Boothe W, Tarbox JA, Tarbox MB. Atopic dermatitis: pathophysiology. In: Fortson EA, Feldman SR, Strowd LC, eds. Management of Atopic Dermatitis: Methods and Challenges. Springer International Publishing; 2017:21-37.
Atopic dermatitis in America. Asthma and Allergy Foundation of America website. Accessed July 30, 2021. https://www.aafa.org/atopic-dermatitis-in-america
Schlichte MJ, Vandersall A, Katta R. Diet and eczema: a review of dietary supplements for the treatment of atopic dermatitis. Dermatol Pract Concept. 2016;6:23-29.
Brown WR, Hansen AE. Arachidonic and linolic acid of the serum in normal and eczematous human subjects. Proc Soc Exp Bio Med. 1937;36:113-117.
Lee J, Bielory L. Complementary and alternative interventions in atopic dermatitis. Immunol Allergy Clin North Am. 2010;30:411-424.
Ferreira MJ, Fiadeiro T, Silva M, et al. Topical γ-linolenic acid therapy in atopic dermatitis. Allergo J. 1998;7:213-216.
Simon D, Eng PA, Borelli S, et al. Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis. Adv Ther. 2014;31:180-188.
Fan Y-Y, Chapkin RS. Importance of dietary γ-linolenic acid in human health and nutrition. J Nutr. 1998;128:1411-1414.
Bamford JTM, Ray S, Musekiwa A, et al. Oral evening primrose oil and borage oil for eczema. Cochrane Database Syst Rev. 2013;4:CD004416.
Williams H. Evening primrose oil for atopic dermatitis. BMJ. 2003;327:2.
Schalin-Karrila M, Mattila L, Jansen CT, et al. Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol. 1987;117:11-19.
Chung BY, Park SY, Jung MJ, et al. Effect of evening primrose oil on Korean patients with mild atopic dermatitis: a randomized, double-blinded, placebo-controlled clinical study. Ann Dermatol. 2018;30:409-416.
Anstey A, Quigley M, Wilkinson JD. Topical evening primrose oil as treatment for atopic eczema. J Dermatolog Treat. 1990;1:199-201.
de Groot AC, Schmidt E. Essential oils, part I: introduction. Dermatitis. 2016;27:39-42.
Reynolds KA, Juhasz MLW, Mesinkovska NA. The role of oral vitamins and supplements in the management of atopic dermatitis: a systematic review. Int J Dermatol. 2019;58:1371-1376.
Bath-Hextall FJ, Jenkinson C, Humphreys R, et al. Dietary supplements for established atopic eczema [published online February 15, 2012]. Cochrane Database Syst Rev. Accessed July 22, 2021. doi:10.1002/14651858.CD005205.pub3
Balic´ A, Vlašic´ D, Žužul K, et al. Omega-3 versus omega-6 polyunsaturated fatty acids in the prevention and treatment of inflammatory skin diseases. Int J Mol Sci. 2020;21:741.
Salem I, Ramser A, Isham N, et al. The gut microbiome as a major regulator of the gut-skin axis. Front Microbiol. 2018;9:1459.
Agrawal R, Wisniewski JA, Woodfolk JA. The role of regulatory T cells in atopic dermatitis. Pathogenesis Manage Atopic Dermatitis. 2011;41:112-124.
Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282-1286.
Lee E, Lee S-Y, Kang M-J, et al. Clostridia in the gut and onset of atopic dermatitis via eosinophilic inflammation. Ann Allergy Asthma Immunol. 2016;117:91-92.e1.
Nylund L, Nermes M, Isolauri E, et al. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria. Allergy. 2015;70:241-244.
Kim H-J, Kim HY, Lee S-Y, et al. Clinical efficacy and mechanism of probiotics in allergic diseases. Korean J Pediatr. 2013;56:369-376.
Song H, Yoo Y, Hwang J, et al. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol. 2016;137:852-860.
Kim S-O, Ah Y-M, Yu YM, et al. Effects of probiotics for the treatment of atopic dermatitis: a meta-analysis of randomized controlled trials. Ann Allergy Asthma Immunol. 2014;113:217-226.
Weston S, Halbert A, Richmond P, et al. Effects of probiotics on atopic dermatitis: a randomised controlled trial. Arch Dis Child. 2005;90:892-897.
Huang R, Ning H, Shen M, et al. Probiotics for the treatment of atopic dermatitis in children: a systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol. 2017;7:392.
Makrgeorgou A, Leonardi-Bee J, Bath-Hextall FJ, et al. Probiotics for treating eczema. Cochrane Database Syst Rev. 2018;11:CD006135.
Knackstedt R, Knackstedt T, Gatherwright J. The role of topical probiotics in skin conditions: a systematic review of animal and human studies and implications for future therapies. Exp Dermatol. 2020;29:15-21.
Woo TE, Sibley CD. The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis. J Am Acad Dermatol. 2020;82:222-228.
Blanchet-Réthoré S, Bourdès V, Mercenier A, et al. Effect of a lotion containing the heat-treated probiotic strain Lactobacillus johnsonii NCC 533 on Staphylococcus aureus colonization in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017;10:249-257.
Nakatsuji T, Hata TR, Tong Y, et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nature Medicine. 2021;27:700-709.
França K. Topical probiotics in dermatological therapy and skincare: a concise review. Dermatol Ther (Heidelb). 2020;11:71-77.
Talbott W, Duffy N. Complementary and alternative medicine for psoriasis: what the dermatologist needs to know. Am J Clin Dermatol. 2015;16:147-165.
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Ford AR, Siegel M, Bagel J, et al. Dietary recommendations for adults with psoriasis or psoriatic arthritis from the medical board of the National Psoriasis Foundation: a Systematic review. JAMA Dermatol. 2018;154:934-950.
Gupta AK, Ellis CN, Tellner DC, et al. Double-blind, placebo-controlled study to evaluate the efficacy of fish oil and low-dose UVB in the treatment of psoriasis. Br J Dermatol. 1989;120:801-807.
Kristensen S, Schmidt EB, Schlemmer A, et al. Beneficial effect of n-3 polyunsaturated fatty acids on inflammation and analgesic use in psoriatic arthritis: a randomized, double blind, placebo-controlled trial. Scand J Rheumatol. 2018;47:27-36.
Søyland E, Funk J, Rajka G, et al. Effect of dietary supplementation with very-long-chain n-3 fatty acids in patients with psoriasis. N Engl J Med. 1993;328:1812-1816.
Heng MCY, Song MK, Harker J, et al. Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters. Br J Dermatol. 2000;143:937-949.
Sarafian G, Afshar M, Mansouri P, et al. Topical turmeric microemulgel in the management of plaque psoriasis; a clinical evaluation. Iran J Pharm Res. 2015;14:865-876.
Reddy S, Aggarwal BB. Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. FEBS Letters. 1994;341:19-22.
Antiga E, Bonciolini V, Volpi W, et al. Oral curcumin (meriva) is effective as an adjuvant treatment and is able to reduce IL-22 serum levels in patients with psoriasis vulgaris. Biomed Res Int. 2015;2015:283634.
Kurd SK, Smith N, VanVoorhees A, et al. Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: a prospective clinical trial. J Am Acad Dermatol. 2008;58:625-631.
Carrion-Gutierrez M, Ramirez-Bosca A, Navarro-Lopez V, et al. Effects of Curcuma extract and visible light on adults with plaque psoriasis. Eur J Dermatol. 2015;25:240-246.
Cheng H-M, Wu Y-C, Wang Q, et al. Clinical efficacy and IL-17 targeting mechanism of indigo naturalis as a topical agent in moderate psoriasis. BMC Complement Altern Med. 2017;17:439.
Lin Y-K, Chang C-J, Chang Y-C, et al. Clinical assessment of patients with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using indigo naturalis. Arch Dermatol. 2008;144:1457-1464.
Naganuma M, Sugimoto S, Suzuki H, et al. Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey. J Gastroenterol. 2019;54:891-896.
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Bax CE, Chakka S, Concha JSS, et al. The effects of immunostimulatory herbal supplements on autoimmune skin diseases. J Am Acad Dermatol. 2021;84:1051-1058.
Scher JU, Ubeda C, Artacho A, et al. Decreased bacterial diversity characterizes an altered gut microbiota in psoriatic arthritis and resembles dysbiosis of inflammatory bowel disease. Arthritis Rheumatol. 2015;67:128-139.
Chen Y-H, Wu C-S, Chao Y-H, et al. Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasis-like mice. J Food Drug Anal. 2017;25:559-566.
Groeger D, O’Mahony L, Murphy EF, et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013;4:325-339.
Hosking A-M, Juhasz M, Atanaskova Mesinkovska N. Complementary and alternative treatments for alopecia: a comprehensive review. Skin Appendage Disord. 2019;5:72-89.
Tkachenko E, Okhovat J-P, Manjaly P, et al. Complementary & alternative medicine for alopecia areata: a systematic review [published online December 20, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.12.027
Ismail FF, Sinclair R. JAK inhibition in the treatment of alopecia areata—a promising new dawn? Expert Rev Clin Pharmacol. 2020;13:43-51. doi:10.1080/17512433.2020.1702878
van den Biggelaar FJHM, Smolders J, Jansen JFA. Complementary and alternative medicine in alopecia areata. AM J Clin Dermatol. 2010;11:11-20.
Hussain ST, Mostaghimi A, Barr PJ, et al. Utilization of mental health resources and complementary and alternative therapies for alopecia areata: a U.S. survey. Int J Trichology. 2017;9:160-164.
Hajheydari Z, Jamshidi M, Akbari J, et al. Combination of topical garlic gel and betamethasone valerate cream in the treatment of localized alopecia areata: a double-blind randomized controlled study. Indian J Dermatol Venereol Leprol. 2007;73:29-32.
Sharquie KE, Al-Obaidi HK. Onion juice (Allium cepa L.), a new topical treatment for alopecia areata. J Dermatol. 2002;29:343-346.
Burian JP, Sacramento LVS, Carlos IZ. Fungal infection control by garlic extracts (Allium sativum L.) and modulation of peritoneal macrophages activity in murine model of sporotrichosis. Braz J Biol. 2017;77:848-855.
Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy. successful treatment for alopecia areata. Arch Dermatol. 1998;134:1349-1352.
Lakshmi C, Srinivas CR. Allergic contact dermatitis following aromatherapy with valiya narayana thailam—an ayurvedic oil presenting as exfoliative dermatitis. Contact Dermatitis. 2009;61:297-298.
Carson CF, Hammer KA, Riley TV. Melaleuca alternifolia (tea tree) oil: a review of antimicrobial and other medicinal properties. Clin Microbiol Rev. 2006;19:50-62.
Groot AC de, Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis. 2016;75:129-143.
de Groot AC, Schmidt E. Essential oils, part I: introduction. dermatitis. 2016;27:39-42.
Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy. successful treatment for alopecia areata. Arch Dermatol. 1998;134:1349-1352.
Ozmen I, Caliskan E, Arca E, et al. Efficacy of aromatherapy in the treatment of localized alopecia areata: a double-blind placebo controlled study. Gulhane Med J. 2015;57:233.
Oh GN, Son SW. Efficacy of Korean red ginseng in the treatment of alopecia areata. J Ginseng Res. 2012;36:391-395.
Yang D-Q, You L-P, Song P-H, et al. A randomized controlled trial comparing total glucosides of paeony capsule and compound glycyrrhizin tablet for alopecia areata. Chin J Integr Med. 2012;18:621-625.
Dermatologic patients are increasingly opting for alternative treatments in addition to or instead of standard therapies for many common skin conditions.
Dermatologists should be aware of the emerging evidence regarding the risks and benefits of some of the most popular alternative treatments in common skin disorders.
Counseling patients on the side effects that accompany many supplements and the lack of data to support others is a crucial component of patient care.
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Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.
Dr. April Armstrong
“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.
In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).
TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.
Favorable characteristics of non–TNF-inhibitor biologics
Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.
IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.
IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.
“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.
One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.
IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.
IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”
IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.
Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.
Accessibility weighs heavily in using TNF inhibitor first
Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.
Dr. Amit Garg
He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.
“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”
However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.
“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.
“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.
Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.
“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.
In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.
Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.
Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,
Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.
Dr. April Armstrong
“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.
In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).
TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.
Favorable characteristics of non–TNF-inhibitor biologics
Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.
IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.
IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.
“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.
One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.
IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.
IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”
IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.
Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.
Accessibility weighs heavily in using TNF inhibitor first
Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.
Dr. Amit Garg
He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.
“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”
However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.
“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.
“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.
Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.
“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.
In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.
Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.
Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,
Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.
Dr. April Armstrong
“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.
In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).
TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.
Favorable characteristics of non–TNF-inhibitor biologics
Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.
IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.
IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.
“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.
One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.
IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.
IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”
IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.
Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.
Accessibility weighs heavily in using TNF inhibitor first
Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.
Dr. Amit Garg
He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.
“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”
However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.
“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.
“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.
Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.
“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.
In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.
Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.
Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,
Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.
Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues2 found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues13 identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),14 which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,15thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.
This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom16 and Turkey.17
Methods
Design, Setting, Sample, and Statistical Analysis The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom16 and Turkey.17 Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.
Phototherapy Protocol All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,18 and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.
Results
Patients Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.
Dermatologic Conditions Treated With Phototherapy Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).
Figure 1. Dermatologic conditions of older patients (N=52). Percentages were rounded to the nearest whole number.
Effectiveness and Safety of Phototherapy Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.
Figure 2. Degree of clearance by dermatologic condition.
Side effects from phototherapy were minimal; 24 patients (46%) experienced grade 1 (mild) erythema at some point during their treatment course. Thirteen (25%) patients experienced grade 2 erythema, but this was a rare event for most patients. Only 1 (2%) patient experienced grade 3 erythema 1 time. Three patients experienced increased itching (6%). Thirteen (25%) patients had no side effects. None developed severe erythema or blisters, and none discontinued phototherapy because of side effects. Over the course of the study year, we found a high degree of acceptance of phototherapy treatments by older patients: 22 (42%) completed therapy after achieving clearance, 10 (19%) were continuing ongoing treatments (maintenance), and 15 (29%) stopped because of life circumstances (eg, other health issues, moving out of the area). Only 4 (8%) stopped because of a lack of effectiveness, and 1 (2%) patient because the treatments were burdensome.
Comparison of Outcomes Our third aim was to compare the outcomes with similar studies in the United Kingdom16 and Turkey.17 This study confirmed that phototherapy is being used in older adults (22.7% of this study’s total patients) and is an effective treatment for older patients experiencing a range of challenging inflammatory and proliferative skin diseases similar to studies in the general population. Prior phototherapy studies in elderly patients also found psoriasis to be the most common skin condition treated, with 1 study finding that 51% (19/37) of older phototherapy patients had psoriasis,16 while another reported 58% (37/95) of older phototherapy patients had psoriasis.17 These numbers are similar to those in our study, which showed 50% (26/52) of elderly phototherapy patients had psoriasis. Psoriasis is the main indication for treatment with NB-UVB phototherapy in the general population,19 and because the risk for psoriasis increases with age,20 it is not surprising that all 3 studies found psoriasis to be the most common indication in elderly phototherapy patients. Table 3 provides further details on conditions treated in all 3 studies.
Comment
Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.16 The other similar study in Turkey17 reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.
Figure 3. Comparison of total treatments and side effects across all conditions. MF indicates mycosis fungoides; DNC, did not clear. Bold rule indicates patients who experienced side effects greater than grade 1.
In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.21 The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.
Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom16 (1.89%) and Turkey17 (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.
Limitations This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom16 and Turkey,17 they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.
Conclusion
Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.
Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.
References
British Photodermatology Group. An appraisal of narrowband (TL-01) UVB phototherapy. British Photodermatology Group Workshop Report (April 1996). Br J Dermatol. 1997;137:327-330.
Foerster J, Boswell K, West J, et al. Narrowband UVB treatment is highly effective and causes a strong reduction in the use of steroid and other creams in psoriasis patients in clinical practice. PLoS ONE. 2017;12:e0181813. doi:10.1371/journal.pone.0181813
Fernández-Guarino M, Aboin-Gonzalez S, Barchino L, et al. Treatment of moderate and severe adult chronic atopic dermatitis with narrow-band UVB and the combination of narrow-band UVB/UVA phototherapy. Dermatol Ther. 2015;29:19-23.
Ryu HH, Choe YS, Jo S, et al. Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy. J Dermatol. 2014;41:622-627.
Tintle S, Shemer A, Suárez-Fariñas M, et al. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J Allergy Clin Immunol. 2011;128:583-593.
Gambichler T, Breuckmann F, Boms S, et al. Narrowband UVB phototherapy in skin conditions beyond psoriasis. J Am Acad Dermatol. 2005;52:660-670.
Schneider LA, Hinrichs R, Scharffetter-Kochanek K. Phototherapy and photochemotherapy. Clin Dermatol. 2008;26:464-476.
Martin JA, Laube S, Edwards C, et al. Rate of acute adverse events for narrow-band UVB and psoralen-UVA phototherapy. Photodermatol Photoimmunol Photomed. 2007;23:68-72.
Mokos ZB, Jovic A, Ceovic R, et al. Therapeutic challenges in the mature patient. Clin Dermatol. 2018;36:128-139.
Di Lernia V, Goldust M. An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly. Exp Opin Biol Ther. 2018;18:897-903.
Napolitano M, Balato N, Ayala F, et al. Psoriasis in elderly and non-elderly population: clinical and molecular features. G Ital Dermatol Venereol. 2016;151:587-595.
Grozdev IS, Van Voorhees AS, Gottlieb AB, et al. Psoriasis in the elderly: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2011;65:537-545.
Click J, Alabaster A, Postlethwaite D, et al. Effect of availability of at-home phototherapy on the use of systemic medications for psoriasis. Photodermatol Photoimmunol Photomed. 2017;33:345-346.
Piaserico S, Conti A, Lo Console F, et al. Efficacy and safety of systemic treatments for psoriasis in elderly. Acta Derm Venereol. 2014;94:293-297.
Soliman A, Nofal E, Nofal A, et al. Combination therapy of methotrexate plus NB-UVB phototherapy is more effective than methotrexate monotherapy in the treatment of chronic plaque psoriasis. J Dermatol Treat. 2015;26:528-534.
Powell JB, Gach JE. Phototherapy in the elderly. Clin Exp Dermatol. 2015;40:605-610.
Bulur I, Erdogan HK, Aksu AE, et al. The efficacy and safety of phototherapy in geriatric patients: a retrospective study. An Bras Dermatol. 2018;93:33-38.
Madigan LM, Al-Jamal M, Hamzavi I. Exploring the gaps in the evidence-based application of narrowband UVB for the treatment of vitiligo. Photodermatol Photoimmunol Photomed. 2016;32:66-80.
Ibbotson SH. A perspective on the use of NB-UVB phototherapy vs. PUVA photochemotherapy. Front Med (Lausanne). 2018;5:184.
Bell LM, Sedlack R, Beard CM, et al. Incidence of psoriasis in Rochester, Minn, 1980-1983. Arch Dermatol. 1991;127:1184-1187.
Cameron H, Yule S, Dawe RS, et al. Review of an established UK home phototherapy service 1998-2011: improving access to a cost-effective treatment for chronic skin disease. Public Health. 2014;128:317-324.
Matthews SW, Simmer M, Williams L, et al. Transition of patients with psoriasis from office-based phototherapy to nurse-supported home phototherapy: a pilot study. JDNA. 2018;10:29-41.
From the University of Washington, Seattle. Drs. Matthews and Pike are from the School of Nursing. Dr. Chien is from the School of Medicine. Drs. Matthews and Chien also are from Kaiser Permanente Dermatology, Bellevue, Washington.
The authors report no conflict of interest.
Correspondence: Sarah W. Matthews, DNP, University of Washington, 1959 NE Pacific St, Box 357263, Seattle, WA 98195-7263 ([email protected]).
From the University of Washington, Seattle. Drs. Matthews and Pike are from the School of Nursing. Dr. Chien is from the School of Medicine. Drs. Matthews and Chien also are from Kaiser Permanente Dermatology, Bellevue, Washington.
The authors report no conflict of interest.
Correspondence: Sarah W. Matthews, DNP, University of Washington, 1959 NE Pacific St, Box 357263, Seattle, WA 98195-7263 ([email protected]).
Author and Disclosure Information
From the University of Washington, Seattle. Drs. Matthews and Pike are from the School of Nursing. Dr. Chien is from the School of Medicine. Drs. Matthews and Chien also are from Kaiser Permanente Dermatology, Bellevue, Washington.
The authors report no conflict of interest.
Correspondence: Sarah W. Matthews, DNP, University of Washington, 1959 NE Pacific St, Box 357263, Seattle, WA 98195-7263 ([email protected]).
Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.
Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues2 found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues13 identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),14 which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,15thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.
This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom16 and Turkey.17
Methods
Design, Setting, Sample, and Statistical Analysis The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom16 and Turkey.17 Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.
Phototherapy Protocol All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,18 and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.
Results
Patients Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.
Dermatologic Conditions Treated With Phototherapy Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).
Figure 1. Dermatologic conditions of older patients (N=52). Percentages were rounded to the nearest whole number.
Effectiveness and Safety of Phototherapy Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.
Figure 2. Degree of clearance by dermatologic condition.
Side effects from phototherapy were minimal; 24 patients (46%) experienced grade 1 (mild) erythema at some point during their treatment course. Thirteen (25%) patients experienced grade 2 erythema, but this was a rare event for most patients. Only 1 (2%) patient experienced grade 3 erythema 1 time. Three patients experienced increased itching (6%). Thirteen (25%) patients had no side effects. None developed severe erythema or blisters, and none discontinued phototherapy because of side effects. Over the course of the study year, we found a high degree of acceptance of phototherapy treatments by older patients: 22 (42%) completed therapy after achieving clearance, 10 (19%) were continuing ongoing treatments (maintenance), and 15 (29%) stopped because of life circumstances (eg, other health issues, moving out of the area). Only 4 (8%) stopped because of a lack of effectiveness, and 1 (2%) patient because the treatments were burdensome.
Comparison of Outcomes Our third aim was to compare the outcomes with similar studies in the United Kingdom16 and Turkey.17 This study confirmed that phototherapy is being used in older adults (22.7% of this study’s total patients) and is an effective treatment for older patients experiencing a range of challenging inflammatory and proliferative skin diseases similar to studies in the general population. Prior phototherapy studies in elderly patients also found psoriasis to be the most common skin condition treated, with 1 study finding that 51% (19/37) of older phototherapy patients had psoriasis,16 while another reported 58% (37/95) of older phototherapy patients had psoriasis.17 These numbers are similar to those in our study, which showed 50% (26/52) of elderly phototherapy patients had psoriasis. Psoriasis is the main indication for treatment with NB-UVB phototherapy in the general population,19 and because the risk for psoriasis increases with age,20 it is not surprising that all 3 studies found psoriasis to be the most common indication in elderly phototherapy patients. Table 3 provides further details on conditions treated in all 3 studies.
Comment
Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.16 The other similar study in Turkey17 reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.
Figure 3. Comparison of total treatments and side effects across all conditions. MF indicates mycosis fungoides; DNC, did not clear. Bold rule indicates patients who experienced side effects greater than grade 1.
In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.21 The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.
Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom16 (1.89%) and Turkey17 (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.
Limitations This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom16 and Turkey,17 they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.
Conclusion
Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.
Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.
Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.
Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues2 found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues13 identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),14 which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,15thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.
This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom16 and Turkey.17
Methods
Design, Setting, Sample, and Statistical Analysis The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom16 and Turkey.17 Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.
Phototherapy Protocol All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,18 and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.
Results
Patients Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.
Dermatologic Conditions Treated With Phototherapy Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).
Figure 1. Dermatologic conditions of older patients (N=52). Percentages were rounded to the nearest whole number.
Effectiveness and Safety of Phototherapy Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.
Figure 2. Degree of clearance by dermatologic condition.
Side effects from phototherapy were minimal; 24 patients (46%) experienced grade 1 (mild) erythema at some point during their treatment course. Thirteen (25%) patients experienced grade 2 erythema, but this was a rare event for most patients. Only 1 (2%) patient experienced grade 3 erythema 1 time. Three patients experienced increased itching (6%). Thirteen (25%) patients had no side effects. None developed severe erythema or blisters, and none discontinued phototherapy because of side effects. Over the course of the study year, we found a high degree of acceptance of phototherapy treatments by older patients: 22 (42%) completed therapy after achieving clearance, 10 (19%) were continuing ongoing treatments (maintenance), and 15 (29%) stopped because of life circumstances (eg, other health issues, moving out of the area). Only 4 (8%) stopped because of a lack of effectiveness, and 1 (2%) patient because the treatments were burdensome.
Comparison of Outcomes Our third aim was to compare the outcomes with similar studies in the United Kingdom16 and Turkey.17 This study confirmed that phototherapy is being used in older adults (22.7% of this study’s total patients) and is an effective treatment for older patients experiencing a range of challenging inflammatory and proliferative skin diseases similar to studies in the general population. Prior phototherapy studies in elderly patients also found psoriasis to be the most common skin condition treated, with 1 study finding that 51% (19/37) of older phototherapy patients had psoriasis,16 while another reported 58% (37/95) of older phototherapy patients had psoriasis.17 These numbers are similar to those in our study, which showed 50% (26/52) of elderly phototherapy patients had psoriasis. Psoriasis is the main indication for treatment with NB-UVB phototherapy in the general population,19 and because the risk for psoriasis increases with age,20 it is not surprising that all 3 studies found psoriasis to be the most common indication in elderly phototherapy patients. Table 3 provides further details on conditions treated in all 3 studies.
Comment
Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.16 The other similar study in Turkey17 reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.
Figure 3. Comparison of total treatments and side effects across all conditions. MF indicates mycosis fungoides; DNC, did not clear. Bold rule indicates patients who experienced side effects greater than grade 1.
In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.21 The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.
Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom16 (1.89%) and Turkey17 (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.
Limitations This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom16 and Turkey,17 they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.
Conclusion
Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.
Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.
References
British Photodermatology Group. An appraisal of narrowband (TL-01) UVB phototherapy. British Photodermatology Group Workshop Report (April 1996). Br J Dermatol. 1997;137:327-330.
Foerster J, Boswell K, West J, et al. Narrowband UVB treatment is highly effective and causes a strong reduction in the use of steroid and other creams in psoriasis patients in clinical practice. PLoS ONE. 2017;12:e0181813. doi:10.1371/journal.pone.0181813
Fernández-Guarino M, Aboin-Gonzalez S, Barchino L, et al. Treatment of moderate and severe adult chronic atopic dermatitis with narrow-band UVB and the combination of narrow-band UVB/UVA phototherapy. Dermatol Ther. 2015;29:19-23.
Ryu HH, Choe YS, Jo S, et al. Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy. J Dermatol. 2014;41:622-627.
Tintle S, Shemer A, Suárez-Fariñas M, et al. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J Allergy Clin Immunol. 2011;128:583-593.
Gambichler T, Breuckmann F, Boms S, et al. Narrowband UVB phototherapy in skin conditions beyond psoriasis. J Am Acad Dermatol. 2005;52:660-670.
Schneider LA, Hinrichs R, Scharffetter-Kochanek K. Phototherapy and photochemotherapy. Clin Dermatol. 2008;26:464-476.
Martin JA, Laube S, Edwards C, et al. Rate of acute adverse events for narrow-band UVB and psoralen-UVA phototherapy. Photodermatol Photoimmunol Photomed. 2007;23:68-72.
Mokos ZB, Jovic A, Ceovic R, et al. Therapeutic challenges in the mature patient. Clin Dermatol. 2018;36:128-139.
Di Lernia V, Goldust M. An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly. Exp Opin Biol Ther. 2018;18:897-903.
Napolitano M, Balato N, Ayala F, et al. Psoriasis in elderly and non-elderly population: clinical and molecular features. G Ital Dermatol Venereol. 2016;151:587-595.
Grozdev IS, Van Voorhees AS, Gottlieb AB, et al. Psoriasis in the elderly: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2011;65:537-545.
Click J, Alabaster A, Postlethwaite D, et al. Effect of availability of at-home phototherapy on the use of systemic medications for psoriasis. Photodermatol Photoimmunol Photomed. 2017;33:345-346.
Piaserico S, Conti A, Lo Console F, et al. Efficacy and safety of systemic treatments for psoriasis in elderly. Acta Derm Venereol. 2014;94:293-297.
Soliman A, Nofal E, Nofal A, et al. Combination therapy of methotrexate plus NB-UVB phototherapy is more effective than methotrexate monotherapy in the treatment of chronic plaque psoriasis. J Dermatol Treat. 2015;26:528-534.
Powell JB, Gach JE. Phototherapy in the elderly. Clin Exp Dermatol. 2015;40:605-610.
Bulur I, Erdogan HK, Aksu AE, et al. The efficacy and safety of phototherapy in geriatric patients: a retrospective study. An Bras Dermatol. 2018;93:33-38.
Madigan LM, Al-Jamal M, Hamzavi I. Exploring the gaps in the evidence-based application of narrowband UVB for the treatment of vitiligo. Photodermatol Photoimmunol Photomed. 2016;32:66-80.
Ibbotson SH. A perspective on the use of NB-UVB phototherapy vs. PUVA photochemotherapy. Front Med (Lausanne). 2018;5:184.
Bell LM, Sedlack R, Beard CM, et al. Incidence of psoriasis in Rochester, Minn, 1980-1983. Arch Dermatol. 1991;127:1184-1187.
Cameron H, Yule S, Dawe RS, et al. Review of an established UK home phototherapy service 1998-2011: improving access to a cost-effective treatment for chronic skin disease. Public Health. 2014;128:317-324.
Matthews SW, Simmer M, Williams L, et al. Transition of patients with psoriasis from office-based phototherapy to nurse-supported home phototherapy: a pilot study. JDNA. 2018;10:29-41.
References
British Photodermatology Group. An appraisal of narrowband (TL-01) UVB phototherapy. British Photodermatology Group Workshop Report (April 1996). Br J Dermatol. 1997;137:327-330.
Foerster J, Boswell K, West J, et al. Narrowband UVB treatment is highly effective and causes a strong reduction in the use of steroid and other creams in psoriasis patients in clinical practice. PLoS ONE. 2017;12:e0181813. doi:10.1371/journal.pone.0181813
Fernández-Guarino M, Aboin-Gonzalez S, Barchino L, et al. Treatment of moderate and severe adult chronic atopic dermatitis with narrow-band UVB and the combination of narrow-band UVB/UVA phototherapy. Dermatol Ther. 2015;29:19-23.
Ryu HH, Choe YS, Jo S, et al. Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy. J Dermatol. 2014;41:622-627.
Tintle S, Shemer A, Suárez-Fariñas M, et al. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J Allergy Clin Immunol. 2011;128:583-593.
Gambichler T, Breuckmann F, Boms S, et al. Narrowband UVB phototherapy in skin conditions beyond psoriasis. J Am Acad Dermatol. 2005;52:660-670.
Schneider LA, Hinrichs R, Scharffetter-Kochanek K. Phototherapy and photochemotherapy. Clin Dermatol. 2008;26:464-476.
Martin JA, Laube S, Edwards C, et al. Rate of acute adverse events for narrow-band UVB and psoralen-UVA phototherapy. Photodermatol Photoimmunol Photomed. 2007;23:68-72.
Mokos ZB, Jovic A, Ceovic R, et al. Therapeutic challenges in the mature patient. Clin Dermatol. 2018;36:128-139.
Di Lernia V, Goldust M. An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly. Exp Opin Biol Ther. 2018;18:897-903.
Napolitano M, Balato N, Ayala F, et al. Psoriasis in elderly and non-elderly population: clinical and molecular features. G Ital Dermatol Venereol. 2016;151:587-595.
Grozdev IS, Van Voorhees AS, Gottlieb AB, et al. Psoriasis in the elderly: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2011;65:537-545.
Click J, Alabaster A, Postlethwaite D, et al. Effect of availability of at-home phototherapy on the use of systemic medications for psoriasis. Photodermatol Photoimmunol Photomed. 2017;33:345-346.
Piaserico S, Conti A, Lo Console F, et al. Efficacy and safety of systemic treatments for psoriasis in elderly. Acta Derm Venereol. 2014;94:293-297.
Soliman A, Nofal E, Nofal A, et al. Combination therapy of methotrexate plus NB-UVB phototherapy is more effective than methotrexate monotherapy in the treatment of chronic plaque psoriasis. J Dermatol Treat. 2015;26:528-534.
Powell JB, Gach JE. Phototherapy in the elderly. Clin Exp Dermatol. 2015;40:605-610.
Bulur I, Erdogan HK, Aksu AE, et al. The efficacy and safety of phototherapy in geriatric patients: a retrospective study. An Bras Dermatol. 2018;93:33-38.
Madigan LM, Al-Jamal M, Hamzavi I. Exploring the gaps in the evidence-based application of narrowband UVB for the treatment of vitiligo. Photodermatol Photoimmunol Photomed. 2016;32:66-80.
Ibbotson SH. A perspective on the use of NB-UVB phototherapy vs. PUVA photochemotherapy. Front Med (Lausanne). 2018;5:184.
Bell LM, Sedlack R, Beard CM, et al. Incidence of psoriasis in Rochester, Minn, 1980-1983. Arch Dermatol. 1991;127:1184-1187.
Cameron H, Yule S, Dawe RS, et al. Review of an established UK home phototherapy service 1998-2011: improving access to a cost-effective treatment for chronic skin disease. Public Health. 2014;128:317-324.
Matthews SW, Simmer M, Williams L, et al. Transition of patients with psoriasis from office-based phototherapy to nurse-supported home phototherapy: a pilot study. JDNA. 2018;10:29-41.
In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.
The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.
Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.
Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.
Dr. Jack Resneck Jr.
Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.
Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
Better outcomes, less anxiety for patients
Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”
Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.
She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.
Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”
One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.
The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.
Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”
Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
State and federal efforts to curb prior authorization
In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.
The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:
Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.
The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.
A version of this article first appeared on Medscape.com.
In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.
The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.
Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.
Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.
Dr. Jack Resneck Jr.
Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.
Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
Better outcomes, less anxiety for patients
Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”
Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.
She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.
Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”
One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.
The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.
Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”
Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
State and federal efforts to curb prior authorization
In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.
The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:
Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.
The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.
A version of this article first appeared on Medscape.com.
In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.
The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.
Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.
Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.
Dr. Jack Resneck Jr.
Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.
Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
Better outcomes, less anxiety for patients
Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”
Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.
She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.
Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”
One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.
The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.
Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”
Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
State and federal efforts to curb prior authorization
In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.
The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:
Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.
The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.
A version of this article first appeared on Medscape.com.
A Elbow and forearm with erythematous, well-demarcated, pink plaques with mild micaceous scale in a 42-year-old White woman.
B Elbow and forearm with violaceous, well-demarcated plaques with micaceous scale and hyperpigmented patches around the active plaques in a 58-year-old Black man.
Epidemiology Psoriasis prevalence in the United States has been estimated at 3.7%.1-3 If broken down by race or ethnicity, the prevalence of psoriasis varies: 2.5% to 3.7% in White adults1-4; 1.3% to 2% in Black adults1-4; 1.6% in Hispanics/ other adults1-3; 1% in children overall; 0.29% in White children1,5; and 0.06% in Black children.1,5
Key clinical features in people with darker skin tones include:
plaques that may appear more violaceous in color instead of pink or erythematous
higher body surface area of involvement4 and thicker, more scaly plaques6
increased likelihood of postinflammatory hyperpigmentation (PIH).
Worth noting Although individuals of all skin tones may experience the psychosocial impact of psoriasis, quality-of-life measures have been found to be worse in those with skin of color (SOC) compared to White patients.1,4 This may be due to the lingering PIH and hypopigmentation that occurs even after inflammatory plaques are treated. Of course, lack of access to care contributes to greater disease burden and more devastating psychological impact.
Health disparity highlight Psoriasis may be underreported and underdiagnosed in individuals with SOC, as factors contributing to health care disparities may play a role, such as access to health care in general,1,7 and access to clinicians proficient in diagnosing cutaneous diseases in SOC may be delayed.8
Biologic medications are used less often in Black patients than in White patients, despite biologic medications being very efficacious for treatment of psoriasis.1,9,10
References
Kaufman BP, Alexis AF. Psoriasis in skin of color: insights into the epidemiology, clinical presentation, genetics, quality-of-life impact, and treatment of psoriasis in non-white racial/ethnic groups. Am J Clin Dermatol. 2018;19:405-423.
Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
Helmick CG, Lee-Han H, Hirsch SC, et al. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47:37-45.
Gelfand JM, Stern RS, Nijsten T, et al. The prevalence of psoriasis in African Americans: results from a population-based study. J Am Acad Dermatol. 2005;52:23-26.
Wu JJ, Black MH, Smith N, et al. Low prevalence of psoriasis among children and adolescents in a large multiethnic cohort in southern California. J Am Acad Dermatol. 2011;65:957-964.
Davis SA, Narahari S, Feldman SR, et al. Top dermatologic conditions in patients of color: an analysis of nationally representative data. J Drugs Dermatol. 2012;11:466-473.
Alexis AF, Blackcloud P. Psoriasis in skin of color: epidemiology, genetics, clinical presentation, and treatment nuances. J Clin Aesthet Dermatol. 2014;7:16-24.
Mundluru SN, Ramalingam ND, Tran HN. Addressing internal medicine residents’ discomfort with basic dermatology in persons of color in the primary care clinic. Am J Med Qual. 2019;34:513-513.
Kerr GS, Qaiyumi S, Richards J, et al. Psoriasis and psoriatic arthritis in African-American patients—the need to measure disease burden. Clin Rheumatol. 2015;34:1753-1759.
Takeshita J, Gelfand JM, Li P, et al. Psoriasis in the US Medicare population: prevalence, treatment, and factors associated with biologic use. J Invest Dermatol. 2015;135:2955-2963.
A Elbow and forearm with erythematous, well-demarcated, pink plaques with mild micaceous scale in a 42-year-old White woman.
B Elbow and forearm with violaceous, well-demarcated plaques with micaceous scale and hyperpigmented patches around the active plaques in a 58-year-old Black man.
Epidemiology Psoriasis prevalence in the United States has been estimated at 3.7%.1-3 If broken down by race or ethnicity, the prevalence of psoriasis varies: 2.5% to 3.7% in White adults1-4; 1.3% to 2% in Black adults1-4; 1.6% in Hispanics/ other adults1-3; 1% in children overall; 0.29% in White children1,5; and 0.06% in Black children.1,5
Key clinical features in people with darker skin tones include:
plaques that may appear more violaceous in color instead of pink or erythematous
higher body surface area of involvement4 and thicker, more scaly plaques6
increased likelihood of postinflammatory hyperpigmentation (PIH).
Worth noting Although individuals of all skin tones may experience the psychosocial impact of psoriasis, quality-of-life measures have been found to be worse in those with skin of color (SOC) compared to White patients.1,4 This may be due to the lingering PIH and hypopigmentation that occurs even after inflammatory plaques are treated. Of course, lack of access to care contributes to greater disease burden and more devastating psychological impact.
Health disparity highlight Psoriasis may be underreported and underdiagnosed in individuals with SOC, as factors contributing to health care disparities may play a role, such as access to health care in general,1,7 and access to clinicians proficient in diagnosing cutaneous diseases in SOC may be delayed.8
Biologic medications are used less often in Black patients than in White patients, despite biologic medications being very efficacious for treatment of psoriasis.1,9,10
Photographs courtesy of Richard P. Usatine, MD.
The Comparison
A Elbow and forearm with erythematous, well-demarcated, pink plaques with mild micaceous scale in a 42-year-old White woman.
B Elbow and forearm with violaceous, well-demarcated plaques with micaceous scale and hyperpigmented patches around the active plaques in a 58-year-old Black man.
Epidemiology Psoriasis prevalence in the United States has been estimated at 3.7%.1-3 If broken down by race or ethnicity, the prevalence of psoriasis varies: 2.5% to 3.7% in White adults1-4; 1.3% to 2% in Black adults1-4; 1.6% in Hispanics/ other adults1-3; 1% in children overall; 0.29% in White children1,5; and 0.06% in Black children.1,5
Key clinical features in people with darker skin tones include:
plaques that may appear more violaceous in color instead of pink or erythematous
higher body surface area of involvement4 and thicker, more scaly plaques6
increased likelihood of postinflammatory hyperpigmentation (PIH).
Worth noting Although individuals of all skin tones may experience the psychosocial impact of psoriasis, quality-of-life measures have been found to be worse in those with skin of color (SOC) compared to White patients.1,4 This may be due to the lingering PIH and hypopigmentation that occurs even after inflammatory plaques are treated. Of course, lack of access to care contributes to greater disease burden and more devastating psychological impact.
Health disparity highlight Psoriasis may be underreported and underdiagnosed in individuals with SOC, as factors contributing to health care disparities may play a role, such as access to health care in general,1,7 and access to clinicians proficient in diagnosing cutaneous diseases in SOC may be delayed.8
Biologic medications are used less often in Black patients than in White patients, despite biologic medications being very efficacious for treatment of psoriasis.1,9,10
References
Kaufman BP, Alexis AF. Psoriasis in skin of color: insights into the epidemiology, clinical presentation, genetics, quality-of-life impact, and treatment of psoriasis in non-white racial/ethnic groups. Am J Clin Dermatol. 2018;19:405-423.
Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
Helmick CG, Lee-Han H, Hirsch SC, et al. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47:37-45.
Gelfand JM, Stern RS, Nijsten T, et al. The prevalence of psoriasis in African Americans: results from a population-based study. J Am Acad Dermatol. 2005;52:23-26.
Wu JJ, Black MH, Smith N, et al. Low prevalence of psoriasis among children and adolescents in a large multiethnic cohort in southern California. J Am Acad Dermatol. 2011;65:957-964.
Davis SA, Narahari S, Feldman SR, et al. Top dermatologic conditions in patients of color: an analysis of nationally representative data. J Drugs Dermatol. 2012;11:466-473.
Alexis AF, Blackcloud P. Psoriasis in skin of color: epidemiology, genetics, clinical presentation, and treatment nuances. J Clin Aesthet Dermatol. 2014;7:16-24.
Mundluru SN, Ramalingam ND, Tran HN. Addressing internal medicine residents’ discomfort with basic dermatology in persons of color in the primary care clinic. Am J Med Qual. 2019;34:513-513.
Kerr GS, Qaiyumi S, Richards J, et al. Psoriasis and psoriatic arthritis in African-American patients—the need to measure disease burden. Clin Rheumatol. 2015;34:1753-1759.
Takeshita J, Gelfand JM, Li P, et al. Psoriasis in the US Medicare population: prevalence, treatment, and factors associated with biologic use. J Invest Dermatol. 2015;135:2955-2963.
References
Kaufman BP, Alexis AF. Psoriasis in skin of color: insights into the epidemiology, clinical presentation, genetics, quality-of-life impact, and treatment of psoriasis in non-white racial/ethnic groups. Am J Clin Dermatol. 2018;19:405-423.
Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
Helmick CG, Lee-Han H, Hirsch SC, et al. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47:37-45.
Gelfand JM, Stern RS, Nijsten T, et al. The prevalence of psoriasis in African Americans: results from a population-based study. J Am Acad Dermatol. 2005;52:23-26.
Wu JJ, Black MH, Smith N, et al. Low prevalence of psoriasis among children and adolescents in a large multiethnic cohort in southern California. J Am Acad Dermatol. 2011;65:957-964.
Davis SA, Narahari S, Feldman SR, et al. Top dermatologic conditions in patients of color: an analysis of nationally representative data. J Drugs Dermatol. 2012;11:466-473.
Alexis AF, Blackcloud P. Psoriasis in skin of color: epidemiology, genetics, clinical presentation, and treatment nuances. J Clin Aesthet Dermatol. 2014;7:16-24.
Mundluru SN, Ramalingam ND, Tran HN. Addressing internal medicine residents’ discomfort with basic dermatology in persons of color in the primary care clinic. Am J Med Qual. 2019;34:513-513.
Kerr GS, Qaiyumi S, Richards J, et al. Psoriasis and psoriatic arthritis in African-American patients—the need to measure disease burden. Clin Rheumatol. 2015;34:1753-1759.
Takeshita J, Gelfand JM, Li P, et al. Psoriasis in the US Medicare population: prevalence, treatment, and factors associated with biologic use. J Invest Dermatol. 2015;135:2955-2963.
People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.
The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.
The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.
“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.
“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”
Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.
Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.
Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.
All participants had low neutralizing titers against the alpha (B.1.1.7) variant.
The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”
A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.
‘Some protection is better than none’
These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.
It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.
“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.
“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.
“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
Temporarily stopping methotrexate
It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.
Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.
“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”
Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.
However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.
This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.
The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.
The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.
“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.
“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”
Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.
Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.
Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.
All participants had low neutralizing titers against the alpha (B.1.1.7) variant.
The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”
A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.
‘Some protection is better than none’
These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.
It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.
“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.
“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.
“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
Temporarily stopping methotrexate
It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.
Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.
“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”
Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.
However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.
This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.
The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.
The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.
“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.
“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”
Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.
Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.
Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.
All participants had low neutralizing titers against the alpha (B.1.1.7) variant.
The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”
A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.
‘Some protection is better than none’
These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.
It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.
“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.
“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.
“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
Temporarily stopping methotrexate
It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.
Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.
“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”
Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.
However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.
This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.1 Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al2 describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.
A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).
Figure 1. A, Erythematous tender nodules with hyperkeratotic scale on the wrist following use of etanercept. B, A 7-cm squamous cell carcinoma was present on the right ankle.
Figure 2. A and B, Histopathology of a lesion on the right medial wrist revealed atypical keratinocytes arranged in a digitate fashion, and some atypical cells were seen in the reticular dermis (H&E, original magnifications ×10 and ×10).
Figure 3. A, At 1-year follow-up after discontinuation of etanercept and initiation of acitretin, baseline porokeratosis lesions resolved. B, Histopathology of the right fourth finger revealed epidermal hyperplasia accompanied by columns of parakeratosis with underlying dyskeratosis (H&E, original magnification ×10).
The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al3 noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.
Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.4
Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.5 There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.
References
Feldmann M, Charles P, Taylor P, et al. Biological insights from clinical trials with anti-TNF therapy. Springer Semin Immunopathol Springer Sem Immunopathol. 1998;20:211-228.
Brewer JD, Schott ARH, Roenigk RK. Multiple squamous cell carcinomas in the setting of psoriasis treated with etanercept: a report of four cases and review of the literature. Int J Dermatol. 2011;50:1555-1559.
Ninomiya Y, Urano Y, Yoshimoto K, et al. p53 gene mutation analysis in porokeratosis and porokeratosis-associated squamous cell carcinoma. J Dermatol Sci. 1997;14:173-178.
Lee HR, Han TY, Son S-J, et al. Squamous cell carcinoma developing within lesions of disseminated superficial actinic porokeratosis. Ann Dermatol. 2011;23:536.
Kwon EJ, Kish LS, Jaworsky C. The histologic spectrum of epithelial neoplasms induced by sorafenib. J Am Acad Dermatol. 2009;61:522-527.
Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.1 Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al2 describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.
A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).
Figure 1. A, Erythematous tender nodules with hyperkeratotic scale on the wrist following use of etanercept. B, A 7-cm squamous cell carcinoma was present on the right ankle.
Figure 2. A and B, Histopathology of a lesion on the right medial wrist revealed atypical keratinocytes arranged in a digitate fashion, and some atypical cells were seen in the reticular dermis (H&E, original magnifications ×10 and ×10).
Figure 3. A, At 1-year follow-up after discontinuation of etanercept and initiation of acitretin, baseline porokeratosis lesions resolved. B, Histopathology of the right fourth finger revealed epidermal hyperplasia accompanied by columns of parakeratosis with underlying dyskeratosis (H&E, original magnification ×10).
The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al3 noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.
Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.4
Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.5 There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.
To the Editor:
Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.1 Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al2 describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.
A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).
Figure 1. A, Erythematous tender nodules with hyperkeratotic scale on the wrist following use of etanercept. B, A 7-cm squamous cell carcinoma was present on the right ankle.
Figure 2. A and B, Histopathology of a lesion on the right medial wrist revealed atypical keratinocytes arranged in a digitate fashion, and some atypical cells were seen in the reticular dermis (H&E, original magnifications ×10 and ×10).
Figure 3. A, At 1-year follow-up after discontinuation of etanercept and initiation of acitretin, baseline porokeratosis lesions resolved. B, Histopathology of the right fourth finger revealed epidermal hyperplasia accompanied by columns of parakeratosis with underlying dyskeratosis (H&E, original magnification ×10).
The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al3 noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.
Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.4
Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.5 There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.
References
Feldmann M, Charles P, Taylor P, et al. Biological insights from clinical trials with anti-TNF therapy. Springer Semin Immunopathol Springer Sem Immunopathol. 1998;20:211-228.
Brewer JD, Schott ARH, Roenigk RK. Multiple squamous cell carcinomas in the setting of psoriasis treated with etanercept: a report of four cases and review of the literature. Int J Dermatol. 2011;50:1555-1559.
Ninomiya Y, Urano Y, Yoshimoto K, et al. p53 gene mutation analysis in porokeratosis and porokeratosis-associated squamous cell carcinoma. J Dermatol Sci. 1997;14:173-178.
Lee HR, Han TY, Son S-J, et al. Squamous cell carcinoma developing within lesions of disseminated superficial actinic porokeratosis. Ann Dermatol. 2011;23:536.
Kwon EJ, Kish LS, Jaworsky C. The histologic spectrum of epithelial neoplasms induced by sorafenib. J Am Acad Dermatol. 2009;61:522-527.
References
Feldmann M, Charles P, Taylor P, et al. Biological insights from clinical trials with anti-TNF therapy. Springer Semin Immunopathol Springer Sem Immunopathol. 1998;20:211-228.
Brewer JD, Schott ARH, Roenigk RK. Multiple squamous cell carcinomas in the setting of psoriasis treated with etanercept: a report of four cases and review of the literature. Int J Dermatol. 2011;50:1555-1559.
Ninomiya Y, Urano Y, Yoshimoto K, et al. p53 gene mutation analysis in porokeratosis and porokeratosis-associated squamous cell carcinoma. J Dermatol Sci. 1997;14:173-178.
Lee HR, Han TY, Son S-J, et al. Squamous cell carcinoma developing within lesions of disseminated superficial actinic porokeratosis. Ann Dermatol. 2011;23:536.
Kwon EJ, Kish LS, Jaworsky C. The histologic spectrum of epithelial neoplasms induced by sorafenib. J Am Acad Dermatol. 2009;61:522-527.
Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Carmel Aghdasi
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
Dr. Kelly M. Cordoro
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Carmel Aghdasi
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
Dr. Kelly M. Cordoro
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Carmel Aghdasi
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
Dr. Kelly M. Cordoro
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
Psoriasis affects over 7.5 million adults in the United States, with prevalence nearly twice as high among Whites as non-Whites, according to an analysis of national survey data from 2011 to 2014.
“The adult prevalence rate of 3.0% continues to place psoriasis as one of the most common immune-mediated diseases affecting adults” in the United States, April W. Armstrong, MD, MPH, and associates said in a report published in JAMA Dermatology. At that rate, approximately 7,560,000 Americans aged 20 years or older have psoriasis.
That overall rate among adults aged 20 years and older, based on data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), did not change significantly when compared with the 2003-2004 NHANES, when it was 3.15% among those aged 20-59, said Dr. Armstrong, professor of dermatology, University of Southern California, Los Angeles, and associates.
For the 2011-2014 period, psoriasis prevalence was similar between women (3.2%) and men (2.8%) but was significantly associated with older age and White/non-White status. Those aged 50-59 years had the highest prevalence of any age group at 4.3% and those aged 70 and older had a rate of 3.9%, while those aged 20-29 were the lowest at 1.6%, the investigators reported.
The prevalence in non-Hispanic Whites in the United States was 3.6% over the study period, and their odds ratio for having psoriasis was 1.92, compared with non-White individuals. Asian respondents had a prevalence of 2.5%, with the Hispanic population at 1.9%, non-Hispanic Black respondents at 1.5%, and those identifying as other (including multiracial persons) at 3.1%, they said.
The NHANES sample consisted of 12,638 people who had participated in the question that asked if they had ever been diagnosed with psoriasis by a physician or other health care professional, of whom 12,625 gave a definitive yes or no answer, the investigators noted.
A much smaller number, 329, also answered a question about the severity of their disease: Fifty-six percent had little or no psoriasis, almost 22% reported 1-2 palms of involvement, 16% had 3-10 palms of involvement, and 5.5% said the coverage was more than 10 palms. Since the survey did not distinguish between treated and untreated patients, however, some “of those reporting low body surface area involvement may be receiving treatments that are controlling their otherwise more extensive disease,” they wrote.
Dr. Armstrong and another investigator said that they have received grants, personal fees, and honoraria from a number of pharmaceutical companies; two other investigators are employees of the National Psoriasis Foundation.
Psoriasis affects over 7.5 million adults in the United States, with prevalence nearly twice as high among Whites as non-Whites, according to an analysis of national survey data from 2011 to 2014.
“The adult prevalence rate of 3.0% continues to place psoriasis as one of the most common immune-mediated diseases affecting adults” in the United States, April W. Armstrong, MD, MPH, and associates said in a report published in JAMA Dermatology. At that rate, approximately 7,560,000 Americans aged 20 years or older have psoriasis.
That overall rate among adults aged 20 years and older, based on data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), did not change significantly when compared with the 2003-2004 NHANES, when it was 3.15% among those aged 20-59, said Dr. Armstrong, professor of dermatology, University of Southern California, Los Angeles, and associates.
For the 2011-2014 period, psoriasis prevalence was similar between women (3.2%) and men (2.8%) but was significantly associated with older age and White/non-White status. Those aged 50-59 years had the highest prevalence of any age group at 4.3% and those aged 70 and older had a rate of 3.9%, while those aged 20-29 were the lowest at 1.6%, the investigators reported.
The prevalence in non-Hispanic Whites in the United States was 3.6% over the study period, and their odds ratio for having psoriasis was 1.92, compared with non-White individuals. Asian respondents had a prevalence of 2.5%, with the Hispanic population at 1.9%, non-Hispanic Black respondents at 1.5%, and those identifying as other (including multiracial persons) at 3.1%, they said.
The NHANES sample consisted of 12,638 people who had participated in the question that asked if they had ever been diagnosed with psoriasis by a physician or other health care professional, of whom 12,625 gave a definitive yes or no answer, the investigators noted.
A much smaller number, 329, also answered a question about the severity of their disease: Fifty-six percent had little or no psoriasis, almost 22% reported 1-2 palms of involvement, 16% had 3-10 palms of involvement, and 5.5% said the coverage was more than 10 palms. Since the survey did not distinguish between treated and untreated patients, however, some “of those reporting low body surface area involvement may be receiving treatments that are controlling their otherwise more extensive disease,” they wrote.
Dr. Armstrong and another investigator said that they have received grants, personal fees, and honoraria from a number of pharmaceutical companies; two other investigators are employees of the National Psoriasis Foundation.
Psoriasis affects over 7.5 million adults in the United States, with prevalence nearly twice as high among Whites as non-Whites, according to an analysis of national survey data from 2011 to 2014.
“The adult prevalence rate of 3.0% continues to place psoriasis as one of the most common immune-mediated diseases affecting adults” in the United States, April W. Armstrong, MD, MPH, and associates said in a report published in JAMA Dermatology. At that rate, approximately 7,560,000 Americans aged 20 years or older have psoriasis.
That overall rate among adults aged 20 years and older, based on data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), did not change significantly when compared with the 2003-2004 NHANES, when it was 3.15% among those aged 20-59, said Dr. Armstrong, professor of dermatology, University of Southern California, Los Angeles, and associates.
For the 2011-2014 period, psoriasis prevalence was similar between women (3.2%) and men (2.8%) but was significantly associated with older age and White/non-White status. Those aged 50-59 years had the highest prevalence of any age group at 4.3% and those aged 70 and older had a rate of 3.9%, while those aged 20-29 were the lowest at 1.6%, the investigators reported.
The prevalence in non-Hispanic Whites in the United States was 3.6% over the study period, and their odds ratio for having psoriasis was 1.92, compared with non-White individuals. Asian respondents had a prevalence of 2.5%, with the Hispanic population at 1.9%, non-Hispanic Black respondents at 1.5%, and those identifying as other (including multiracial persons) at 3.1%, they said.
The NHANES sample consisted of 12,638 people who had participated in the question that asked if they had ever been diagnosed with psoriasis by a physician or other health care professional, of whom 12,625 gave a definitive yes or no answer, the investigators noted.
A much smaller number, 329, also answered a question about the severity of their disease: Fifty-six percent had little or no psoriasis, almost 22% reported 1-2 palms of involvement, 16% had 3-10 palms of involvement, and 5.5% said the coverage was more than 10 palms. Since the survey did not distinguish between treated and untreated patients, however, some “of those reporting low body surface area involvement may be receiving treatments that are controlling their otherwise more extensive disease,” they wrote.
Dr. Armstrong and another investigator said that they have received grants, personal fees, and honoraria from a number of pharmaceutical companies; two other investigators are employees of the National Psoriasis Foundation.
Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.
Dr. Mark Lebwohl
Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.
Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.
In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.
The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.
Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.
The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.
Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.
However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.
“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.
Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.
Dr. Flavia Fedeles
However, she noted that the study has a number of limitations, including the use of clinical trials data, which have stringent inclusion/exclusion criteria that can lead to selection bias, the use of postmarketing surveillance data, the post hoc nature of the analysis, and the fact that the sponsor of the trial was the manufacturer of secukinumab, which “potentially can lead to bias to this study.”
She added that “registry data are needed to fully understand the real-world long-term effect of secukinumab on malignancy risk.”
The study was funded by Novartis. Lead author Dr. Lebwohl disclosed participating in advisory boards and/or as an investigator and/or speaker and receiving grants and/or honoraria from multiple companies including Novartis. Several study coauthors are employees of Novartis.
Dr. Fedeles had no financial conflicts to disclose.
Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.
Dr. Mark Lebwohl
Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.
Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.
In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.
The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.
Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.
The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.
Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.
However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.
“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.
Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.
Dr. Flavia Fedeles
However, she noted that the study has a number of limitations, including the use of clinical trials data, which have stringent inclusion/exclusion criteria that can lead to selection bias, the use of postmarketing surveillance data, the post hoc nature of the analysis, and the fact that the sponsor of the trial was the manufacturer of secukinumab, which “potentially can lead to bias to this study.”
She added that “registry data are needed to fully understand the real-world long-term effect of secukinumab on malignancy risk.”
The study was funded by Novartis. Lead author Dr. Lebwohl disclosed participating in advisory boards and/or as an investigator and/or speaker and receiving grants and/or honoraria from multiple companies including Novartis. Several study coauthors are employees of Novartis.
Dr. Fedeles had no financial conflicts to disclose.
Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.
Dr. Mark Lebwohl
Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.
Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.
In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.
The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.
Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.
The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.
Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.
However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.
“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.
Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.
Dr. Flavia Fedeles
However, she noted that the study has a number of limitations, including the use of clinical trials data, which have stringent inclusion/exclusion criteria that can lead to selection bias, the use of postmarketing surveillance data, the post hoc nature of the analysis, and the fact that the sponsor of the trial was the manufacturer of secukinumab, which “potentially can lead to bias to this study.”
She added that “registry data are needed to fully understand the real-world long-term effect of secukinumab on malignancy risk.”
The study was funded by Novartis. Lead author Dr. Lebwohl disclosed participating in advisory boards and/or as an investigator and/or speaker and receiving grants and/or honoraria from multiple companies including Novartis. Several study coauthors are employees of Novartis.
Dr. Fedeles had no financial conflicts to disclose.
