Treating Psoriasis
In the first of a two-part article on treating psoriasis, Dr Priya Patel reviews the topical treatment options available for the disorder
Psoriasis is a chronic inflammatory disorder of the skin, but it also affects other organs and joints.1 In addition, psoriasis can have devastating effects on psychological, emotional and social wellbeing, as it can be a stigmatising condition. Psoriasis independently contributes to other co-morbidities such as the metabolic syndrome, gastrointestinal disease, malignancy and arthritis.1 Consideration of these comorbidities is important when deciding on the most appropriate therapy for an individual so that good holistic care can be provided for every individual patient. Largely, psoriasis is a clinical diagnosis; however, blood tests for inflammatory and rheumatological markers, such as HLA-B27, or skin biopsies, can be performed in clinically challenging cases, although these are rarely executed.1 Many different treatment options exist, and their use depends on clinical severity and the distribution of disease.1 Largely, topical therapies form first-line management and these will be discussed in this article. However, patients with more severe, or refractory, symptoms may need dermatological assessment and systemic treatment but this is beyond the scope of this article and will be discussed in Part Two.
Background
Psoriasis affects 1-3% of the world’s population,2 with both genders equally affected.2,3 Primarily, the skin is affected, but the impact of disease on quality of life and its burden should not be underestimated.2 Psoriasis comes in many different forms. The most common is chronic plaque psoriasis, which will be discussed in this article in the most detail; however, others subtypes such as guttate, pustular, palmoplantar, flexural/inverse, erythrodermic and psoriatic arthropathy also exist.3 Psoriasis can also be subdivided by site, such as the scalp or nails, as these areas are often refractory to treatment.2,3 The subtype, site, distribution and severity help determine the therapeutic options. Mild to moderate cases could be treated with topical therapies alone.1,3 However, as disease severity increases, treatment can be escalated to systemic modalities, either in isolation or in combination with topicals.2 Psoriasis is typically assessed by the psoriasis area severity index (PASI), which measures the clinical severity and extent of psoriasis, and the dermatology life quality index (DLQI), which determines the functional and psychological impact on patients.3 These scores help categorise psoriasis into mild, moderate, and severe, which helps to steer therapy options. No current standardised guidelines exist for psoriasis management, although some European countries such as Italy or Germany have a general consensus, which are based on trials and expert opinions.2 However, treatment is largely left to the discretion of the clinician based on individualised holistic patient care.
Lifestyle modifications
Given that psoriasis is a multisystem disorder, patient education regarding their condition is essential to manage not only the visible effects of psoriasis, but also the metabolic and psychosocial aspects.3 Patients should maintain healthy lifestyles via regular exercise, healthy diets, smoking cessation and reduced alcohol intake. As the above contribute to atherosclerotic process, altering these factors will help to prevent the vascular risks associated with psoriasis.3 Living a healthier lifestyle also helps positive wellbeing and decreases stress, which overall has a positive effect on patients and can independently reduce the rate of psoriatic flares.4,5 These lifestyle modifications must be addressed alongside medicated therapies as they, in isolation, do not improve psoriasis to an effective degree.5
Topical treatments
Alongside medicated topical therapies, described below, emollients and moisturisers are recommended as they help improve skin function and provide an effective barrier.3,6,7 Many patients find topical therapies challenging as they are time-consuming and can feel greasy or unpleasant due to smells or staining; therefore compliance is often low.7 However, there are almost no contraindications to using topical therapies and their side-effect profile is lower compared to systemic agents, so these should always be used as a first-line treatment.3 Currently, no clinical trials have demonstrated one topical therapy to be markedly superior to the other and options are based on individuals’ disease severity and personal preference on discussion with a clinician.3,6-7 All topicals reviewed have shown efficacy but have their own side-effect profiles. Further long-term trials with larger patient numbers, clear measurable and comparable outcomes are needed for all topicals to determine superiority.
Corticosteroids
Corticosteroids are topical steroids used to decrease local inflammation.3 They have shown efficacy in psoriasis, particularly for scalp psoriasis. Pooled data from five trials of 646 patients demonstrated statistically significant difference in psoriasis with a 3-point improvement on a 12-point scale when comparing very potent formulations of steroids against placebo.6 Additionally, 12 trials with 1,040 patients demonstrated even potent steroids had a 1.6-point improvement on a 12-point scale which was also statistically significant 95% CI: -0.99 to -0.68).6 However, many patients are reluctant to use steroids in the long-term due to the side effects of skin thinning, easy bruising, vessel dilatation, striae and pigmentary changes.3 Steroids can be combined with almost all other topical or systemic agents, thus lowering the sideeffect profile of both therapies as they work synergistically.
Dithranol
Dithranol, or anthralin, are hydroxyanthrones, which interfere with mitochondria and DNA replication, resulting in decreased skin turnover.3 They are slower acting compared to steroids, as they work on changing DNA replication, but they have fewer rebound or withdrawal effects. Their main disadvantages include: skin irritation and staining of the skin and surrounding objects, thus patients must be warned about this. It can be combined with phototherapy, topical tazarotene or steroids to enhance compliance as these therapies are fast acting so patients will see a clinical response, allowing the slower acting dithranol to take effect for long-term management.3
Vitamin D3
Vitamin D3 analogues can be natural or synthetic and work by reducing skin turnover, but it can also cause drying or pruritus. They may be used in isolation or in combination with steroids, phototherapy or systemic therapies like ciclosporin or acitretin.3 Generally, when combined with steroids, there is less skin irritation, which is a noted side effect.8 Vitamin D analogues, e.g. calcipotriol (Dovonex), are used as one of the mainstay topical treatments for psoriasis, particularly in combination with steroids e.g. Dovobet.3,8
Patients find these preparations easy to use and less irritating to the skin.8
Pooled data from 14 trials reported significant improvement versus placebo with a 1.6-point improvement on a 12-point scale.7 Additionally, when directly compared with corticosteroids, there was no statistical difference in clinical efficacy, withdrawal or adverse events; with the best results from combination of topical Vitamin D analogues and corticosteroids.6 They also demonstrated greater efficacy when compared with dithranol.
Vitamin A
Vitamin A derivatives, or retinoids such as tazarotene, can also be used to slow skin growth, but have a common side-effect profile of skin irritation, dryness and photosensitivity, and cannot be used in pregnancy as they are teratogenic.3 A placebo-controlled trial with 318 patients suggested a clinical benefit of tazarotene by -0.77 (95% CI:-1.01 to -0.53).6 However, many other trials have smaller patient numbers and short follow-up periods, making it difficult to draw meaningful conclusions.6
Salicylic acids
Salicylic acids are types of hydroxy acids and help to remove hyperkeratotic scale and plaques.3 Salicylic acid can sometimes be used prior to phototherapy as they reduce the hyperkeratosis associated with psoriasis allowing for better UV penetration.3 It can also be used in combination with steroids, coal tar or anthralin but does cause skin irritation.3 It tends to be combined with topical steroids to reduce skin irritation rather than in isolation as it doesn’t treat the underlying inflammatory process of psoriasis when used in isolation.3 Trials comparing Calcipotriol with combination therapy of potent steroid and salicylic acid in two trials with 320 patients found no difference in clinical effect between therapies (-0.04, 95%CI -0.26 to 0.18).6
Coal tar
Crude coal tar mixed with paraffin is an older therapy which has been used for centuries to treat psoriasis.3 It slows skin growth and has anti-inflammatory properties. It can be applied directly onto the skin, via a bath or in combination with phototherapy. However, it causes skin irritation, redness, dryness and stains, and in high doses it can be carcinogenic.
Urea
Urea works as a keratolytic agent, but can cause skin irritation.3 Urea-based agents provide good skin care by moisturising the skin and forming a barrier, and acts as an antipruritic and antimicrobial agent. However, it has less effect on psoriasis overall as it doesn’t actively treat the inflammation associated with psoriasis but rather the hyperkeratotic by-products of the inflammatory process.6-7
Calcineurin inhibitors
Calcineurin inhibitors, for example, tacrolimus or pimecrolimus, are used for eczema but have shown some success in psoriasis, although it remains unlicensed. Using pooled data from nine double-blind and 13 open studies, efficacy was demonstrated for psoriasis, especially facial, flexural and genital psoriasis.9
Phototherapy
Light therapy is generally offered when topicals have failed.2,3 This encompasses either phototherapy or chemo-phototherapy, which uses psoralen. Some smaller studies have also suggested blue-light to be effective, however these are only case reports so will not be covered.10 Both forms of light therapy have unclear mechanisms of action, but appear to have anti-inflammatory, immunosuppressive and anti-proliferative effects.10-11 Psoralen can be administered topically or orally in addition to UVA light (wavelengths 320-400 nm),10,12 known collectively as PUVA. The advantage of systemic PUVA is it allows for widespread disease to be treated in one setting. However, systemic PUVA leaves patients susceptible to sun damage; therefore, sun-protection must be advised.11 PUVA (either topical or systemic psoralens) can also be combined with topicals (steroids or vitamin D analogues), with combinations of topical retinoids and PUVA demonstrating the best results.13 Comparatively, narrow band UVB (NBUVB) has similar efficacies, although is slightly less efficacious than PUVA, with the advantage of not requiring psoralen. NBUVB has shown safer profiles in children and pregnancy, whereas PUVA is contraindicated in these groups.13,14-15 NBUVB uses wavelengths of 311-312 nm, compared with broad-based UVB (BBUVB) ranging from 300-313nm. Previously, BBUVB was used, but now NBUVB is preferred as there are fewer side effects and better remission rates.14 The exact mechanism of action remains unclear, but phototherapy has shown inhibition of DNA synthesis and keratinocyte hyperproliferation.2 It also induces immunosuppression, T-cell apoptosis and anti-inflammatory cytokines.2 In the UK, the British Association of Dermatology (BAD) and the National Institute for Health and Care Excellence (NICE) recommend pre-testing to calculate the minimum erythema dose (MED) needed to initiate phototherapy, as all individuals respond differently; thus, the dose will vary based on skin type and photosensitivity.16-17 Treatment is then initiated at 50% minimum erythema dose, with -20% increments until a maximum dose is achieved or skin clears.14 Currently, the number of cumulative doses is limitless; however, both guidelines recommend that after 150-200 PUVA or 200-300 NBUVB sessions the risk of skin cancer is significant, and therapy should only be given in exceptional circumstances by clinicians balancing the patients risks and benefits from phototherapy.16,17 The majority of patients undergo five to 20 treatments before 50% clearance is achieved, with 63-80% achieving total clearance.14,18 Comparatively, PUVA achieves partial/complete clearance in 70- 90%.11,19 The disadvantages of phototherapy include short-term side effects such as erythema, burning, pruritus, blistering and dry skin.14,18 Long-term skin ageing, photo-damage, irregular pigmentation, actinic keratoses and skin cancers are more common and more prevalent with higher cumulative doses.10,11,20,21 Hence, the minimal dose of phototherapy should be used and only in patients with moderate to severe disease refractory to topicals. Additionally, facial and genital protection is recommended to protect sensitive areas from sun damage.2 Caution should also be taken with patients who have a history of skin cancer and Fitzpatrick skin type I-II skin.14 Furthermore, patients on calcium channel antagonists, phenothiazine or nonsteroidal anti-inflammatories (NSAIDs) have shown photosensitivity, although this is not common; if this occurs, these medications should be discontinued.2 Phototherapy is contraindicated in patients with xeroderma pigmentosa and lupus as these are photosensitive conditions.2 With PUVA there are additional contraindications to patients with immunosuppression, aphakia or allergic reactions to psoralens.10,20 Of note, patients will often experience relapses after treatment cessation, therefore they should be warned of this during consultation. Another disadvantage is that this therapy can be time-consuming at two to three sessions per week.14,15 Phototherapy can be combined with topicals, although corticosteroids are not recommended as this potentially increases the risk of psoriasis reactivation after discontinuation of phototherapy.22 Systemic retinoids combined with phototherapy results in reduced cumulative UV exposure as fewer sessions are needed.2 However, as retinoids cause skin thinning, this can lead to increased phototoxicity.2 Overall, the risk/benefit balance must be individually considered as patients may willingly accept side effect profiles in preference of disease.10 Patients with darker skin (Fitzpatrick type V-VI) and elderly populations may benefit more from phototherapy as the long-term cancer risk is lower in these groups.19
Conclusion
Psoriasis is a multisystem disorder that requires good holistic care by clinicians to encompass both the skin disorder, the psychosocial aspect and the systemic comorbidities associated with the disease. The psychosocial impact of this disease should not be overlooked and these burdens must be addressed for patients to feel valued and treated as a person not a disease. Generally, for mild to moderate psoriasis, emollients and topical therapies should be administered and can be managed in the community by primary care physicians. Complex cases will likely need dermatological assessment and review for possible systemics either in isolation or combination with topicals. From the literature there is no one topical therapy that is superior to the other, with all showing efficacy particularly when active agents are combined with keratolytic agents. Overall, therapy must ultimately be individualised, based on the patient’s site severity and functional impairment of psoriasis, as well as any additional medications and comorbidities that could interact with their disease and treatment options.
Dr Priya Patel is a core medical trainee at East Surrey Hospital. She is an aspiring dermatologist, and takes an active interest in topics involving allergy and immunology.
REFERENCES:
1. Kim WB; Jerome D; Yeung J. Diagnosis and management of psoriasis. Canadian family physician Medecin de famille canadien; 2017; 63(4): 278-285
2. Naldi L; Griffiths CEM. Traditional Therapies in the Management of Moderate to Severe Chronic Plaque Psoriasis: An Assessment of the Benefits and Risks. British Journal of Dermatology. 2005; 152(4): 597-615.
3. Young M; Aldredge L; Parker P. Psoriasis for the primary care practitioner. Journal of the American Association of Nurse Practitioners; 2017; 29(3): 157-178.
4. Barrea L; Nappi F; Di Somma C; Savanelli MC; Falco A; Balato A; Balato N; Savastano S. Environmental Risk Factors in Psoriasis: The Point of View of the Nutritionist. International journal of environmental research and public health. 2016; 13( 5).
5. M J Kaplan. Cardiometabolic risk in psoriasis: differential effects of biologic agents. Vascular health risk management. 2008.4(6):1229-1235.
6. Mason J; Mason AR; Cork MJ. Topical preparations for the treatment of psoriasis: a systematic review. The British journal of dermatology; 2002; 146(3): 351-364.
7. Thaçi D; Augustin M; Krutmann J; Luger T. Importance of basic therapy in psoriasis. Journal of the German Society of Dermatology. 2015; 13(5): 415-418.
8. Stein Gold LF. Topical Therapies for Psoriasis: Improving Management Strategies and Patient Adherence. Seminars in cutaneous medicine and surgery; 2016; 35(2) supplement 2: 36-44; quiz S45
9. Wang C, Lin A. Efficacy of topical calcineurin inhibitors in psoriasis. Journal of Cutanous Medicine and Surgery. 2014;18(1):8-14.
10. Lowe NJ; Chizhevsky V; Gabriel H. Photo(chemo)therapy: general principles. Clinical Dermatology. 1997;15:745-52.
11. Lauharanta J. Photochemotherapy. Clinical Dermatology. 1997; 15: 769-80
12. Lebwohl M; Menter A; Koo J et al. Combination therapy to treat moderate to severe psoriasis. Journal of American Academy of Dermatology. 2004; 50: 416-30.
13. Griffiths CEM; Clark CM; Chalmers RJG et al. A systematic review of treatments for severe psoriasis. Health Technology Assessment. 2000; 4:1-125.
14. Ibbotson SH; Bilsland D; Cox NH et al. An update and guidance on narrowband ultraviolet B phototherapy: a British Photodermatology Group Workshop Report. British Journal of Dermatology. 2004; 151: 283-97.
15. Gawkrodger DJ, on behalf of the Therapy Guidelines and Audit Subcommittee of the British Association of Dermatologists. Current management of psoriasis. Journal of Dermatological Treatment. 1997; 8: 27-55
16. National Institute for Health and Care Excellence (NICE) (2012): Psoriasis: assessment and management Clinical guideline [CG153].
17. British association of Dermatologists (BAD) (2016), British Photodermatology Group (BPG): Phototherapy service guidance.
18. Zanolli M. Phototherapy treatment of psoriasis today. Journal of American Academy of Dermatology. 2003; 49:78-86
19. Morison WL; Baughman RD; Day RM et al. Consensus workshop on the toxic effects of long-term PUVA therapy. Archives of Dermatology 1998; 134: 595-8.
20. ICN Pharmaceuticals Inc. Oxsoralen-Ultra® capsules (methoxsalen capsules, USP 10 mg). Prescribing information, March 2003.
21. Stern RS; Lange R. Non-melanoma skin cancer occurring in patients treated with PUVA five to ten years after first treatment. J Invest Dermatology. 1988; 91:120-124.
22. Honigsmann H. Phototherapy for psoriasis. Clinical Experimental Dermatology. 2001; 26: 343-50.
