Published August 18, 2023 AUTOIMMUNE Treating Psoriasis Vulgaris Manouchehr Saljoughian, PharmD, PhDU.S. PharmacistNewark, New Jersey US Pharm. 2023;48(8):44-47. Psoriasis vulgaris is a chronic dermatosis of unknown etiology characterized by hyperproliferation and inflammation of the skin. The most common form of the disease is plaque psoriasis, in which skin develops scaly, raised red lesions. Lesions vary in size from pinpoint papules to large plaques and tend to be symmetrically distributed on the scalp, postauricular skin, elbows, and knees. Disease presentation is extremely variable among patients, and the clinical findings can change quickly, even within the same patient.1 Psoriasis is thought to be an immune-system problem. Triggers include infections, stress, and cold weather. The most common symptom is a rash on the skin, but sometimes the rash involves nails or joints. Plaque psoriasis is caused by an overactive immune system that induces skin cells to rapidly build up, forming psoriasis plaques. It is not fully known why some people develop plaque psoriasis and others do not, but a family history and environmental factors are thought to play a role. Psoriasis can be an extremely frustrating disease for patients and providers.2 Approximately 8 million Americans have plaque psoriasis. Of those, nearly 2 million have moderate-to-severe plaque psoriasis. The female-to-male ratio in children is 2:1; in adults, the ratio is 1:1. It is more common in whites and less common in blacks, Japanese, and American Indians. Most cases present during the fall and winter months. Treatment aims to remove scales and stop skin cells from growing quickly. Topical ointments, light therapy, and medications can help relieve the symptoms. Management of psoriasis involves addressing both psychosocial and physical aspects of the disease, and patients with severe psoriasis generally require care by a dermatologist.2,3 Signs and Symptoms Common signs and symptoms of psoriasis include a patchy rash that varies widely in appearance from person to person, ranging from spots of dandruff-like scaling to major eruptions over much of the body. Rashes vary in color from gray scale, on brown or black skin, to pink or red with silver scales. Other symptoms include dry, cracked skin that may bleed, itch, or burn and cyclic rashes that flare for weeks or months and then subside. Pitted nails separated from the nail bed and small, silvery scaling spots are also a common symptom among children.1,4 Types of Psoriasis There are several types of psoriasis, each of which varies in its signs and symptoms: Plaque Psoriasis: The most common type of psoriasis; causes dry, itchy, raised skin patches (plaques) covered with scales. The patches vary in color, depending on skin color. The affected skin might heal with temporary changes in color (postinflammatory hyperpigmentation), particularly on brown or black skin. Lesions are sharply demarcated and round with silvery scales. Plaque size is highly variable—ranging from millimeters to centimeters—but individual lesions are bigger than those seen in guttate psoriasis and are often symmetrically distributed. Common sites of involvement include the scalp, eyebrows, elbows, knees, umbilicus, and genitalia. Involvement may be induced in areas of local injury, such as scratches or insect bites (known as Koebner phenomenon). Guttate Psoriasis: Primarily affects young adults and children. It is usually triggered by a bacterial infection such as streptococcus (strep throat). It is marked by small, drop-shaped, scaling spots on the trunk, arms, or legs. The term is derived from the Latin word gutta (a drop), which describes the type of lesions seen. Lesions appear abruptly, often 1 to 2 weeks after a streptococcus infection. Guttate lesions are symmetrically distributed over the trunk and proximal extremities; they usually persist for 3 to 4 months and then resolve spontaneously. Nail Psoriasis: Can affect fingernails and toenails, causing pitting, abnormal nail growth, and discoloration. Psoriatic nails might loosen and separate from the nail bed (onycholysis). Severe disease may cause the nail to crumble. Inverse Psoriasis: Mainly affects the skin folds of the groin, buttocks, and breasts. It causes smooth patches of inflamed skin that worsen with friction and sweating. Fungal infections may trigger this type of psoriasis. Pustular Psoriasis: Causes reddish, scaly, pus-filled bumps. Anyone who has pus-filled bumps over much of the body needs immediate medical care. Pustular psoriasis can be life-threatening. The pus-filled bumps are called pustules. They can occur in widespread patches or on small areas of the palms or soles. Erythrodermic Psoriasis: Is the least common type of psoriasis. Erythrodermic psoriasis can cover the entire body with a peeling rash that can itch or burn intensely. It can be acute or chronic.1,5,6 Pathogenesis The exact pathogenesis and relative importance of genetic and environmental factors are still unknown. Family studies, epidemiologic studies, and human leukocyte antigen (HLA) studies suggest that psoriasis is genetically rooted. Researchers have discovered a significantly higher than normal incidence of certain HLAs in families with psoriasis, suggesting a possible immune disorder. The prevalence of psoriasis is higher among first- and second-degree relatives of patients with psoriasis than in the general population.4 Normal skin cells take 14 days to move from the basal layer to the stratum corneum, where after 14 days of normal wear and tear they are sloughed off. The life cycle of a normal skin cell is 28 days, compared with only 4 days for a psoriatic skin cell. This markedly shortened cycle does not allow time for the cell to mature. Consequently, the stratum corneum becomes thick and flaky, producing the cardinal manifestations of psoriasis.4 Risk Factors and Triggers A variety of local and systemic stimuli have been reported to trigger the onset of psoriasis as follows: medications such as nonsteroidal anti-inflammatory drugs, antimalarials, systemic corticosteroids, pregnancy, use of progesterone-containing oral contraceptives, and streptococcal infections (especially with guttate psoriasis).2,7 Trauma can trigger the isomorphic effect in which lesions develop at sites of injury. Infections, especially those resulting from beta-hemolytic streptococci, may cause a flare-up of drop-shaped lesions. Other triggering factors include endocrine changes, climate (cold weather tends to exacerbate psoriasis), and emotional stress.7 Diet and Nutrition Patients with psoriasis should limit the intake of saturated fatty acids and replace them with the omega-3 family, which have an anti-inflammatory effect. In diet therapy for psoriasis, the use of antioxidants such as vitamins A, C, and E, carotenoids, flavonoids, and selenium is extremely important. Vitamin D supplementation is also recommended. Many researchers suggest that alternative diets have a positive effect on the course of psoriasis. These include a gluten-free diet, a vegetarian diet, and a Mediterranean diet. Diet therapy for patients with psoriasis should also be tailored to pharmacologic treatment. For instance, folic acid supplementation is introduced in people taking methotrexate.8,9 Medical Management Numerous topical and systemic therapies are available for the treatment of the cutaneous manifestations of psoriasis. There is no known cure, and the goal is to slow the rapid turnover of epidermis and to promote resolution of the psoriatic lesions. The therapeutic approach should be cosmetically acceptable and not too disruptive of lifestyle.3 Topical Therapy: This therapy is used to slow the overactive epidermis without affecting other tissues. Medications include tar preparations and anthralin, salicylic acid, and corticosteroids in the form of lotions, ointments, pastes, creams, and shampoos. Topical therapy may provide symptomatic relief and can help minimize required doses of systemic medications.3,7,10 Intralesional Agent Therapy: This treatment involves he injection of a higher concentration of an agent directly into skin lesions without significant systemic absorption. Corticosteroid injection may be a beneficial therapeutic approach in cases where the topical formulation is not appropriate for use, mainly due to low potency and inefficient epidermal-barrier penetration. The intralesional injection of triamcinolone acetonide is currently the most preferred such therapy.3 Systemic Therapy: Systemic cytotoxic preparations (e.g., methotrexate) may be used in treating unresponsive psoriasis. Other systemic medications in use include hydroxyurea and cyclosporine A. Laboratory studies are monitored to ensure that hepatic, hematopoietic, and renal systems are functioning adequately. Oral retinoids (synthetic derivatives of vitamin A) and etretinate may be prescribed. Patient should avoid drinking alcohol while taking methotrexate, as this increases the possibility of liver damage.3 Photochemotherapy: Psoralen and ultraviolet A (PUVA) therapy may be used for severely debilitating psoriasis. Photochemotherapy is associated with long-term risks of skin cancer, cataracts, and premature aging of the skin. This technique of phototherapy decreases cellular proliferation. PUVA therapy can cause photosensitivity, and patients should avoid exposure to sunlight during this time. Ultraviolet B light therapy may be used to treat generalized plaque and may be combined with topical coal tar.3,11 Current Treatment The FDA has approved tapinarof cream 1%, a once-daily, steroid-free topical treatment for plaque psoriasis in adults regardless of disease severity. It is becoming the first FDA-approved, steroid-free topical medication. This drug is a lipid-lowering, proprotein convertase subtilisin/kexin type 9 inhibitor.3,12,13 The FDA has also approved a series of new drugs with different modes of action for psoriasis. One example is apremilast, a phosphodiesterase-4 inhibitor. Apremilast is a tablet taken twice daily that is used to lower inflammation in the treatment of specific types of psoriatic arthritis and plaque psoriasis. This drug works by inhibiting an enzyme within the immune system that can affect certain cells and contribute to inflammation in the body. Other FDA-approved medications, such as adalimumab (SC), infliximab (IV), and etanercept (SQ), are tumor necrosis factor (TNF) blockers that are used for moderate-to-severe chronic plaque psoriasis.3,14 The newest systemic treatment for plaque psoriasis is the tyrosine kinase 2 (TYK2) inhibitor deucravacitinib. TYK2 inhibitors work by inhibiting TYK2, an intracellular-signaling kinase that mediates signaling of interleukin (IL)-23, IL-12, and type I interferon—naturally occurring cytokines involved in inflammatory and immune responses.3 Other new systemic treatments for plaque psoriasis are IL-23 antagonists risankizumab, tildrakizumab, and guselkumab.3,14 Spesolimab-sbzo is an interleukin-36 receptor antagonist approved by the FDA in September 2022 for the treatment of generalized pustular psoriasis.3 In general, education about psoriasis is important, and patient referrals to organizations such as the National Psoriasis Foundation (www.psoriasis.org) are often helpful. REFERENCES 1. National Institute for Health and Care Excellence. Psoriasis: assessment and management. September 1, 2017. www.nice.org.uk/guidance/cg153. Accessed April 2023.2. World Health Organization. Global report on psoriasis. 2016. https://apps.who.int/iris/handle/10665/204417. Accessed May 2023.3. Feldman SR. Treatment of psoriasis in adults. UpToDate. June 2023. www.uptodate.com/contents/treatment-of-psoriasis-in-adults. Accessed May 2023.4. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370:263-271.5. Hamilton MP, Ntais D, Griffiths CE, Davies LM. Psoriasis treatment and management—a systematic review of full economic evaluations. Bri J Dermatol. 2015;172:574-583.6. Chularojanamontri L, Griffiths CE, Chalmers RJ. The Simplified Psoriasis Index (SPI): a practical tool for assessing psoriasis. J Invest Dermatol. 2013;133:1956-1962.7. Samarasekera EJ, Sawyer L, Wonderling D, et al. Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses. Br J Dermatol. 2013;168:954-967.8. Garbicz J, Calyniuk B, Gorski M, et al. Nutritional therapy in persons suffering from psoriasis. Nutrients. 2021;14(1):119.9. Montaudié H, Sbidian E, Paul C, et al. Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity. J Eur Acad Dermatol Venereol. 2011;25(suppl 2):12-18.10. Sekhon S, Jeon C, Nakamura M, et al. Review of the mechanism of action of coal tar in psoriasis. J Dermatolog Treat. 2018;29:230-238.11. Berneburg M, Herzinger T, Rampf J, et al. Efficacy of bath psoralen plus ultraviolet A (PUVA) vs. system PUVA in psoriasis: a prospective, open, randomized, multicentre study. Br J Dermatol. 2013;169:704-708.12. Armstrong AW, Puig L, Joshi A, et al. Comparison of biologics and oral treatments for plaque ssoriasis: a meta-analysis. JAMA Dermatol. 2020;156:258-269.13. Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2021;4:CD011535.14. Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol. 2010;159:842-855. The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk. To comment on this article, contact rdavidson@uspharmacist.com.