Publish date: Posted on
Last updated: October 21, 2023
Keywords #
Psoriasis
Plaque psoriasis
Autoimmune disease
Diagnosis #
Psoriasis is a chronic, immune-mediated disease of the skin, nails, and joints. It is characterized by erythematous plaques and papules often with overlying adherent silver scale, however, it can present with different skin findings as well as psoriatic arthritis.[1] Psoriasis also has other associated comorbidities such as cardiovascular disease, obesity, and depression.[1] The exact cause of psoriasis is not fully understood but it is known that immune dysregulation and unregulated inflammation lead to uncontrolled keratinocyte proliferation and dysfunctional differentiation. A variety of topical and systemic treatments exist with biologic medications being an active area of research and development.
Key Concepts #
- Psoriasis is an immune-mediated disease of the skin, associated with psoriatic arthritis, numerous comorbidities, and a significant negative impact on quality of life.
- It results from a variety of factors that lead to immune dysregulation causing thickening and inflammation of the skin.
- Numerous treatment modalities, including topicals, phototherapy, and oral/biologic systemics. Choice of therapy is dependent on the severity, location, presence of psoriatic arthritis, patient preference and other comorbidities.
Epidemiology #
Psoriasis affects approximately 2-3% of the world’s population with a bimodal age of onset in adolescence and late adulthood, though it can present at any age. Earlier onset psoriasis (before age 40) is associated with family history as well as more severe disease.[1]
Clinical Features #
- The most common presentation is plaque psoriasis, classically described as well-demarcated, indurated, erythematous papules and plaques with overlying silvery scale.
- The most commonly affected areas include the extensor elbows, knees, and scalp. It can also involve the body folds, umbilicus, and gluteal cleft, referred to as inverse or intertriginous psoriasis.
- The nails may also be affected with pits, onycholysis, subungal debris, and discoloration.[3]
- Other variants include guttate psoriasis, an eruptive form that tends to follow streptococcal infection, palmoplantar psoriasis, which may or may not be pustular, generalized pustular psoriasis, and erythrodermic psoriasis.
Although the exact cause of psoriasis is unknown, genetic and environmental factors likely interact and eventually trigger the disease. Psoriasis often runs in families and often starts following an environmental trigger such as infection or trauma. The triggering event is thought to stimulate plasmacytoid dendritic cells to make interleukin-23 which triggers the differentiation of T cells to make interleukin-17, which in the presence of tumor necrosis factor-alpha, causes keratinocytes to proliferate and mature abnormally creating the thick erythematous plaques with silver scale.[4] Activated keratinocytes in turn make chemokines and cytokines to further propagate a cycle of inflammation. Histologically, there is epidermal hyperplasia with a thinned or absent granular layer, retention of keratinocyte nuclei (parakeratosis), thinning of the suprapapillary plates, elongated rete ridges, and dilated and tortuous vessels; all of which correspond to the clinical features of thickened, erythematous, scaling plaques that bleed easily. CD4 and CD8 T cells populate the epidermis and dermis, respectively. Neutrophils are typically present in the stratum corneum (microabscesses) and the epidermis, and large collections correspond clinically to pustules.
Table1: Common Psoriasis Subtypes
| Plaque Psoriasis | Guttate Psoriasis | Intertriginous Psoriasis | Pustular psoriasis | Erythrodermic psoriasis |
|---|---|---|---|---|
|
|
|
|
|
Differential Diagnoses #
- Atopic dermatitis
- Seborrheic dermatitis
- Lichen simplex chronicus
- Nummular eczema
- Fungal infections
- Lupus
- Mycosis fungoides
- Pityriasis rosea
Diagnostic Workup #
The diagnosis of psoriasis is usually made clinically, and biopsy is rarely needed for diagnostic confirmation of plaque psoriasis but should be considered for generalized pustular psoriasis and erythrodermic psoriasis. Patients with guttate psoriasis should have a workup of underlying streptococcal infection (pharyngitis, perianal streptococcal infection). A family history of psoriasis, onset following streptococcal infection, and presence of psoriatic arthritis can also assist in confirming the diagnosis.
Treatment #
Treatment is largely determined by the extent/severity, location, type of psoriasis, previous treatments that have failed, and presence of underlying comorbidities.
The most commonly used method for determining severity is body surface area involved with psoriasis; however, the thickness of plaques and the location of disease such as face, scalp, palms, soles, intertriginous areas, and genitals are important factors in their severity.[7] The disease may be considered mild to moderate if less than 5% BSA is involved, it responds well to topical agents, and spares areas of the body like genitals, hands, feet, and face. Moderate-severe disease is classified as involving greater than 5% BSA or involving of the hands, feet, face, or genitalia.[5] Patients who also have psoriatic arthritis should have systemic therapy that is efficacious for both skin and joints. Patients should also be screened for co-morbid conditions, such as Crohn’s disease, multiple sclerosis, malignancy, infection, and depression, as these affect choice of therapy. Patients with psoriasis are at risk for metabolic syndrome and are at increased risk for cardiovascular disease. Increased mortality in patients with severe disease has been observed, and effective treatment may reduce this risk.[6]
Initial treatment for mild to moderate disease includes topical corticosteroids, vitamin D analogues, and phototherapy. Topical agents are considered first line due to their efficacy, relative low cost, ease of application, and safety profile. Suprapotent corticosteroids are the most effective topical agents, given their anti-inflammatory, anti-proliferative, vasoconstrictive, and immunomodulatory effects.[8] Vitamin D analogues have anti-proliferative effects, but are less effective than topical corticosteroids, so are used in conjunction with topical glucocorticoids as steroid-sparing agents. Inverse and facial psoriasis is treated with low potency topical steroids, vitamin D agents, or immunomodulators like pimecrolimus or tacrolimus.
Ultraviolet light is also very effective and safe for psoriasis. Most phototherapy regimens use narrowband ultraviolet-B (NBUVB) owing to its relative safety compared to psoralen with ultraviolet A (PUVA). Phototherapy is thought to work by effecting cytokine profiles, inducing apoptosis, and inducing immunosuppression in the skin.[9]
Patients with moderate-severe psoriasis often requires systemic treatment with oral drugs (methotrexate, cyclosporine, retinoids, apremilast) or biologic agents. Methotrexate has been the most commonly used drug in the world for psoriatic disease but requires monitoring of effects on bone marrow and liver. Apremilast is a newer oral drug that inhibitors phosphodiesterase 4 with comparable efficacy to methotrexate but a better safety profile. Cyclosporine is a calcineurin inhibitor that can work quickly but side effects prevent it long term use. Acitretin is an oral retinoid that effects abnormal cellular differentiation; however, it lacks efficacy unless used in combination with phototherapy.
Biologics are injectable therapies derived from living cells that specifically target cytokines that drive the pathogenesis of psoriasis. Biologics used for psoriasis fall into three classes: tumor necrosis factor-alpha inhibitors (TNFi), interleukin-23 inhibitors ((IL-23i), and interleukin-17 inhibitors (IL17i).11. TNFi are considered first line for patients with also have psoriatic arthritis. Biologics, especially in the IL17i and IL23i class, have rapid onset and high rates of efficacy. Patients have to be screened and monitored for infection but enjoy a better long-term safety profile compared to oral therapies.
Slide Viewer #
https://utahderm.med.utah.edu/image-viewer/References #
- R G B Langley, G G Krueger, C E M Griffiths. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis 2005;64(Suppl II):ii18–ii23. doi: 10.1136/ard.2004.033217
- Frank O. Nestle, M.D., Daniel H. Kaplan, M.D., Ph.D., and Jonathan Barker, M.D. Psoriasis. N Engl J Med 2009; 361:496-509. DOI: 10.1056/NEJMra0804595
- Michael P. Schön, M.D., and W.-Henning Boehncke, M.D. Psoriasis. N Engl J Med 2005; 352:1899-1912. DOI: 10.1056/NEJMra041320
- J G Krueger, A Bowcock. Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis 2005;64(Suppl II):ii30–ii36. doi: 10.1136/ard.2004.031120
- Nancy Weigle MD and Sarah McBane PharmD. Psoriasis. Am Fam Physician. 2013 May 1;87(9):626-633.
- Joel M. Gelfand, MD, MSCE; Andrea B. Troxel, ScD; James D. Lewis, MD, MSCE; Shanu Kohli Kurd, MHS; Daniel B. Shin, BA; Xingmei Wang, MS; David J. Margolis, MD, PhD; Brian L. Strom, MD, MPH. The Risk of Mortality in Patients With Psoriasis. Arch Dermatol. 2007;143(12):1493-1499.
- Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Annals of the Rheumatic Diseases 2005;64:ii65-ii68.
- Uva L, Miguel D, Pinheiro C, et al. Mechanisms of action of topical corticosteroids in psoriasis. Int J Endocrinol. 2012;2012:561018. doi:10.1155/2012/561018
- Wong T, Hsu L, Liao W. Phototherapy in psoriasis: a review of mechanisms of action. J Cutan Med Surg. 2013;17(1):6–12. doi:10.2310/7750.2012.11124
- Bruce E. Strober, MD, PhD. Methotrexate and Cyclosporine in Psoriasis Revisited. Seminars in Cutaneous Medicine and Surgery. Vol. 33, No. 2S, March 2014, DOI: 10.12788/j.sder.0069
- Rønholt K, Iversen L. Old and New Biological Therapies for Psoriasis. Int J Mol Sci. 2017;18(11):2297. Published 2017 Nov 1. doi:10.3390/ijms18112297
