Psoriasis & Comorbidities

Psoriasis

Psoriasis is a chronic inflammatory disease mediated by the immune system. Psoriasis is also likely an autoimmune disease. The buildup of skin cells causes itchy, white scales or plaques to form on the skin. It is mostly located on the elbows, knees, or scalp, but can occur on other parts of the body as well. It is often associated with other comorbidities like psoriatic arthritis, mood disorders, cardiovascular disease, and metabolic syndrome. Psoriasis is the result of sustained inflammation leading to uncontrolled proliferation of keratinocytes and dysfunctional differentiation (Rendon, A., & Schäkel, K.). Sustained inflammation is due to changes in the innate and adaptive immune responses in the skin. The innate immune system is activated and there is also an autoinflammatory or autoimmune reaction. Dendritic cells are activated in the initial stages of psoriasis. There is activation of T cells during the maintenance phase of psoriasis. Dysregulation of the IL-23/Th-17 signaling pathway also drives the disease.

Treatment for psoriasis has evolved over time. In the 19th century and first half of the 20th century, arsenic was used for psoriasis before it was determined that there was toxicity associated with it. X-rays were also used in the 20th century, but it was determined that there were carcinogenic side effects associated with it. In the 1950s, corticosteroids were discovered. Oral prednisolone and triamcinolone were effective. Topical steroids like betamethasone and fluocinolone were used in the 1960s and showed significant effects. Topical steroids are only able to treat psoriasis temporarily and are not a permanent solution. Steroids are anti-inflammatory, immunosuppressive, and anti-proliferative. Methotrexate was first used in the 1950s and is currently the first line treatment for patients that can be treated systemically and also for psoriatic arthritis (Reid, C., & Griffiths, C. E. M.). Another treatment is the use of psoralens (photosensitizers) with UVA. This treatment can increase risk of cutaneous squamous cell carcinoma so its use has declined. Ciclosporin is an immunosuppressive drug that is used for psoriasis. The success of ciclosporin helped determine that psoriasis is mediated by T cells. Furthermore, ciclosporin can cause nephrotoxicity so it is dosed in short courses of therapy. Vitamin D analogues like calcipotriol can be used in combination with the topical steroid betamethasone valerate as an effective treatment. Biologics have become a growing focus in the modern century. They are indicated in moderate-severe psoriasis after failure of first line therapies. T cell targeted biologics included alafacept and efalizumab which were both withdrawn from the market. Tumor necrosis factor (TNF)-α is the target of etanercept, infliximab, and adalimumab. Adalimumab is the biologic that is the first line recommended treatment for psoriasis with psoriatic arthritis. Currently, the focus is on targeting cytokines IL-23 or IL-17 and disrupting their signaling. Three biologics against IL-17 include secukinumab, ixekizumab, and brodalumab ((Reid, C., & Griffiths, C. E. M.).

Psoriasis is associated with comorbidities like metabolic syndrome. They are both associated with Il-23/Th-17 signaling pathways. About 20-50% of patients with psoriasis have metabolic syndrome (Wu, J. J. et al.). There has not been a definitive link between psoriasis and metabolic syndrome, but genetics, the overlapping signaling pathways, and the environment can contribute. Family members of patients with psoriasis have an increased risk of developing psoriasis. Treating one condition may help improve the other. When treating patients for psoriasis, they should be screened for comorbidities before creating a treatment plan because systemic treatment may be warranted to treat multiple conditions.

Resources:

Reid, C., & Griffiths, C. E. M. (2020). Psoriasis and Treatment: Past, Present and Future Aspects. Acta dermato-venereologica, 100(3), adv00032. https://doi.org/10.2340/00015555-3386

Rendon, A., & Schäkel, K. (2019). Psoriasis Pathogenesis and Treatment. International journal of molecular sciences, 20(6), 1475. https://doi.org/10.3390/ijms20061475

Wu, J. J., Kavanaugh, A., Lebwohl, M. G., Gniadecki, R., & Merola, J. F. (2022). Psoriasis and metabolic syndrome: implications for the management and treatment of psoriasis. Journal of the European Academy of Dermatology and Venereology : JEADV, 36(6), 797–806. https://doi.org/10.1111/jdv.18044

Psoriasis: Overview

Psoriasis is a chronic inflammatory skin disease which affects around 2% of the world. It is characterized by chronic inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. It is an immune-mediated disease in which T lymphocytes, dendritic cells, and cytokines (interleukin 23, interleukin 17, and tumor necrosis factor) play a central role.

There are several different subtypes of psoriasis. The most common is plaque psoriasis which presents as sharply demarcated, erythematous, pruritic plaques covered in silvery scales usually present on the trunk, extensor surfaces of the limbs, and the scalp. The next type is guttate psoriasis which is characterized by acute onset of small erythematous papules and plaques. The trunk and proximal extremities are the main areas affected by the guttate type. Pustular psoriasis is a severe form of psoriasis with multiple, coalescing sterile pustules. It is associated with malaise, fever, diarrhea, leukocytosis, and hypocalcemia. Erythrodermic psoriasis is uncommon but is characterized by generalized erythema and scaling on all or most of the body surface. Patients with this type are at high risk for infection and electrolyte abnormalities.

Psoriasis was originally thought to be just a disease of the skin but was found that it affects the body as a whole with related comorbidities in other organ systems. The most common comorbidity is psoriatic arthritis, occurring in about 40% of patients with psoriasis. Symptoms of psoriatic arthritis include joint pain, joint stiffness, and back pain. Dactylitis and enthesitis present in oligoarticular or polyarticular patterns.

In addition to the psoriatic arthritis risk, patients with psoriasis also have increased hyperlipidemia, hypertension, coronary artery disease, type 2 diabetes, and increased body mass index as compared to patients without psoriasis. Psoriasis can also cause patients to experience depression or low self-esteem due to the appearance of their condition.

Treatment of psoriasis may be topical or systemic depending on the severity of disease. Topical medications are most commonly used for mild to moderate psoriasis. Topical corticosteroids demonstrate high efficacy and safety. They have anti-inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive effects. They are available in seven different classes of potency and several different vehicles which are chosen based on the disease location, severity and patient preference. As a general rule, lower potency steroids should be used on the face, intertriginous areas, and areas susceptible to atrophy such as the forearms. Areas with thick, stubborn plaques should be treated with ultrahigh-potency corticosteroids. Some adverse effects of topical corticosteroids include skin atrophy, folliculitis, and purpura however they are effective in treating mild to moderate disease.

Calcineurin inhibitors are another class of topical therapy for psoriasis. They work by binding to calcineurin, blocking phosphorylation which inhibits T-cell activation and the synthesis of proinflammatory cytokines which have a role in the development of psoriasis. Tacrolimus and pimecrolimus are effective on thinner skin on the face and intertriginous areas which is helpful if patients do not want to use steroids on these delicate areas. Vitamin D analogues such as calcipotriene inhibit keratinocyte proliferation and enhance keratinocyte differentiation. Calcipotriene is used mostly in patients with mild to moderate psoriasis. While these topical therapies may be effective for mild to moderate psoriasis, systemic treatments have higher efficacy and may be necessary to see improvement of severe psoriasis.

Systemic treatments for psoriasis include methotrexate, apremilast, cyclosporine, acitretin, and tofacitinib. Methotrexate is a dihydrofolate reductase competitive inhibitor. It has a potent effect on rapidly dividing cells in psoriasis. Patients being treated with methotrexate must be supplemented with folic acid to decrease the occurrence of adverse effects of methotrexate. Adverse effects include fatigue, anorexia and nausea. Apremilast is another systemic treatment approved for psoriasis in 2014. It is a phosphodiesterase 4 inhibitor which causes decreased inflammatory mediators like TNF-alpha, interleukin-23, and interleukin-10. It has a better side effect profile compared with methotrexate. Side effects include diarrhea, nausea, upper respiratory tract infection, and headache.

The therapies listed are only some of the treatments available for psoriasis. The wide variety of treatment options for psoriasis gives hope to patients with the disease but these treatments come with their own side effects. Patients may need to use topical and systemic treatment intermittently throughout their whole lifetime in order to keep the disease controlled.

Resources:

Elmets CA, Korman NJ, Prater EF, et al. Joint AAD–NPF guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. Journal of the American Academy of Dermatology. 2021;84(2):432-470. doi:10.1016/j.jaad.2020.07.087

Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. Journal of the American Academy of Dermatology. 2020;82(6):1445-1486. doi:10.1016/j.jaad.2020.02.044

Rendon A, Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019;20(6):1475. Published 2019 Mar 23. doi:10.3390/ijms20061475

Psoriasis

Psoriasis is a skin disorder concerning the hyperproliferation of the epidermis. There is an increased numbers of cells undergoing DNA synthesis and a faster turnover rate of the epidermis. It is an immune-mediated disease where T lymphocytes, dendritic cells, cytokines, and tumor necrosis factor are heavily involved. Psoriasis can be visibly characterized by plaques of red or pink color, covered by white or silvery scales. The plaques are most active around the edges and rapidly progressing. They are found commonly at the elbows, knees, scalp and lower back in a symmetric pattern. However, new lesions can form at atypical spots such as sites of trauma or pressure known as the Koebner phenomenon. There are four major subtypes of psoriasis: chronic plaque, guttate, pustular and erthyrodermic psoriasis. Chronic plaque psoriasis is the most common subtype. It can be described as having erythematous plaques with defined margins ranging from localized sites to the majority of the body surface area. Guttate psoriasis consists of the sudden appearance of small papules and plaques that are usually less than 1 cm in diameter, referring to a "drop-like" shape. The plaques primarily form at the trunk and proximal extremities. Pustular psoriasis can be life-threatening presenting with widespread erythema and sheets of superficial pustules. Other symptoms include fever, diarrhea, leukocytosis with possible renal and hepatic complications. Erythrodermic psoriasis encompasses erythema and scaling involving all of the body with a loss of barrier protection resulting in infections and electrolyte abnormalities.

There are a variety of treatments available. For mild psoriasis, one can utilize topical corticosteroids. They can be divided based off their potency with class I corticosteroids having the strongest potency and class VII having the weakest. For moderate psoriasis, phototherapy may be useful including UV-B, and UV-A. Narrowband UV-B is the preferred treatment due to its efficacy. It decreases DNA synthesis causing keratinocyte apoptosis and reduced the number of inflammatory cytokines. Lastly, there are TNF-α inhibitors which are biologics approved for psoriasis treatment. They inhibit TNF- α, interfering with the inflammatory cascade responsible for psoriasis.

References:

Armstrong AW, Read C. Pathophysiology, Clinical Presentation, and Treatment of

Psoriasis: A Review. JAMA.2020;323(19):1945–1960.

Feldman, Steven. “Psoriasis: Epidemiology, Clinical Manifestations, and Diagnosis.”

UpToDate, UpToDate, Dec. 2019.

Psoriasis. What is it? How serious can it be? Does it affect the day-to-day life? Psoriasis is known as an immune-mediated disease. This means that the body’s own immune system (aka the body’s defense mechanism against any foreign substances) is attacking itself leading to inflammation of the body. Normal skin cells take about 30 days to regrow and fall off; this process is called skin cell turnover. With psoriasis, the skin cell turnover time takes only three to four days. As opposed to the skin shedding, it piles up instead. Psoriasis can occur at any part of the body and the build-up appears as plaques and scales; it can be described as felling itchy, burning, and stinging. Psoriasis is most commonly seen on elbows, knees and scalp. Although it seems superficial, psoriasis can affect other organs as well. The inflammation caused by the immune system leads to certain comorbidities.

Psoriasis is not very common as a disease and its cause is unknown. Contrary to one’s belief, psoriasis is not contagious. If the causes are unknown then who is at risk? Psoriasis may occur due to an incident or a trigger that changes the immune system. A person with no family history may develop psoriasis. Triggers are different from each person but a few triggers that can initiate psoriasis are stress, injury to the skin, illness, weather, and although less common but allergies can also be a trigger. It is important to track triggers over time in order to be able to acknowledge what causes the flares as well as to be able to treat them.

There are different types of psoriasis, five to be exact. They are Guttate, Pustular, Plaque, Inverse, and Erythrodermic Psoriasis. Guttate Psoriasis appears as small, round, red spots. Pustular Psoriasis include pustules which are pus-filled painful bumps and may be inflamed on the surrounding area. Plaque Psoriasis is one of the most common types and it appears as raised patched of inflamed, itchy and painful skin with scales. Inverse Psoriasis is shown as inflamed deep-red skin that is smooth and it can cause itching and pain. Erythrodermic Psoriasis is the rarest out of all types and it can cause intense redness and shedding of skin layers in large sheets. Erythrodermic affects the whole body and it can be life-threatening by changing heart rate, temperature, causing dehydration and changes in the nail.

Psoriasis is linked to other health conditions as well. Psoriatic arthritis (PsA) is one of the more common health conditions that may occur when having psoriasis. It is a chronic disease that leads to inflammation of the joints as well as areas where the tendons and ligaments connect to the bone. A few symptoms that people with PsA experience include stiffness, pain and swelling, nail changes, redness and pain of the eye. There is no cure for PsA but there are treatments that are available to slow the disease progression. Treatments include topical, phototherapy, oral treatments, as well natural medicine approaches. There are other health conditions linked to psoriasis as well such as cardiovascular diseases and obesity. It is important to understand what aggravates a person’s psoriasis in order to manage the flares better.

“Causes, Triggers and Treatments.” Psoriasis, National Psoriasis Foundation, www.psoriasis.org/about-psoriasis/.

“Locations & Types of Psoriasis.” Locations & Types of Psoriasis: National Psoriasis Foundation, National Psoriasis Foundation, www.psoriasis.org/locations-and-types/.

“What Is Psoriatic Arthritis?” What Is Psoriatic Arthritis?: National Psoriasis Foundation, National Psoriasis Foundation, www.psoriasis.org/about-psoriatic-arthritis/.

See Source 1: Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques. Psoriasis pathogenesis is driven by proinflammatory cytokines and psoriasis is associated with increased risk for comorbidities, including, but not limited to, psoriatic arthritis, cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease compared with the general population.

Like many skin conditions, psoriasis can be treated to lessen the severity and frequency of occurrence, but cannot be cured. Because of this, it is a chronic condition which can last for years or the rest of the patient’s life. Topical steroids and Vitamin A derivatives are first line treatment. It is important to educate the patient on proper skin cleansing and moisturization techniques as well. Fatty, oil-based products such as petroleum jelly used once daily along with stress management and other lifestyle modifications can make psoriasis manageable.

If the patient prefers more hydrophilic products which may be less sticky in comparison, other vehicles noted by source 4 are the following -

· Ointments - administered for thick hyper-keratotic lesions; the most potent vehicle since they are the most occlusive and should not be administered on hair-bearing regions because it may result in folliculitis

· Creams - less potent than ointment but cosmetically more appealing since they leave no residue; the drying, non-occlusive nature leads to their administration for acute exudative inflammation and dermatitis within the intertriginous areas.

· Lotions - less occlusive and greasy; work well in hair-bearing regions

· Gels - like lotions, less occlusive and greasy; work well in hair-bearing regions; more beneficial for the scalp as they do not cause matting of thleast occlusive and greasye hair

· Foams - highly effective for steroid delivery to the scalp but are costly

1. Management of psoriasis as a systemic disease: what is the evidence? https://pubmed.ncbi.nlm.nih.gov/31225638/

2. Psoriasis Pathogenesis and Treatment, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471628/

3. Diagnosis and management of psoriasis, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389757/

4. Topical corticosteroids, https://www.ncbi.nlm.nih.gov/books/NBK532940/

The American Academy of Dermatology (AAD) Association defines psoriasis as “an inflammatory, immunologically mediated condition stemming from inappropriate activation of cutaneous T cells and dendritic cells with subsequent release of a variety of cytokines and other soluble mediators” (1). The resulting keratinocyte proliferation, skin cell buildup, and chronic inflammation can contribute to comorbidities such as arthritis, dyslipidemia, metabolic syndrome, and cardiovascular disease. Generally, psoriasis manifests as thick, dry, scaly patches of skin that may be itchy, but there are several types of psoriasis with various symptoms. Plaque psoriasis is the most common and it appears as dry, silver scales on the skin, usually on the elbows, scalp, knees, or lower back (but can be anywhere on the body). Scalp psoriasis is when the psoriatic patches are isolated in the scalp area. Nail psoriasis appears as yellow-brown spots on the nails, pitted nails, and weak nails that easily crumble or fall off. Guttate psoriasis appears as small, scaly spots that usually occur in children after an infection. Inverse psoriasis is located where skin frequently rubs against itself, like the armpit or groin area, and appears as shiny, smooth, red patches instead of scaly ones. Pustular psoriasis causes painful pus-filled blisters and thick scales on the hands and feet. It can progress to generalized pustular psoriasis when it spreads to the rest of the body, which is a medical emergency. Finally, there is erythrodermic psoriasis which makes large areas of the skin appear bright red and burnt. When psoriasis affects the joints, it is called psoriatic arthritis and the joints tend to become swollen and tender, the heels may hurt, there may be swelling on the back of the legs, and there may be morning stiffness. Psoriasis is typically a lifelong skin condition that can never be fully cured, only acutely treated and managed using topical and systemic medications and/or phototherapy. The cycle of inflammation that drives psoriasis increases the risk of cardiovascular disease and other comorbidities, which makes regular checkups with their health care providers even more important for patients with psoriasis.

Works Cited:

1. Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113. doi:10.1016/j.jaad.2018.11.058

2. Menter A, Gottlieb A, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58:826-50.