Different therapies in Psoriasis

Psoriasis is a chronic, autoimmune disorder that primarily affects the skin, leading to the rapid growth and shedding of skin cells. This condition results from an overactive immune system where T-cells mistakenly attack healthy skin cells, triggering inflammation and accelerating the skin cell turnover cycle. Under normal conditions, skin cells take about 28–30 days to grow, mature, and shed, but in psoriasis, this process is sped up to just 3–4 days. As a result, skin cells build up on the surface, forming thick, scaly patches that are characteristic of the disease. Psoriasis can appear at any age but is most commonly diagnosed in early adulthood, with a higher incidence in individuals with a family history of the condition. The severity of psoriasis varies, ranging from small, localized patches to widespread involvement of the skin. Psoriasis can also affect joints, leading to psoriatic arthritis, a condition that causes joint pain, stiffness, and swelling.

There are several different types of psoriasis, each with unique characteristics. The most common form is plaque psoriasis, which accounts for around 80% of cases. It is characterized by raised, red patches covered with silvery scales, commonly found on the scalp, elbows, knees, and lower back. Guttate psoriasis often presents after a streptococcal throat infection and is marked by small, drop-shaped lesions on the torso and limbs. Inverse psoriasis appears in skin folds, such as under the arms or in the groin, where lesions are smooth, red, and shiny, often without scales. Pustular psoriasis involves the formation of white pustules surrounded by red skin and can be localized or widespread. The rarest form, erythrodermic psoriasis, leads to widespread redness and shedding of the skin, and can be life-threatening, as it may cause severe fluid loss, infection, and temperature regulation problems.

The exact cause of psoriasis is not fully understood, but it is believed to be influenced by both genetic and environmental factors. Certain genetic markers, particularly those related to immune system function, increase the risk of developing psoriasis. Environmental triggers such as infections, physical injury to the skin, stress, smoking, and alcohol use can all contribute to the onset or exacerbation of the disease. Moreover, psoriasis is associated with other comorbidities, including cardiovascular disease, depression, and metabolic syndrome, making management more complex.

Although there is no cure for psoriasis, various treatment options are available to control symptoms and prevent flare-ups. Topical treatments are the first line of defense for mild to moderate psoriasis and include corticosteroids, which reduce inflammation and itching, and vitamin D analogs like calcipotriene, which slow skin cell turnover. Topical retinoids, coal tar, and calcineurin inhibitors may also be used to manage symptoms. For more severe cases, systemic treatments may be required. These include oral medications like methotrexate, acitretin, and cyclosporine, which suppress the immune system and reduce skin cell production. Biologic therapies are newer treatments that target specific immune molecules, such as TNF-alpha inhibitors or interleukin inhibitors, and are often prescribed for moderate to severe psoriasis that does not respond to topical or oral therapies.

Additionally, lifestyle modifications can help manage psoriasis. Patients are advised to avoid triggers such as infections and stress, maintain a regular moisturizing routine to prevent skin dryness, and consider phototherapy, which involves controlled exposure to ultraviolet light to slow skin cell turnover. Psoriasis can have a significant impact on a patient’s quality of life, affecting physical appearance, emotional well-being, and social interactions. Therefore, effective management, including a combination of medical treatments and lifestyle changes, is essential for improving the quality of life of individuals living with psoriasis. While there is no cure, advancements in treatment have provided patients with more options to control symptoms and live healthier lives.

https://my.clevelandclinic.org/health/diseases/6866-psoriasis

https://www.niams.nih.gov/health-topics/psoriasis

Psoriasis, a persistent autoimmune skin disorder marked by the excessive growth of skin cells, manifests as thick, red, scaly patches on the skin. Its origins remain somewhat elusive, likely stemming from a blend of genetic, environmental, and immune system factors. Triggers such as stress, infections, skin injury, and certain medications can exacerbate symptoms.

Various psoriasis types exist, each presenting distinct features and necessitating tailored treatments. The primary goal of treatment is symptom alleviation, inflammation reduction, and inhibition of abnormal skin cell growth. Although a permanent cure is yet to be found, diverse treatment modalities aim to effectively manage the condition.

Initial treatment often involves topical medications like corticosteroids, vitamin D analogs, and coal tar preparations, directly applied to affected areas to mitigate inflammation and scaling. Phototherapy, or light therapy, under medical supervision, employs ultraviolet light exposure to slow skin cell proliferation and inflammation, either alone or in combination with other treatments.

For more severe cases resistant to conventional therapies, systemic medications are prescribed, targeting the underlying immune dysfunction. These may include methotrexate, cyclosporine, acitretin, or biologic agents like TNF-alpha inhibitors, IL-17 inhibitors, and IL-23 inhibitors. Due to potential side effects and immune system implications, close monitoring is necessary.

Lifestyle modifications complement medical interventions. Strategies such as stress reduction, avoidance of triggers like smoking and excessive alcohol consumption, maintaining a healthy diet, managing weight, and regular exercise contribute to overall skin health and immune function.

Living with psoriasis poses physical and emotional challenges. Support groups, counseling, and education provide valuable resources. Collaborating closely with healthcare professionals ensures the development of personalized treatment plans, addressing individual needs and concerns.

In summary, psoriasis presents as a chronic autoimmune skin condition characterized by rapid skin cell growth. While a permanent cure remains elusive, diverse treatment options aim to manage symptoms effectively. By implementing comprehensive approaches, individuals can navigate psoriasis, minimizing its impact on their daily lives.

Psoriasis is a common chronic inflammatory disease that affects many worldwide. Not only does it affect the skin, but it can cause emotional distress because the disease is not curable and is visible. “Psoriasis is a T-lymphocyte-mediated systemic inflammatory disease that results from a complex interplay between multiple genetic factors and environmental influences (1)”.  The initial psoriatic skin lesions occur from an abnormal immune response triggered by some precipitating factors. Some of these precipitating factors include, “injury to the skin, infection, drugs, smoking, alcohol consumption, obesity, and psychogenic stress (1)”. To prevent further exacerbations of psoriasis, lifestyle intervention to mitigate risk factors has been recommended. Patients with psoriasis often have associated comorbidities like psoriatic arthritis, metabolic syndrome, and psychological illnesses. Treating psoriasis involves making an individualized treatment plan that focuses on optimal care to increase a patient’s quality of life.

The treatment goals are to reduce disease morbidity and improve quality of life. In addition “minimize signs such as plaques and scales, alleviate symptoms such as pruritus, and reduce the frequency of flare ups (1).” Management of psoriasis involves both nonpharmacologic and pharmacologic therapies. Nonpharmacologic management is important for all patients no matter the severity of the disease. Patients should be counseled on proper stress reduction strategies that are effective for them. In addition, they should be counseled on proper unscented moisturizers, oatmeal baths, and skin protection using sunscreens. Nonpharmacologic management also includes smoking cessation therapy as studies have shown a direct relationship between smoking and the exacerbation of psoriasis. 

Pharmacologic therapies for psoriasis include topical agents, phototherapy, systemic agents, and biologic agents. Different treatment algorithms exist based on the severity of the plaque psoriasis. For mild to moderate psoriasis, topical agents are first line. If that is inadequate, phototherapy can be added on. If that is further inadequate, systemic agents can be added on. The treatment algorithm for moderate to severe psoriasis includes systemic agents +/- topical agent, or phototherapy, or even a biologic agent.  If this regimen is inadequate, more potent systemic or biologic agents can be added. Treatment regimens should be revisited according to the drug manufacturer's guidance to assess effectiveness and overall quality of life for the patient. The goal is always to improve the patient’s quality of life and alleviate their symptoms as best as we can. 

Many topical agents can be used for psoriasis. For example, research shows a vitamin D3 analog such as calcipotriol or calcitriol, and topical corticosteroids are effective in treating mild to moderate psoriasis. Combining topical therapy with phototherapy has shown promising results. Phototherapy consists of using nonionizing electromagnetic radiation, either UVA or UVB, to treat psoriatic lesions (1). Systemic agents have been the preferred treatment for patients with moderate to severe psoriasis. For decades, methotrexate has been used. In addition to oral systemic agents, biologic agents are popular amongst use for moderate to severe psoriasis. “Currently available biologic agents include tumor necrosis factor­α (TNF­α) inhibitors (etanercept, infliximab, adalimumab, certolizumab), ustekinumab, IL­17 inhibitors (secukinumab, ixekixumab, brodalumab), IL­23 inhibitors (guselkumab, tildrakizumab, risankizumab), and others (1).” While the use of biologic agents has been effective, there are general concerns. The efficacy of biologics may not be sustainable for more than three years, and patients have psoriasis for life.  

The use of complementary and alternative medicine among patients with psoriasis is common. Some of these agents are Mahonia aquafolium (mountain grape), fish oil, and dead sea salts. 

In conclusion, psoriasis is a complex skin condition that significantly impacts individuals' quality of life, necessitating ongoing research, compassionate care, and effective treatments to better manage and alleviate its symptoms.

References:

1. Law R.M., & Gulliver W.P. Psoriasis. DiPiro J.T., & Yee G.C., & Haines S.T., & Nolin T.D., & Ellingrod V.L., & Posey L(Eds.), [publicationyear2] DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=3097&sectionid=271955913

Psoriasis is a chronic multi-factorial skin disease characterized by skin cells to build up and form scales and itchy, dry patches. This is a result from the immune system becoming overactive and causing skin cells to multiply too quickly. The patches of the skin become inflamed and appear most often on the scalp, elbows, or knees, but other parts of the body can be affected as well. Various factors believed to play a crucial role in the development of psoriasis include T cells, antigen-presenting cells (APCs), keratinocytes, Langerhans' cells, macrophages, natural killer cells, a range of Th1 type cytokines, and specific growth factors such as vascular endothelial growth factor (VEGF) and keratinocyte growth factor (KGF), and more.

The prevailing hypothesis suggests that the onset of the disease involves the activation of T cells by an unidentified antigen, leading to the secretion of various cytokines by activated T cells, inflammatory cells, and keratinocytes. The distinctive psoriasis lesions result from the hyper-proliferation of keratinocytes. Activated Langerhans' cells migrate from the skin to lymph nodes, presenting the antigen to naïve T cells in the nodes (cells that have not been previously activated by antigen). Scientists do not fully understand the cause of psoriasis, but they know that it involves a mix of genetics and environmental factors. Common psoriasis triggers include stress, skin injury, such as a cut or bad sunburn, infection, such as strep throat, some medications, including lithium, prednisone, and hydroxychloroquine, weather, especially cold, dry weather, tobacco, and alcohol, specifically heavy drinking. Psoriasis flare-ups can be prompted by various triggers, and these triggers vary among individuals. While periods of high stress might trigger psoriasis for some, cold weather may not have the same effect. Anyone can get psoriasis, but it is more common in adults than in children. It affects men and women equally.

Different types of psoriasis include plaque psoriasis, guttate psoriasis, pustular psoriasis, inverse psoriasis, and erythrodermic psoriasis. Plaque psoriasis is the most comment and manifests as elevated, red skin patches covered with silvery-white scales. These patches typically form in a symmetrical fashion on the body and are commonly found on the scalp, trunk, and limbs, with a particular affinity for the elbows and knees. Guttate psoriasis typically emerging in children or young adults, this type presents as small red dots, usually found on the torso or limbs. Outbreaks are frequently induced by upper respiratory tract infections, such as strep throat. Pustular psoriasis is characterized by pus-filled bumps called pustules surrounded by red skin appear. It usually affects the hands and feet, but there is a form that covers most of the body. Symptoms can be triggered by medications, infections, stress, or certain chemicals. Inverse psoriasis appears as smooth, red patches in folds of skin, such as beneath the breasts or in the groin or armpits. Rubbing and sweating can make it worse. Finally, erythrodermic psoriasis is a rare but severe form of psoriasis characterized by red, scaly skin over most of the body. It can be triggered by a bad sunburn or taking certain medications, such as corticosteroids. Erythrodermic psoriasis often develops in people who have a different type of psoriasis that is not well controlled, and it can be very serious.

Psoriasis treatments involve topical medications, such as corticosteroids and vitamin D analogs, which aim to reduce inflammation and promote skin cell turnover. Phototherapy, utilizing ultraviolet B (UVB) or psoralen plus ultraviolet A (PUVA) light, is another effective option, targeting affected areas and slowing down cell growth. For more severe cases, systemic treatments like oral medications or biologics may be prescribed to modulate the immune system's response. The evolving landscape of psoriasis therapies reflects a commitment to providing patients with diverse and personalized options to manage their symptoms and improve their quality of life.

References:

https://www.niams.nih.gov/health-topics/psoriasis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800878/#:~:text=The%20characteristic%20lesion%20of%20psoriasis,been%20activated%20by%20antigen%20previously).

https://www.aad.org/public/diseases/psoriasis/what/causes

https://www.mayoclinic.org/diseases-conditions/psoriasis/in-depth/psoriasis-treatment-options/art-20300893?utm_source=google_search&utm_medium=cpc&utm_campaign=mc_cs_ag_147292986643&utm_content=mc_cs_cid_{adid}&gad_source=1&gclid=Cj0KCQiAhomtBhDgARIsABcaYyk-wdoiOw1AArnTOa-E23YT_F0BEI5nfYn9bTkEheqUgKEOOfYu0D4aAiaAEALw_wcB

soriasis

       Psoriasis is a chronic inflammatory skin disorder more common in adults. psoriasis is an autoimmune disorder, where the T-cells become uncontrolled. they increase inflammation by increasing the release of tumor necrosis factor, interleukin-2, and interferon-gamma. The most common type of psoriasis is chronic plaque psoriasis. This is characterized by well-defined, coarse, red plaques. Plaques are areas of thick scales. It can be found on the scalp. knees, gluteal cleft, palms, soles, and ears. Guttate psoriasis is the onset of multiple, small, and inflamed plaques. They are sized about 1 cm in diameter and can be an acute onset in children. Other types of psoriasis include pustular psoriasis and erythrodermic psoriasis. Pustular psoriasis is the most severe form. There is a characterization of erythema, scaling, and superficial pustules across the body. Generally, psoriasis is defined by scaling, hardening, and redness of the skin. Patients with psoriasis usually have cycles, with flares occurring, and then diminishing. Risk factors include genetics, smoking, obesity, and alcohol use.  It can be triggered by stress, skin injuries, and medicines, such as lithium, prednisone, and hydroxychloroquine. Psoriasis is also associated with different comorbidities. All patients with psoriasis should be screened for psoriatic arthritis. Common symptoms of this include joint pain, stiffness, and back pain. Other comorbidities include obesity, hypertension, metabolic syndromes, and atherosclerotic diseases. Psoriasis can also increase the risk of eye improvements disorders such as conjunctivitis, xerosis, and corneal lesions. Symptoms of this include swollen, crusty, and red eyes. 

         Although psoriasis is not life-threatening, the physical and social impacts may negatively impact people's lives. The treatment regimen depends on the severity, comorbidities, and patient preference and response. For limited psoriasis, topical corticosteroids and emollients are commonly used. Corticosteroids are used due to their antiproliferative and anti-inflammatory actions. It is recommended to only use corticosteroids in the presence of active psoriasis, then wean off it. Abruptly discontinuing corticosteroids can cause a rebound flare-up of psoriasis. Calcipotriene is a vitamin D analog that can be used for short-term treatment. For sensitive areas, such as the face and armpits, topical tacrolimus or pimecrolimus can be used. Severe psoriasis systemic therapies such as retinoids, methotrexate, cyclosporine, or biologic immune modifying agents. Examples of biologics used TNF agents (adalimumab, infliximab), IL-12/IL-23 antibodies (ustekinumab) and anti-IL-23/IL-39 antibodies (guselkumab, tildrakizumab, and risankizumab). the biologics target t-cells, inhibiting their action, and in return, inhibiting the actions and release of tumor necrosis factor-alpha, interleukin 17-A, or interleukins 12 and 23. It may take a few weeks to see improvements in severe psoriasis. For scalp psoriasis, it is more common to use topical corticosteroids in the form of shampoos, lotions, and gels. 

Boehncke WH, Schön MP. Psoriasis. Lancet. 2015 Sep 5;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7. Epub 2015 May 27. PMID: 26025581.

Tam A, Geier KA. Psoriatic arthritis. Orthop Nurs. 2004 Sep-Oct;23(5):311-4. doi: 10.1097/00006416-200409000-00006. PMID: 15554467.

Psoriasis is a common chronic inflammatory disease that involves both adaptive and innate immunity. It is an immune-mediated disease in which skin inflammatory changes are dependent on immune cells and their cytokines. The interaction between dermal dendritic cells, activated T cells of the TH-1, TH-17 lineage on concert with a multitude of cytokines and growth factors are responsible for the epidermal hyperplasia and dermal inflammation that is seen in the skin of patients with psoriasis. Crosstalk between the innate and adaptive immune system mediated by cytokines including TNF-alpha, interferon gamma, and interleukin 1 is a major research focus. Psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic disease, and depression. There are different types of psoriasis, with plaque psoriasis being the most common type. Treatment of psoriasis is based on managing the underlying pathophysiology. Agents that modulate the abnormal immune response, such as topical corticosteroids and biologic agents, are important treatment strategies for psoriasis. In addition, nonpharmacologic therapies are effective adjuncts and should be considered for all patients with psoriasis. A treatment regimen should be individualized, taking into consideration disease severity, patient response, and tolerability of interventions. Goals of treatment include minimizing or eliminating the visible signs of psoriasis, such as plaques and scales, alleviating pruritus and minimizing excoriations, reducing the frequency of flare-ups, ensuring appropriate treatment of associated comorbid conditions such as psoriatic arthritis, hypertension, dyslipidemia, diabetes, or clinical depression.

For limited to moderate disease, topical treatments are the mainstay of care. Phototherapy and photochemotherapy are used in moderate-to-severe cases. For patients presenting with extensive or moderate to severe disease, systemic therapies with or without the use of topical treatments are usual standards of care. Newer systemic treatments such as biologic agents may be the treatments of choice, especially for patients with comorbidities such as PsA or if traditional systemic treatments are contraindicated. Once the disease is under control, it would be important to step down to the least potent, least toxic agent that maintains control. Rotational therapy may minimize drug associated toxicities. However, continuous treatment has replaced rotational or sequential therapy and is now the standard of care. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids vitamin D analogues, calcineurin inhibitors, and keratolytic. The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles.

Corticosteroids are the topical agents used for psoriasis, these have anti-inflammatory, anti-mitotic, and immunosuppressive effects. Potent steroids are used for two weeks, where its used less frequently or the dose is then reduced using a lower potency steroid. Some side effects of this therapy include skin atrophy, striae, telangiectasis, and purpura. The higher potency corticosteroids include clobetasol propionate and betamethasone propionate, lower potency include amcinonide and mometasone furoate.  Some of the systemic agents include methotrexate which inhibits purine biosynthesis, and induction of lymphocyte apoptosis, cyclosporine is a systemic calcineurin inhibitor that works as an immunosuppressant.

Gabros, Sarah. “Topical Corticosteroids - Statpearls - NCBI Bookshelf.” Topical Corticosteroids, 7 Mar. 2023, www.ncbi.nlm.nih.gov/books/NBK532940/.

Law R.M., & Gulliver W.P. (2020). Psoriasis. DiPiro J.T., & Yee G.C., & Posey L, & Haines S.T., & Nolin T.D., & Ellingrod V(Eds.), Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?bookid=2577&sectionid=239761543

Different Therapies for Psoriasis

Psoriasis is a chronic, non-communicable inflammatory skin condition characterized by different subtypes: psoriasis vulgaris, inverse psoriasis, guttate psoriasis, and pustular psoriasis. Globally, it is prevalent in 2% of the population and affects both males and females, although it has been shown psoriasis has an earlier onset in females and those with a family history. Psoriasis vulgaris, also synonymous to chronic plaque-type psoriasis, is the most common type and is prevalent in 90% of psoriasis cases. Its clinical manifestations include sharply demarcated, erythematous, pruritic plaques covered in silvery scales that may coalesce. The plaques may cover large areas of the skin, such as the trunk, extensor surfaces of the limbs (skin surfaces on the outside of a joint susceptible to lesions and skin disorders, i.e. knees and elbows), and the scalp. Inverse psoriasis, also referred to as flexural psoriasis, affects intertriginous locations, which are areas of the skin that come in contact with each other, “skin folds” (i.e. armpit, genital area). It is characterized by slightly erosive, erythematous plaques and patches. Guttate psoriasis commonly affects children or adolescents and is often triggered by group-A streptococcal infections or tonsils. It is characterized by small, drop-like erythematous plaques that appear as small, raised, round papules and can be scaly. Those with guttate psoriasis may later develop plaque psoriasis. Lastly, pustular psoriasis is characterized by multiple, coalescing sterile pustules that can be localized or generalized, often affecting the hands and feet. There are two phenotypes that describe pustular psoriasis: psoriasis pustulosa palmoplantaris (PPP) and acrodermatitis continua of Hallopeau (ACH). PPP affects the palms and soles whereas ACH affects the fingertips, toes, and the nail apparatus.

Genetics is a primary factor that determines the likelihood of an individual developing plaque psoriasis. The pathogenesis of psoriasis begins with a disturbance in the innate and adaptive cutaneous immune response. The innate immune system is activated and specific T-cell populations are stimulated by as-yet undefined antigen(s) presented by antigen-presenting cells. The T cells release pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), that induce keratinocyte and endothelial cell proliferation. Interleukin-23 (IL-23) cytokine and T-helper cell 17 (Th17) have central involvement in psoriasis that result in immune activation, chronic inflammation, and keratinocyte proliferation. In psoriasis, keratinocytes interact with the innate and adaptive immune cells, and secrete antimicrobial peptides (AMPs) in response to injury and are overexpressed in psoriasis. The different types of AMPs include LL37, β-defensins, and S100 proteins. It is found that LL37 has a pathogenic role in psoriasis. Damaged keratinocytes release LL37 which form complexes with self-genetic material from other damaged cells and bind to DNA, stimulating toll-like receptor 9 (TLR-9) in plasmacytoid dendritic cells (pDCs). Activation of pDC initiates the development of psoriatic plaque. The epidermal layer also is inflamed, leading to the development of psoriatic plaque. Sustained inflammation ensues, leading to uncontrolled keratinocyte proliferation. Psoriatic plaques become visible and histologic findings include inflammatory infiltrates constituting dermal dendritic cells, macrophages, T cells, neutrophils, and neovascularization. Psoriasis may be triggered by trauma, infection, or medication use. Due to the mechanism of psoriasis, medications that block cytokine production or inhibition of T-cell activation are useful treatment modalities.

Selection of pharmacological therapy for psoriasis is dependent on the severity: mild-moderate, moderate-severe, the surface area of the affected skin, and the patient’s quality of life. Mild to moderate psoriasis is generally treated with topical agents, a combination of glucocorticoids, vitamin D analogues, and phototherapy. Topical agents include corticosteroids, emollients, tar, topical retinoids, topical vitamin D, anthralin, and topical calcineurin inhibitors. Systemic agents are usually reserved for patients with moderate to severe psoriasis and can be combined with topical agents or biological response modifiers. Systemic agents include retinoids, methotrexate, cyclosporine, and biologic immune modifying agents. In addition, maintaining proper moisturization of the skin is advised regardless of psoriasis severity. The goal of treatment is to control psoriasis (cure is not possible), skin normalization, increased pliability of skin, decrease or clear erythema, papules, plaques, and scales, and improve quality of life.

Below are examples of treatment agents.

Topical Agents:

Corticosteroids: anti-inflammatory, anti-mitotic, and immunosuppressive effects

Application: Potent steroid x 2 weeks, then “reduce dose”; lower potency of steroid or use less frequently

*Abrupt d/c can lead to rebound

SE: skin atrophy, striae, telangiectasias, purpura

Superpotent -Clobetasol propionate -Betamethasone dipropionate Potent

-Amcinonide -Mometasone furoate

Systemic Agents:

Methotrexate: Dihydrofolate reductase inhibition blocks purine biosynthesis; induction of lymphocyte apoptosis

Dose: 7.5-15 mg/wk po; increase by 2.5 mg every 2-4 wk

SE: nausea, pulmonary toxicity, pancytopenia, megaloblastic anemia

Monitoring Parameters: CBC; liver & renal function; chest x-ray

*May supplement with oral folic acid

*Pregnancy: Category X

Cyclosporine: systemic calcineurin inhibtor; immunosuppressant

Dose: titrated to the lowest effective dose

Usual doses 3- 5 mg/kg/ day

If D/C, gradual taper of 1mg/kg/day each week to prevent relapse and rebound

AE: renal toxicity, HTN, and hypertriglyceridemia; GI discomfort; hypertrichosis; gingival hyperplasia; headaches

Monitoring Parameters: Blood levels (range of 100-400 ng/mL), renal function, BP, Lipid profile

*DI: CYP3A4 inhibitors (CCB, amiodarone, SSRIx, antifungals), inducers (anticonvulsants, efavirenz)

*Grapefruit juice may increase drug concentration

References

Gabros, Sarah. “Topical Corticosteroids - Statpearls - NCBI Bookshelf.” Topical Corticosteroids, 7 Mar. 2023, www.ncbi.nlm.nih.gov/books/NBK532940/.

Raharja, Antony, et al. “Psoriasis: A Brief Overview.” Clinical Medicine (London, England), May 2021, www.ncbi.nlm.nih.gov/pmc/articles/PMC8140694/.

Psoriasis is characterized as an immune mediated disease that affects both the skin and the joints. This condition may become quite complex and tends to have disabling, chronic effects that are very bothersome for certain patients. Psoriasis can provide many challenges that can disturb a person’s quality of life. However, throughout the years, new products and treatments have been released into the market for this serious and life altering condition.

Some of the symptoms of psoriasis may include itching, redness, flaking of the skin, bleeding, and severe pain. According to the World Health Organization, psoriasis is prevalent among two percent of the population in Europe and North America. Some of the common risk factors that may aggravate this condition include weather conditions, sun exposure, UV radiation, ethnicity, gender, and race. The most common form of psoriasis is plaque psoriasis or "psoriasis vulgaris". This condition usually accounts for 90% of psoriatic cases (Boehncke, 2015). Other types of psoriasis include eruptive psoriasis, inverse psoriasis, pustular psoriasis, palmoplantar, generalized, and erythrodermic. In addition, nail psoriasis can also affect patients with who have this condition.

Some factors that may potentially trigger this condition include constant scratching of the skin, piercings, tattoos, sunburns, cytokines, and chemicals that cause skin irritation (Boehncke, 2015). Psoriasis is usually diagnosed by skin biopsies and is rated using the Psoriasis Area and Severity Index score (PASI). This condition may also require full body examinations and a deeper look into the patient genetics.

There are many different types of medications that can be used for the management and prevention of this disease. Phototherapy is known to be one of the first line treatments, along with biologics and non-pharmacological related treatments- such as self-care. According to UptoDate, “Patients with limited plaque psoriasis can be initially treated with topical corticosteroids and emollients. Alternatives include tar, topical retinoids and topical vitamin D. For facial areas, topical tacrolimus may be used as an alternative or as corticosteroid-sparing agents” (UptoDate). According to this information, improvements can usually be seen within one to two months. In certain cases, combination therapy is recommended and highly recognized with patient adherence. In patients who have contraindication to phototherapy, guidelines recommend medications such as methotrexate, cyclosporin, apremilast, and deucravacitinib. Howvever, the benefits of phototherapy include limited side effects and drug related interactions.

Resources:

Boehncke, Wolf-Henning, and Michael P Schön. “Psoriasis.” Lancet (London, England) vol. 386,9997 (2015): 983-94. doi:10.1016/S0140-6736(14)61909-7

Zhang, Ping, and Mei X Wu. “A clinical review of phototherapy for psoriasis.” Lasers in medical science vol. 33,1 (2018): 173-180. doi:10.1007/s10103-017-2360-1

UptoDate Data Base:

https://www-uptodate-com.jerome.stjohns.edu/contents/treatment-of-psoriasis-in-adults?search=psoriasis%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H45

Psoriasis is a skin condition characterized by numerous clinical manifestations including the formation of plaques (patches of this, red, and scaly skin, dry or cracked skin, itchiness and discomfort, as well as swelling or sore joints. This condition is a chronic disease state that constitutes increased inflammation and the pathogenesis of psoriasis is often connected to genetics that predispose patients to later development. The presence of psoriasis in many patients may lead to the development or exacerbation of comorbidities such as psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, and cancer. While psoriasis was initially considered a disorder or disease of the keratinocytes found within the skin, further research and development has shown that the immune system and its response to the body is what instigates & hastens the development of psoriasis. Therefore, research has shown that the most efficacious methods to treat psoriasis would lie in medications that can directly interact with the patient’s immune system to prevent an auto-immune response.

For patients who do not suffer from psoriasis severe enough to warrant biologic use, first-line treatment is often relegated to topical or systemic corticosteroids as well as a vitamin D3 supplement. Such treatment is indicated for mild psoriasis. For moderate psoriasis, systemic methotrexate is recommended due to its immunosuppressive capability. In the case of severe psoriasis, patients may be relegated to more intensive medication therapy that readily targets the root-cause of psoriasis.

Biologics are considered one of the most impactful medications utilized in modern-day treatment of psoriasis. Biologic medications are a class of drugs that consists of large, complex molecules that represent targeted therapy, including monoclonal antibodies and receptor fusion proteins. Monoclonal antibodies are medications that are quickly degraded within the gastro-intestinal tract, leading to rapid inactivation of the medication. Due to this mechanism, biologics must be administered parenterally as an injection to ensure that the drug is able to provide a therapeutic effect without automatic inactivation. One of the many biologic medications utilized in the treatment of psoriasis is known as adalimumab, or more commonly known by its brand name--Humira. Adalimumab is linked to the neutralization of TNF-alpha, preventing it from interacting with its corresponding receptors on cell surfaces. By interfering with the TNF-alpha process, inflammatory cytokines such as IL-6 are prohibited from beginning an inflammatory cascade. In doing so, the mechanism by which psoriasis flare-ups are triggered are then mitigated. Many studies have been conducted regarding the efficacy of Adalimumab and many phase 3 trials have shown that Humira has a far more rapid onset of action in comparison to methotrexate.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389757/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713267/

Psoriasis is a chronic autoimmune condition that has effects on the skin such as inflammation and scaling. In a patient with psoriasis, skin cells are maturing at a rate 10 times faster than normal. This causes a buildup of skin cells that present themselves as thick patches with silvery scales. These patches can develop to be very thick and red, which sometimes can crack and bleed and be extremely itchy and painful. Usually the lifecycle of a skin cell is one month but in people who have psoriasis, the lifecycle of a skin cell can be just a few days. Because the cycle is shortened so extremely, skin cells are not given a chance to be shed from the body before new ones start growing, resulting in a buildup. Psoriasis scales can develop anywhere on the body but are really common on joints such as the elbows and knees.

There are five types of psoriasis: plaque psoriasis, guttate psoriasis, pustular psoriasis, inverse psoriasis and erythrodermic psoriasis. They differ in the way and areas which they present but ultimately are very similar. The most common type of psoriasis is plaque psoriasis, which presents with whitish silver scales or plaques most commonly found on the elbows, knees, and scalp. There are some prevention strategies that can be taken to prevent flareups. It has been found that smoking tobacco and drinking alcohol can aggravate or cause flareups. Alcohol can be enjoyed in moderation but if a person is in the middle of a flareup, they should abstain from alcohol. People with psoriasis should be very consistent with hydration and moisturization to prevent flareups caused by dry skin. Thick, greasy creams and ointments might even be the most beneficial. Lowering stress levels can prevent flareups. Therapy, exercise, and meditation can all be ways of introducing relaxation into a person’s day.

People with psoriasis should be counseled to treat their skin as they would the skin of a baby. Any type of irritation can cause a flareup and therefore the skin should be protected at all times. Injuries, shaving, bug bites, and even adhesives from bandages can all trigger flareups. Receiving shots or vaccines at your doctor’s office may even cause flareups. Patients may also benefit from allergy testing to see if anything in their diet is worsening or triggering their psoriasis flare ups. For example, gluten, which is a protein found in wheat, has been linked to psoriasis flare ups. Eating a heart healthy diet is also important. Lowering intake of saturated fats, but increasing intake of lean proteins that contain omega-3 fatty acids, such as salmon, can benefit your skin. There are certain trigger foods that cause inflammation and avoiding them might improve symptoms. Red meat, refined sugar, processed food, and dairy products all can be linked to inflammation and worsening of psoriasis.

Lifestyle changes can be the ultimate solution for patients struggling with psoriasis. Patient education is key for prevention and should be a goal of all healthcare providers as well as estheticians dealing with the skin.

· Causes and triggers. (2018). psoriasis.org/about-psoriasis/causes

· Kiraly-Liebendorfer A. (2018). Psoriasis and diet: Researchers examine the relationship between food and disease. psoriasis.org/advance/diet-psoriasis-research

· Mayo Clinic Staff. (2018). Psoriasis. mayoclinic.org/diseases-conditions/psoriasis/symptoms-causes/syc-20355840

· What is psoriasis? (2017). niams.nih.gov/health_info/psoriasis/psoriasis_ff.asp

Guselkumab also known as Tremfya, is a human immunoglobulin G1 lambda monoclonal antibody used for the treatment of plaque psoriasis. It is effective by binding to the p19 subunit of IL-23, however IL-39 also contains this p19 subunit. The mechanism of action of Guselkumab is inhibition of IL-23 signaling. This signal inhibition reduces serum levels of IL-17A, IL-17F, and IL-22. This action inhibits the release of proinflammatory cytokines and chemokines, which alleviates the symptoms of psoriasis. Guselkumab is a subcutaneous injection that should be dosed at 100 mg for the first week, fourth week, and then every eight weeks after. Unlike Stelara, which was previously mentioned, this medication is not approved in pediatric patients. Guselkumab, like many of the other monoclonal antibodies for psoriasis, appears to have efficacy for psoriatic arthritis and its efficacy for this indication is currently being evaluated. The major concerns and side effects of this medication include hypersensitivity to the injection and medication, as well as opportunistic infection, due to the immunosuppressant effect of the drug.

https://pdf.hres.ca/dpd_pm/00042101.PDF

https://www.ncbi.nlm.nih.gov/pubmed/28635018

Considered the keystone of topical treatment, topical corticosteroids are widely prescribed for mild to moderate psoriasis( <5% Body Surface Area Involvement) because of their anti-inflammatory, immunosuppressant, and antipruritic properties. Despite extensive use, large randomized control trials and head-to-head comparisons are rather limited. It is interesting to note that in the Cochrane Database System Review with randomized trials comparing treatments against placebo or against vitamin D analogues in people with chronic plaque psoriasis, corticosteroids were non-inferior to vitamin D analogues and are associated with a lower incidence of local adverse events. The standardized mean differences ranging from -0.89 (95% CI -1.06 to -0.72) to -1.56 (95% CI -1.87 to -1.26) for strong and very strong corticosteroids, respectively.

Advantages:

1. Rapid response

2. control inflammation and itching

3. convenient, not messy

4. mainstay topical treatment modality for psoriasis

Disadvantages:

1. Temporary relief

2. less effective with continued use (tachyphylaxis occurs)

3. withdrawal can produce flare-ups

4. atrophy, telangiectasia, and striae with continued use after skin returns to normalized state

5. expensive

6. adrenal suppression possible

Mason AR, Mason J, Cork M, Dooley G, Edwards G. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev 2009;(2):CD005028. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009;60(4):643-59. Epub 2009 Feb 13

Remicade also known as infliximab is another medication that can be used to treat psoriasis. It is a monoclonal antibody that binds to human tumor necrosis factor alpha (TNFα) and inhibits its activity in vivo. Increased levels of TNFα have been found in patients with psoriasis and by inhibiting its role in the body, the idea is that it should help these patients.The mechanism of action is broad, complex and affects many pathways but it mostly works by blocking pro-inflammatory cytokines. Remicade can also be used to treat numerous other conditions such as crohn’s disease, rheumatoid arthritis, and ulcerative colitis. The dosing for plaque psoriasis, psoriatic arthritis, and pustular psoriasis is 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks. Four randomized controlled trials were conducted to provide efficacy and safety data for infliximab. All of these trials used the Psoriasis Area and Severity Index as a measure of outcome to determine efficacy. The target was set at 75 meaning that patients needed to see at least a 75% improvement from baseline scores to reach the favorable outcome. By week 10, every study showed at least 70% of patients reached this threshold regardless of the dose being administered. For some studies that number was as high as 80% suggesting its efficacy in treating psoriasis. It is important to note that patients taking this medication may be more susceptible to infections especially if taken with other immunosuppressants.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727775/

https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103772s5359lbl.pdf

Home phototherapy is another treatment option for light therapy as well. A research team from the University Medical Center Utrecht, the University of Groningen, and St. Antonius Hospital compared the safety and efficacy of home phototherapy with standard hospital based phototherapy which is narrow-band UVB phototherapy. 196 people with psoriasis were randomized during the trial to either receive either UVB light therapy at home or at an outpatient site at a hospital. Both groups completed questionnaires that asked about their quality of life and satisfaction with the treatment. The effectiveness was significant in both groups and notably, patients who used home therapy had a significantly lower burden of treatment and greater satisfaction with their therapy. The baseline psoriasis area and severity index score (PASI) and self administered psoriasis area and severity index score (SAPSI) were decreased by 74% and 82% respectively by the home setting patients versus 70% and 79% with outpatient setting patients.

https://www.webmd.com/skin-problems-and-treatments/psoriasis/news/20090507/treat-psoriasis-at-home-ultraviolet-lamps#2

https://www.bmj.com/content/338/bmj.b1542

Patients with psoriasis covering more than 5% of the body require more specialized systemic therapies. One such drug is Acitretin. It is a second-generation synthetic retinoid that is reserved for the treatment of moderate to severe psoriasis. It plays a role in adjunctive therapy to other systemic agents to improve efficacy. Using this agent can lower doses and reduce the occurrence of side effects of other agents. There are not concrete clinical data or trials studying to support using it as a monotherapy.

Advantages:

1. Enhance efficacy when given with phototherapy. It is given as a pretreatment for 1–3 weeks prior to PUVA phototherapy session to escalate the response rate. Also for patients who fail to respond to UVB with anthralin or tar

2. less hepatotoxic than methotrexate (can be an option for patient who cannot take methotrexate)

Disadvantages

1. Side effects such as "mucocutaneous dryness, arthralgia, gastrointestinal upset, and photosensitivity"

2. Potent teratogen. Women of childbearing age are recommended not to get pregnant 3 years after stopping

3. Contraindicated with liver or renal dysfunction

4. Increases triglyceride levels

5. Hypervitaminosis

Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009;61(3):451-85.

Lebwohl M, Drake L, Menter A, Koo J, Gottlieb AB, Zanolli M, et al. Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis. J Am Acad Dermatol 2001;45(4):544-53

Another therapy is the Vitamin D3 analogues (Calcipotriol). It is a first-line topical agent for the treatment of plaque psoriasis and moderately severe scalp psoriasis. It decreases symptoms by "modulating keratinocyte proliferation and differentiation, and by inhibiting T lymphocyte activity". There was a quantitative systematic review of 37 randomized controlled trials with 6038 patients to evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis. The researchers concluded that calcipotriol to be safe and efficacious for patients with mild plaque psoriasis and not inferior to most corticosteroids with respect to efficacy. However, this agent does come with side effects such as mild irritant dermatitis and more uncommonly, hypercalcemia with prolonged use. It is important to note that calcipotriol cannot be concomitantly used with lipophilic monohydroxybenzoic acid such salicylic acid or before phototherapy.

Kim, W. B., Jerome, D., & Yeung, J. (2017). Diagnosis and management of psoriasis.Canadian family physician Medecin de famille canadien,63(4), 278–285.

Ashcroft DM, Po AL, Williams HC, Griffiths CE. Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis. BMJ 2000;320(7240):963-7.

A relatively new medication that has been used for psoriasis is SIILIQ. SILIQ also known as brodalumab is a biologic medication for patients with moderate to severe plaque psoriasis indicated for patients who are candidates for systemic therapy or phototherapy and have failed to respond to other systemic therapies. It is a human interleukin-17 receptor A antagonist that works by blocking cytokine responses and preventing the release of pro-inflammatory chemokines precipitating psoriasis. The recommended dose of SILIQ is 210 mg SQ every week for 3 weeks followed by 210 mg every 2 weeks. If there is not an adequate response after 12-16 weeks the medication should be discontinued. This medication was approved based on multiple trials that included 2915 patients in four different countries. These clinical trials showed that brodalumab was better than the placebo in improving symptoms and maintaining this level for an entire year. Some serious side effects of this medication include suicidal thoughts/behavior and infections. Because of the nature of this medication and the suicidal risk, patients need to enroll in the SILIQ REMS Program.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761032lbl.pdf

https://jamanetwork-com.jerome.stjohns.edu/journals/jama/fullarticle/2614167

https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-siliq

Another option is PUVA which is psoralen plus ultraviolet A therapy. This involves the skin being exposed to UVA light as well as using a medication called psoralen as well. The medication helps the skin react better to the UVA light and makes the therapy more effective. Psoralen is available as a tablet, gel or cream. Topical PUVA is when you apply either as a lotion or soaking in a bath. Oral PUVA is taken as a tablet and is helpful is a patient has thick plaques. The therapy treatment can last between 4 weeks to 3 months. Some possible side effects of UV light therapy could be dry and itchy skin, cold sores, or red patches. These can be treated by applying moisturizer to the skin after the treatment or sunscreen before the treatment. Nausea and vomiting can occur when taking psoralen for PUVA therapy as well, but you can take this medicine as a bath solution instead. Light therapy is shown to have promising effects. In about 50 to 90 out of 100 people, it is shown to have improved symptoms.

https://www.ncbi.nlm.nih.gov/books/NBK435696/

https://www.aad.org/public/diseases/psoriasis/treatment/medications/phototherapy

https://www.medicalnewstoday.com/articles/323593#types-of-light-therapy

Ustekinumab, also known as Stelara, is a human monoclonal antibody, which targets interleukin 12 and 23. Ustekinumab is indicated for the treatment of adults and children 12 years and up that have moderate to severe psoriasis. Ustekinumab by inhibiting IL-12 and IL-23, the autoimmune response that causes the effects of psoriasis are prevented. The biological responses affected include the proinflammatory cytokines; natural killer (NK) cell activation, CD4+ T-cell differentiation and activation. Ustekinumab also interferes with the expression of monocyte chemotactic protein-1, tumor necrosis factor-alpha, interferon-inducible protein-10, and interleukin-8. These patients must also be candidates for phototherapy or systemic therapy. Ustekinumab is a subcutaneous injection and the dosing is weight based. The dosing for adults ≤100 kg is 45 mg on the first week, fourth week and every 12 weeks thereafter. For adults who weigh more than 100 kg, A dose of 90 mg is given with same regimen. As for pediatric patients less than 60 kg, the initial dose is 0.75 mg/kg for the first week, fourth weeks, followed by a maintenance dose of 0.75 mg/kg every 12 weeks after. For pediatric patients between ≥60 to ≤100 kg, the initial dose is 45 mg with the same time regimen. Patients greater than 100kg should receive 90 mg with the same time regimen.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761044lbl.pdf

https://www.ncbi.nlm.nih.gov/pubmed/30772098?dopt=Abstract

Excimer laser therapy is a special type of therapy that is for specific parts of the skin. It can administer higher doses of UVB. Some side effects include blistering, burns, and pigment changes. Compared to the narrow band UV therapy, the excimer laser therapy has shown to give less number of treatment sessions and smaller UVB exposure to the patient. This reduces a skin cancer risk to the patient and gives a great benefit to this therapy. Some types of psoriasis which excimer laser therapy is great for is scalp, nail, palmoplantar psoriasis. This therapy is also beneficial in combination with other medications such as clobetasol propionate spray and calcitriol ointment.

https://www.uptodate.com/contents/treatment-of-psoriasis-in-adults#H26

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683125/