PSORIASIS AND PSORIATIC ARTHRITIS

---

• Psoriasis affects approximately 3% of the U.S. population and 125 million people worldwide. The incidence is bimodal, with peaks occurring between 18 and 39 and 50 and 69 years. Men and women are affected equally, and lighter skin tones are affected more than darker ones.
• Psoriatic arthritis is prevalent among 0.1 - 0.2% of the population. It mostly affects people with psoriasis, who have a lifetime risk of 30%. However, up to 20% of patients with psoriatic arthritis do not exhibit skin symptoms. [1,2]

---

• Psoriasis
• Family history (most important) - Risk is as high as 40% with two affected parents, 14% with one affected parent, and 6% with an affected siblingd
• Inflammatory bowel disease (IBD) - Psoriasis affects 6 - 10% of people with IBD


• Psoriatic arthritis
• Severe psoriasis
• Obesity
• Scalp, genital, and intertriginous psoriasis
• Nail disease
• Deep lesions at sites of trauma


• Psoriasis triggers
• Stress
• Skin trauma
• Upper respiratory infections - upper respiratory infections like strep throat often precede the onset of guttate psoriasis
• Weather: dry and cold weather may worsen psoriasis
• Certain foods and alcohol (less common) [1,2,3]

---

• Psoriasis

• Plaque psoriasis - plaque psoriasis is the most common type of psoriasis, comprising 80 - 90% of all cases. It presents as well-circumscribed, itchy, scaly pink-to-red plaques ranging in size from < 1 cm to many inches wide. The scalp, trunk, gluteal fold, and extensor surfaces of the elbows and knees are most commonly affected. Lesions can also develop at sites of trauma (e.g., scratching, cuts, pressure), something known as the Koebner phenomenon. Psoriasis that occurs in the intertriginous areas (also called inverse psoriasis) often lacks the characteristic scaly appearance and is sometimes misdiagnosed as tinea. Genital psoriasis occurs in about one-third of affected individuals. Nail disease, seen in 40 - 50% of patients, causes pitting, onycholysis (separation of the nail plate from the nail bed), and dystrophy. [1,3]
• Plaque psoriasis images
• Inverse psoriasis (intertriginous) images
• Psoriatic nail images

• Guttate psoriasis - guttate psoriasis, which accounts for 2 - 8% of psoriasis cases, is characterized by the sudden appearance of small (3 - 5 mm), round, pink papules that are sometimes scaly. They have a scattered appearance and typically occur on the arms, legs, and torso; however, the face, scalp, and ears can also be affected. Guttate psoriasis is preceded by an upper respiratory infection in 66% of cases, typically strep throat. Most cases resolve spontaneously in weeks to months. However, it can become chronic, requiring treatment. [1,3]
• Guttate psoriasis images

• Pustular psoriasis - pustular psoriasis, which accounts for approximately 3% of psoriasis cases, is characterized by white, fluid-filled bumps surrounded by red or discolored skin. It may be generalized or localized. The localized type is typically confined to the hands and feet, while the generalized type is marked by acute widespread pustular eruptions that often coalesce to form large areas of weeping scaly skin. Episodes are typically recurrent and may be triggered by medications (e.g., lithium, aspirin, indomethacin, iodide), the sudden withdrawal of corticosteroids, pregnancy, hypocalcemia, and infections. Severe generalized pustular psoriases (GPP) can cause septic shock and cardiorespiratory failure and has a mortality of 2 - 16%. Pustular psoriasis is caused by genetic abnormalities in interleukin-36 (IL-36) receptor antagonist signaling. Spevigo (spesolimab-sbzo), an antibody that binds IL-36 receptors and inhibits their signaling, was FDA-approved to treat GPP in 2022. [Spevigo PI] [1,3,11]
• Generalized pustular psoriasis images
• Palmar and plantar pustular psoriasis images

• Erythrodermic psoriasis - erythrodermic psoriasis is a rare, severe form of psoriasis that is marked by intense redness and shedding of the skin over large parts of the body. It can be fatal if not treated promptly. Erythrodermic psoriasis triggers include allergic reactions to medications and infections. [1,3]
• Erythrodermic psoriasis images

• Psoriatic arthritis
• The diagnosis of psoriatic arthritis is based on a constellation of symptoms, including the following:


• Psoriasis - psoriasis typically precedes the onset of psoriatic arthritis by an average of 10 years. In 15% of patients, the rash and arthritis appear simultaneously, or the arthritis precedes the rash.
• Arthritis - psoriatic arthritis is typically asymmetric and involves ≤ 4 joints. Unlike rheumatoid arthritis, the distal joints of the fingers and toes are commonly affected, and every joint in a digit may be affected while other digits are completely spared. Spine involvement and sacroiliitis are common (50% of patients). On X-ray, joint disease is marked by bone loss, joint-space narrowing, eccentric erosions, and periosteal new bone formation (e.g., ankylosis, enthesophytes) that does not include osteophytes.
• Psoriatic nail disease - psoriatic nail disease (e.g., pitting, onycholysis) is present in 80 - 90% of patients with psoriatic arthritis
• Enthesitis - enthesitis, inflammation where a tendon or ligament attaches to a bone, is seen in 30 - 50% of patients, with the plantar fascia and Achilles' tendon being most commonly affected.
• Dactylitis - dactylitis, acute or chronic swelling of an entire toe or finger, is seen in 40% - 50% of patients. Toes, particularly the second one, are more commonly affected than fingers. Dactylitis is associated with a more severe disease course. [1,2]

---

• Psoriasis
• The pathology behind psoriasis is complex and not completely understood. The following processes are believed to represent the major steps in its development.
• Plasmacytoid dendritic cells, macrophages, and natural killer T cells become inappropriately activated in the dermis, causing them to secrete inflammatory cytokines (e.g., TNF, Interferon, Interleukin)
• Inflammatory cytokines stimulate dermal dendritic cells to migrate to lymph nodes where they release IL-12 and IL-23
• IL-12 and IL-23 stimulate naïve T cells to differentiate into subtypes 1, 17, and 22
• T-helper 17 cells secrete IL-17, which, along with other inflammatory mediators, stimulates keratinocyte hyperproliferation, recruits immune cells into the dermis, induces the secretion of other inflammatory mediators, and stimulates angiogenesis.


• Psoriatic arthritis
• Psoriatic arthritis develops when the abnormal signaling and immune stimulation present in psoriasis progresses to involve joint synovial tissue and the surrounding bone [1,2]

---

• Psoriasis
• Psoriasis is typically diagnosed by the presence of the characteristic rash. If the diagnosis is uncertain, a biopsy can be performed. Other conditions to consider when diagnosing psoriasis include:
• Atopic dermatitis
• Seborrheic dermatitis
• Pityriasis rosea (may appear similar to guttate psoriasis)
• Syphilis (may appear similar to palmar and plantar pustular psoriasis)
• Cutaneous T-cell lymphoma [1]

• Psoriatic arthritis (PsA)
• No psoriatic arthritis diagnostic criteria have been published or endorsed by major professional organizations. The condition also lacks a defining laboratory or pathognomonic feature. Therefore, most experts use the Classification Criteria for Psoriatic Arthritis (CASPAR), a tool published in 2006 that is widely used when enrolling patients in PsA trials. The criteria are presented in the table below, and an online calculator is available here - CASPAR online calculator. [1,2]

---

• Psoriatic arthritis
• ACR/NPF 2018 PsA treatment guidelines are presented in the table below. The guidelines divide patients into treatment-naïve and those who have failed previous therapy. Most of the recommendations are based on "low" to "very low" evidence and were published before newer therapies were approved (e.g., Janus kinase inhibitors). See biologics and nonbiologic systemic therapies for more.

• Reference [10]

2018 ACR/NPF Recommendations for the Treatment of Psoriatic Arthritis
Therapy classes Oral small molecules✝ Methotrexate Sulfasalazine Cyclosporine Leflunomide Apremilast TNF inhibitors Etanercept Infliximab Adalimumab Golimumab Certolizumab IL-12/23 inhibitor Ustekinumab IL-17 inhibitors Secukinumab Ixekizumab T-cell agent Abatacept Janus kinase inhibitor Tofacitinib Upadacitinib (Rinvoq®) ✝Only apremilast is FDA-approved to treat psoriatic arthritis
All patients Weight loss if overweight Exercise Smoking cessation
Treatment-naïve patients TNF inhibitor (first-line) Oral small molecule (second-line) IL-17 inhibitor (third-line) IL-12/23 inhibitor (fourth-line)
TNF inhibitor failure Switch to different TNF inhibitor (first-line) IL-17 inhibitor (second-line) IL-12/23 inhibitor (third-line)
Oral small molecule failure TNF inhibitor (first-line) IL-17 inhibitor (second-line) IL-12/23 inhibitor (third-line)
IL-17 failure TNF inhibitor (first-line) IL-12/23 inhibitor (second-line)
IL-12/23 failure TNF inhibitor (first-line) IL-17 inhibitor (second-line)
TNF inhibitor + MTX failure Switch to different TNF inhibitor + MTX IL-17 inhibitor monotherapy IL-12/23 inhibitor monotherapy

• Disease categories
• Psoriasis disease severity is often categorized as low, moderate, or severe. While definitions for these categories can vary, body surface area (BSA) affected, as described below, is frequently used.
• Psoriasis categories based on body surface area (BSA):
• Mild psoriasis: < 3% of BSA
• Moderate psoriasis: 3 - 10% of BSA
• Severe psoriasis: > 10% of BSA
• Body surface area of 1% = Surface area of the palmar surface of an individual's hand

• AAD/NPF plaque psoriasis treatment recommendations
• The AAD/NPF psoriasis guidelines divide psoriasis therapy into 4 categories: topical, phototherapy, biologics, and nonbiologic systemic therapies. The guidelines state that most cases of mild to moderate psoriasis can be controlled with topical medications or phototherapy, while moderate to severe cases may require biologic or nonbiologic systemic therapy. The topical therapy guidelines provided below give some specifics on treatment approaches, but the biologic and nonbiologic guidelines are mainly a review of available therapies and do not recommend one treatment over another.
• Therapy choices in psoriasis should be individualized and take into account disease severity, disease location, medication access, costs, and patient motivation

• ^✝Steroid-sparing agents include vitamin D analogues, topical retinoids, and calcineurin inhibitors
• Reference [7]

AAD / NPF 2020 Recommendations for Topical Therapy in Plaque Psoriasis
Acute therapy Steroids and vitamin D analogues Class 1 - 5 topical steroids twice daily (see topical steroid table) for up to 4 weeks is recommended. Topical steroids for > 12 weeks can be considered if under close supervision of a physician. Use of combination treatments with vitamin D analogues and potent Class II and Class III topical steroids up to 52 weeks is recommended for the treatment of psoriasis The application of morning high potency topical steroids and evening topical vitamin D analogues is an effective treatment regimen Tacrolimus The combination of Tacrolimus 0.1% and 6% salicylic acid for 12 weeks may be considered Tazarotene Topical tazarotene can be used for the treatment of mild to moderate psoriasis. The use of mid-potency or high-potency topical steroid in combination with tazarotene for 8 - 16 weeks is more effective than monotherapy with tazarotene and is recommended for the treatment of mild to moderate psoriasis. The use of topical steroids along with tazarotene is recommended to decrease the duration of treatment as well as increase the length of remission Salicylic acid Topical salicylic acid can be used for 8 - 16 weeks for the treatment of mild to moderate psoriasis The combination of salicylic acid with topical corticosteroids can be used for the treatment of moderate to severe psoriasis (BSA ≤ 20%) Other Non-medicated moisturizers (i.e., creams, ointments, lotions, gels, etc.) can be used with steroids to help reduce itching, desquamation, and total body surface area and prevent quick relapse of psoriasis when topical corticosteroids are discontinued Coal tar preparations are recommended for the treatment of mild to moderate psoriasis
Maintenance therapy regimens Steroid-sparing agent✝ twice daily on weekdays and steroid twice daily on weekends is one regimen that may prevent relapses. Twice weekly treatment of areas that are prone to flares is another approach that may be effective. The long-term use of topical vitamin D analogues (up to 52 weeks) including calcipotriene, calcitriol, tacalcitol, and maxacalcitol is recommended for the treatment of mild to moderate psoriasis. Tacalcitol and maxacalcitol are not available in the U.S.
Scalp psoriasis Class 1 - 7 topical steroids (see topical steroid table) for a minimum of up to 4 weeks is recommended as initial and maintenance treatment of scalp psoriasis Use of calcipotriene foam and calcipotriene plus betamethasone dipropionate gel is recommended for 4 - 12 weeks for the treatment of mild to moderate scalp psoriasis Foams and solutions may be preferred on the scalp because they are less greasy than ointments and creams
Intertriginous (inverse) psoriasis Tacrolimus 0.1% or Pimecrolimus 1% for up to 8 weeks. Long-term use can be considered.
Facial psoriasis Tacrolimus 0.1% for up to 8 weeks Topical tacalcitol ointment or calcipotriene combined with hydrocortisone for 8 weeks can be used for the treatment of facial psoriasis
Nail psoriasis Topical vitamin D analogues combined with betamethasone dipropionate can be used Topical tazarotene can be used for the treatment of nail psoriasis
Topical therapies in combination with systemic therapy Biologics The addition of an ultra-high potency (Class 1) topical corticosteroid to standard dose etanercept for 12 weeks is recommended for the treatment of moderate to severe psoriasis The addition of calcipotriene/betamethasone to standard dose adalimumab for 16 weeks is recommended for the treatment of moderate to severe psoriasis to accelerate clearance of psoriatic plaques All topical steroids can be used in combination with any biologics for the treatment of moderate to severe psoriasis Methotrexate The addition of topical calcipotriene to standard dose methotrexate therapy is recommended for the treatment of moderate to severe psoriasis. It may lead to lower cumulative doses of methotrexate and increased time to relapse following methotrexate discontinuation. Cyclosporine The addition of calcipotriene/betamethasone dipropionate ointment to low dose (2 mg/kg/day) cyclosporine can be used for the treatment of moderate to severe psoriasis Acitretin The addition of calcipotriene to standard dose acitretin is recommended for the treatment of moderate to severe psoriasis.

---

---

Non-FDA-approved Systemic Therapies for Plaque Psoriasis (PP) and Psoriatic Arthritis (PsA)
Dimethyl fumarate The AAD/NPF guidelines list dimethyl fumarate, a nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activator approved to treat multiple sclerosis, as a possible PP treatment. A small study comparing it to placebo is available here - PMID 27515097
Azathioprine The AAD/NPF guidelines list azathioprine, a ribonucleotide synthesis inhibitor, as a possible PP treatment. They recommend a starting dose of 0.5 mg/kg and state that the usual dose in psoriasis is 75 - 150 mg/day.
Leflunomide The AAD/NPF guidelines list leflunomide, an immunosuppressant approved for rheumatoid arthritis, as a possible PP treatment. The ACR/NPF guidelines also list it as a possible PsA therapy. A study comparing it to placebo for PP and PsA is available here - PMID 15188371
Sulfasalazine The ACR/NPF guidelines list sulfasalazine, an immunosuppressant primarily used to treat ulcerative colitis, as a possible PsA treatment. Studies comparing it to placebo for PsA are available here - PMID 8670601, PMID 8587078, PMID 8961906
Hydroxyurea The AAD/NPF guidelines list hydroxyurea, an antineoplastic agent used to treat sickle cell disease, as a possible PP treatment. They recommend starting with 500 mg twice daily, with titration to 1500 mg/day as tolerated.

---

• Phototherapy has been used for decades to treat psoriasis. However, its use has declined with the advent of highly effective biological therapies. UV light has the following anti-psoriasis actions: (1) induction of keratinocyte apoptosis, (2) inhibition of angiogenesis, and (3) reduction in cutaneous T-cells. Phototherapy machines deliver therapeutic UV wavelengths while limiting carcinogenic ones. Treatments, which can be targeted or full-body, are typically performed 2 to 3 times a week in a healthcare office or at home. UV-B machines are generally preferred, but UV-A in combination with topical psoralen (PUVA therapy) is also utilized. [1,3]

---

• 1 - PMID 29893227 - Pathophysiology, Clinical Presentation, and Treatment of Psoriasis, JAMA (2020)
• 2 - PMID 28273019 - Psoriatic Arthritis, NEJM (2017)
• 3 - National Psoriasis Foundation website
• 4 - PMID 15222650 - Spondyloarthropathies, Am Fam Physician, (2004)
• 5 - Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy, Medscape
• 6 - Reactive arthritis, Medscape
• 7 - PMID 32738429 - Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures, J Am Acad Dermatol (2020)
• 8 - PMID 30772098 - Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics, J Am Acad Dermatol (2019)
• 9 - PMID 32119894 - Joint American Academy of Dermatology/National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies, J Am Acad Dermatol (2020)
• 10 - PMID 30499246 - 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis, Arthritis Rheumatol (2019)
• 11 - PMID 34936739 - Trial of Spesolimab for Generalized Pustular Psoriasis, NEJM (2021)