- ACRONYMS AND DEFINITIONS
- AAD - American Academy of Dermatology
- ACR - American College of Rheumatology
- IL - Interleukin
- MTX - Methotrexate
- NPF - National Psoriasis Foundation
- PA - Psoriatic arthritis
- PASI - Psoriasis area and severity index
- PP - Plaque psoriasis
- RA - Rheumatoid arthritis
- RCT - Randomized controlled trial
- RF - Rheumatoid factors
- TNF - Tumor necrosis factor
- ULN - Upper limit of normal
- EPIDEMIOLOGY
- Psoriasis affects approximately 3% of the U.S. population. Worldwide, around 125 million people have psoriasis. Men and women are affected equally, and there is a bimodal peak age of incidence at 18 - 39 years and 50 - 69 years.
- Psoriatic arthritis is thought to affect up to 30% of patients with psoriasis. It's prevalence in the general population is 0.1 - 0.2%, and it has an annual incidence of 2 - 3% among patients with psoriasis. [1,2]
- RISK FACTORS
- Psoriasis
- Family history (most important) - risk is as high as 40% with two affected parents, 14% with one affected parent, and 6% if a sibling is affected
- Inflammatory bowel disease - the prevalence of psoriasis is much higher in patients with inflammatory bowel disease
- 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]
- TYPES AND SYMPTOMS
- Psoriasis
- Plaque psoriasis - plaque psoriasis is the most common type of psoriasis comprising 80 - 90% of all psoriasis cases. Plaque psoriasis presents as well circumscribed, itchy, scaly pink-to-red plaques that can range 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 1/3 of affected individuals. Nail disease causes pitting, onycholysis (separation of the nail plate from the nail bed), and dystrophy. [1,3]
- Guttate psoriasis - guttate psoriasis accounts for 2 - 8% of psoriasis cases. Guttate psoriasis 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 after weeks to months, but it can become a chronic condition that requires treatment. [1,3]
- Pustular psoriasis - pustular psoriasis accounts for about 3% of psoriasis cases and is characterized by white, fluid-filled bumps surrounded by red or discolored skin. Pustular psoriasis may be generalized or localized. The localized type is typically confined to the hands and feet, where generalized pustular psoriasis (GPP) is marked by acute widespread eruptions of pustules 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. In severe GPP, septic shock and cardiorespiratory failure can occur with a mortality of 2 - 16%. The underlying pathology in pustular psoriasis is genetic abnormalities in interleukin-36 (IL-36) receptor antagonist signaling. In 2022, a drug called Spevigo (spesolimab-sbzo) was FDA-approved to treat GPP. Spevigo is an antibody that binds IL-36 receptors, inhibiting their signaling. [Spevigo PI] [1,3,11]
- Erythrodermic psoriasis - erythrodermic psoriasis is a very 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. Triggers of erythrodermic psoriasis include allergic reactions to medications and infections. [1,3]
- Psoriatic arthritis
- There is no single clinical or laboratory finding that definitively establishes a diagnosis of psoriatic arthritis, so it is important to distinguish psoriatic arthritis from other types of arthritis (see arthritis differential below). The diagnosis is based on a constellation of symptoms and clinical features that are discussed below.
- Psoriasis - psoriasis typically precedes the onset of psoriatic arthritis by an average of 10 years. In about 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 seen in 80 - 90% of patients with psoriatic arthritis
- Enthesitis - enthesitis is inflammation of the site where a tendon or ligament inserts on a bone. It is seen in 30 - 50% of patients with psoriatic arthritis, and the plantar fascia and Achilles' tendon are most commonly affected.
- Dactylitis - dactylitis is diffuse swelling of a toe or finger. Dactylitis may be acute or chronic, and it is seen in 40 - 50% of patients with psoriatic arthritis. The third and fourth toes are most commonly affected, but it also occurs in the fingers. Dactylitis is associated with a more severe disease course. [1,2]
- PATHOLOGY
- Psoriasis
- The pathology behind psoriasis is complex and not completely understood. In short, the steps listed below are believed to represent the major processes by which the disease occurs.
- 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 the other inflammatory mediators, stimulates keratinocytes to divide, promotes recruitment of immune cells into the dermis, and propagates inflammation
- Psoriatic arthritis
- In psoriatic arthritis, the abnormal signaling and immune stimulation that occurs in psoriasis progresses to involve joint synovial tissue and the surrounding bone [1,2]
- DIAGNOSIS
- Psoriasis
- Psoriasis is typically diagnosed clinically by the appearance of the characteristic rash. If clinical diagnosis is uncertain, a biopsy can be performed. Other conditions to consider when diagnosing psoriasis include the following:
- 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
- No diagnostic criteria for psoriatic arthritis have been published or endorsed by major professional organizations. The condition also lacks a defining laboratory or pathognomonic feature. Given this, most experts use the Classification Criteria for Psoriatic Arthritis (CASPAR) which is a set of criteria that was published in 2006 and is widely used when enrolling patients in clinical trials. The CASPAR criteria are presented in the table below. An online calculator for the criteria is available here - CASPAR online calculator. Other arthritis syndromes (see differential below) should be excluded when considering a diagnosis of psoriatic arthritis. [1,2]
CASPAR Criteria for Diagnosing Psoriatic Arthritis | ||
---|---|---|
|
||
Criteria | Finding | Points |
Psoriasis |
|
2 |
|
1 | |
|
1 | |
Psoriatic nail dystrophy |
|
1 |
Negative rheumatoid factor |
|
1 |
Dactylitis |
|
1 |
|
1 | |
Juxtaarticular new bone formation |
|
1 |
Features of Different Arthritis Syndromes | |||||||
---|---|---|---|---|---|---|---|
Finding | Psoriatic arthritis | Rheumatoid arthritis | Lupus | Gout | Ankylosing spondylitis | Reactive arthritis | IBD-associated arthritis |
Age of onset Male:Female |
30 - 40s 1:1 |
35 - 50s 1:3 |
20 - 30s 1:9 |
30 - 60s 3:1 |
17 - 30s 3:1 |
20 - 30s 5:1 |
30s 2:1 |
Distal joints |
Fingers and toes including DIP Asymmetric ≤ 4 joints |
Fingers and toes, spares DIP Symmetric > 4 joints |
Hands, wrists, knees Symmetric > 4 joints |
Great toe, foot, ankle, knees, elbow Asymmetric < 4 joints |
Lower limbs (30 - 50%) Asymmetric < 4 joints |
Knees, ankles, hips Asymmetric < 4 joints |
Hands and knees Asymmetric |
Spine disease | Axial joints - 50% Sacroiliitis - 40% |
Uncommon | Uncommon | Absent | 100% | Sacroiliitis - 50% Back pain - 50% |
30% |
Enthesitis | 30 - 50%, Plantar fascia and Achilles's tendon | Absent | Absent | Absent | Common | Common, Achilles tendon and plantar fascia | Uncommon |
Dactylitis | 40 - 50% | Absent | Absent | Uncommon | Uncommon | Common | Absent |
HLA-B27 positive | 40 - 50% | Not associated | Not associated | Not associated | 90 - 95% | 75% | 30% |
Eye disease | Uveitis - 8% | Dry eyes - 20% | Dry eyes - 15% | Absent | Uveitis - up to 30% | Conjunctivitis (common) Anterior uveitis - 25% |
Uveitis - up to 7% |
Other features | Psoriasis - 100% Nail disease - 85% |
Positive RF and Anti-CCP | Positive ANA Joint disease is non-erosive |
Elevated uric acid | Primarily affects the spine and pelvis | ✝Preceding infection Urethritis (common) Self-limited - 80% |
Occurs in 10 - 20% of patients with IBD |
- TREATMENT
Psoriatic arthritis drugs | |
---|---|
Biologicals
|
Immunosuppressants
|
- Psoriatic arthritis
- The ACR/NPF published guidelines on the treatment of psoriatic arthritis in 2018. The guidelines divide patients into treatment-naïve and those who are already receiving therapy. Most of the recommendations are based on "low" to "very low" evidence, and they don't offer much guidance beyond the fact that TNF inhibitors are the recommended first-line biologic followed by IL-17 inhibitors and IL-12/23 inhibitors. The table below outlines the major points from the guideline. See biologics and nonbiologic systemic therapies below for a review of the different therapies.
2018 ACR/NPF Recommendations for the Treatment of Psoriatic Arthritis | ||||
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Therapy classes
|
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All patients
|
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Treatment-naïve patients
|
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TNF inhibitor failure
|
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Oral small molecule failure
|
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IL-17 failure
|
||||
IL-12/23 failure
|
||||
TNF inhibitor + MTX failure
|
Psoriasis drugs | |
---|---|
Biologicals
|
Immunosuppressants
|
- AAD/NPF 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 and that patients with moderate to severe psoriasis may require a biologic or nonbiologic systemic therapy. The topical therapy guidelines give some specifics on treatment approaches, but the biologic and nonbiologic guidelines are mainly a review of available therapies, and they 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
- Disease categories
- In psoriasis, disease severity is often categorized as low, moderate, or severe, but the specifics that define these classes are inconsistent across the medical literature. Body surface area (BSA) affected is one of the more common methods for categorizing patients, and it is defined below.
- 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

- TOPICAL THERAPY
- Overview
- The AAD/NPF guidelines for the topical treatment of psoriasis are presented in the table below. The guidelines do not recommend one therapy over another, but they do offer some guidance in treating different types of psoriasis.
AAD / NPF 2020 Guidelines for Topical Therapy in Psoriasis |
---|
Plaque psoriasis
|
Maintenance therapy regimens
|
Scalp psoriasis
|
Intertriginous (inverse) psoriasis
|
Facial psoriasis
|
Nail psoriasis
|
In combination with systemic therapies
|
- BIOLOGIC THERAPY
- Overview
- Biologic therapies have revolutionized the treatment of psoriasis. Four classes of biologics are approved to treat psoriasis, and five classes are approved to treat psoriatic arthritis. The table below lists each biologic by class and includes results from studies where the drug was compared to placebo and other therapies if available. Endpoints in psoriasis trials are typically measured by improvement in the Psoriasis Area and Severity Index (PASI). The index is explained here - PASI score explanation - and an online calculator is available here - PASI online calculator. Endpoints in psoriatic arthritis trials typically use the ACR20 response which is explained here - ACR20 response.
Biologics for the Treatment of Plaque Psoriasis (PP) and Psoriatic Arthritis (PA) | ||
---|---|---|
Drug | PP/PA approved | Effect (PP: 75% or 90% improvement in PASI | PA: ACR20 response) |
TNF inhibitors | ||
Adalimumab (Humira®) | PP / PA |
PP: Placebo - 7%, Adalimumab - 71% (16 weeks) [PMID 17936411] PP: MTX - 35.5%, Adalimumab - 80% (16 weeks) [PMID 18047523] PP: Guselkumab - 79%, Adalimumab - 70% (16 weeks) [PMID 26154787] PP: Risankizumab - 91%, Adalimumab - 72% (16 weeks) [PMID 31280967] PA: Placebo - 14%, Adalimumab - 58% (12 weeks) [PMID 16200601] PA: Ixekizumab - 57.9%, Adalimumab - 57.4% (24 weeks) [PMID 27553214] PA: Tofacitinib - 50%, Adalimumab - 52% (3 months) [PMID 29045212] PA: Upadacitinib - 71%, Placebo - 36%, Adalimumab - 65% (12 weeks) [PMID 33789011] |
Certolizumab (Cimzia®) | PP / PA |
PP: Placebo - 9.9%, Certolizumab - 82% (16 weeks) [PMID 29660421] PP: Etanercept - 53.3%, Certolizumab - 66.7% (12 weeks) [PMID 29660425] PA: Placebo - 24.3%, Certolizumab - 58% (12 weeks) [PMID 23942868] |
Etanercept (Enbrel®) | PP / PA |
PP: Placebo - 4%, Etanercept - 49% (12 weeks) [PMID 14627786] PP: Secukinumab - 77.1%, Etanercept - 44% (12 weeks) [PMID 25007392] PP: Tofacitinib (5 mg) - 39.5%, Tofacitinib (10 mg) - 63.6%, Etanercept - 58.8% (12 weeks) [PMID 26051365] PP: Ixekizumab - 89.7%, Etanercept - 41.6% (12 weeks) [PMID 26072109] PP: Infliximab - 72%, Etanercept - 35% (24 weeks) [PMID 27416891] PP: Tildrakizumab - 61%, Etanercept - 48% (12 weeks) [PMID 28596043] PP: Certolizumab - 66.7%, Etanercept - 53.3% (12 weeks) [PMID 29660425] PP: Apremilast - 39.8%, Etanercept - 48.2% (16 weeks) [PMID 27768242] PA: Placebo - 15%, Etanercept - 59% (12 weeks) [PMID 15248226] PA: MTX - 50.7%, Etanercept - 60.9%, Etanercept + MTX - 65% (24 weeks) [PMID 30747501] |
Golimumab (Simponi®) | PA | PA: Placebo - 9%, Golimumab - 51% (14 weeks) [PMID 19333944] |
Infliximab (Remicade®) | PP / PA |
PP: Placebo - 6%, Infliximab - 88% (10 weeks) [PMID 15389187] PP: MTX - 42%, Infliximab - 78% (16 weeks) [PMID 21910713] PP: Etanercept - 35%, Infliximab - 72% (24 weeks) [PMID 27416891] PA: Placebo - 11%, Infliximab - 58% (14 weeks) [PMID 15677701] |
Interleukin-17 inhibitors | ||
Brodalumab (Siliq®) | PP | PP: Placebo - 3%, Brodalumab - 83% (12 weeks) [PMID 26914406] |
Ixekizumab (Taltz®) | PP / PA |
PP: Placebo - 2.4%, Ixekizumab - 89.7% (12 weeks) [PMID 26072109] PP: Etanercept - 41.6%, Ixekizumab - 89.7% (12 weeks) [PMID 26072109] PP: Ustekinumab - 59%, Ixekizumab - 76.5% (52 weeks) [PMID 29969700] PA: Placebo - 30.2%, Ixekizumab - 57.9% (24 weeks) [PMID 27553214] PA: Adalimumab - 57.4%, Ixekizumab - 57.9% (24 weeks) [PMID 27553214] |
Secukinumab (Cosentyx®) | PP / PA |
PP: Placebo - 4.5%, Secukinumab - 81.6% (12 weeks) [PMID 25007392] PP: Etanercept - 44%, Secukinumab - 77.1% (12 weeks) [PMID 25007392] PP: Ustekinumab - 57.6%, Secukinumab - 79% (16 weeks) [PMID 26092291] PP: Guselkumab - 84%, Secukinumab - 70% (48 weeks) [PMID 31402114] PA: Placebo - 15%, Secukinumab - 54% (24 weeks) [PMID 26135703] PA: Adalimumab - 62%, Secukinumab - 67% (52 weeks) [PMID 32386593] |
Interleukin-23 inhibitors | ||
Guselkumab (Tremfya®) | PP / PA |
PP: Placebo - 5%, Guselkumab - 79% (16 weeks) [PMID 26154787] PP: Adalimumab - 70%, Guselkumab - 79% (16 weeks) [PMID 26154787] PP: Secukinumab - 70%, Guselkumab - 84% (48 weeks) [PMID 31402114] PA: Placebo - 18%, Guselkumab - 58% (24 weeks) [PMID 29893222] |
Risankizumab (Skyrizi®) | PP / PA |
PP: Placebo - 4.9%, Risankizumab - 75% (16 weeks) [PMID 30097359] PP: Ustekinumab - 42%, Risankizumab - 75% (16 weeks) [PMID 30097359] PP: Adalimumab - 72%, Risankizumab - 91% (16 weeks) [PMID 31280967] PA: Placebo - 34%, Risankizumab - 57% (24 weeks) [PMID 34911706] |
Tildrakizumab (Ilumya®) | PP |
PP: Placebo - 6%, Tildrakizumab - 61% (12 weeks) [PMID 28596043] PP: Etanercept - 48%, Tildrakizumab - 61% (12 weeks) [PMID 28596043] |
Interleukin-12/23 inhibitor | ||
Ustekinumab (Stelara®) | PP / PA |
PP: Placebo - 4.9%, Ustekinumab - 42% (16 weeks) [PMID 30097359] PP: Risankizumab - 75%, Ustekinumab - 42% (16 weeks) [PMID 30097359] PP: Ixekizumab - 76.5%, Ustekinumab - 59% (52 weeks) [PMID 29969700] PP: Secukinumab - 79%, Ustekinumab - 57.6% (16 weeks) [PMID 26092291] PA: Placebo - 14%, Ustekinumab - 42% (12 weeks) [PMID 19217154] |
T-cell agent | ||
Abatacept (Orencia®) | PA |
PA: Placebo - 22.3%, Abatacept - 39.4% (24 weeks) [PMID 28473423] |
- NONBIOLOGIC SYSTEMIC THERAPY
- Overview
- Some nonbiologic systemic therapies have been used for many years to treat psoriasis and psoriatic arthritis (e.g. methotrexate, cyclosporine, acitretin) while others have only become available recently (e.g. apremilast, tofacitinib). Nonbiologic therapies have largely been replaced by biologics which are typically less toxic and more effective, but nonbiologics like methotrexate are very cheap and may still be preferred in cost-sensitive patients.
- The table below details the available therapies
Nonbiologic Systemic Therapies for Psoriasis |
---|
FDA-approved therapies |
Methotrexate (MTX)
|
Apremilast (Otezla®)
|
Cyclosporine (Neoral®, Sandimmune®)
|
Tofacitinib (Xeljanz®)
|
Upatacitinib (Rinvoq®)
|
Acitretin (Soriatane®)
|
Non-FDA approved therapies |
Dimethyl fumarate
|
Azathioprine
|
Leflunomide
|
Sulfasalazine
|
Hydroxyurea
|
- PHOTOTHERAPY
- Phototherapy has been used for decades to treat psoriasis, but with the advent of biologic therapies, it is used less frequently today. UV light works by inducing apoptosis in keratinocytes, inhibiting angiogenesis, and decreasing T-cell number in the skin. Phototherapy machines deliver therapeutic wavelengths of light while limiting wavelengths that are carcinogenic. Phototherapy can be targeted if lesions are localized or full body if extensive. Therapy is typically performed 2 - 3 times a week in a healthcare office or at home. UV-B machines are preferred, but UV-A in combination with a topical psoralen (PUVA therapy) can also be used. [1,3]
- BIBLIOGRAPHY
- 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)