Management of Psoriasis and Psoriatic Arthritis in a Multidisciplinary Rheumatology/Dermatology Clinic

Abstract

Early diagnosis, use of newly developed targeted therapies, and a multispecialty approach are essential for the treatment of patients with psoriasis and psoriatic arthritis.

Psoriasis is a commonly encountered systemic condition, usually presenting with chronic erythematous plaques with an overlying silvery white scale.¹ Extracutaneous manifestations, such as joint or spine (axial) involvement, can occur along with this skin disorder. Psoriatic arthritis (PsA) is a chronic, heterogeneous disorder characterized by inflammatory arthritis in patients with psoriasis.^2,3 Until recently treatment of PsA has been limited to a few medications.

Continuing investigations into the pathogenesis of PsA have revealed new treatment options, targeting molecules at the cellular level. Over the past few years, additional medications have been approved, giving providers more options in treating patients with psoriasis and PsA. Furthermore, a multidisciplinary approach by both rheumatologists and dermatologists in evaluating and managing patients at VA clinics has helped optimize care of these patients by providing timely evaluation and treatment at the same visit.

PSORIASIS PRESENTATION AND DIAGNOSIS

Genetic predisposition and certain environmental factors (trauma, infection, medications) are known to trigger psoriasis, which can present in many forms.⁴ Chronic plaque psoriasis, or psoriasis vulgaris, is the most common skin pattern with a classic presentation of sharply demarcated erythematous plaques with overlying silver scale.⁴ It affects the scalp, lower back, umbilicus, genitals, and extensor surfaces of the elbows and knees. Guttate psoriasis is recognized by its multiple small papules and plaques in a droplike pattern. Pustular psoriasis usually presents with widespread pustules. On the other hand, erythrodermic psoriasis manifests as diffuse erythema involving multiple skin areas.⁴ Erythematous psoriatic plaques, which are predominantly in the intertriginous areas or skin folds (inguinal, perineal, genital, intergluteal, axillary, or inframammary), are known as inverse psoriasis.

A psoriasis diagnosis is made by taking a history and a physical examination. Rarely, a skin biopsy of the lesions will be required for an atypical presentation. The course of the disease is unpredictable, variable, and dependent on the type of psoriasis. Psoriasis vulgaris is a chronic condition, whereas guttate psoriasis is often self-limited.⁴ A poorer prognosis is seen in patients with erythrodermic and generalized pustular psoriasis.⁴

PSORIATIC ARTHRITIS PRESENTATION, CLASSIFICATION, AND DIAGNOSIS

Prevalence of PsA is not known, but it is estimated to be from 0.3% to 1% of the U.S. population. In the psoriasis population, PsA is reported to range from 7% to 42%,³ although more recently, these numbers have been found to be in the 15% to 25% range (unpublished observations). This type of inflammatory arthritis can develop at any age but usually is seen between the ages of 30 and 50 years, with men being affected equally or a little more than are women.³ Clinical symptoms usually include pain and stiffness of affected joints, > 30 minutes of morning stiffness, and fatigue.

The presentation of joint involvement can vary widely. Five subtypes of arthritis were identified by Moll and Wright in 1973, which included arthritis with predominant distal interphalangeal involvement, arthritis mutilans, symmetric polyarthritis (> 5 joints), asymmetric oligoarthritis (1–4 joints), and predominant spondylitis (axial).⁵ Patients with PsA may also have evidence of spondylitis (inflammation of vertebra) or sacroiliitis (inflammation of the sacroiliac joints) with back pain > 3 months, hip or buttock pain, nighttime pain, or pain that improves with activity but worsens with rest.⁶ The cervical spine is more frequently involved than is the lumbar spine in patients with PsA.³

Psoriatic arthritis can have a diverse presentation not only with the affected joints, but also involving nails, tendons, and ligaments. An entire digit of the hand or foot can become swollen, known as dactylitis, or “sausage digit.” Inflammation at the insertion of tendons or ligaments, known as enthesitis, is also seen in PsA. Most common sites include the Achilles tendon, plantar fascia, and ligamentous insertions around the pelvic bones.³ Nail changes that are typically seen in patients with psoriasis can be seen in PsA as well, including pitting, ridging, hyperkeratosis, and onycholysis.³ Ocular inflammation, which is classically seen with other spondyloarthropathies, can be seen in patients with PsA as well, frequently manifesting as conjunctivitis.^2,3

Psoriatic arthritis is commonly classified under the broader category of seronegative spondyloarthropathies, given the low frequency of a positive rheumatoid factor.³ Currently, there are no laboratory tests that can help with a PsA diagnosis.³ Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein may be elevated, indicating active inflammation.

Radiographic data, such as X-rays of the hands and feet, can confirm the clinical distribution of joint involvement and show evidence of erosive changes. Further destructive changes include osteolysis (bone resorption) that may cause the classic pencil-in-cup deformity, typically seen in arthritis mutilans (Figure 1).³ Other radiographic evidence of PsA can include proliferative changes with new bone formation seen along the shaft of the metacarpal and metatarsal bones.³ Patients with axial involvement can have evidence of asymmetric sacroiliitis, which can be seen on radiographs. Asymmetric syndesmophytes, or bony outgrowths, can also be seen throughout the axial spine.³

Figure 1.

Radiograph of the Right Hand and Right Foot

Right hand shows advanced narrowing of the second and third distal interphalangeal joints with erosive changes. Classic pencil-in-cup deformity is seen involving an erosion on the base of the fifth distal phalanx and osteolysis of the distal aspect of the fifth middle phalanx. Right foot shows erosive changes involving the tuft and base of the distal phalanx of the first digit as well as erosions of the distal and middle phalanges of the remainder of the toes in a pencil-in-cup deformity.

Diagnosis is based on the history and clinical presentation of a patient with the help of laboratory work and radiographs. Other forms of arthritis (such as rheumatoid arthritis, crystal arthropathies, osteoarthritis, ankylosing spondylitis) should be excluded. Given the varied presentation of PsA, classification criteria have been developed to assist in clinical research. Classification Criteria for Psoriatic Arthritis (CASPAR) have been developed and validated as an adjunct to clinical diagnosis and a source for clinical research (Table 1).⁷ Musculoskeletal pain in patients with psoriasis can be due to causes other than PsA, such as osteoarthritis and gout. A close working relationship in a combined rheumatology/dermatology clinic is vital to providing optimal diagnostic and treatment care for patients with psoriasis and PsA.⁸

Table 1.

Classification Criteria for Psoriatic Arthritis (CASPAR)³,⁴,⁷

Inflammatory articular disease (joint, spine, or enthesis) AND at least 3 points from the following categories: Current psoriasis (2 points), a personal history of psoriasis (1 point), or a family history of psoriasis (1 point) Typical psoriatic nail dystrophy (1 point) Negative rheumatoid factor test (1 point) Dactylitis: current or previous episode noted by a rheumatologist (1 point) Juxta-articular new bone formation on hand or foot radiographs (1 point)

The etiology of PsA is currently unknown, although many genetic, environmental, and immunologic factors have been identified that play a role in the pathogenesis of the disease. In this setting, immunologically mediated processes that cause inflammation occur in the synovium of joints, enthesium, bone, and skin of patients with PsA.⁹ Studies have shown that activated T cells and T-cell–derived cytokines play an important role in cartilage degradation, joint damage, and stimulating bone resorption.⁹

One particular proinflammatory cytokine, tumor necrosis factor alpha (TNFα), has been the target for many treatment modalities for several years. With new and ongoing research into the PsA pathogenesis, other treatment options have been discovered, targeting different cytokines and T cells that are involved in the disease process. This has led to drug trials and recent FDA approvals of several new medications, which provide further options for clinicians in managing and treating PsA.

MANAGEMENT OF PSORIASIS

Choice of therapy is determined by the extent and severity of psoriasis (body surface area [BSA] involvement) as well as the patient’s comorbidities and preferences.⁴ Providers have a wide spectrum of effective therapies to prescribe, both topically and systemically. Topical therapy options include corticosteroids, vitamin D3 and analogs (calcipotriene), anthralin, tar, tazarotene (third-generation retinoid), and calcineurin inhibitors (tacromlimus).⁴ Phototherapy with or without saltwater baths helps improve skin lesions.

These treatments are beneficial for all patients with psoriasis, but the disease can be controlled with monotherapy in patients with mild-to-moderate disease (< 10% BSA). Limiting these treatment options are some long-term effects of the medications because of the potential for toxicity as well as decreasing efficacy of the medication over time.⁴ For patients with more BSA involvement (> 10%), systemic treatment options include methotrexate (MTX), systemic retinoids (acitretin), calcineurin inhibitors (cyclosporine), and biologics. Many of these systemic treatment options overlap for patients with both psoriasis and PsA, and topical treatments can be used adjunctively to better control the skin disease.

MANAGEMENT OF PSORIATIC ARTHRITIS

It is important to identify PsA and begin treatment early, because it has been shown that patients tend to fare better in their disease course if treated early.¹⁰ Once a diagnosis of PsA is made, disease activity needs to be determined by clinical examination and radiographs of joints. Scoring systems, by assessing bone erosions and deformities on joint radiographs, can aide with this assessment. Based on these, PsA can be categorized as mild, moderate, or severe. Several disease activity measures that have been developed for clinical trials in monitoring of disease activity can be used as an aide in the office setting. These tools are still being studied to determine the optimal measure of disease activity.

NSAIDs and Glucocorticoids

Controlling inflammation and providing pain relief are the primary treatment goals for patients with PsA. In mild, predominantly peripheral PsA, nonsteroidal anti-inflammatory drugs (NSAIDs) can be used, but they do not halt disease progression. If the disease is controlled and not progressing, NSAIDs may be used as the only treatment. However, if symptoms persist and/or there is more joint involvement, the next level of therapy should be sought. Intra-articular corticosteroids for symptomatic relief can be given if only a few joints are affected. Oral corticosteroids can be used occasionally in patients with multiple joint aches, but they are typically avoided or tapered slowly to avoid worsening the patient’s skin psoriasis or having it evolve into a more severe form, such as pustular psoriasis.¹⁰ All these treatments can alleviate symptoms, but they do not prevent the progression of disease.

Disease-Modifying Antirheumatic Drugs

For patients who fail NSAIDs or present initially with more joint involvement (polyarthritis or > 5 swollen joints), traditional disease-modifying antirheumatic drugs (DMARDs) should be started (Table 2). Methotrexate is one of the first-line DMARD prescriptions. It is commonly used because of its effectiveness in treating both skin and joint involvement, despite limited evidence of its efficacy in controlled clinical trials for slowing the progression of joint damage in PsA.^2,9–11 Methotrexate can be given orally or subcutaneously (SC) every week. Routine laboratory monitoring is required given the known effects of MTX on liver and bone marrow suppression. Clinical monitoring is needed as well due to its well-known risk for pulmonary toxicity and teratogenicity.²

Table 2.

Disease-Modifying Antirheumatic Drug Therapies^a

Drug	Mechanism of Action	Approved for		Laboratory Monitoring
		Psoriasis	PsA
Methotrexate	Folate antimetabolite inhibiting DNA synthesis, repair and cellular replication	Yes	Yes	- CBC with differential - Serum creatinine - LFTs Every 2–4 wk initially, every 12 wk after reaching stable dose
Leflunomide	Immunomodulatory agent inhibiting pyrimidine synthesis leading to antiproliferative and anti-inflammatory effects	No	Yes	- CBC with differential - Serum creatinine - LFTs Monthly until stable results, then every 8–12 wk on stable dose
Sulfasalazine	Exact mechanism unknown; anti-inflammatory and immunomodulatory effects	Yes	No	- CBC with differential - Serum creatinine - LFTs Initially every mo for 3 mo, then every 3 mo
Cyclosporine	Inhibition of production and release of interleukin 2	Yes	No	- Blood pressure - Serum creatinine With any dosage changes or addition/deletion of other medications

Abbreviations: CBC, complete blood count; LFT, liver function test; PsA, psoriatic arthritis.

^aAdapted from Boehncke WH, Alverez Martinez D, Solomon JA, Gottlieb AB. Safety and efficacy of therapies for skin symptoms of psoriasis in patients with psoriatic arthritis: a systematic review. J Rheumatol. 2014;41(11):2301–2305.

Leflunomide is another traditional oral DMARD that is administered daily. It has be shown to be effective in PsA, with only a modest effect in improving skin lesions.¹² Laboratory monitoring is identical to that required with MTX. Adverse effects (AEs) include diarrhea and increased risk of elevated transaminases.⁹ Sulfasalazine (SSZ) is also used as a traditional DMARD and shown to have an effective clinical response in treating peripheral arthritis but not in axial or skin disease.^9,12 Not all studies have shown effective responses to SSZ. The primary AE is gastrointestinal, making this a frequently discontinued medication.² Cyclosporine is more commonly used in psoriasis but can be used on its own or with MTX for treating patients with PsA.¹⁰ It is often not tolerated well and frequently discontinued, due to major AEs, including hypertension and renal dysfunction.^2,10

These traditional DMARDs are usually given for 3 to 6 months.¹³ After this initial period, the patient’s clinical response is reassessed, and the need for changing therapy to another DMARD or biologic is determined.

Biologic Therapies

With the discovery of TNFα as a potent cytokine in inflammatory arthritis came a new class of medications that has provided patients and providers with more effective treatment options. This category of medications is known as tumor necrosis factor inhibitors (TNFis). Five medications have been developed that target TNFα, each in its own way: etanercept, infliximab, adalimumab, golimumab, and certrolizumab pegol. These medications were initially studied in patients with rheumatoid arthritis, with further clinical trials performed for treatment of PsA. Each is prescribed differently: Adalimumab and certrolizumab are given SC every 2 weeks, etanercept is given weekly, and golimumab is given once a month. Infliximab is the only medication prescribed as an infusion, which is administered every 8 weeks after receiving 3 loading doses.

Studies have shown that all TNFis are effective in treating PsA: improving joint disease activity, inhibiting progression of structural damage, and improving function and overall quality of life.¹⁰ The TNFi drugs also improve psoriasis along with dactylitis, enthesitis, and nail changes.¹³ Patients with axial disease benefit from TNFi, but the evidence of TNFi effectiveness is extrapolated from studies in axial spondyloarthritis.^13,14 Tumor necrosis factor inhibitors can be used as monotherapy, although there is some evidence for using TNFi drugs with MTX in PsA. Combination therapy can potentially prolong the survival of the TNFi drug or prevent formation of antidrug antibodies.^14,15

The current evidence for monotherapy vs combination therapy in patients with PsA is not consistent, and no formal guidelines have been developed to guide physicians one way or another. The TNFi drugs are generally well tolerated, although the patient needs to learn how to self-inject if given the SC route. Adverse effects include infusion or injection site reactions and infections. Prior to starting a TNFi, it is prudent to screen for latent tuberculosis infection as well as hepatitis B and C, given the risk of reactivation. Clinical response is monitored for 3 months, and if remission or low disease activity is not reached, a different TNFi may be tried.¹³ Importantly, patients receiving infliximab without clinical improvement in 3 months may have their dose and frequency increased before switching to an alternative TNFi. Some studies show that a trial of a second TNFi has a less potent response than with a first TNFi, and the drug survival is shorter in duration.¹³

One of the newest biologic agents approved for treating PsA is ustekinumab, a human monoclonal antibody (MAB) that inhibits receptor binding of cytokines interleukin (IL)-12 and IL-23. These cytokines have been identified in patients with psoriasis and PsA as further promoting inflammation. Ustekinumab recently received approval for the treatment of PsA and is given SC every 12 weeks after 2 initial doses. Further studies have also confirmed ustekinumab significantly suppressed radiographic progression of joint damage in patients with active PsA.¹⁵ Notable AEs included infections, but there have been no cases of tuberculosis or opportunistic infections reported.¹⁶

The most recent FDA-approved medication for PsA is apremilast. It is a phosphodiesterase-4 inhibitor, which causes the suppression of other proinflammatory mediators and cytokines active in the immune system.¹⁰ It is given orally, uptitrating the doses over a few days until the twice-daily maintenance dosing is achieved. It is generally well tolerated with nausea and diarrhea as the most common AEs.¹⁷ Further studies need to be conducted to assess whether this agent is able to prevent or decrease joint damage.

Other potential treatment options are currently undergoing trials to assess their efficacy and safety in treating psoriasis and/or PsA. One class targets the IL-17 cytokine pathway and includes brodalumab, a monoclonal antibody (MAB) anti-IL-17 receptor, ixekizumab and secukinumab, both MABs anti-IL-17A. Secukinumab has already received FDA approval for the treatment of plaque psoriasis (2015). Other agents currently undergoing trials are abatacept (cytotoxic T-lymphocyte antigen 4-Ig), a recombinant human fusion protein that blocks the co-stimulation of T cells⁹ and tofacitinib, a janus kinase inhibitor.¹⁸ Early studies show patients achieving a response with these medications, but further long-term studies are needed.¹⁹

Treatment Recommendations

Treatment approaches differ for patients with only psoriasis and patients with psoriasis and PsA, although some treatment modalities overlap. Recommendations for PsA have been set for each domain affected (Figure 2). The treatment approach is based on several factors, including severity or the degree of disease activity, any joint damage, and the patient’s comorbidities. Certain comorbidities are associated with PsA—cardiovascular disease, obesity, metabolic syndrome, diabetes, inflammatory bowel disease, fatty liver disease, chronic viral infections (hepatitis B or C), and kidney disease. These comorbidities can affect the choice of therapy for the patient.^20,21 Other factors affecting treatment choices include patient preference regarding mode and frequency of administration of the medication, potential AEs, requirements of laboratory monitoring or regular doctor visits, and the cost of medications.^10,22

Figure 2.

Management Algorithm for Psoriasis and Psoriatic Arthritis^a

Abbreviations: BMI, body mass index; DMARDs, disease-modifying antirheumatic drugs; IA, Intra-articular; MSKU, musculoskeletal ultrasound, NSAIDs, nonsteroidal anti-inflamatory drugs; PsA, psoriatic arthritis. ^aAt each treatment level, clinical response to the therapy should be assessed. Adverse effects or toxicities of the medications addressed and adjusted appropriately.

In treating patients with psoriasis and PsA, a multidisciplinary approach is needed. Because skin manifestations of psoriasis usually develop prior to arthritis symptoms in most patients, primary care providers and dermatologists can routinely screen patients for arthritis.¹⁰ Rheumatologists can confirm arthritis and musculoskeletal involvement, but the treatment and management of these patients will need to be in collaboration with a dermatologist. The goal of comanagement is to choose appropriate therapies that may be able to treat both the skin and musculoskeletal manifestations.

A multidisciplinary approach can also limit polypharmacy, control costs, and reduce AEs. The existence of VA combined rheumatology and dermatology clinics makes this an invaluable experience for the veteran with direct and focused patient management. In addition to controlling disease activity, the goal of treatment is to improve function and the patient’s quality of life, halting structural joint damage to prevent disability.¹⁰ Physical and occupational therapies play an important role in PsA management as does exercise. Patients should be educated about their disease and treatment options discussed. It is also important to identify and reduce significant comorbidities, such as cardiovascular disease, to decrease mortality and improve life expectancy.¹⁰

CONCLUSION

Psoriasis is a distinct disease entity but can occur along with extracutaneous features. Patients with psoriasis need to be screened for PsA, and it is important to diagnose PsA early to begin appropriate treatment. Disease activity, severity, and any joint damage will determine therapy. Over the past decade, new treatment options have become available that provide more choices for patients than those of the standard DMARDs. The TNFis have proven to be efficacious in treating psoriasis and PsA. With a better understanding of pathogenesis of these diseases, new medications have been discovered targeting different parts of the immune system involved in dysregulation and ultimately inflammation. Additional clinical research is needed to provide physicians with more effective ways of controlling these diseases. Ultimately, the management of PsA is not solely based on medications, but the authors’ VA experience highlights the importance of a multispecialty approach to the management of psoriasis and PsA.