History of Psoriatic Arthritis

Psoriatic arthritis (PsA) is a complex inflammatory condition with a wide range of clinical manifestations that can worsen psoriasis of the skin or nails in up to 30% of cases. There are no diagnostic criteria or testing for PsA. Inflammatory musculoskeletal characteristics in the joints, entheses, or spine are most typically identified in the presence of skin and/or nail psoriasis, and in the absence of rheumatoid factor and anti-cyclic citrullinated peptide.1 

Psoriatic arthritis, conventionally described as inflammatory arthritis associated with psoriasis and usually seronegative for rheumatoid factor, has proven to be a significant diagnostic and therapeutic challenge for treating physicians over the last two decades.2 Psoriatic arthritis was initially described in the early nineteenth century, but it was not recognized as a unique entity until 1964 by the American Rheumatology Association.3

Psoriatic arthritis was once thought to be the result of the occurrence of two very common illnesses, arthritis, and psoriasis. Prof. Verna Wright was the first one to suggest that PsA was a separate disease entity. He stated that the symptoms of PsA are more similar with spondyloarthropathy than rheumatoid arthritis (RA). Psoriatic arthritis was first identified in the 1970s by Wright and Moll, who identified five clinical disease patterns: distal, oligoarticular, polyarticular, predominantly axial, and arthritis mutilans.4 

Psoriatic arthritis has been diagnosed using a variety of diagnostic criteria, including the widely used Moll and Wright criteria. Other criteria are Bennett, Vasey, Espinoza, McGonagle (Modified criteria), Fournie, and the European Spondyloarthropathy Study Group have all offered additional diagnostic criteria (Modified criteria). Publication of The Classification of Psoriatic Arthritis (CASPAR) categorization criteria for psoriatic arthritis was done in 2005. The CASPAR group has also developed a more simpler classification scheme for PsA, splitting the disease into axial and peripheral disease.5 

The classification of PsA according to Moll and Wright, published in 1973, has been the most widely used. PsA is divided into five subtypes, each of which is defined by the number of joints involved and characterized by a different course. (Table 1).6 After systematic analysis of patient data, an international working group (CASPAR, Classification of Psoriatic Arthritis Criteria) created the CASPAR criteria for PsA in 2005. (Table 2). PsA is diagnosed when at least three criteria are met, according to this criteria.7

Table1: Moll and Wright Classification of PsA.6 

Asymmetric oligoarthritis (about 70 %) 
Symmetric polyarthritis (up to 20 %) 
Distal interphalangeal arthritis (5–10 %) 
Mutilating arthritis (about 5 %)
Spinal column involvement (5–40 %)

Table2: CASPAR Classification of PsA.7 

Inflammatory musculoskeletal disease (joints, spinal column, enthesitis) and fulfillment of at least three of the following criteria:
1. Evidence for psoriasis of the skin
— Current psoriasis present (2 points)
— Positive history (1 point)
— Positive family history (1 point)
2. Nail psoriasis (1 point)
3. A rheumatoid factor not detectable (1 point)
4. Dactylitis (inflammatory swelling of an entire finger or toe) 
— Current dactylitis (1 Point)
— Positive history (1 point)
5. Radiologic detection of ossification in proximity to joints (1 point)

Epidemiology

PsA was once thought to be uncommon, but new research based on CASPAR criteria suggests that it affects up to 30% of psoriasis patients. Based on these findings, the prevalence of psoriatic arthritis is estimated to be between 30 and 100 cases per 10,000 people in the United States, suggesting that 3% of the population has psoriasis. Undiagnosed psoriatic arthritis affects around 15% of psoriasis patients who are examined by dermatologists.

In a prospective study of psoriasis patients, the annual incidence of psoriatic arthritis was estimated to be 2 to 3%. Psoriasis usually manifests 10 years before arthritis, yet in 15% of cases, arthritis and psoriasis manifest simultaneously or psoriatic arthritis manifests before the skin illness. In Asians and blacks, psoriatic arthritis is rare, and the male-to-female ratio is 1:1.8 In the general population, PsA is a relatively rare disease seen in 0.10–0.25 percent of adults. It is most common in people 30–60 years old.1

Figure 1: Worldwide prevalence of psoriatic arthritis among patients with psoriasis.9 

Etiology and Risk Factors

The cause of psoriatic arthritis is yet to be determined. In a genetically susceptible population, environmental conditions (such as injury and infection) are considered. HLA-B27 antigen involvement is more common in patients with involvement of spine and sacroiliac joints, whereas HLA-DR4 association is more common in an erosive subgroup and HLA-DR7 in cases with involved DIP joints. Lymphocytic infiltrates and neoangiogenesis, synoviocyte activation, and the release of proinflammatory cytokines, particularly tumor necrosis factor-α) (TNF-α), characterize synovitis, similar to rheumatoid arthritis (RA).10 

A variety of potential risk factors for the development of psoriatic arthritis in psoriasis patients have been found in studies.These include genetic predisposition within the HLA region, variations in genes associated with interferon and NF-κB signaling, comorbid conditions like hyperlipidemia and obesity, and factors related to psoriasis such as disease severity, site, and nail dystrophic alterations.1 

Triggering factors that are exogenous play an important role in the development of psoriatic arthritis. Microbial infections, especially bacterial and viral infections, are particularly important. PsA can be activated by Beta-hemolytic group A streptococci (M protein-positive), like psoriasis, however, streptococci triggering is infrequent and non – specific in PsA. An association with HIV is more typically seen. In comparison to psoriasis, triggering the disease with certain drugs plays a relatively minor role in psoriatic arthritis. Interferon-alpha is an exception to this.12

Prognosis of Psoriatic Arthritis

Estimating prognosis in PsA is difficult due to a lack of evidence and significant individual variability. PsA can evolve over time with variable joint and extra-articular involvement, according to multiple investigations. The pattern of peripheral joint disease appears to evolve with time, with oligoarthritis being more common in early disease patients than late disease individuals. In majority of the cases, increasing disease duration leads to increased joint involvement, with a large proportion of individuals with monoarthritis or oligoarthritis progressing to polyarthritis. Axial involvement becomes more likely as the disease progresses.1

PsA is a disease that can cause severe morbidity and have a negative impact on patients’ quality of life. Some characteristics are thought to indicate a severe disease course and a poor prognosis. A high number of actively inflamed joints or polyarticular presentations, raised ESR, clinical or radiographical damage, loss of function and a lower quality of life are all indicators.11 

Psoriatic Arthritis Diagnosis & Presentation

Because there are no particular biomarkers for psoriatic arthritis, the diagnosis is primarily based on the detection of clinical and radiological findings.8 PsA is a clinically heterogeneous disease that affects peripheral joints (peripheral disease) or the sacroiliac joints, as well as the spine (axial disease), where inflammatory responses in other tissues, such as enthesitis and dactylitis, are seen in addition to synovitis. Chronic inflammatory spinal pain, bi- or unilateral sacroiliac joint pain, and pain at entheses, defined clinically as enthesitis, peripheral arthritis, dactylitis, and skin and nail psoriasis are all seen in the course of PsA.10 

Psoriatic arthritis has a wide range of clinical manifestations. Moll and Wright’s first classification of psoriatic arthritis comprised five subtypes:11 

  • Oligoarticular arthritis shows asymmetric involvement. It affects less than 5 small or large joints
  • Polyarticular arthritis shows symmetric involvement with presentation identical to rheumatoid arthritis but it involves the distal interphalangeal joints (DIP) and rheumatoid factor (RF) is negative
  • Distal arthritis shows the involvement of the DIP joints predominantly
  • Arthritis mutilans shows the severe form of the destructive joint disease with the presence of deformities, particularly in hands and feet
  • Spondyloarthritis pattern with the presence of sacroiliitis and spondylitis. (this can be seen either with or without peripheral joint disease).11

Figure 2: Presenting features of psoriatic arthritis.13

Physical Examination Findings

  • Symmetric polyarthritis: More than five joints are affected with symmetric polyarthritis. It is symmetrical and shows alterations in several joints of the fingers, wrists, and toes, and it cannot be distinguished from RA in 15–20 percent of cases because it attacks joints in a similar manner. The patients are however negative for RA.10 
  • Asymmetric oligoarthritis is the most common type of psoriatic arthritis (affecting around 70% of patients), which involves less than five peripheral joints with asymmetrical involvement of many small joints (interphalangeal and metacarpophalangeal) or large joints, particularly the ankle, knee, and shoulder.10
  • Axial spondyloarthritis involves the sacroiliac joints and the spine and can lead to vertebral fusion. This uncommon variety of PsA affects about 5% of patients with the disease. In roughly 40% of patients with Spondyloarthritis, concomitant peripheral arthritis is documented.10
  • DIP joint involvement of the hand and feet, which is typically accompanied by nail dystrophy, is a different form of PsA with unique clinical manifestations and changes in DIP joints (5–12 percent of patients), which shows proliferative changes in addition to erosions.10
  • Arthritis mutilans, seen in 5–16 percent of psoriatic arthritis patients, cause severe deformations by causing osteolysis in the DIP and proximal interphalangeal (PIP) joints of the feet and hands. This erosive condition affects small joints causing dissolution or resorption of the distal sections of bones, leading to a “pencil in cup” or whittling appearance, notably in phalangeal tufts, shortening of the digits, known clinically as telescoping or “opera glass” digits, occurs as the disease advances, along with significant finger deformations described as arthritis mutilans. Ankylotic and dislocated joints are common in this condition.10 

Diagnostic Workup

PsA diagnosis is on the basis of the recognition of clinical and imaging features since there are no specific biomarkers.8 In 95 percent of psoriatic arthritis patients, tests for rheumatoid factor, anti-cyclic citrullinated peptide antibodies, or both are negative. Clinical and imaging criteria must be used to distinguish psoriatic arthritis from rheumatoid arthritis when a test result is positive. HLA-B27 positivity is seen in about 25% of psoriatic arthritis patients. 40% of patients show an increase in their serum C-reactive protein level, erythrocyte sedimentation rate, or both.8 

A correct and timely diagnosis is important for psoriatic arthritis patients. When diagnosing psoriatic arthritis, a variety of factors including patient history, physical examination, laboratory and imaging findings, are taken into account.1 A variety of hematological, serological, and imaging tests are helpful, though, not specific for diagnosis.5

Laboratory Testing

Non-specific tests including erythrocyte sedimentation rate and C-reactive protein may be elevated. A test for rheumatoid factors should be done. Despite the fact that a negative serology can exclude RA diagnosis, roughly 25% of cases of psoriatic arthritis of rheumatoid form can have a positive or equivocal test result. HLA-B27 test, another nonspecific test, is an indicator of axial disease. For assessment of comorbid conditions, tests like lipid profile, HbA1C, liver function tests (LFT), and body mass index (BMI) are being used.5

Imaging Studies

  • Hand and foot X-rays are done. Same as RA, early changes which are limited to periarticular soft tissue swelling and joint erosions are seen. Periostitis and new bone formation are possible at the sites of entheseal attachments.The progression of the disease, particularly of Arthritis mutilans type, can exhibit widespread joint destruction, as well as “penciling” or narrowing of the metacarpal and metatarsal heads. The “pencil-in-cup” look is caused by the destruction of the middle section of the articular surface. Bony ankylosis can develop when the interphalangeal joints, particularly the distal ones, are damaged. The sacroiliac abnormalities in psoriatic arthritis are identical to those seen in ankylosing spondylitis, but the paravertebral tissues in the thoracic and lumbar regions ossify laterally.5
  • Ultrasound and Magnetic resonance imaging (MRI) are more useful to detect enthesitis.5 When the axial skeleton is mainly involved, MRI can be used to detect early bone remodeling and inflammatory activities.12 
  • Arthro-sonography.can detect tendonosynovialitides, bursitides, cysts, and joint effusion. 12

Differential Diagnosis

Below are common types of arthritis that must be differentiated. Psoriatic arthritis is characterized by oligoarticular disease, asymmetrical involvement, DIP involvement, enthesitis, and negative serology. 

  • RA: In addition to rheumatoid nodules and extra-articular signs, those with RA can have enthesitis and central axial involvement.
  • Osteoarthritis: Affects the knee and hip joints and is caused by “wear and tear” of the joints. 
  • Connective Tissue Disease: Lupus arthritis cases are positive for antinuclear antibodies (ANA) and dsDNA, affecting the hands, wrists, and knees. 
  • Infective Arthritis: Presents with an acutely painful joint swelling. In infective arthritis, culture examination of the joint fluid identifies the causative organism while a negative culture. along with raised serum uric acid levels, indicates gouty arthritis.
  • Gouty Arthritis: Generally monoarticular, with the metatarsophalangeal joint being the most commonly affected joint. A radiograph of the afflicted joint reveals “rat-bite” lesions with lytic regions and sclerotic margins.5

Management of Psoriatic Arthritis

PsA can be treated with a variety of strategies and, depending on the severity, chronicity, and other comorbidities, low remission or low disease activity should be the target.11 The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the European League Against Rheumatism (EULAR), and the American College of Rheumatology and the National Psoriasis Foundation in collaboration (ACR–NPF) have all published and revised psoriatic arthritis treatment recommendations.1

Figure 3:  Suggested treatment algorithm for patients with psoriasis and/or psoriatic arthritis.15

Nonpharmacologic Treatment

Lifestyle & Therapies

According to the ACR/NPF recommendations, non-pharmacological interventions such as low-impact (vs. high-impact) exercise, physical therapy, occupational therapy, loss of weight in overweight or obese patients, massage, and acupuncture should be advised when appropriate. Apart from weight loss, which has evidence to support it, these are all conditionally suggested methods due to a lack of evidence, notably in psoriatic arthritis. Smoking cessation was one of the few strongly recommended ACR/NPF guidelines, as smoking is linked to cardiovascular disease and shows association with poor treatment results. 1 

Surgery

In a patient with persistent arthritis of a single joint, a synovectomy could be performed. In patients who have severe arthritis in their hips or knees, joint replacement may be an option.3

Balneotherapy

Balneotherapy in the Dead Sea area appears to result in a statistically significant reduction in the number of active joints and painful spots in both male and female PsA patients.17

Pharmacologic Treatment

Adjunctive therapies1

  • NSAIDs, glucocorticosteroids (oral, intra-articular, intramuscular or topical administration)
  • Conventional synthetic DMARDs (cs-DMARDs)
    • Methotrexate, sulfasalazine, leflunomide, cyclosporine
  • Biological DMARDs (bDMARDs)
    • TNF inhibitors
      – Etanercept, infliximab, adalimumab, golimumab, certolizumab
    • IL-12/IL-23 inhibitors – Ustekinumab
    • IL-17 inhibitors – Secukinumab, ixekizumab, brodalumabb, bimekizumabc
    • IL-23 inhibitors – Guselkumab, risankizumabb, tildrakizumabb
    • T cell modulator – Abatacept

Targeted synthetic DMARDs

  • PDE4 inhibitor (apremilast)
  • JAK inhibitors (tofacitinib, upadacitinib; baricitinibc, filgotinibc)

Monitoring for Psoriatic Arthritis Side Effects

Though Abatacept’s effects are modest, one benefit of the drug is its comparatively low risk of side effects.1 Apremilast has a low risk of major side effects, such as infection, and does not require laboratory tests.1 The potential of serious infection, the requirement for laboratory monitoring of liver function tests and blood counts, and the rare side effect of lymphoma are all included in JAK inhibitors’ safety profile, which is comparable to that of rheumatoid arthritis treatment. Data shows that taking the medication at a larger dose than indicated increases the risk of thromboembolic episodes, which could be a class effect.1

Comorbidities of Psoriatic Arthritis

PsA is linked to a number of chronic illnesses that can shorten life and reduce the quality of life. Even though most studies suggest that overall mortality in individuals with psoriatic arthritis is not greater than in the general population, obesity and cardiovascular comorbid conditions are more common, which might affect lifespan and quality of life. 

When compared to the general population, the prevalence of cardiovascular risk factors such as hypertension, hyperlipidemia, type 2 diabetes mellitus, and the combination of these (known as metabolic syndrome) is higher in psoriatic arthritis. Even after adjusting for established risk variables, psoriatic arthritis is linked to an elevated risk of cardiovascular events like myocardial infarction. Similarly, people with psoriatic arthritis have a higher chance of developing type 2 diabetes and fatty liver.1

PsA has also been linked to extra-articular symptoms such as uveitis and inflammatory bowel disease, such as Crohn’s disease and ulcerative colitis. In patients with psoriatic arthritis, a meta-analysis found a 3% prevalence of uveitis and a 3% prevalence of inflammatory bowel disease. Because not all psoriatic arthritis treatments cover various manifestations, these conditions can have a significant impact on treatment choices.1

Psoriatic Arthritis Complications

PsA, once thought to be a mild illness, is now recognized as a disabling condition that necessitates focused treatment as well as frequent monitoring and follow-up care. Although complete symptomatic relief is possible, the majority of patients nevertheless persist with a chronic inflammatory condition.11

Patient Education

Patients should be well-informed and advised on the chronic nature of psoriatic arthritis and the necessity of non-pharmacological treatments such as exercise, quitting smoking, loss of weight, physical therapy, and occupational therapy.

They should be informed about the disease’s fluctuating nature, which needs constant monitoring by the multidisciplinary treatment team. Immunosuppressive medicine adverse effects must be thoroughly explained, and an effort must be made to educate the patient’s family as well. Patient cooperation is critical for good treatment outcomes in psoriatic arthritis, as it is for many chronic diseases.

FAQs

What is psoriatic arthritis?

Psoriatic arthritis (PsA) is a complex inflammatory condition with a wide range of clinical manifestations that can worsen psoriasis of the skin or nails in up to 30% of cases. There are no diagnostic criteria or testing for psoriatic arthritis. Inflammatory musculoskeletal characteristics in the joints, entheses, or spine are most typically identified in the presence of skin and/or nail psoriasis, and in the absence of rheumatoid factor and anti-cyclic citrullinated peptide. 

What causes psoriatic arthritis?

The cause of psoriatic arthritis is yet to be determined. In a genetically susceptible population, environmental conditions (such as injury and infection) are considered. HLA-B27 antigen involvement is more common in patients with the spine and sacroiliac joints, whereas HLA-DR4 association is more common in an erosive subgroup and HLA-DR7 in DIP joints. Lymphocytic infiltrates and neoangiogenesis, synoviocyte activation, and the release of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α), characterize synovitis, similar to rheumatoid arthritis (RA).

What are the symptoms of psoriatic arthritis?

Psoriatic arthritis symptoms has a wide range of clinical manifestations. Moll and Wright’s first classification of PsA comprised five subtypes:

  1. Oligoarticular arthritis shows asymmetric involvement. It affects less than 5 small or large joints.
  2. Polyarticular arthritis shows symmetric involvement with presentation identical to rheumatoid arthritis but it involves the distal interphalangeal joints (DIP) and rheumatoid factor (RF) is negative.
  3. Distal arthritis shows the involvement of the DIP joints predominantly.
  4. Arthritis mutilans shows the severe form of the destructive joint disease with the presence of deformities, particularly in hands and feet.
  5. Spondyloarthritis pattern with the presence of sacroiliitis and spondylitis. This can be seen either with or without peripheral joint disease.

What parts of the body does it affect?

PsA involves fingers, wrists, spine, feet, eyes, and or neck. There can be tender, inflamed tendons and muscles, particularly around these areas.

How is psoriatic arthritis diagnosed?

The diagnosis of psoriatic arthritis is based on the recognition of clinical and imaging features since there are no specific biomarkers. In 95 percent of psoriatic arthritis patients, tests for rheumatoid factor, anti-cyclic citrullinated peptide antibodies, or both are negative.

Clinical and imaging criteria must be used to distinguish psoriatic arthritis from rheumatoid arthritis when a test result is positive. HLA-B27 positivity is seen in about 25% of psoriatic arthritis patients. 40% of patients show an increase in their serum C-reactive protein level, erythrocyte sedimentation rate, or both.

A correct and timely diagnosis is important for PsA patients. When diagnosing PsA, a variety of factors including patient history, physical examination, laboratory and imaging findings, are taken into account. A variety of hematological, serological, and imaging tests are helpful, though, not specific for diagnosis. 

How is psoriatic arthritis treated?

The most effective way to limit disease activity and reduce joint damage is to use the Treat-to-Target approach. Depending on the severity, chronicity, and other comorbidities, low remission or low disease activity should be the target. PsA can be treated with a variety of strategies, including: 

  • Nonpharmacological strategies such as weight loss, smoking cessation, and exercise. Physical therapy, such as balneotherapy and exercise, should be started early in conjunction with PsA medication therapy to enhance joint mobility and minimize pain. 
  • Pharmacological, such as nonsteroidal anti-inflammatory medications (NSAIDs) and corticosteroid injections are used to treat symptoms. In PsA patients, DMARDs like methotrexate (MTX) and newer biological-based medications like adalimumab and secukinumab have been shown to be effective.

References

  1. FitzGerald O, Ogdie A, Chandran V, et al. Psoriatic arthritis – PubMed (nih.gov). Nat Rev Dis Primers. 2021;7(1):59. Published 2021 Aug 12. doi:10.1038/s41572-021-00293-y
  2. Van den Bosch F, Coates L. Clinical management of psoriatic arthritis – PubMed (nih.gov). Lancet. 2018;391(10136):2285-2294. doi:10.1016/S0140-6736(18)30949-8
  3. Sharma A, Dogra S. Management of psoriatic arthritis – PubMed (nih.gov). Indian J Dermatol Venereol Leprol. 2010;76(6):645-651. doi:10.4103/0378-6323.72457
  4. Hackett S, Coates L. Psoriatic arthritis: An up to date overview. Indian Journal of Rheumatology. 2020 Jun 1;15(5):45.
  5. Balakrishnan C, Madnani N. Diagnosis and management of psoriatic arthritis – PubMed (nih.gov). Indian J Dermatol Venereol Leprol. 2013;79 Suppl 7:S18-S24. doi:10.4103/0378-6323.115507
  6. Moll JM, Wright V. Psoriatic arthritis – PubMed (nih.gov). Semin Arthritis Rheum. 1973;3(1):55-78. doi:10.1016/0049-0172(73)90035-8
  7. Helliwell PS, Taylor WJ. Classification and diagnostic criteria for psoriatic arthritis – PubMed (nih.gov). Ann Rheum Dis. 2005;64 Suppl 2(Suppl 2):ii3-ii8. doi:10.1136/ard.2004.032318
  8. Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis – PubMed (nih.gov) [published correction appears in N Engl J Med. 2017 May 25;376(21):2097]. N Engl J Med. 2017;376(10):957-970. doi:10.1056/NEJMra1505557
  9. Alinaghi F, Calov M, Kristensen LE, et al. Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies – PubMed (nih.gov). J Am Acad Dermatol. 2019;80(1):251-265.e19. doi:10.1016/j.jaad.2018.06.027
  10. Sudoł-Szopińska I, Matuszewska G, Kwiatkowska B, Pracoń G.Diagnostic imaging of psoriatic arthritis. Part I: etiopathogenesis, classifications and radiographic features (nih.gov). J Ultrason. 2016;16(64):65-77. doi:10.15557/JoU.2016.0007
  11. Tiwari V, Brent LH. Psoriatic Arthritis – PubMed (nih.gov). In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 11, 2021.
  12. Amherd-Hoekstra A, Näher H, Lorenz HM, Enk AH. Psoriatic arthritis: a review – PubMed (nih.gov). J Dtsch Dermatol Ges. 2010;8(5):332-339. doi:10.1111/j.1610-0387.2009.07334.x
  13. Jara S. Different Types of Psoriatic Arthritis: Symptoms, Treatments, Outcomes (creakyjoints.org). Published on Nov 20, 2019. Accessed on Jan 16, 2022. 
  14. Singh JA, Guyatt G, Ogdie A, et al. 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis – Singh – 2019 – Arthritis Care & Research – Wiley Online Library. Arthritis Rheumatol. 2019;71(1):5-32. doi:10.1002/art.40726
  15. ​​Gan EY, Chong WS, Tey HL. Therapeutic strategies in psoriasis patients with psoriatic arthritis: focus on new agents – PubMed (nih.gov). BioDrugs. 2013;27(4):359-373. doi:10.1007/s40259-013-0025-6
  16. Ogdie A, Coates LC, Gladman DD. Treatment guidelines in psoriatic arthritis – PubMed (nih.gov). Rheumatology (Oxford). 2020;59(Suppl 1):i37-i46. doi:10.1093/rheumatology/kez383
  17. Sukenik S, Baradin R, Codish S, et al. Balneotherapy at the Dead Sea area for patients with psoriatic arthritis and concomitant fibromyalgia – PubMed (nih.gov). Isr Med Assoc J. 2001;3(2):147-150.