Rheumatoid arthritis and Psoriatic arthritis

Rheumatoid arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications, early death, and socioeconomic costs. The cause of rheumatoid arthritis is unknown, and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The mortality rate is higher among patients with rheumatoid arthritis than among healthy persons, and cardiovascular (myocardial infarction, heart failure and stroke) and other systemic complications remain a major challenge. These increased rates are not explained by traditional risk factors, use of glucocorticoids or nonsteroidal antiinflammatory drugs, or shared genetic features. Inflammation in rheumatoid arthritis also affects the brain (fatigue and reduced cognitive function), liver (elevated acute-phase response and anemia of chronic disease), lungs (inflammatory and fibrotic disease), exocrine glands (secondary Sjögren’s syndrome), muscles (sarcopenia), and bones (osteoporosis).

Rheumatoid arthritis is characterized by synovial inflammation and hyperplasia (“swelling”), autoantibody production (rheumatoid factor and anti–citrullinated protein antibody [ACPA]), cartilage and bone destruction (“deformity”), and systemic features, including cardiovascular, pulmonary, psychological, and skeletal disorders.

Infectious agents (e.g., Epstein–Barr virus, cytomegalovirus, proteus species, and Escherichia coli) and their products (e.g., heat-shock proteins) have long been linked with rheumatoid arthritis, and although unifying mechanisms remain elusive, some form of molecular mimicry is postulated has been postulated in rheumatoid arthritis. Increased T cell senescence may contribute to molecular mimicry.

Smoking and other forms of bronchial stress (e.g., exposure to silica) increase the risk of rheumatoid arthritis among persons with susceptibility HLA–DR4 alleles.

Why are women more susceptible to rheumatoid arthritis? Molecular explanations for such phenomena are emerging from animal models of inflammation, which show a link between the hypothalamic–pituitary–adrenal axis and cytokine production.

Why the systemic loss of tolerance is linked to a localized onset of inflammation in the joint is still unclear (transitional phase of rheumatoid arthritis).  Autoantibodies, such as rheumatoid factor and ACPA, are often (but not always) detected in patients before the development of arthritis (pre-articular phase of rheumatoid arthritis); in some series, autoantibody levels have increased and there has been evidence of epitope spreading as the onset of disease approaches.

Psoriasis begins as a relatively benign skin diseases but progresses to complicated skin disease and arthritis. Psoriatic arthritis is  chronic and inflammatory and involves the joints, entheses, bone, axial skeleton, and skin, with heterogeneous clinical features associated with substantial disability and reduced life expectancy. There is accumulating evidence that interleukin-17 is central to the pathogenesis of psoriatic arthritis and other spondyloarthritides, such as ankylosing spondylitis. In the management of psoriatic arthritis inhibition of interleukin-17 signaling by brodalumab induces significant clinical responses in patients with psoriasis. By contrast, efficacy has not been observed for brodalumab in clinical trials involving patients with rheumatoid arthritis or Crohn’s disease.

Five subtypes of  psoriatic arthritis have been described.

  • The oligoarticular subtype affects four or fewer joints and typically occurs in an asymmetric distribution.
  • The polyarticular subtype affects five or more joints; the involvement may be symmetric and resemble rheumatoid arthritis.
  • The distal subtype, which affects distal interphalangeal joints of the hands, feet, or both, usually occurs with other subtypes, occurring alone in only 5% of patients.
  • Arthritis mutilans, a deforming and destructive subtype of arthritis that involves marked bone resorption or osteolysis, is characterized by telescoping and flail digits.
  • The axial or spondyloarthritis subtype primarily involves the spine and sacroiliac joints.

These patterns may change over time. Given below is the CASPAR classification for psoriatic arthritis.

The diagnosis of psoriatic arthritis is based on the recognition of clinical and imaging features, since there are no specific biomarkers. Involvement of at least five domains is possible; these include psoriasis, peripheral joint disease, axial disease, enthesitis, and dactylitis. Patients should be carefully assessed for these domains, with the understanding that various domain combinations may be present in an individual patient. The personal history and family history of psoriasis are often positive. Inflammatory arthritis, enthesitis, dactylitis, and joint distribution provide important clues, as do extraarticular features such as inflammatory bowel disease and uveitis. It is important to look for psoriatic skin lesions, particularly in the groin, umbilical area, hairline, ears, and natal (i.e., intergluteal) cleft. Nail lesions, including pits and onycholysis, as well as the presence of spinal disease, support the diagnosis.

Risk factors.

There are several environmental risk factors for psoriatic arthritis. These include obesity; severe psoriasis; scalp, genital, and inverse (or intertriginous) psoriasis; nail disease; and trauma or deep lesions at sites of trauma (Koebner’s phenomenon)

Differential diagnosis.

It is necessary to differentiate psoriatic arthritis from rheumatoid arthritis, osteoarthritis, gout, pseudogout, systemic lupus erythematosus, and other forms of spondyloarthritis.

Rheumatoid arthritis is characterized by proximal, symmetric involvement of the joints of the hands and feet, with sparing of the distal interphalangeal joints, whereas in more than 50% of patients with psoriatic arthritis, the distal joints are affected; the involvement tends to be characterized by a “ray” distribution, with all the joints of the same digit involved and other digits spared. This is noticeable both clinically and radiographically. At its onset, psoriatic arthritis tends to be oligoarticular and less symmetric than rheumatoid arthritis, although with time, psoriatic arthritis may become polyarticular and symmetric. The affected joints are less tender in psoriatic arthritis than in rheumatoid arthritis and may have a purplish discolorationSpinal involvement (sacroiliac joints or the lumbar, thoracic, or cervical spine) occurs in more than 40% of patients with psoriatic arthritis but is uncommon in patients with rheumatoid arthritis.

Psoriatic monoarthritis, particularly involving the toes, or dactylitis may be misdiagnosed as gout or pseudogout. The uric acid level may be elevated in patients with psoriatic arthritis, as well as in those with gout, making the differential diagnosis difficult, particularly if crystal analysis of joint fluid is negative or cannot be performed.

The distal-joint involvement that is characteristic of psoriatic arthritis is also observed in osteoarthritis. In psoriatic arthritis, palpation of distal joints reveals soft swelling due to inflammation, whereas in osteoarthritis, swelling arises from a bony osteophyte and is solid.

Ankylosing spondylitis typically begins late in the second decade of life or early in the third decade, whereas psoriatic spondyloarthritis is more likely to develop in the fourth decade of life. Psoriatic spondyloarthritis may be less severe than ankylosing spondylitis, with less pain and infrequent sacroiliac-joint ankylosis; an asymmetric distribution of syndesmophytes (bony growths originating inside a ligament of the spine) is more common in cases of psoriatic arthritis.

Bone erosions are observed in 47% of patients within the first 2 years, despite the use of traditional disease-modifying medications in more than half the patients. In an observational trial involving patients with psoriatic arthritis treated with anti–tumor necrosis factor (TNF) agents such as  adalimumab, etanercept, or infliximab, the rate of partial remission was 23%. However, relapse rates are high when biologic agents are discontinued.

Differential responses in patients with rheumatoid arthritis versus those with psoriatic arthritis provide further evidence that these diseases have different causal mechanisms. The observed clinical response to brodalumab among patients with psoriatic arthritis in this study (March 9, 2017 N Engl J Med 2017; 376:957-970
DOI: 10.1056/NEJMra1505557) supports the concept that interleukin-17 pathways are critical in the pathogenesis of psoriatic skin and joint disease. The clinical response of psoriatic skin disease to brodalumab has been established in previous studies among patients with psoriasis, including approximately 20% who also had psoriatic arthritis.

Genetic differences between rheumatoid arthritis and psoriatic arthritis.

Rheumatoid arthritis, is associated with class II major histocompatibility complex (MHC) alleles, psoriasis and psoriatic arthritis are associated with class I MHC alleles.

Psoriatic arthritis is a highly heritable polygenic disease. The recurrence risk ratio (defined as the risk of disease manifestation in siblings vs. the risk in the general population) is greater than 27, which is substantially higher than the recurrence risk ratio for psoriasis or rheumatoid arthritis. Most notably, HLA-C*06 is a major risk factor for psoriasis but not for psoriatic arthritis. In psoriatic arthritis, frequencies of HLA-B*08, B*27, B*38, and B*39 have been observed, with specific subtypes of those alleles linked to subphenotypes, including symmetric or asymmetric axial disease, enthesitis, dactylitis, and synovitis. It has been shown consistently that T cells are important in psoriasis and psoriatic arthritis.

A central role for CD8+ T cells in disease pathogenesis is supported by the association with HLA class I alleles, oligoclonal CD8+ T-cell expansion, and the association of psoriatic arthritis with human immunodeficiency virus disease.

When should a diagnosis of rheumatoid arthritis be made?

  • Inflammation of three or more joints.
    • Arthritis is typically present in the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hands. The wrists are also commonly involved, as are the metatarsophalangeal (MTP) joints in the feet, but any upper or lower extremity joint may be affected. Symmetric polyarthritis, particularly of the MCP, MTP, and/or PIP joints, strongly suggests RA.
    • Although distal interphalangeal (DIP) joint disease can occur in patients with RA, DIP involvement strongly suggests a diagnosis of osteoarthritis or psoriatic arthritis
  • Positive rheumatoid factor (RF) and/or anti-citrullinated peptide/protein antibody (such as anti-cyclic citrullinated peptide [CCP])) testing.
  • Elevated levels of C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR).
  • Diseases with similar clinical features have been excluded, particularly psoriatic arthritis, acute viral polyarthritis, polyarticular gout or calcium pyrophosphate deposition disease, and systemic lupus erythematosus (SLE).
  • The duration of symptoms is more than six weeks.
  • Serology: RFs occur in 70 to 80 percent of patients with RA. Their diagnostic utility is limited by their relatively poor specificity, since they are found in 5 to 10 percent of healthy individuals, 20 to 30 percent of people with SLE, virtually all patients with mixed cryoglobulinemia (usually caused by hepatitis C virus [HCV] infections).
  • Anti-citrullinated peptide antibodies.  The specificity of ACPA for RA is relatively high, usually over 90 percent. ACPA can occur in other diseases, including several autoimmune rheumatic diseases, tuberculosis, and sometimes chronic lung disease.
  • Other factors such as genetic factors, tissue factors, epitopes and acute phase reactants such as IL-6 have not found to correlate with disease activity or prevention of bone destruction.

2013 Update of the EULAR recommendations (the table of 2010 recommendations can be seen in the online supplement or the original publication). The 2020 EULAR has been cancelled because of COVID-19 pandemic.




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I am a Professor of Medicine and a Nephrologist. Having served in the Army Medical College, Pakistan Army for 27 years I eventually became the Dean and Principal of the Bahria University Medical and Dental College Karachi from where I retired in 2016. My passion is teaching and mentoring young doctors. I am associated with the College of Physicians and Surgeons Pakistan as a Fellow and an examiner. I find that many young doctors make mistakes because they do not understand how they should answer questions; basically they do not understand why a question is being asked. My aim is to help them process the information they acquire as part of their education to answer questions, pass examinations and to best take care of patients without supervision of a consultant. Read my blog, interact and ask questions so that I can help you more.

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