Background

• About 20% of psoriasis patients suffer from psoriatic arthritis (PsA), a chronic inflammatory arthritis. It shares clinical features with other spondyloarthropathies, such as ankylosing spondylitis and rheumatoid arthritis (RA). While PsA is typically seronegative, meaning that specific autoantibodies like rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) are not commonly present, a small percentage of patients may test positive for these markers. 
• The clinical manifestations of PsA are diverse and can vary over time, with patients experiencing different patterns of joint involvement. PsA imposes a significant burden on patients, both financially and psychologically. The chronic nature of the disease, along with its associated pain, stiffness, and functional limitations, can impact affected individuals’ quality of life and daily activities.  

Epidemiology

• The prevalence of PsA in the general population has been estimated to range from 0.05% to 0.25%, indicating that it is a relatively uncommon condition. However, the prevalence is significantly higher in individuals with psoriasis, with 6% to 41% estimates. This wide range is partly due to underdiagnosis, as some cases of PsA may go unrecognized or undiagnosed. The prevalence of undiagnosed PsA could be as high as 15.5%. 
• The onset of PsA typically occurs in the 30s and 40s, and there is an equal distribution between males and females. In most patients, the skin manifestations of psoriasis precede the onset of arthritis, but there are cases where arthritis can occur before skin involvement, particularly in childhood PsA. 
• The incidence and cumulative prevalence of PsA in patients with psoriasis increase over time. The annual incidence has been reported to range from 1.9% to 2.7% per 100 psoriasis patients. The cumulative prevalence at different time intervals shows that PsA can develop in a significant proportion of patients with psoriasis, reaching 20.5% at 30 years. 
• The prevalence of PsA also varies geographically and among different ethnic groups. Europe and North America have higher prevalence rates, while the Middle East, South Asia, Southeast Asia, East Asia, and South America have relatively lower rates. Genetic, environmental, and cultural factors may influence these regional differences. 

Anatomy

Pathophysiology

• Genetic Factors: PsA has a vital genetic component with a significant heritability. Specific genes, such as human leukocyte antigen (HLA) genes, particularly HLA-B27, have been associated with an increased risk of developing PsA.  
• Immune Dysregulation: PsA is an autoimmune disease characterized by an abnormal immune response against self-tissues. Inflammation occurs when normal joint tissues are inappropriately attacked by the immune system.  
• Inflammatory Pathways: It is characterized by an overactive immune response, with increased production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-23 (IL-23). These cytokines contribute to the recruitment and activation of immune cells, leading to joint inflammation. 
• Synovial Hyperplasia: In PsA, there is the proliferation of synovial tissue lining the joints (synovial hyperplasia), which further contributes to joint inflammation and damage. The synovium becomes infiltrated with immune cells, including T cells, B cells, and macrophages, which release inflammatory mediators and enzymes that degrade joint tissues. 
• Enthesitis:  It is an important characteristic of PsA and may cause discomfort, edoema, and stiffness in tissues including the plantar fascia, Achilles tendon, and other entheses. Enthesitis is thought to result from immune-mediated inflammation at these sites. 
• Bone Erosion: Bone erosions result from the inflammatory process and the release of enzymes that break down bone tissue.  

Etiology

The etiology of psoriatic arthritis (PsA) is multifactorial and involves genetic, immunological, and environmental factors.  

• Genetic Predisposition: Specific genes have been associated with increased susceptibility to PsA, including genes within the major histocompatibility complex (MHC) region, particularly HLA-B27. Other genetic markers, such as HLA-Cw6 and several non-HLA genes, have also been implicated in PsA susceptibility. 
• Immunological Abnormalities: PsA is characterized by dysregulation of the immune system, leading to an abnormal immune response. T cells, particularly CD8+ T cells, play a significant role in the pathogenesis of PsA. Pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-), interleukin-23 (IL-23),  interleukin-22 and interleukin-17 (IL-17) are produced by activated T cells that have infiltrated the synovium. These cytokines contribute to inflammation, synovial hyperplasia, and joint damage in PsA. 
• Environmental Triggers: Environmental factors, such as infections or trauma, may trigger the development of PsA in genetically susceptible individuals. Infections, particularly streptococcal throat infections, have been suggested as potential triggers, as they can initiate an immune response that leads to the development of PsA.  
• Interactions between Genetic and Environmental Factors: The development of PsA is likely a result of complex interactions between genetic susceptibility and environmental triggers.  

Genetics

Prognostic Factors

• Early Disease Onset: The age at which PsA develops can influence the disease outcome. Early-onset PsA, particularly in individuals under the age of 40, has been associated with a higher risk of joint damage, disability, and more aggressive disease progression. 
• Severity of Skin and Nail Involvement: Patients with extensive skin disease, pustular or erythrodermic psoriasis, or nail psoriasis may have a higher likelihood of developing more severe joint symptoms and a more challenging disease course. 
• Joint Involvement: Involvement of the axial skeleton, such as the spine and sacroiliac joints, can also contribute to a poorer prognosis. 
• HLA-B27 Positivity: The presence of HLA-B27, a genetic marker associated with certain spondyloarthropathies, including PsA.HLA-B27 positivity is often linked to axial involvement, including sacroiliitis and spondylitis, which can lead to spinal fusion and functional impairment. 

Clinical History

Physical Examination

Skin Examination: 

• Assessment of psoriatic skin lesions 
• Nail examination 
• Joint Examination 
• Range of motion assessment 
• Palpation 
• Assessment of joint involvement 
• Dactylitis examination 

Spinal Examination: 

• Assessment of spinal mobility 
• Sacroiliac joint examination 

Age group

Associated comorbidity

• Psoriasis: PsA is strongly associated with psoriasis, and most patients with PsA have a history of psoriatic skin lesions. Psoriasis may precede, coincide with, or follow the onset of arthritis. 
• Nail involvement: Nail psoriasis, such as pitting, crumbling, or oil spots on the nails, is frequently seen in PsA patients. 
• Enthesitis: Inflammation at the sites where tendons or ligaments attach to bones, known as enthesitis, is a common feature of PsA.  
• Dactylitis: Dactylitis, also called “sausage digit,” is characterized by an entire finger or toe swelling. It is a distinct feature of PsA. 

Associated activity

Acuity of presentation

PsA often has an insidious onset, meaning the symptoms gradually develop over time rather than appearing suddenly. 

Variable Joint Involvement: PsA can affect different joints, leading to various patterns of joint involvement. These include: 

• Asymmetric oligoarthritis involves a few joints on one side of the body. 
• Symmetric polyarthritis involves multiple joints on both sides of the body, like rheumatoid arthritis. 
• Distal interphalangeal (DIP) arthritis: Predominantly affecting the small joints of the fingers and toes. 
• Arthritis mutilans: A severe form of PsA characterized by rapid joint destruction and deformity. 
• Axial involvement: Inflammation of the spine and sacroiliac joints, leading to axial spondyloarthritis. 

Differential Diagnoses

The following are some of the standard differential diagnoses for PsA: 

• Rheumatoid arthritis (RA): RA is an autoimmune condition that primarily affects the joints. It can cause joint pain, swelling, and stiffness, which may resemble the symptoms of PsA.  
• Osteoarthritis (OA): The degradation of cartilage in the joints is a hallmark of OA, a degenerative joint disease. It can cause joint pain, stiffness, and limited range of motion, like PsA.  
• Ankylosing spondylitis (AS): It is a type of spondyloarthritis that primarily affects the spine and sacroiliac joints. It can cause inflammation, pain, and stiffness in the lower back and buttocks, like PsA.  
• Reactive arthritis: Reactive arthritis, also called Reiter’s syndrome, is an inflammatory arthritis that typically follows an infection, usually in the genitourinary or gastrointestinal tract. It can cause joint pain, swelling, and other symptoms like urethritis and conjunctivitis.  

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

• Patient education: Providing information about the disease, its course, and self-management strategies. 
• Physical and occupational therapy: Exercises and techniques to improve joint mobility, reduce pain, and enhance function. 
• Assistive devices: Use assistive devices such as splints, braces, or walking aids to support affected joints and improve mobility. 

• Nonsteroidal anti-inflammatory drugs (NSAIDs) help reduce pain, inflammation, and joint stiffness. 
• Disease-modifying antirheumatic drugs (DMARDs): Drugs like methotrexate, sulfasalazine, and leflunomide may slow disease progression and preserve joint function. 
• Biologic agents: Biologic drugs, such as tumor necrosis factor (TNF) inhibitors (e.g., adalimumab, etanercept) and other targeted therapies (e.g., interleukin-17 inhibitors, interleukin-23 inhibitors), can be used to suppress the immune response and reduce inflammation. 
• Corticosteroids: Short-term oral or injectable corticosteroids may be considered to manage severe symptoms during flares.

• Intra-articular steroid injections: These injections can be used to deliver corticosteroids directly into inflamed joints to reduce pain and inflammation. 
• Synovectomy: Surgical removal of the inflamed synovial lining of the joints may be considered in persistent joint swelling and pain cases. 

• Induction phase: The initial phase of treatment aims to control symptoms and reduce inflammation using medications such as NSAIDs, intra-articular corticosteroid injections, or short-term systemic corticosteroids. 
• Maintenance phase: Once symptoms are under control, DMARDs or biologic agents may be prescribed to achieve long-term disease control and prevent joint damage. 
• Monitoring and adjustment: Regular monitoring of disease activity, response to treatment, and potential side effects are essential. Treatment adjustments may be made based on individual response and disease progression. 

Medication

Future Trends

Media Gallary

References

• Psoriatic arthritis:ncbi.nlm.nih