Chronic Inflammatory Arthritis – Causes, Symptoms, Treatment

Types of Chronic Inflammatory Arthritis
Causes of Chronic Inflammatory Arthritis
Symptoms of Chronic Inflammatory Arthritis
Diagnosis of Chronic Inflammatory Arthritis
Treatment of Chronic Inflammatory Arthritis
Treatment Planning

Chronic Inflammatory Arthritis/Psoriatic arthritis (PsA) is chronic inflammatory arthritis associated with psoriasis (PsO) and found in about 20 to 30% of such patients. It shares many clinical features with other spondyloarthropathies and also rheumatoid arthritis (RA). It is usually seronegative, but a small percentage of patients may be positive for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies). The clinical manifestations are varied and can change over time, evolving from one articular pattern to another. There is a considerable financial and psychological burden associated with this disease. There has been significant progress recently in understanding the disease pathogenesis, which has translated into new therapies.[rx]

Chronic Inflammatory Arthritis

Types of Chronic Inflammatory Arthritis

The earliest classification of psoriatic arthritis by Moll and Wright included five subtypes:

Oligoarticular arthritis which is asymmetric and involves less than five small or large joints
Polyarticular arthritis which is usually symmetric and presents similar to rheumatoid arthritis but may involve the DIP joints, rheumatoid factor negative
Distal arthritis signified by prominent involvement of the DIP joints
Arthritis mutilans characterized by a severe destructive joint disease with deformities especially in hands and feet
Spondyloarthritis pattern with sacroiliitis and spondylitis (this may occur with or without peripheral joint disease)

Types of Psoriatic Arthritis and Their Symptoms

Symmetric arthritis – Symmetric arthritis occurs in the same joints on both sides of the body. Similar to rheumatoid arthritis (RA), symmetric arthritis symptoms include joint pain, inflammation, and stiffness. However, symmetric arthritis symptoms are usually milder than RA symptoms.
Asymmetric arthritis – With asymmetric arthritis, many joints can be affected, including the wrist, hip, knee, and ankle, but it doesn’t occur in the same joints on both sides of the body. Symptoms include joint pain that comes and goes, and joints may become warm, tender, and/or red. Some people also develop dactylitis—a condition that causes pain and swelling of the fingers and/or toes. Dactylitis is sometimes referred to as “sausage digit” because when the fingers or toes become inflamed, they can resemble a sausage.
Distal interphalangeal predominant (DIP) – This type of psoriatic arthritis is pretty rare and is sometimes confused with osteoarthritis (OA). But what distinguishes distal interphalangeal predominant from OA is that it usually involves the finger and/or toe joints closest to the fingernail and/or toenail. (“Distal” means “near” and “phalanges” are fingers and toes, so “interphalangeal” means “between fingers/toes”).
Spondylitis: Spondylitis – also known as ankylosing spondylitis is inflammation in the spinal column. Common symptoms are inflammation, reduced flexibility, and stiffness in the neck and low back, which can make moving or bend painfully and very difficult to do.
Arthritis mutilans – This type of psoriatic arthritis is a severe and often destructive form of the condition. It mostly affects the hands and feet, but fortunately, it’s rare.

Subtypes of PsA and enthesitis

A subtype of psoriatic arthritis	Characteristics
Symmetrical polyarthritis	≥ 5 joints are involved Symmetrical joint involvement Occurs typically in small joints of hands and feet Less common in large joints More common in women
Asymmetrical oligoarthritis	Asymmetric joint involvement of < 5 joints Occurs in distal interphalangeal joints, large joints, feet Typical early knee involvement More common in men
Distal interphalangeal predominant arthritis	Symmetric or asymmetric Affects few or many distal interphalangeal joints > 50% of all affected joints are distal interphalangeal joints Leads to progressive bony lesions
Arthritis mutilans	The most severe and destructive form of psoriatic arthritis Finger shortening with severe osteolysis on imaging studies Pencil-in-cup changes, total joint erosion, ankylosis, subluxation Leads to irreversible deformity and loss of functional independence
Predominant spondyloarthropathy	Degenerative changes and inflammation of sacroiliac joints and apophyseal joints of the spine Radiographic sacroiliitis Typically localized in lumbar spine Inflammatory backache
Enthesitis	Present in 23% to 53% of patients with psoriatic arthritis, prominent in 38% of patients More frequent in lower extremities Might be asymptomatic in the early stages of psoriatic arthritis Can cause severe, disabling pain, particularly in lower extremities Tenderness over entheses or occasional soft tissue swelling may be found on physical examination Typically localized in Achilles tendon, plantar fascia, greater trochanter[rx–rx]

Causes of Chronic Inflammatory Arthritis

Non-articular etiologies: hypothyroidism, depression, somatoform pain disorder
Peri-articular etiologies: bursitis, tendinitis, neuropathic pain, metabolic bone diseases, soft tissue injury, fibromyalgia
Non-inflammatory articular etiologies: osteoarthritis

Inflammatory arthritis etiologies

Bacterial (Lyme disease, endocarditis, septic arthritis)
Viral (hepatitis B and C, Epstein Barr virus, parvovirus, dengue, alphaviruses, rubella, human immunodeficiency virus, mumps, coxsackievirus)
Collagen-vascular disease (rheumatoid arthritis, palindromic rheumatism, rheumatic fever, lupus, vasculitis, systemic sclerosis, myositis, ankylosing spondylitis, psoriatic arthritis, Behcet syndrome, relapsing polychondritis)
Crystal-induced arthritis (uric acid deposition of gout, calcium pyrophosphate deposition of pseudogout)
Post-infectious or reactive arthritis (post enteric infections, disseminated gonococcal infection)
Familial Mediterranean fever

Symptoms of Chronic Inflammatory Arthritis

The clinical features of psoriatic arthritis are described in terms of articular and extra-articular manifestations.

Articular/periarticular manifestations of psoriatic arthritis

Peripheral arthritis presenting in an oligoarticular vs. polyarticular pattern
Periarticular disease including enthesitis (inflammation around the insertion of ligaments, tendons, or joint capsules), dactylitis (swelling of the entire digit, finger or toe, “sausage digit”), and tenosynovitis
Axial disease involving sacroiliac joints, usually asymmetric and spondylitis with discontinuous involvement with bulky non-marginal syndesmophytes

Extra-articular manifestations of psoriatic arthritis

Psoriatic skin disease usually presents before the onset of arthritis but can occur simultaneously and even before the onset of joint disease. The severity of skin disease does not correlate well with the severity of the articular disease.[rx]
Nail disease characterized by onycholysis, pitting, and splinter hemorrhages. The severity of nail disease correlates with the severity of both skin and joint disease.[rx] It is present in 80 to 90% of patients with psoriatic arthritis and is associated with DIP joint involvement.
Ocular disease in the form of uveitis but unlike that associated with ankylosing spondylitis, it is often chronic, bilateral, and often involves posterior elements.

Common Psoriatic Arthritis Symptoms

Back pain
Changes to your nails (eg, the nails can begin to separate from the nail bed)
Decreased range of motion
Eye pain and eye redness
Fatigue
Painful, swollen joints
Sausage-like swelling of the fingers or toes (although this is more common during the advanced stages)
Stiffness (especially in the morning)
Tenderness at the points where muscles and/or ligaments connect to bones, especially the heel and bottom of the foot

Diagnosis of Chronic Inflammatory Arthritis

Lesions suspected of polyarthritis (PsA)

Early lesions period (0–6 months).

Isotope examination

– Ultrasound examination of joints found to be abnormal on isotope examination;
– Hand X-ray (initial radiographs).

MRI

– In the case of equivocal ultrasound;
– Lesions involving axial skeleton (CT alternatively).

Later period (over 6 months).

Monitoring of treatment:

- - – Ultrasound of abnormal joints;
  - – Scintigraphy/ultrasound/MRI (alternatively) in case of symptoms suggesting the involvement of other joints.
Follow-up hand X-ray after 2 years.

Advanced lesions

Bilateral hand X-ray examination (if involved) every 2 years.
Ultrasound for monitoring activity of the inflammatory process.
Magnetic resonance imaging in case of axial skeleton involvement.

In the 60’s and 70’s five clinical forms of PsA were distinguished by Moll and Wright:

The classic course of the disease with involvement of the distal interphalangeal joints (5% of cases).
The destructive form of arthritis (arthritis mutilans) (5% of cases).
Symmetric polyarthritis is indistinguishable from rheumatoid arthritis with a negative rheumatoid factor (approximately 15% of cases).
An asymmetric form involving a few interphalangeal joints (also distal) and metacarpophalangeal joints. It is the most common form of arthritis in psoriasis (approximately 70% of all cases).
A form resembling ankylosing spondylitis (5% of cases).

A group of diseases with similar clinical manifestations called seronegative spondyloarthropathies (SpA) has also been defined [rx]. The group includes:

Ankylosing spondylitis (AS).
Psoriatic Arthritis (PsA).
Spondylitis with associated bowel disease (or enteropathic spondylitis).
Reactive arthritis.
Undifferentiated spondyloarthropathies.

To support the diagnosis of seronegative spondyloarthropathies, the European Spondyloarthropathy Study Group (ESSG) created some clinical criteria. Basing on these criteria the assessment includes the following features:

Inflammatory back pain.
Arthritis.
Positive family history.
Psoriasis.
Inflammatory bowel disease.
Buttock pain.
Enthesitis.
Episodes of acute diarrhea.
Urethritis.
Sacroiliitis.

The following examinations and tests can help to diagnose psoriatic arthritis and distinguish it from other inflammatory conditions of the joints:

Physical examination – Certain changes are more typical of psoriatic arthritis. For instance, the inflammation may affect a whole finger (dactylitis) or the tendons and tendon sheaths of the hands or feet, such as the Achilles tendon (enthesitis).
Blood tests – 90% of people with psoriatic arthritis don’t have any of the antibodies in their blood that is typical of rheumatoid arthritis. So if none of these “rheumatoid factors” are found, it’s more likely to be psoriatic arthritis.
Measuring uric acid levels – High levels of uric acid in the blood are a sign that the joint problems are being caused by gout rather than psoriatic arthritis.
Imaging techniques – X-rays and ultrasound scans can help to find out whether someone has psoriatic arthritis, rheumatoid arthritis, or osteoarthritis. The images can also help doctors get an idea of the severity and type of joint damage. But changes in the joints are often not yet clearly visible in the early stages of psoriatic arthritis.[rx, rx, rx, rx]
Ultrasound – is readily available in the clinics and hospitals and is has utility for a variety of functions, but it has a limited role in polyarticular arthritis for detecting erosions and synovitis. Clinicians can easily perform joint injection under the guidance of ultrasound.[rx][rx] Computed tomography has almost no role other than ruling out other etiologies, and the role of MRI is to pick very early joint inflammation or early bone/soft tissue infection.
Radionuclide scans – are rarely done but have specific purposes. Picking up metastases, Paget disease of the bone, and osteomyelitis represent several of these indications.
Erythrocyte sedimentation rate and C-reactive protein – are non-specific markers of inflammation but usually helpful in ruling in a pathology causing significant inflammation and also monitoring its response to treatment.[9]
Polarized microscopy – of synovial fluid can help with crystal arthritis diagnoses, such as gout and pseudo-gout. Clinicians also analyze synovial fluid for cell count, gram stain and cultures. Synovial fluid leukocyte counts less than 200/mm are normal, between 200/mm and 2000/mm are associated with non-inflammatory arthritis, and over 2000/mm with inflammatory arthritis. If the cell count is over 50000/mm, physicians should treat the fluid as infectious.[10]

Radiologic findings in PsA

Radiologic findings in psoriatic arthritis
X-ray	Soft tissue swelling – sausage fingers New bone formation with “fuzzy” appearance Periostitis Periarticular osteoporosis Joint destruction with erosions Joint space narrowing Ankylosis Distal phalanx bone resorption
Ultrasound	Synovitis Tenosynovitis Subcutaneous soft tissue thickening Inflammation of entheses Thickening and erosions of entheses
Magnetic resonance imaging	Cartilage degeneration Bone erosions Synovial proliferation Synovitis Tenosynovitis Bone marrow edema

Classification Criteria

The most accepted classification criteria for psoriatic arthritis are the CASPAR criteria (Classification of Psoriatic Arthritis ) which have been in use since 2006.[rx] Other classification criteria that clinicians have used include the original Moll and Wright (1973), Bennet (1979), and Vassey and Espinoza (1984), the modified ESSG (1991) criteria.[rx]

Moll and Wright criteria (1973)[rx]

Inflammatory arthritis (peripheral arthritis and/or sacroiliitis or spondylitis)
The presence of psoriasis
The absence of serologic tests for rheumatoid factor

CASPAR Criteria (2006)[rx]

Clinical features/Characteristics/Points

Skin psoriasis: present – 2 / previously present -1 / family history, patient not affected – 1
Nail lesions: onycholysis, pitting, hyperkeratosis – 1
Dactylitis: present or past, documented by a rheumatologist – 1
Rheumatoid factor: negative by any method except for latex – 1
Juxta-articular bone formation: distinct from osteophytes – 1

Per CASPAR criteria, psoriatic arthritis is considered to be present in patients with inflammatory arthritis who have at least 3 points; this has a specificity of 98.7% and a sensitivity of 91.4%.[rx]

Treatment of Chronic Inflammatory Arthritis

General Principles

Treatment should be guided by disease severity, degree of joint damage, the extent of extra-articular disease, patient preference, and other co-morbidities.
Non-pharmacological therapies, including physical therapy, occupation therapy, exercise program, and smoking cessation, should be strongly encouraged and incorporated in the treatment plan.[rx]
The Treat-to-Target approach is the most effective way to control disease activity and minimize joint damage.[rx][rx] A target of low remission or low disease activity should be employed depending on disease extent, chronicity, and other co-morbidities.
Due to the heterogeneous presentation of psoriatic arthritis, the type of treatment initiated depends on the domains involved, including peripheral arthritis, enthesitis, dactylitis, axial disease, and skin/nail disease.
In treatment-naïve patients, NSAIDs ( non-steroidal anti-inflammatory drugs ) are generally useful for symptoms of mild peripheral arthritis.[rx]
Mild to moderate peripheral arthritis may be treated with conventional synthetic DMARDs (disease-modifying antirheumatic drug ) such as methotrexate or occasionally sulfasalazine, the latter is not effective for skin disease.[rx]
Severe peripheral arthritis usually receives treatment with biologic DMARDs, especially TNF (tumor necrosis factor) inhibitors.
Axial disease and enthesitis are usually treated the same way except for the fact that there is a minimal role of conventional synthetic DMARDs. Patients who fail NSAIDs should automatically transition to biologic DMARDs.
A TNF inhibitor is usually recommended over an IL-17 inhibitor, IL-12/23 inhibitor, abatacept, or tofacitinib.
An IL-17 inhibitor is usually recommended over an IL-12/23 inhibitor, abatacept, or tofacitinib.
An IL-12/23 inhibitor is usually recommended over abatacept or tofacitinib.
In patients with severe psoriasis, an IL-12/23 inhibitor or an IL-17 inhibitor may be used instead of a TNF inhibitor.
Tofacitinib may be used instead of a TNF inhibitor in patients preferring oral medication who do not have severe psoriasis.
ACR/NPF (American College of Rheumatology/National Psoriasis Foundation) 2018 guidelines recommend a TNF inhibitor over conventional synthetic DMARDs (labeled as OSM, oral small molecules) as a first-line treatment in treatment-naïve psoriatic arthritis patients.

Active Psoriatic Arthritis (as defined in ACR/NPF 2018 guidelines)[rx]

Defined as “disease-causing symptoms at an unacceptably bothersome level as reported by the patient, and judged by the examining clinician to be due to psoriatic arthritis” based on ≥1 of the following:

Swollen joints
Tender joints
Dactylitis
Enthesitis
Axial disease
Active skin and/or nail involvement
Extra-articular inflammatory manifestations such as uveitis or inflammatory bowel disease

ACR/NPF Guidelines for the Treatment of Psoriatic Arthritis: 2018. Initial Treatment

Treat with TNF inhibitor over oral small molecule (OSM) – May consider OSM with mild psoriatic arthritis and psoriasis, patient preference, contraindication to TNF inhibitor
Treat with TNF inhibitor over IL-17 inhibitor – May consider IL-17 inhibitor with severe psoriasis or contraindication to TNF inhibitor
Treat with TNF inhibitor over IL-12/23 inhibitor – May consider IL-12/23 inhibitor with severe psoriasis of contraindication to TNF inhibitor
Treat with OSM over IL-17 inhibitor – May consider IL-17 inhibitor with severe psoriasis and/or psoriatic arthritis
Treat with OSM over IL-12/23 inhibitor – May consider IL-12/23 inhibitor with severe psoriasis and/or psoriatic arthritis, or concomitant IBD (inflammatory bowel disease)
Treat with Methotrexate over NSAIDs – May consider NSAIDs with mild psoriatic arthritis and psoriasis
Treat with IL-17 inhibitor over IL-12/23 inhibitor – May consider IL-12/23 inhibitor in a patient with concomitant inflammatory bowel disease

Treatment Planning

Basic therapy (skincare) – Care of the affected areas of skin using lipid-replenishing ointments, creams, or lotions. This is done to keep the skin supple, protect it from injury, and relieve itching. Some products also contain medications that are supposed to reduce sheddings, such as urea or salicylic acid.
Topical treatment – Products containing corticosteroids or vitamin D analogs are typically used in topical treatment (treatment applied to the skin from the outside). These are available in the form of creams, ointments lotions or foams.
Light therapy – Light therapy, also known as phototherapy, involves exposing the plaques to ultraviolet light (UV light). The UV light reduces inflammation in the skin, and also slows the production of cells. Sometimes medications called psoralens are used in combination with light therapy. Psoralens make the skin more sensitive to light. Light therapy is best suited for people who have moderate or severe psoriasis and in whom topical treatment alone wasn’t effective enough.
Medications that are taken orally or injected – These medicines are a treatment option for moderate or severe psoriasis. They inhibit the body’s immune response. Methotrexate (MTX), fumaric acid esters, apremilast and biological drugs (biologics) are commonly used for this purpose.

Various parameters used in assessing disease activity in psoriatic arthritis:

Tender and swollen joint counts of 68 joints and 66 joints, respectively, in peripheral arthritis
Axial disease activity determined by BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) also used in ankylosing spondylitis
Health-related QoL (Quality of Life) as measured by indices like PsAQOL
Fatigue assessment by FACIT (Functional Assessment of Chronic Illness Therapy)
Composite indices like DAPSA (Disease Activity Index for Psoriatic Arthritis), MDA (Minimal Disease Activity), America’s College of Rheumatology criteria viz ACR 20/50/70 (Table 3), Psoriatic Arthritis Response Criteria (PsARC)(Table 4), and CDPAI (Composite Psoriatic Disease Activity Index)(Table 5)
The RAPID3 (Routine Assessment of Patient Index Data), which is useful for assessment of disease activity in rheumatoid arthritis, is simple to administer and does not require any laboratory indices. It compares favorably to other, more complicated measures of disease activity in psoriatic arthritis and is more practical for routine clinical care.[rx] The DAS28 (Disease Activity Score using 28 joints) is used frequently in the measurement of disease activity in rheumatoid arthritis, but it is inadequate as it focuses on peripheral arthritis.

A treat-to-target approach to attain remission or minimal disease activity (MDA) is a strong recommendation.[rx] A patient is considered to have achieved MDA if they meet 5 of 7 following criteria.[rx]

Minimal Disease Activity (MDA)

Tender joint count of less than or equal to 1
Swollen joint count less than or equal to 1
Psoriasis Area and Severity Index of less than or equal to 1 or body surface area less than or equal to 3
Patient pain visual analog scale (VAS) score less than or equal to 15 mm
Patient global disease activity VAS score less than or equal to 20 mm
Health Assessment Questionnaire score less than or equal to 0.5
Tender entheseal points less than or equal to 1

Novel therapeutic options for PsA (biological medicinal products) [rx–rx]

Agent	Mechanism of action	Indications	Outcomes
Etanercept	dimeric p75 TNF-α receptor Fc fragment fusion protein	Severe peripheral PsA in patients with erosive disease and functional limitation Moderate to severe axial disease Severe dactylitis affecting many digits or with functional limitation Enthesitis Choice of agent based on patient’s preferences for drug administration	Limit joint damage, restore joint function Reduce radiographic progression Comparable efficiency of all conventional TNF-inhibitors Therapy can be switched from one to another TNF inhibitor
Adalimumab	human monoclonal antibody against TNF-α
Infliximab	human/mouse chimeric anti-TNF-α antibody
Certolizumab pegol	Pgylated Fab fragment of humanized anti-TNF monoclonal antibody
Golimumab	Fully human anti-TNF IgG monoclonal antibody
Secukinumab	Human anti-IL17A monoclonal antibody	Peripheral arthritis resistant to TNF inhibitor Enthesitis and dactylitis	Reduces radiographic progression compared with placebo Reduces the frequency of enthesitis and dactylitis
Ixekizumab	Anti-IL-17A monoclonal antibody	Recommended for plaque psoriasis Efficiency for PsA demonstrated in several clinical trials	Reduces radiographic progression; improves physical function Improves skin lesions
Ustekinumab	Human monoclonal antibody to the shared p40 subunit of IL-12 and IL-23	Peripheral and axial PsA resistant to initial TNF inhibitor Enthesitis, dactylitis	Effective and safe Reduces radiographic progression of joint injury and improve joint function
Tofacitinib	Inhibitor of Janus kinase (JAK)	PsA in patients with inadequate response or intolerance to MTX or other DMARDs Peripheral arthritis	Improves physical function
Abatacept	CTLA4-Ig a selective T-cell costimulation modulator	PsA Recommended when other drugs have failed or are contraindicated	Improves changes in MRI of affected joints in the hands or feet
Apremilast	Phosphodiesterase-4 inhibitor	PsA and nonerosive inflammatory arthritis with multiple comorbidities Early stage of enthesitis and dactylitis Recommended for patients who prefer oral drug administration	Good safety profile Not recommended for patients

Surgical Treatment

Orthopedic procedures in lower extremities in patients with PsA or psoriasis, including indications, likely outcomes, and potential complications [rx, rx–rx]

Procedure	Indications	Benefits	Potential complications
Synovectomy	Synovitis, persistent joint effusion	Removal of inflammatory synovium, decrease in proinflammatory cytokines, and effusion control	Side effects were not reported [rx, rx, rx] Potential complications include infection, hematoma, and joint contractures [rx]
Osteotomy	Joint malalignment	Restoration of mechanical properties of joints	Complications were not reported in patients with psoriatic arthritis [rx] Potential complications include infection, hematoma, persistent pain, over- and under correction [rx]
Debridement [rx]	Loose bodies, degenerative changes of labrum, menisci, or articular cartilage	Decrease in proinflammatory cytokines	Complications were not reported in patients with psoriatic arthritis [rx]. Potential complications include infection, hematoma, iatrogenic joint destruction [rx]
Tissue reconstruction [rx] (ligaments, menisci, labrum, cartilage)	Ligament insufficiency, chondral defects, labral tears, meniscus tears	Restoration of mechanical properties of joints	Complications were not reported in patients with psoriatic arthritis [rx]. Potential complications include infection, hematoma, iatrogenic joint destruction
Arthrodesis	Painful end-stage arthrosis in patients with contraindications to arthroplasty	Painless weight-bearing joints	The following have been reported: delayed bone union, nonunion of arthrodesis, Koebner phenomenon [rx, rx]. Potential surgical side effects include loss of motion in adjacent joints, infection, malalignment, hematoma, persistent pain, deep venous thrombosis [rx]
Arthroplasty	Painful end-stage arthrosis	Restoration of painless range of motion in joints	Reported complications [rx, rx] include infection, pulmonary embolism, paralytic ileus, deep venous thrombosis, exacerbation of psoriasis (similar risk as in the general population). Potential complications include periprosthetic fractures, hematoma, implant failure, osteolysis, dislocation [rx]

Complications

Infections
Chronic anemia
Gastrointestinal cancers
Pleural effusions
Osteoporosis
Heart disease
Sicca syndrome
Felty syndrome
Lymphoma

References