OSTEOARTHRITIS

OSTEOARTHRITIS. GOUT.

 

Osteoarthritis.

 

Osteoarthritis (OA, osteoarthrosis or degenerative joint disease) is not a single disease. Rather it is the end result of a variety of patterns of joint failure. To a greater or lesser extent it is always characterised by both degeneration of articular cartilage and simultaneous proliferation of new bone, cartilage and connective tissue.

 

 

The proliferative response results in some degree of remodelling of the joint contour. Inflam­matory changes in the synovium are usually minor and secondary.

“Osteoarthritis” is derived from the Greek word “osteo“, meaning “of the bone”, “arthro“, meaning “joint”, and “itis“, meaning inflammation, although many sufferers have little or no inflammation. A common misconception is that OA is due solely to wear and tear, since OA typically is not present in younger people. However, while age is correlated with OA incidence, this correlation merely illustrates that OA is a process that takes time to develop. There is usually an underlying cause for OA, in which case it is described as secondary OA. If no underlying cause can be identified it is described as primary OA. “Degenerative arthritis” is often used as a synonym for OA, but the latter involves both degenerative and regenerative changes.

 

Epidemiology

World statistics: Osteoarthritis affects more than 20 million individuals in the United States, though statistical figures are influenced by how the condition is defined—that is, by self-report, by radiographic or symptomatic criteria, or by a combination of these. On the basis of the radiographic criteria for osteoarthritis, more 50% of adults older than 65 years are affected by the disease.

Internationally, osteoarthritis is the most common articular disease. Estimates of its frequency vary across different populations.

Age-related demographics: primary osteoarthritis is a common disorder of the elderly, and patients are often asymptomatic. Approximately 80-90% of individuals older than 65 years have evidence of radiographic primary osteoarthritis. Symptoms typically do not become noticeable until after the age of 50 years. The prevalence of the disease increases dramatically among persons older than 50 years, likely because of age-related alterations in collagen and proteoglycans that decrease the tensile strength of the joint cartilage and because of a diminished nutrient supply to the cartilage.

Sex-related demographics: in individuals older than 55 years, the prevalence of osteoarthritis is higher among women than among men. Women are especially susceptible to osteoarthritis in the DIP joints of the fingers. Women also have osteoarthritis of the knee joints more frequently than men do, with a female-to-male incidence ratio of 1.7:1. Women are also more prone to erosive osteoarthritis, with a female-to-male ratio of about 12:1.

Race-related demographics: interethnic differences in the prevalence of osteoarthritis have beeoted. The disorder is more prevalent in Native Americans than in the general population. Disease of the hip is seen less frequently in Chinese patients from Hong Kong than in age-matched white populations. Symptomatic knee osteoarthritis is extremely common in China. In persons older than 65 years, osteoarthritis is more common in whites than in blacks. Knee osteoarthritis appears to be more common in black women than in other groups. Jordan et al found that in comparison with whites, African American men and women had a slightly higher prevalence of radiographic and symptomatic knee osteoarthritis but a significantly higher prevalence of severe radiographic knee osteoarthritis.

Etiology

The daily stresses applied to the joints, especially the weight-bearing joints (eg, ankle, knee, and hip), play an important role in the development of osteoarthritis. Most investigators believe that degenerative alterations in osteoarthritis primarily begin in the articular cartilage, as a result of either excessive loading of a healthy joint or relatively normal loading of a previously disturbed joint. External forces accelerate the catabolic effects of the chondrocytes and further disrupt the cartilaginous matrix. Etiological factors for the primary osteoarthritis include the following:

1.Advancing age

With advancing age come reductions in cartilage volume, proteoglycan content, cartilage vascularization, and cartilage perfusion. These changes may result in certain characteristic radiologic features, including a narrowed joint space and marginal osteophytes. However, biochemical and pathophysiologic findings support the notion that age alone is an insufficient cause of osteoarthritis.

Primary osteoarthritis is mostly related to aging. With aging, the water content of the cartilage increases, and the protein makeup of cartilage degenerates. Eventually, cartilage begins to degenerate by flaking or forming tiny crevasses. In advanced cases, there is a total loss of cartilage cushion between the bones of the joints. Repetitive use of the worn joints over the years can irritate and inflame the cartilage, causing joint pain and swelling. Loss of the cartilage cushion causes friction between the bones, leading to pain and limitation of joint mobility. Inflammation of the cartilage can also stimulate new bone outgrowths (spurs, also referred to as osteophytes) to form around the joints. Osteoarthritis occasionally can develop in multiple members of the same family, implying a hereditary (genetic) basis for this condition.

2.Obesity

Obesity increases the mechanical stress in a weight-bearing joint. It has been strongly linked to osteoarthritis of the knees and, to a lesser extent, of the hips. Higher body mass index (BMI) at year 1 and a significant increase in BMI over 15 years is predictor of bilateral knee pain at year. In addition to its mechanical effects, obesity may be an inflammatory risk factor for osteoarthritis. Obesity is associated with increased levels (both systemic and intra-articular) of adipokines (cytokines derived from adipose tissue), which may promote chronic, low-grade inflammation in joints.

3.Other causes

Trauma or surgery (including surgical repair of traumatic injury) involving the articular cartilage, ligaments, or menisci can lead to abnormal biomechanics in the joints and accelerate osteoarthritis. Although repairs of ligament and meniscal injuries usually restore joint function, osteoarthritis has been observed 5-15 years afterward in 50-60% of patients. Insults to the joints may occur even in the absence of obvious trauma. Microtrauma may also cause damage, especially in individuals whose occupation or lifestyle involves frequent squatting, stair-climbing, or kneeling. Muscle dysfunction compromises the body’s neuromuscular protective mechanisms, leading to increased joint motion and ultimately resulting in osteoarthritis. This effect underscores the need for continued muscle toning exercises as a means of preventing muscle dysfunction.Valgus malalignment at the knee has been shown to increase the incidence and risk of radiographic progression of knee osteoarthritis involving the lateral compartment.

4.Genetics

A hereditary component, particularly in osteoarthritis presentations involving multiple joints, has long been recognized.  Several genes have been directly associated with osteoarthritis, and many more have been determined to be associated with contributing factors, such as excessive inflammation and obesity. Genes in the BMP (bone morphogenetic protein) and WNT (wingless-type) signaling cascades have been implicated in osteoarthritis. Two genes in particular,GDF5 (growth and differentiation factor 5) and FRZB (frizzled related protein) have been identified in the articular cartilage in animal studies and share a strong correlation with osteoarthritis. Genetic factors are also important in certain heritable developmental defects and skeletal anomalies that can cause congenital misalignment of joints. These may result in damage to cartilage and the structure of the joint.

Etiological factors for secondary OA:

A. Miscellaneous

                                        Frostbite

                                        Caisson’s disease

                                        Hemoglobinopathies

B. Congenital or developmental

                                        Localized diseases: Legg-Calve ´-Perthes, congenital hip dislocation, slipped epiphysis

                                        Mechanical factors: unequal lower extremity length, valgus/ varus deformity, hypermobility syndromes

                                        Bone dysplasias: epiphyseal dysplasia, spondyloepiphyseal dysplasia, osteonychondystrophy

C. Metabolic

                                        Ochronosis (alkaptonuria)

                                        Hemochromatosis

                                        Wilson’s disease

                                        Gaucher’s disease

D. Endocrine

                                        Acromegaly

                                        Hyperparathyroidism

                                        Diabetes mellitus

                                        Obesity

                                        Hypothyroidism

E. Calcium deposition diseases

                                        Calcium pyrophosphate dihydrate deposition

                                        Apatite arthropathy

F. Other bone and joint diseases

                                        Localized: fracture, avascular necrosis, infection, gout

                                        Diffuse: rheumatoid (inflammatory) arthritis, Paget’s disease, osteopetrosis, osteochondritis

G. Neuropathic (Charcot joints)

H. Endemic

                                        Kashin-Beck

                                        Mseleni

Pathogenesis

OA is a chronic degenerative disorder related to but not caused by aging, as there are people well into their nineties who have no clinical or functional signs of the disease. As a person ages, the water content of the cartilage decreases due to a reduced proteoglycan content, thus causing the cartilage to be less resilient. Without the protective effects of the proteoglycans, the collagen fibres of the cartilage can become susceptible to degradation and thus exacerbate the degeneration.

http://www.orthopaedicsurgeon.com.sg/patients-education/knee/knee-pain-due-to-osteoarthritis/

 

         Inflammation of the surrounding joint capsule can also occur, though often mild (compared to that which occurs in rheumatoid arthritis). This can happen as breakdown products from the cartilage are released into the synovial space, and the cells lining the joint attempt to remove them. New bone outgrowths, called “spurs” or osteophytes, can form on the margins of the joints, possibly in an attempt to improve the congruence of the articular cartilage surfaces. These bone changes, together with the inflammation, can be both painful and debilitating.

The cartilage consists of predominantly collagen type 2 fibres linked by covalent bonds, conferring tensile strength. The matrix of the cartilage is formed by the chondrocytes which are embedded within it. The matrix consists of proteoglycans and non collagenous glycoproteins. Within the matrix, is water, tightly bound to the glycoprotein macromolecules. The chondrocytes get their nutrition from the surrounding fluid. The chondrocytes communicate via the fluid within the matrix by diffusion. The macromolecules give the cartilage the capacity for reversible deformation. They are hydrophilic and allow water molecule adherence between the collagen fibrillary network. The largest glycoprotein molecule is aggrecan. This consists of glycosaminoglycan chains predominantly made of keratan sulphate (KS), N-Acetyl glucosamine-galactose sulphated dimer, and chondroitin sulphate (CS), a dimer of N-acetyl galactosamine and glucuronic acid.

In disease there is loss of matrix, release of cytokines including IL-1, TNF and mixed metalloproteinase’s as well as prostaglandins by the chondrocytes. Fibrillation of the cartilage surface and attempted repair with osteophyte formation then occurs. The adjacent synovium is frequently observed to be inflamed and symptoms of inflammation, with rest pain and stiffness and findings of swelling, heat of joints and effusions may be present. In OA, a variety of potential forces – hereditary, developmental, metabolic, and mechanical – may initiate processes leading to loss of cartilage a strong protein matrix that lubricates and cushions the joints. As the body struggles to contain ongoing damage, immune and regrowth process can accelerate damage. When bone surfaces become less well protected by cartilage, subchondral bone may be exposed and damaged, with regrowth leading to a proliferation of ivory- like, dense, reactive bone in central areas of cartilage loss, a process called eburnation.

Subchondral bone cyst (A). Eburnated bone with focal necrosis of osteocytes (B).  Crack with leakage of synovial fluid into bone (C,D).

 

 

A.                 Normal articular cartilage. Note the intact surface and even distribution of chondrocytes. Mitotic figuresare not present iormal adult articular cartilage.

B.               Osteoarthritic cartilage.

 

As osteoarthritis progresses, however, the level of proteoglycans eventually drops very low, causing the cartilage to soften and lose elasticity and thereby further compromising joint surface integrity. Microscopically, flaking and fibrillations (vertical clefts) develop along the normally smooth articular cartilage on the surface of an osteoarthritic joint. Over time, the loss of cartilage results in loss of joint space.

Note the disruption of surface integrity, with vertical fissures (fibrillation) and irregular distribution of cells. Many of the chondrocytes have replicated and exist in clusters. Stained with safranin-O, which binds to the sulfated glycosaminoglycan chains of proteoglycans. Note patchy areas of diminished staining (pale extracellular matrix) due to proteoglycan depletion.

Classification

Osteoarthritis can be classified into either primary or secondary depending on whether or not there is an identifiable underlying cause.

Both primary generalized nodal OA and erosive OA (EOA. also called inflammatory OA) are sub-sets of primary OA. EOA is a much less common, and more aggressive inflammatory form of OA which often affects the distal interphalangeal joints and has characteristic changes on x-ray.

 

CLASSIFICATION OF OSTEOARTHRITIS

·       Idiopathic

·       Secondary

 

Localization of  OA

1. Hands:

                                        Heberden’s and Bouchard’s nodes (nodal),

                                        erosive interphalangeal arthritis,

                                        1st carpometacarpal joint

2. Feet:

                                        hallux valgus,

                                        hallux rigidus,

                                        contracted toes (hammer/cock-up toes),

                                        talonavicular

3. Knee:

                                        Medial compartment

                                        Lateral compartment

                                        Patellofemoral compartment

4. Hip:

                                        Eccentric (superior)

                                        Concentric (axial, medial)

                                        Diffuse (coxae senilis)

5. Spine:

                                        Apophyseal joints

                                        Intervertebral joints (disks)

                                        Spondylosis (osteophytes)

                                        Ligamentous (hyperostosis, Forestier’s disease, diffuse idiopathic skeletal hyperstosis)

6. Other single sites, e.g., glenohumoral, acromioclavicular, tibiotalar, sacroiliac, temporomandibular

Сlinical forms

1. Polyarthritis (5 and more joints)

2. Oligoarthritis (2-4 joints)

3. Monoarthritis

4. In combination with spinal osteochondrosis, spondyloarthrosis.

Synovitis:

– present;

– absent.

Kellgren-Lawrence XR-Grading Scale

 Grade I: doubtful narrowing of joint space and possible osteophytic lipping.

 Grade II: definite osteophytes, definite narrowing of joint space.

 Grade III: moderate multiple osteophytes, definite narrowing of joints space, some sclerosis and possible deformity of bone contour.

 Grade IV: large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone contour.

 

The functional ability of the patient:

1. Limited ability to work temporarily (FA I).

2. Lost working capacity (FA II).

3. Needs constant care (FN III).

Clinical features

Clinical symptoms of OA may include

·       joint pain

·       stiffness

·       “crepitus” of joints

·       inflammation

The main symptom is acute pain, causing loss of ability and often stiffness. “Pain” is generally described as a sharp ache, or a burning sensation in the associated muscles and tendons. OA can cause a crackling noise (called “crepitus“) when the affected joint is moved or touched, and patients may experience muscle spasm and contractions in the tendons. Occasionally, the joints may also be filled with fluid. Humid and cold weather increases the pain in many patients. The patient increasingly experiences pain upon weight bearing, including walking and standing. Due to decreased movement because of the pain, regional muscles may atrophy, and ligaments may become more lax.

In some cases it may be due to stretching of nerve endings in the periosteum covering osteophytes; in others, to microfractures in subchondral bone or medullary hyper-tension caused by distortion of blood flow by thickened subchondral trabeculae. Joint instability, leading to stretching of the joint capsule, and muscle spasm may also be sources of pain.

Causes of Joint Pain and Patients with OA

 

Stiffness appear after rest and disappears quickly as activity begins again. Morning stiffness lasting no longer than 30 minutes.

Bony crepitus (the sensation of bone rubbing against bone, evoked by joint movement) is characteristic.

Periarticular  muscle atrophy may be due to disuse or reflex inhibition of muscle contraction.  Physical examination of the OA joint may reveal localized tenderness and bony or soft tissue swelling. Palpation may reveal some warmth over the joint. In the

advanced stages of OA, there may be gross deformity, bony hypertrophy, subluxation, and marked loss of joint motion. The notion that OA is inexorably progressive, however, is incorrect.

In some patients with OA, joint pain may be due to synovitis. In advanced OA, histologic evidence of synovial inflammation may be as marked as that in synovium of a patient with rheumatoid arthritis. Synovitis in OA may be due to phagocytosis of shards of cartilage and bone from the abraded joint surface (wear particles), release from the cartilage of soluble matrix macromolecules, or crystals of calcium pyrophosphate or hydroxyapatite. In other cases, immune complexes, containing antigens derived from cartilage matrix, may be sequestered in collagenous tissues of the joint, leading to lowgrade chronic synovitis. In contrast, in the earlier stages of OA, synovial inflammation may be absent, suggesting that the joint pain is due to one of the other factors mentioned above.

As the disease progresses, movement in the affected joint becomes increasingly limited, initially as a result of pain and muscular spasm, but later because of capsular fibrosis, osteophyte formation and remodelling of bone.

The joints most frequently involved are those of the spine, hips, knees and hands. The disease is confined to one or only a few joints in the majority of patients. Common patterns of joint of primary generalised OA with prominent involvement of the knees and hands (distal interphalangeal joints, proximal interphalangeal joints, carpometacarpal joints of thumbs) involvement, as well include next types:

·                   nodal

·                   non-nodal

OA commonly affects the hands, feet, spine, and the large weight bearing joints, such as the hips and knees, although in theory, any joint in the body can be affected. As OA progresses, the affected joints appear larger, are stiff and painful, and usually feel worse, the more they are used throughout the day, thus distinguishing it from rheumatoid arthritis.

http://www.arthritis.co.za/osteoarthritis_update.html

 

 

SIGNS AND SYMPTOMS CHARACTERISTIC OF OSTEOARTHRITIS IN THE MOST FREQUENTLY AFFECTED JOINTS:

 

Hands:  squaring of the base of the hand; medial and lateral deviation at the DIPs (distal interphalangeal joint) and PIPs (proximal interphalangeal joint), affects:

·       DIPs (Heberden nodes)

·       PIPs (Bouchard nodes)

·       CMC (carpometacarpal joints)

 

 

http://articles.mercola.com/sites/articles/archive/2011/01/31/curcumin-relieves-pain-and-inflammation-for-osteoarthritis-patients.aspx

 

 

 

 

http://www.cedars-sinai.edu/Patients/Health-Conditions/Osteoarthritis.aspx

 

                                

http://arthritis.webmd.com/heberdens-and-bouchards-nodes

 

 

 

Bouchard’s nodes are hard, bony outgrowths or gelatinous cysts on the proximal interphalangeal joints (the middle joints of fingers or toes). Seen commonly in osteoarthritis, they are caused by formation of calcific spurs of the articular (joint) cartilage.  Bouchard’s nodes are comparable in presentation to Heberden’s nodes, similar osteoarthritic growths on the distal interphalangeal joints, but are significantly less common.

 

 

http://wikidoc.org/index.php/Bouchard’s_nodes

 

 

 

http://www.internalizemedicine.com/2012/09/heberdens-and-bouchards-nodes-mnemonic.html

 

 

 

Heberden’s nodes are hard or bony swellings that can develop in the distal interphalangeal joints (DIP). They are caused by formation of osteophytes (calcific spurs) of the articular (joint) cartilage in response to repeated trauma at the joint. Heberden’s nodes typically develop in middle age, beginning either with a chronic swelling of the affected joints or the sudden painful onset of redness, numbness, and loss of manual dexterity. This initial inflammation and pain eventually subsides, and the patient is left with a permanent bony outgrowth that often skews the fingertip sideways.

Heberden’s nodes are more common in women than in men, and there seems to be a genetic component involved in predisposition to the condition. Women carry the dominant gene and men carry the recessive.

 

 

 

http://www.patient.co.uk/doctor/osteoarthritis

 

 

http://www.clinicaladvisor.com/arthritis/slideshow/240/#0

 

 

Classification Criteria for Osteoarthritis of the Hand:

Hand pain, aching, or stiffness and 3 or 4 of the following features:

·         Hard tissue enlargement of 2 of 10 selected hand joints*

·         Metacarpophalangeal joint swelling in 2 joints

·         Hard tissue enlargement of 2 distal interphalangeal joint joints

·         Deformity of 1 of 10 selected hand joints

* The 10 selected joints are the second and third distal interphalangeal (DIP), the second and third proximal interphalangeal, and the first carpometacarpal joints of both hands. This classification method yields a sensitivity of 94% and a specificity of 87%.

 MCP = metacarpophalangeal.

 

Knees: Patellofemoral joint symptoms worse on the stairs than on the flat; varus changes with medial compartment disease, valgus with lateral; Baker’s (popliteal) cysts and tenderness of the pes anserine bursa are common.

http://arthritiskerala.com/disease-treatment.php?id=7

 

http://www.orthopaedicsurgeon.com.sg/patients-education/knee/knee-pain-due-to-osteoarthritis/

 

 

Criteria for Classification of Idiopathic Osteoarthritis (OA) of the Knee

 

 

* ESR = erythrocyte sedimentation rate (Westergren); RF = rheumatoid factor; SF OA = synovial fluid signs of OA (clear, viscous, or white blood cell count <2,000/mm³).

† Alternative for the clinical category would be 4 of 6, which is 84% sensitive and 89% specific.

EULAR Criteria of knee OA

–Persistent Knee pain (1 month, most days)

–Limited Morning Stiffness (< 30 min.)

–Impaired Function

–Crepitus

–↓ ROM LR

–Bony enlargement

 

Hips: Typically groin pain, but may present in buttocks; less so in knee or below knee; flexion contractures and Trendelenberg sign may be present.

 

Criteria for Classification of  Osteoarthritis (OA) of the Hip

Hip pain and at least 2 of the following 3 features:

·         ESR<20 mm/hour

·         Radiographic femoral or acetabular osteophytes

·         Radiographic joint space narrowing (syperior, axial, and/or medial)

*This classification method yields a sensitivity of 89% and a specificity of 91%. ESR = erythrocyte sedimentation rate 

Cervical spine: Local spine pain, muscle spasm, and limited motion (lateral flexion and extension); radicular pain with pain, sensory loss or muscle weakness/atrophy ierve root distribution; cervical myelopathy with long tract signs, bladder dysfunction

Lumbar spine: Local pain and muscle spasm, limited extension, buttock pain, worse in PM, but not nocturnal; radicular pattern with pain, sensory and motor changes ierve root distribution; spinal stenosis pattern pain with back/leg pain with standing, walking relieved by sitting

Laboratory and instrumental  findings

No laboratory studies are diagnostic for OA, but laboratory testing may help identify an underlying causes of secondary OA. Because primary OA is not systemic, the erythrocyte sedimentation rate, serum chemistry determinations, blood counts, and urinalysis are normal. ESR: usually normal.

 Synovial fluid analysis reveals mild leukocytosis (< 2000 white blood cells per microliter), with a predominance of mononuclear cells. Synovial fluid analysis is of particular value in excluding other conditions, such as calcium pyrophosphate dihydrate deposition disease, gout or septic arthritis.

The diagnosis of OA is usually based on clinical and radiographic features. In the early stages, the radiograph may be normal but joint space narrowing becomes evident as articular cartilage is lost. Other characteristic findings include subchondral bone sclerosis, subchondral cysts, and osteophytosis. A change in the contour of the joint, due to bony remo-deling, and subluxation may be seen. Although tibiofemoral joint space narrowing has been considered to be a radiographic surrogate for articular cartilage thinning, joint space narrowing alone does not accurately indicate the status of the articular cartilage in patients with early OA who do not have radiographic evidence of bony changes (e.g., subchondral sclerosis or cysts, osteophytes). Similarly, osteophytosis alone, in the absence of other radiographic features of OA, may be due to aging rather than OA. As indicated above, there is often great disparity between the severity of radiographic findings, severity of symptoms, and functional ability in OA; while >90% of persons over age 40 have some radiographic changes of OA in weight-bearing joints, only 30% are symptomatic.

Although the diagnosis of OA is often straightforward, because of the high prevalence of radiographic changes of OA in asymptomatic individuals, it is important to ensure that joint pain in a patient with radiographic evidence of OA is not due to some other cause, such as soft tissue rheumatism (e.g., anserine bursitis at the knee, trochanteric bursitis at the hip), radiculopathy, referral of pain from another joint (25% of patients with hip disease have pain referred to the knee), entrapment neuropathy, vascular disease (claudication), or some other type of arthritis (e.g., crystal-induced synovitis, septic arthritis). It is usually not difficult to differentiate OA from a systemic rheumatic disease, such as rheumatoid arthritis, because joint involvement in the latter disease is usually symmetric and polyarticular, with arthritis in wrists and metacarpophalangeal joints (sites not usually involved in OA), and constitutional features, such as prolonged morning stiffness, fatigue, weight loss, or fever, may be seen.

The Kellgren–Lawrence  grading system is  radiological classification osteoarthritis.  It is based  on x- rays and consists of normal, Grade I, Grade II, Grade II and Grade IV. This categorical scale incorporates important radiographic features of osteoarthritis:

·       Joint space narrowing – bone is visible on x-ray but the articular cartilage that covers it is not. A normal joint therefore appears to have a space between the bones. Any decrease in space implies a reduction in cartilage cover.

·       Osteophytes – small bony projections that from around joint margins. They are responsible for limiting range of motion and can cause pain.

·       Sclerosis – this means ‘hardening’ and is a sign of osteoarthritis, seen as increased white areas in the bone at the joint margins.

 

http://www.eradiography.net/radrep/Hand/Hand_osteoarthritis_001/Hand_Osteoarthritis_001.htm
There is osteoarthritic change in both CMC joints with evidence of subluxation

 

 

 

Gonarthritis : In this AP X-ray of both knees, taken from the front, we can see the difference between an arthritis that has evolved (red circle), where the thickness of the joint line has diminished, known as “compressed joint”, if compared with the healthy knee (blue circle).

 

 

 

http://www.kingorthopedics.com/hip-osteoarthritis.html

Hip XR: Left side-normal joint space, right side- narrowed joint space, verified OA

 

 

 

The left image is OA of the spine with resulting scoliosis. Note the asymmetric disk space as well as the large osteophytes which develop in attempt to bear some of the weight of the body (arrow). The right image is a photo of a gross spine from another patient with OA of the spine. Note the the large bulky osteophytes and subchondral sclerosis of the abnormal disk as compared to the normal disk above (arrow).

Magnetic resonance imaging and ultrasonography have not been sufficiently validated to justify their routine clinical use for diagnosis of OA or monitoring disease progression. The diagnosis of OA is usually based on clinical and radiographic features. In the early stages, the radiograph may be normal, but joint space narrowing becomes evident as articular cartilage is lost. Other characteristic radiographic findings include subchondral bone sclerosis, subchondral cysts, and osteophytosis. A change in the contour of the joint, due to bony remodeling, and subluxation may be seen. Although tibiofemoral joint space narrowing has been considered to be a radiographic surrogate for articular cartilage thinning, in patients with early OA who do not have radiographic evidence of bony changes (e.g., subchondral sclerosis or cysts, osteophytes), joint space narrowing alone does not accurately indicate the status of the articular cartilage. Similarly, osteophytosis alone, in the absence of other radiographic features of OA, may be due to aging rather than to OA.As indicated above, there is often great disparity between the severity of radiographic findings, the severity of symptoms, and functional ability in OA. Thus, while more than 90% of persons over the age of 40 have some radiographic changes of OA in weight-bearing joints, only 30% of these persons are symptomatic.

http://www.hss.edu/osteoarthritis-diagnosis.asp

 

Analysis of synovial fluid reveals mild leukocytosis (<2000 white blood cells per microliter), with a predominance of mononuclear cells. Synovial fluid analysis is of particular value in excluding other conditions, such as calcium pyrophosphate dihydrate deposition disease, gout, or septic arthritis.

Prior to the appearance of radiographic changes, the ability to diagnose OA clinically without an invasive procedure (e.g., arthroscopy) is limited. Approaches such as magnetic resonance imaging (MRI) and ultrasonography have not been sufficiently validated to justify their routine clinical use for diagnosis of OA or monitoring of disease progression.

Treatment

         No single treatment is considered sufficient for managing OA. The consensus is that a multifaceted approach that involves both nonpharmacological and pharmacological therapies should be used, especially for weight-bearing joints, where mechanics and lifestyle play a significant role in determining the symptoms. Nonpharmacological treatments should form the basis of any OA regimen, but they often are underutilized and underemphasized. The Figure shows a flowchart that summarizes the general strategy in OA management.

 

 

EULAR Evidence-based Recommendations

Non-pharmacological Therapy:  include

·       exercise

·       body mass index (BMI),

·       prevention of injury,

·       misalignment (e.g. orthesis)

·       local measures (e.g. thermal modalities, transcutaneous electrical nerve stimulation [TENS], acupuncture).

Among these treatment options, exercise may help by improving motion and strengthening muscles, weight loss could reduce disease progression, especially in overweight patients with knee or hip OA, while prevention of injury may help to prevent the development of OA.

Strength of Recommendation for Hand, Knee Osteoarthritis Interventions

SOR Intervention:

A – Glucosamine, chondroitins  sulphate, exercise, education,

paracetamol, conventional NSAIDs, coxibs, topical NSAIDs,

topical capsaicin

B – Diacerin, ASU, nutrients, herbal remedies, telephone, acupuncture,

laser, pulsed EMF, opioid analgesics, antidepressants

C – Minerals/vitamins, sex hormones

Strength of recommendation (SOR) is based on both evidence and expert opinion.

A = fully recommended, B = strongly recommended, C = moderately recommended.

ASU = avocado soybean unsaponifiable; EMF = extracellular fragment matrix;

NSAID = non-steroidal anti-inflammatory drug.

 

Recommendations for the Management of Hip Osteoarthritis

Combination of non-pharmacological and pharmacological

treatment modalities.

Treatment should be tailored according to:

·         hip risk factors;

·         general risk factors;

·         pain intensity;

·         disability and handicap;

·         degree of structural damage;

·         wishes and expectations of the patient.

A.   Regular education, exercise, appliances and weight reduction if obese

or overweight.

B.   Paracetamol (up to 4g/day) is the oral analgesic of first choice, and is the

preferred long-term oral analgesic.

C.  NSAIDs, at the lowest effective dose, in paracetamol non-responders. In patients

    with increased GI risk, non-selective NSAIDs plus a gastro-protective agent or

    coxibs according to the GI risk.

D.  Opioid analgesics, with or without paracetamol.

E.   SySADOAs (glucosamine, chondroitins 4 and 6 sulphate, diacerin, ASU and

     hyaluronic acid) have symptomatic effect and low toxicity.

F.   Intra-articular steroid injections (guided by ultrasound or X-ray) in patients with a refractory flare.

G.  Consideration of osteotomy and joint-preserving surgical procedures, preferably

in young adults (dysplasia or varus/valgus deformity).

H.  Joint replacement with radiographic evidence + refractory pain and disability.

ASU = avocado soybean unsaponifiable; GI = gastrointestinal; NSAID = non-steroidal anti-inflammatory drug; SySADOAs = symptomatics

 

Surgery.

If the above management is ineffective, joint replacement surgery may be required. Individuals with very painful OA joints may require surgery such as fragment removal, repositioning bones, or fusing bone to increase stability and reduce pain. Surgical intervention for osteoarthritis of the knee may be no better than placebo at relieving symptoms.

Prognosis

The most common course of OA is an intermittent, progressive worsening of symptoms over time, although in some patients the disease stabilizes. Prognosis also varies depending on which joint is involved.

Factors associated with progression of OA:

·                     Knees: High body mass index, varus or valgus knee deformity.

·                     Hips: Night pain, presence of femoral osteophytes, and subchondral sclerosis in females.

·                     Hands: Older age.

·                     Feet/Ankles

·                    

 

 

Gout

 

Gout is an inflammatory arthritis characterized by self-limiting  but excruciatingly painful acute attacks. These  are a consequence of monosodium urate (MSU) crystal

deposition within articular or periarticular tissue. After  years of acute intermittent gout, chronic tophaceous   gout can develop. Tophi, nodular masses of uric acid  (UA) crystals, can form anywhere but most commonl  affect finger tips or hands. Recent advances in understanding  of intracellular events have occurred along with   new treatment development.

 

This illustration is by the caricaturist, Jame Gillray (1757-1815). The image conveys a feeling of intense pain brought on by gout

 

History

Hippocrates and many other physicians of the ancient world were acquainted with the  symptoms and signs of gout, but it was Paul of Aegina, who lived a thousand years after Hippocrates, who apparently was the first physician to comment that emotional factors, among others, could set off an attack of acute gouty arthritis. Many since have noted that emotional stress and dietary indiscretion seem to be the two most common proximal antecedents of the acute episode. Any mention of the history of gout must include the remarkable fact that some of the most notable personages in history, including artists, philosophers, poets, scientists, physicians, soldiers, rulers and statesmen, have supposedly been afflicted by gout (A partial listing includes King Priam, Oedipus, Ulysses, Alexander the Great, Charlemagne, Michelangelo, the Medici Family, Henry VII and VIII, Cardinal Wolsey,  Lord Burghley, Erasmus,  John Calvin,  Martin Luther, Oliver Cromwell,  James 1, John Milton, Louis XIV, Sir Isaac Newton, William Harvey, Samuel Johnson,  Sir Horace Valpole, Thomas Sydenham, William Pitt the Elder and the Younger, Lord Chesterfield, Edward Gibbon, Lord Beaverbrook, Benjamin Franklin, Alexander Hamilton, and Theodore Koosevelt.) This fact was commented upon in 1778 by  Cullen, himself a sufferer from gout, who noted that the disease “more frequently attacks the wise than the foolish.” This impression continues to linger wilh many students of gout. On the other hand, the fact that they had gout islikely to be recorded by history only for the great and famous; obviously, many whom history does not mention were also afflicted by it. Surely, correlations between fame, creativity, genius, or notoriety and, for instance, mental illness, tuberculosis, malignancy or heart disease also could be and have been made. Nevertheless, later in this paper we shall review data which do suggest a correlation between hyperuricemia and certain achievementrelated variables. Hence, Cullen’s original  observation may have been indeed valid and not

based on investigator bias or sampling error.

Epidemiology

Gouty arthritis is predominantly a problem of post-pubertal males and is seldom seen in women before the menopause. It is the most common cause of inflammatory joint disease in men over 40 years old. In a typical UK general practice of 2000 patients, there may be 17 men and 3 women with gouty arthritis and 10 times that number with asymptomatic hyperuricaemia. Serum uric acid concentrations are distributed in the community as a continuous variable and are determined by a number of demographic factors, of which age, sex, body bulk and genetic constitution are the most important. Serum uric acid levels are higher in urban than in rural communities and are positively correlated with intelligence, social class, weight, haemoglobin, serum proteins and a high protein diet.

Etiology

More than 99% of primary gout cases are referred to as idiopathic, meaning that the cause of the hyperuricemia cannot be determined. Primary gout is most likely the result of a combination of genetic, hormonal, and dietary factors. Secondary gout is caused by Purines can be generated by the body itself (via the breakdown of cells iormal cellular turnover) or can be ingested in purine-rich foods (e.g. seafood, beer). Most people with gout, however, do not produce more than the normal amount of uric acid. Instead, most people with gout tend to be underexcretors. The kidney is responsible for about one third of uric acid excretion, with the gut responsible for the rest. It may be possible that defects in the kidney that may be genetically determined are responsible for the predisposition of individuals for developing gout.

Secondary gout and hyperuricemia can be promoted by:

►Eating too many food rich of purine such as: shellfish, organ meats: liver, kidney and brain.

►Dried beans, peas and anchovies are also rich in purines.

►Drinking too much alcohol interferes with the body’s ability to get rid of extra uric acid.

►Exposure to high levels of lead.

►Being overweight.

►Polycythaemia

►Certain diseases lead to excessive production of uric acid in the body e.g. of these diseases include Leukemia, diabetes, lymphomas, and hemoglobin disorders.

►Certain drugs: which interferes the ability of kidney to excrete uric acid, such as thiazide diuretics, low-dose aspirin, and tuberculosis medications (pyrazinamide and ethambutol) can also cause gout.Patients who are on cyclosporine (medication used in transplantation ot prevent the organs rejection).

The following factors increase your risk for gout:

·                    Advancing age

·                    Male gender

·                    Family history of the condition

·                    Obesity

·                    Use of certain drugs, including diuretics (“water pills”), low-dose aspirin, cyclosporine, or levodopa

·                    Binge drinking

·                    Lead toxicity

·                    Organ transplants

·                    Thyroid problems

·                    Other serious illness

Each risk factor is discussed in more detail below.

Age

Middle-Aged Adults. Gout usually occurs in middle-aged men, peaking in the mid-40s. It is most often associated in this age group with obesity, high blood pressure, unhealthy cholesterol levels, and heavy alcohol use.

Elderly. Gout can also develop in older people, when it occurs equally in men and women. In this group, gout is most often associated with kidney problems and the use of diuretics. It is less often associated with alcohol use.

Children. Except for rare inherited genetic disorders that cause hyperuricemia, gout in children is rare.

Gender

Men. Men are significantly at higher risk for gout. In males, uric acid levels rise substantially at puberty. In about 5 – 8% of American men, levels exceed 7 mg/dL (indicating hyperuricemia). However, gout typically strikes after 20 – 40 years of persistent hyperuricemia, so men who develop it usually experience their first attack between the ages of 30 and 50.

Women. Before menopause, women have a significantly lower risk for gout than men, possibly because of the actions of estrogen. This female hormone appears to facilitate uric acid excretion by the kidneys. (Only about 15% of female gout cases occur before menopause.) After menopause the risk increases in women. At age 60 the incidence is equal in men and women, and after 80, gout occurs more often in women.

Family History

A family history of gout is present in close to 20% of patients with this condition. Three genetic locations have been associated with the body’s uric acid handling and gout. Some people with a family history of gout have a defective protein (enzyme) that interferes with the way the body breaks down purines.

Obesity

Researchers report a clear link between body weight and uric acid levels. In one Japanese study, overweight people had two to more than three times the rate of hyperuricemia as those who maintained a healthy weight. Children who are obese may have a higher risk for gout in adulthood.

Medications

Thiazide diuretics are “water pills” used to control hypertension. The drugs are strongly linked to the development of gout. A large percentage of patients who develop gout at an older age report the use of diuretics.

Several other medications can increase uric acid levels and raise your risk for gout. These include:

·                    Aspirin — low doses of aspirin reduce uric acid excretion and increase the chance for hyperuricemia. This may be a problem for older people who take baby aspirin (81 mg) to protect against heart disease.

·                    Niacin (used to treat cholesterol problems)

·                    Pyrazinamide (used to treat tuberculosis)

Alcohol

Drinking excessive amounts of alcohol can raise your risk of gout. Beer is the kind of alcohol most strongly linked with gout, followed by spirits. Moderate wine consumption does not appear to increase the risk of developing gout.

Alcohol use is highly associated with gout in younger adults. Binge drinking particularly increases uric acid levels. Alcohol appears to play less of a role among elderly patients, especially among women with gout.

Alcohol increases uric acid levels in the following three ways:

·                    Providing an additional dietary source of purines (the compounds from which uric acid is formed)

·                    Intensifying the body’s production of uric acid

·                    Interfering with the kidneys’ ability to excrete uric acid

Pathogenesis

Uric acid ——►Crystals——►Crystals deposits in joint——►Joint inflammation

 

Biologically significant hyperuricemia occurs when serum urate levels exceed solubility (~6.8 mg/dL).  Hyperuricemia is a common serum abnormality that does not always progress to gout. Humans generate about 250 to 750 mg of uric acid per day. The uric acid comes from dietary purines and the breakdown of dying tissues. The exact cause of gout is not yet known, although it may be linked to a genetic defect in purine metabolism. Uric acid, the most insoluble of the purine substances, is a trioxypurine containing three oxygen groups. The pathogenesis of gout starts with the crystallization of urate within the joint, bursa, or tendon sheath, which leads to inflammation as a result of phagocytosis of monosodium urate crystals; the disease is usually associated with an elevated concentration of uric acid in the blood. Specifically, uric acid is a breakdown product of the purines adenine, guanine, hypoxanthine, and xanthine. Adenine and guanine are found in both DNA and RNA. Hypoxanthine and xanthine are not incorporated into the nucleic acids as they are being synthesized, but they are important intermediates in the synthesis and degradation of the purine nucleotides. Both undissociated uric acid and monosodium salt, which is the primary form found in the blood, are only sparingly soluble. The amount of urate in the body depends on the balance between dietary intake, synthesis, and excretion. In people with primary gout, defects in purine metabolism lead to hyperuricemia, or high levels of uric acid in the blood. This can be caused by increased production of uric acid, abnormal retention of uric acid, or both. Urate in the blood can accumulate either through an overproduction or an underexcretion of uric acid.  Hyperuricemia results from the overproduction of urate found in 10% of gout patients and from underexcretion of urate found in the remaining 90%. The majority of patients with endogenous overproduction of urate have the condition as a result of salvaged purines arising from increased cell turnover in proliferation and inflammatory disorders, from pharmacologic intervention resulting in increased urate production, and from tissue hypoxia. The renal mechanism for handling urate is one of glomerular filtration followed by partial tubular reabsorption. The final fractional excretion of uric acid is about 20% of what was originally filtered. Uric acid levels independently predict renal failure in patients with preexisting renal disease. Hyperuricemia causes interstitial and glomerular changes that are independent of the presence of crystal, and the changes very much resemble what hypertensive changes would look like chronically. In addition, serum hyperuricemia is epidemiologically linked to hypertension and seems to be an independent factor for the development of hypertension. Finally, hyperuricemia is defined as a serum uric acid level greater than 6.8 mg/dL. Serum uric acid can be normal, especially during the gout attack. The target goal for uric acid treatment is to achieve a level less than 6.0 mg/dL.

Classification

 

Etiopathogenetic

1.                primary

2.                secondary

 

Сlinical forms:

–      typical acute attack of gouty arthritis;

–      pseudophlegmonous form;

–      rheumatoid  form;

–      subacute form;

–      psoriatic;

–      abortive;

–      extra-articular form

In the clinical development of gout has four stages:

      • Asymptomatic

      • Acute

      • Intercritical;

      • Chronic

 

According to the character of time joint damage:

• Acute arthritis – an inflammation of the joints produration of no more than 3 weeks;

• Intercritial – from 3 to 12 weeks;

• Chronic – more than 12 weeks.

 

Periods:

–                  preclinical,

–                  intermittent (acute recurrent),

–                  chronic.

 

Variants of the course:

–                  mild,

–                  moderately,

–                  severe.

Phase:

1.                exacerbation

2.                remission

Radiographic stage of joint damage:

1.                I – large cysts (tophi) in the subchondral bone, and in the deeper layers,  sometimes sealing of soft tissue;

2.                II – large cyst near the joints and minor erosion of the articular surfaces permanent seal the periarticular soft tissues, sometimes with   calcifications;

3.                III – large erosion by at least one third of the articular surface, osteolysis  the pineal gland, a significant soft tissue seal with the deposition of lime.\

Peripheral tophi:

1.                present

2.                absent

The degree of functional insufficiency:

1.                0 – function is maintained;

2.                I – kept a professional capacity;

3.                II – lost a professional capacity;

4.                III – lost the capacity for self-care.

Type nephropathy:

1.                Urolithiasis.

2.                Interstitial nephritis.

3.                Glomerulonephritis.

4.                Arteriolonefroskleroz.

Clinical features

Stages of gout. Gout has four distinct stages:

1st stage-Asymptomatic:

Purine is a chemical compound that is present in all of the cells of the body. Extra purine is secreted out of the body in the urine in form of uric acid.

At times, there may be abnormally high levels of uric acid in blood, this condition is called “Hyperuricemia”. Plasma uric acid level increases due to extra purine secreted out in the urine in form of uric acid, but there are no symptoms. This condition is called “Hyperuricemia”.

2nd stage-Acute:

When there is a lot of uric acid, it begins to form crystals and deposits under the skin, forming a lump that can sometimes be felt on the outside of the body. The first attack of gout marks the second, mild attacks usually go away quickly, whereas severe attacks can last days or even weeks. The immune system, the body’s defense against sickness, realizes that the crystals should not be there and starts attacking them. This is what cause joint pain, tenderness which can be intense so that even a blanket touching the skin over the affected joint can be unbearable.

The metatarsophalangeal joint of a great toe is the site of the first attack of acute gouty arthritis in 70% of patients; the ankle, the knee, the small joints of the feet and hands, and the wrist and elbow follow in decreasing order of frequency.

The onset may be insidious or explosively sudden. Оften waking the patient from sleep. The affected joint is hot, red and swollen, with shiny overlying skin and dilated veins;it is excruciatingly painful and tender. Very acute attacks may be accompanied by fever, leucocytosis and a raised ESRI and are occasionally preceded by prodromal symptoms such as anorexia, nausea or a change in mood. If untreated, the attack lasts for days or weeks but it eventually subsides spontaneously. Resolution of the acute attack may be accompanied by local pruritus and desquamation of the overlying skin.Some patients have only a single attack, or suffer another only after an interval of many months or years. More often there is a tendency to have recurrent attacks.

 

 These increase in frequency and duration so that eventually one attack may merge into another and the patient remains in a prolonged state of subacute gout. Acute attacks are occasionally polyarticular, and tenosynovitis, bursitis or cellulitis may be the presenting feature.

Acute attacks may be precipitated by sudden rises in serum urate following dietary excess, alcohol, severe dietary restriction or diuretic drugs, or by sudden falls following initiation of therapy with allopurinol or uricosuric drugs. Acute attacks may also be provoked by trauma, unusual physical exercise, surgery or severe systemic illness.

http://doctorrennie.wordpress.com/2012/03/13/so-i-have-gout-what-does-that-mean-how-to-prevent-the-gout-flare/

 

http://www.myfootshop.com/detail.asp?condition=gout

 

 

http://health-fts.blogspot.com/2012/03/gout.html

 

Similar to the previous image, inflammation of the skin caused by gout is characterised by swelling and a smooth appearance to the skin.

The classic picture is:

►Excruciating and sudden pain

►Stiffness in the joint

►Low-grade fever may also be present

►Warmness

►Redness

►Swelling

The patient usually suffers from two sources of pain:

1-The crystals inside the joint cause intense pain whenever the affected area is moved.

2-The inflammation of the tissues around the joint also causes the skin to be swollen, tender and sore if it is even slightly touched. For example, a blanket draping over the affected area could cause extreme pain.

Gout usually attacks one joint at a time, while other arthritic conditions, such as systemic lupus and rheumatoid arthritis, usually attack multiple joints simultaneously.

Uric acid crystals can deposit in tiny fluid-filled sacs (bursae) around the joints. These urate crystals can incite inflammation in the bursae leading to pain and swelling around the joints, a condition called bursitis. In rare instances, gout leads to a more chronic type of joint inflammation which mimics rheumatoid arthritis.

Gout usually attacks the big toe (approximately 75% of first attacks), however it can also affect other joints such as the ankle, heel, instep, knee, wrist, elbow, fingers, and spine. In some cases the condition may appear in the joints of the small toes which have become immobile due to impact injury earlier in life, causing poor blood circulation that leads to gout.

The symptoms of gout usually appear at night and come on like a freight train. The weight of the bed sheets is often intolerable. One joint or several may be involved. The most common site is the first metatarsal phalangeal joint (big toe joint). The pain is described as crushing and excruciating. Attacks tend to last several days.

Acute gouty attacks occur in much the same manner. Most acute gouty attacks occur in the late hours of the night. As we sleep, our bodies tend to focus on the primary metabolic functions such as digestion, breathing, etc. The extremities, such as the feet tend to cool as a result of this ‘lack of attention’. As they cool, and if the dissolved amount of uric acid is high enough, the result is the change of uric acid from a liquid to a crystal. The hallmark symptoms of gout is the acute onset, usually at night with severe pain.

3rd stage-Intercritical:

After the initial attack, the person enters the intercritical stage or symptom-free interval that may last months or even years. Most gout patients have their second attack within 6 months to 2 years from their initial episode.

4th stage-Chronic:

In the last or chronic stage, gout attacks become frequent and become polyarticular (affecting multiple joints at one time). Large tophi can also be found in many joints. In advanced cases of chronic gout, the extra uric acid may also deposits in the kidney leading to kidney stones and hypertension.

First attacks of gouty arthritis are seldom associated with residual disability but recurrent acute attacks are followed by progressive cartilage and bone erosion in association with deposition of tophi and secondary degenerative changes. Severe functional impairment and gross joint deformities may occur in chronic tophaceous gout. 

Tophi  are deposits of monosodium  urate  crystals  in soft tissue that may occur in the helix of the ear, over olecranon processes, and over interphalangeal joints. Tophi can occur over osteoarthritic Heberden’s or Bouchard’s nodes in the distal and proximal interphalangeal joints, especially in older women. Tophus formation is related to serum uric acid and to local factors. Tophi seldom develop in indivi­duals with asymptomatic hyperuricaemia; however, they may develop rapidly in the feet or hands in post-menopausal women with heart failure and renal insufficiency who develop acute or subacute gouty arthritis following prolonged diuretic administration. Tophaceous gout may lead to significant morbidity and, if untreated, can cause joint erosion and destruction. Occasionally, polyarticular tophaceous gout presents as subcutaneous nodules that can mimic rheumatoid arthritis. In this case, the presence of monosodium urate crystals in the nodule aspirate can confirm gout.

Tophi or uric acid deposits are found in :

§                    cartilage

§                    synovial membrane (membrane covering the joints)

§                    tendons

§                    soft tissues

Tophi can occur in various organs, including:

§                    finger

§                    hand

§                    knee

§                    foot

§                    ear

§                    elbow

§                    Achiles tendon

§                    spine

§                    internal organs, such as kidney and even heart

 

http://www.skinsight.com/adult/gout.htm

 

The skin over the tophi lumps can form ulcers and secrete pus.

In advanced chronic gout, damage to the kidney caused by uric acid deposit can cause kidney failures. Other conditions, such as hypertension (high blood pressure), albuminuria (abnormal presence of albumin protein in the urine indicating kidney disease), and urolithiasis (urinary stone in the urinary tract) can also develop.

 

 

http://malformalady.tumblr.com/post/20428297781/tophaceous–gout–is–a–chronic–form–of–gout–wherein

 

 

http://www.inpodiatrygroup.com/gout.html

 

 

http://www.healthinplainenglish.com/health/musculoskeletal/gout/index.htm

 

Surgical removal of the the uric acid deposit.

 

 

Laboratory and instrumental  findings

Hyperuricemia is a serum uric acid (SUA) level consistently higher than 6.8 mg/dL. Hyperuricaemia is arbitrarily denned as a serum uric acid level greater than two standard deviations from the mean, i.e. above 7.0mg/dl (0.42mmol/l) in adult males and 6.0mg/dl (0.36 mmol/l) in adult females.

The serum urate level is usually raised but it is important to appreciate that this does not prove the diagnosis, because asymptomatic hyperuricaemia is very common. Also note that asymptomatic hyperuricemia does not need to be managed when you have pseudogout.

 

Comparison of Gout and Pseudogout

 

 

The criterion standard in the diagnosis of gout is the analysis of synovial fluid samples obtained with aspiration. Wet mounts of the synovial fluid in gout reveal negatively birefringent urate crystals. Also, the synovial fluid usually reveals an inflammatory process, with a white blood cell count in the range of 7,000-10,000 x 103 per microliter. Synovial fluid findings can help in making differential diagnose:

 

Differential Diagnosis of Acute Gout

note: This table applies to immunocompetent patients.

WBC = white blood cell.

*—The synovial fluid WBC count should not be used alone to exclude infection.

†—Septic arthritis may coexist with crystalline arthritis.

 

Radiographic Appearance
Plain-film radiography may be used to evaluate gout; however, findings generally do not appear until after at least 1 year of uncontrolled disease. Bone scanning may also be used to examine gout; the key finding on bone scans is an increased radionuclide concentration at affected sites.

 

http://www.aafp.org/afp/2007/0915/p801.html
Another appearance showing multiple erosion locations including first MTP, base of third and fourth metacarpals, and possibly the head of the fifth metacarpal and second proximal phalanx.

High-resolution CT. The advantages are superiority to plain radiography for detecting early disease and tophi changes. The disadvantages are high cost, high radiation exposure, moderate availability, and a lack of specificity.

DECT. The advantages of this newer diagnostic study are sensitivity and specificity for urate deposits, especially those in soft tissue and bone structures.⁹ The disadvantages: expensive and high radiation exposure.

MRI. This modality detects tophi with representative decreased signal in both T1- and T2-weighted images with variable enhancement.⁸ MRI is a useful examination when the presence of tophi is suspected but not proven. MRI often demonstrates greater-sized tophi than expected or appreciated on physical examination. The advantages are superiority to plain radiography in early detection and characterization of tophi and no radiation exposure. The disadvantages are less benefit than CT scanning, a lack of specificity for tophi, moderate availability, and high expense.

 

http://www.sciencedirect.com/science/article/pii/S0033838908001528

Gout. (A) The tophaceous form of gout can result in extensive, multiple soft tissue masses. This long-axis, reformatted, CT image shows mineralized tophi (arrows) destroying the first metatarsal and the midfoot. (B) Sagittal T1-weighted image of multifocal gout in a different patient presents with extensive intermediate signal soft tissue masses throughout the synovial joints of the hind- and midfoot.

 

Management

Lifestyle factors

Dietary factors are thought to play a significant role in the increasing prevalence. Obesity is the commonest comorbidity that highlights the importance of addressing diet . Despite long-standing links between diet and gout, only recently have studies described protective or causative components. Higher intakes of alcohol (especially beer), fructose (found in many soft drinks), meat and seafood increase risk, whereas coffee [23], dairy products and low BMI are protective. Both vitamin C  and cherries lower sUA levels. Traditionally, patients were advised to adopt low purine diets, avoiding meat, seafood and purine-rich vegetables. Such diets are broadly unappealing and rarely followed. A calorie-restricted diet with low carbohydrate (40% of energy), high protein (30% of

energy) and unsaturated fat (30% of energy)  should be recommended. Although life style modification is unlikely to significantly reduce sUA, it carries additional

benefits in controlling other components of metabolic syndrome associated with gout.

Hyperuricaemia should also trigger assessment for common associated disease, principally those of metabolic syndrome, present in 63% of men with gout. Hypertriglyceridaemia, hypertension, type 2 diabetes, hyperlipidaemia and obesity are the features of metabolic syndrome, which is strongly associated with cardiovascular disease risk. A key physiological change in metabolic syndrome is insulin resistance which decreases renal clearance of UA. Gout is associated with insulin-resistance syndrome, hypertension and hyperlipidaemia. Hyperuricaemia itself may even be an independent risk factor for cardiovascular disease.

 

Treatment of acute gout 

Following lifestyle advice, there are three main aspects to gout management; acute flare treatment, depletion of excess UA stores and sUA reduction.The algorithms summarize the current medical treatment of acute gout and chronic treatment. Products that are currently licensed for the chronic management of gout in the UK are used as the first- and second-line treatments and those that are used on a named patient basis can be used thereafter. National institute of clinical excellence (NICE) guidance has indicated that febuxostat can only be used in patients who have contraindications to, or are intolerant of allopurinol.

 

Fig. 1. Algorithm for the medical treatment of acute gout.

PPI: proton pump inhibitor.

The aim of treating attacks is to promptly and safely resolve pain. Joint aspiration is not essential to diagnose acute gout, but remains the gold standard and should be performed if there is any uncertainty in diagnosis or suspicion of sepsis. Without treatment, the pain of an acute attack will last for at least a week. Time from treatment to termination is the only guide to judge the efficacy of acute treatments as few placebo-controlled trials exist. In addition to pharmacological agents, affected joints should be rested for 1–2 days and treated with ice which has a significant analgesic effect.

NSAIDs (conventional and COX-2 inhibitors)

NSAIDs are the most commonly used first-line treatment in an acute flare. Maximum doses of an NSAID should be commenced quickly, tapering 24 h after complete symptom resolution. Head to head NSAID studies show few differences amongst agents. NSAIDs have many adverse effects (AEs) and should be avoided in gastrointestinal ulcer disease, bleeding or perforation, renal insufficiency, heart failure and those taking oral anti-coagulants. AEs are increased in the elderly and co-administration of a proton pump inhibitor should be considered. When contemplating NSAIDs, pre-morbid conditions and drug history should be taken into account on an individual patient basis and any current national guidance adhered to.

Colchicine

Colchicine is an alkaloid derived from the autumn crocus (Colchicum autumnale), and first used in the 6th century AD by Alexander of Tralles. The earliest mechanism described is the ability of colchicine to block microtubule assembly in neutrophils reducing phagocytosis and transport of MSU crystals. Colchicine also affects neutrophil migration into joints by reducing adhesion molecules on endothelial cells and neutrophils in response to IL-1 or TNF-α. More recently, it has been demonstrated that colchicine also reduces NALP3 inflammasome-driven caspase-1 activation by microtubule inhibition which decreases MSU delivery.

Corticosteroids

Corticosteroids act on the cytosolic glucocorticoid receptor to alter gene expression. Steroids also have non-genomic effects mediated by the cytosolic glucocorticoid receptor, membrane-bound glucocorticoid receptor and additional interactions with cellular membrane proteins . Corticosteroids are a good alternative where NSAID and colchicine cannot be used or in refractory cases.

IL-1 inhibitors

Anakinra, an IL-1 receptor antagonist, is a new treatment in development. The therapeutic basis for this treatment stems from the discovery that MSU crystals stimulate the inflammasome leading to IL-1β secretion. In current experiments, IL-1 inhibitors prevent IL-1 secretion via this mechanism and also block IL-1 secretion by marcophages via a TLR-dependent mechanism . IL-1 inhibition has also shown success in treating hereditary autoinflammatory syndromes, where mutations in theNALP3 gene result in spontaneous activation of the NALP3 inflammasome.

Chronic management

 

 

Fig. 2. Algorithm for the medical treatment of chronic gout.

 

Currently, no evidence suggests that asymptomatic hyperuricaemia should be treated, although lifestyle advice should be offered. Urate lowering therapy (ULT) is indicated to treat recurrent attacks, arthropathy, tophi, UA renal lithiasis and radiographic evidence of gout. There is currently no defined point at which to initiate ULT. ULT can be divided into uricostatic agents that decrease UA production, uricosuric agents that increase renal excretion or uricolytic agents that metabolise UA. Figure 3 summarizes how ULTs exert their effects.

 

Fig. 3. Summary of the final part of purine metabolism and site of drug action (XO = xanthine oxidase).

 

The therapeutic goal is to prevent MSU crystal formation by following BSR or EULAR MSU targets of ⩽ 0.30 mmol/L or 0.36 ⩽ mmol/L. These values within the normal range of 0.20–0.42 mmol/l quoted by most British laboratories and can cause confusion. Sustained control of sUA below target levels gives good long-term clinical outcomes and decreases flare frequency. However, the optimum target of sUA is unknown and could vary in different patient groups.

Prophylaxis

Prophylaxis against acute attacks should be given when ULT is initiated, either with an NSAID or colchicine. If no prophylaxis is initiated, 77% of the patients experience flares in the first 6 months of commencing allopurinol. One must minimize flares on initiation of ULT, as this is a commonly cited reason for non-concordance.

Colchicine provides effective prophylaxis at low dose, and fewer subjects experience diarrhoea as a side effect than at treatment dose. Results from RCT indicate prophylactic colchicine 600 µg twice a day should be used for at least 3 months and up to 6 months upon initiating ULT, as this significantly reduces flare frequency and severity. 

Uricostatic agents, xanthine oxidase inhibitors

Allopurinol

For the past 30 years, allopurinol has been the mainstay of chronic treatment and accounts for 90% of ULT . It is an effective agent and there is a significant inverse relationship between allopurinol dose and sUA . Allopurinol reduces sUA by inhibiting xanthine oxidase (XO) thereby preventing xanthine, a product of purine catabolism, being converted into UA as shown in Fig. 3. It should be commenced at 100 mg daily and increased by 100 mg every 1–2 weeks titrated against sUA and creatinine clearance (maximum dose is 900 mg) . AEs of allopurinol include rash (2%), vasculitis, eosinophilia, life-threatening hypersensitivity reaction, hepatitis, decreased renal function and bone-marrow suppression. Allopurinol requires reduced dosing in renal impairment, this being its route of excretion. Oxypurinol, the active metabolite of allopurinol, is an alternative in allopurinol allergy, but there is a 40% chance of cross reactivity.

Febuxostat

Febuxostat is a new agent which selectively inhibits XO independent of the redox state and does not affect other enzymatic pathways in purine/pyrimidine metabolism. Febuxostat is extensively metabolized by conjugation via uridine diphosphate glucuronosyltransferase and to lesser extent by the cytochrome P450 system. No dose reduction in moderate renal impairment (or moderate hepatic impairment) is required. Other advantageous properties include no interaction with warfarin  and a safe alternative in patients with allopurinol allergy. Febuxostat appears to be well tolerated, the most common AEs being abnormal liver function tests (LFTs). Others include diarrhoea, joint-related/musculoskeletal/connective tissue symptoms, flushing, dizziness, confusion, myalgia and tachycardia.

Uricosuric agents

These drugs enhance renal clearance of urate and were first introduced at the end of the 19th century. They are used in <15% of gout patients.  Benzbromarone, sulphinpyrazone and probenecid all directly inhibit URAT-1 and therefore reduce urate reabsorption. Uricosurics are contraindicated in urate nephropathy or history of acute nephrolithiasis. An increased fluid input and output is therefore recommended for all patients. UA stone formation is not common; however, the most important risk factor for UA crystallization and stone formation is a low urine pH (<5.5), rather than an increased urinary UA excretion. To prevent a low urinary pH and decrease the risk of nephrolithiasis, one can alkalinize the urine using potassium citrate or bicarbonate, with the goal of increasing urine pH to values >6.0, and up to 7.0. Usually, advice from a renal physician should be sought and all patients should be encouraged and instructed about maintaining urine volumes of at least 2 l per day.

Benzbromarone

Benzbromarone is metabolized by cytochrome P450 and was withdrawn from widespread use because of serious hepatotoxicity. It has been estimated that the risk of hepatotoxicity is 1 : 17 000 taking into account four published cases and 11 cases reported by Sanofi-Synthelabo (Paris, France). nBenzbromarone is a highly effective drug with 100% of the patients achieving target urate levels of <6 mg/dl in a trial showing comparable efficacy to allopurinol . Benzbromarone doses of 50–200 mg daily are used and generally well tolerated, although regular LFT monitoring is essential. Benzbromarone additionally inhibits SLC2A9, and is the only uricosuric that is effective in moderate renal impairment. It is particularly useful where allopurinol is contraindicated or not tolerated, such as in the management of renal transplant patients. This suggests that benzbromarone is a better choice following treatment failure or AEs with allopurinol.

Sulphinpyrazone

Sulphinpyrazone inhibits prostaglandin synthesis much like the NSAIDs and therefore its AEs are similar including gastro-intestinal ulceration, acute renal failure, fluid retention and rarely elevation of liver enzymes and blood disorders. Sulphinpyrazone 200–800 mg daily in divided doses is used. It has no efficacy in renal impairment and adverse reactions make its clinical use difficult.

Probenecid

Probenecid can be effective as an add-in therapy when allopurinol alone is insufficient, but is ineffective in renal impairment. Divided doses of 0.50–2.0 g are used but it is rarely utilized due to difficulties with supply.

Uricolytics

Humans unlike nearly all mammals have mutations in the genes encoding the enzyme uricase. The human uricase gene underwent two separate mutations that independently resulted in truncation of gene transcription. This decreased uricase function, but may have increased antioxidant activity, increased intelligence and improved the ability of humans to retain salt. The action of uricase converts urate to allantoin, which is 10 times more soluble and thus more readily excreted. During the past seven decades, there have beeumerous attempts to administer uricase; however, it now appears that this exogenous enzyme has been successfully converted into an effective drug.

Rasburicase

In 1996, rasburicase was developed by recombinant DNA technique from a genetically modified strain of Saccharomyces cerevisiae. The efficacy of rasburicase in prevention and treatment of tumour lysis syndrome (TLS) has been well demonstrated despite its cost. However, allergenicity and development of antibodies compromise its effectiveness, the risk of which increases with repeated use . Rasburicase is given IV at a dose of 0.20 mg/kg for 5–7 days to treat TLS.

Others

Losartan, an angiotensin II receptor antagonist used for hypertension, and fenofibrate, a fibric acid derivative used in hyperlipidaemia, both have uricosuric actions and reduce sUA . The action on sUA is not a class effect for either drug and neither is licensed in treating gout.  Losartan inhibits URAT-1, whereas fenofibrate can down-regulate the expression of the inducible COX-2 enzyme, but its exact mechanism is less well understood.

This effect of losartan and fenofibrate on sUA is particularly beneficial, given the frequent co-existence of hypertension and hyperlipidaemia with gout. Preferential use of these agents when treating comorbidities of gout is recommended. Together, these agents can decrease sUA by 40%; however, fractional UA clearance is increased by 110% and there is a risk of urolithiasis.

 

 References.

A – Main:

1.                Davidson’s Principles and practice of medicine (21^st revised ed.) / by Colledge N.R., Walker B.R., and Ralston S.H., eds. – Churchill Livingstone, 2010. – 1376 p.

2.                Harrison’s principles of internal medicine (18^th edition) / by Longo D.L., Kasper D.L., Jameson J.L. et al. (eds.). – McGraw-Hill Professional, 2012. – 4012 p.

3.                The Merck Manual of Diagnosis and Therapy (nineteenth Edition)/ Robert Berkow, Andrew J. Fletcher and others. – published by Merck Research Laboratories, 2011.

4.                Web -sites:

A.                      http://intranet.tdmu.edu.ua/data/kafedra/internal/index.php?&path=vnutrmed2/classes_stud

B.                       www.eular.org

C.                      www.rheumatology.org

D.                      http://emedicine.medscape.com/

E.                       http://meded.ucsd.edu/clinicalmed/introduction.htm

B – Optional:

1.                Clinical Rheumatology  (The Clinical Medicine Series) 12 edition/ Pacific Primary Care Software PC/ M.D., C. G. Weber.- 2011.-526 p.

2.                Kelley’s Textbook of Rheumatology, 9th Revised edition / Firestein, Gary S.; Budd, Ralph C.; Gabriel, Sherine E.; O’Dell, James R.; McInnes, Iain B.-2012.- 229 p.

3.                Fast Facts: Osteoarthritis, 2 edition / Philip G.; Ph.D. Conaghan , Amanda E., M.D. Nelson; Health Pr.- 2012.- 112 p.

4.                Medifocus Guidebook on: Osteoarthritis of the Knee/ Elliot Jacob PhD; CreateSpace Independent Publishing Platform. – 2012.- 174 p. 

5.                Gout: Causes, Symptoms, Signs, Diagnosis and Treatments, Revised Edition/  S. Smith.; U.S. Department of Health and Human Services.; National Institutes of Health.; National Institute of Arthritis and Musculoskeletal and Skin Diseases.;/ CreateSpace Independent Publishing Platform:- 2012.- 40 p.

6.                Gout & Kidney Stones Causes Exposed / Dr Noreen Picken BA DC.;/ Dr Noreen Picken; 1 edition- 2012.- 60 p.