Management of patients with arthritic syndrome

 

Management of patients with arthritic syndrome

 

 

 

Ankylosing spondylitis

 

Ankylosing spondylitis (AS) is a chronic, multisystem inflammatory disorder primarily involving the sacroiliac (SI) joints and the axial skeleton.

Etiology

The strong association of AS with HLA-B27 is direct evidence of the importance of genetic predisposition. Of the various genotypic subtypes of HLA-B27, HLA-B*2705 has the strongest association with the spondyloarthropathies. HLA-B*2702, *2703, *2704, and *2707 are also associated with AS. People who are homozygous for HLA-B27 are at a greater risk for AS than those who are heterozygous. AS is more common in persons with a family history of AS or another seronegative spondyloarthropathy.

Clinical features

Chest pain aggravated by breathing results from involvement of the costovertebral joints. Plantar fasciitis, Achilles tendonitis and tenderness over bony prominences such as the iliac crest, ischial tuberosity and greater trochanter are typical. Around 25% of patients have an attack of acute anterior uveitis during the course of the disease and this may occasionally be the presenting feature. A peripheral joint is first affected in 10% and in a further 10% symptoms begin in childhood as one variety of pauciarticular juvenile idiopathic arthritis.

 

 A few develop kyphosis of the dorsal and cervical spine, which can be incapacitating, especially when associated with hip involvement.

Symptoms

The severity of symptoms can vary from mild to very severe.

Common symptoms may include:

·                     Stiffening and pain (arthritis) of the:

o                                            Lower back

o                                            Sacroiliac joint, where the back and hip meet, possibly radiating down the legs

·                     Pain that is often worse at night

·                     Stiffness that is worse in the morning

·                     Symptom improvement with exercise or activity

·                     Occasionally, pain and stiffness in other joints:

o                                            Knee

o                                            Upper back

o                                            Rib cage

o                                            Neck

o                                            Shoulders

o                                            Feet

·                     Chest pain, which may suggest heart, heart valve (aortic insufficiency), or lung involvement

·                     Eye pain, visual changes, increased tearing which may suggest eye involvement.

Iritis occurs in up to 25% of patients but other extra-articular features are rare.

Less common symptoms may include:

·                     Fatigue

·                     Loss of appetite or weight loss

·                     Fever

·                     Numbness (if arthritic spurs compress the spinal nerves)

Diagnostic tests used to detect pain and limited mobility determine the spine with ankylosing spondylitis:

1)    Definition of pain lengthwise  the spinous processes of the spine and paravertebral points.

2)    Zacepin  symptom: pain with pressure near the point of attachment to the vertebrae X-XII ribs due to inflammation in the edge-vertebral joints.

3)    Forestier  symptom: to determine the shape of posture. The patient stands with his back to the wall, touching them heels, torso, head. In patients with ankylosing spondylitis, due to the development of kyphosis would not be clash with the wall in any point.

 

4)    Determination of the mobility of the cervical spine from the cervical vertebra VII metered top 8 cm and make a mark. Then ask the patient to tilt his head down and the maximum distance is measured again. In healthy individuals, it is increased by 3 cm lesion of the cervical spine is the distance increases little or no change. In patients with ankylosing spondylitis, with a short neck sample is not informative.

5)    Test chin-sternum: a healthy person freely touching the chin to the sternum, with lesions of the cervical spine the distance between the chin and chest will increase.

6)    Otta’s  test: to determine the mobility of the thoracic spine.  Put dot on VII of the cervical vertebra, and  measure down out 30 cm and make a  second mark. Then the distance between these points is measured again at the maximum slope of the subject forward.  In healthy people, this distance increases by 4.5 cm, and the patient’s disease spondylitis virtually unchanged.

7)    Determination  of  limiting  respiratory  excursion  of the chest: the measurement is made  by the centimeter on  level  of IV ribs. Normally the chest circumference difference between the maximum inhalation and exhalation is 6-8 cm, in the development of ankylosis  of  costo – vertebral joints, this difference is reduced to 2.1 cm (in the presence of emphysema sample is not informative).

8)     Schober’s  test:  to identify  limitationin of  motion in  the lumbar spine. Find LV of the lumbar vertebrae, put a dot, measure   upwards a 10 cm and make a  second mark. At maximum lean forward in healthy subjects, this distance increases for 4-5 cm, and in patients  with  ankylosing spondylitis this distance do not enlarge.

9)     Thomayer’s test:  to evaluate the overall mobility of the spine. Determined by measuring the distance in centimeters from the end of  the middle fingers outstretched arms to the floor with a maximum slope ahead. This distance is normally “0” and increases when restricted bending the spine.

Clinical and functional tests used to identify sacroiliitis:

1)    Kushelevsky’s  symptom (I): the patient lies on his back on a firm foundation. The doctor puts his hands on the iliac crests and sharply presses on them.  The pain occurs in the sacrum when inflammation is presence in the sacroiliac joint.

2)    Kushelevsky’s  symptom (II): the patient lies on his side, the doctor  puts his hands on the iliac bone and jerkly press on it. The patient in this case feels pain in the sacrum.

3)    Kushelevsky’s  symptom (III): the patient lies on his back, one leg is bent at knee and turned .  Physician put  one hand ron this knee, and the other hand presses down on the opposite iliac bone. The patient in this case feels pain in the sacral iliac joint. After that perform the same from opposite side.

4)    Symptom Makarova (I): characterized by the occurrence of pain effleurage diagnostic hammer in the sacro- iliac joints.

5)    Symptom Makarova (II): the patient lies on his back, the doctor grabs his leg above the ankle, causing the muscles to relax the feet, and then jerkly press on it apart and pulls together up. Pain in the sacro – iliac region.

Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess disease activity in ankylosing spondylitis (AS). It fulfils important aspects of truth, feasibility and discrimination. Criteria for disease activity states and improvement scores are important for use in clinical practice, observational studies and clinical trials and so far have not been developed for the ASDAS.

             Ankylosing Spondylitis Disease Activity Score (ASDAS)

BASFI = Bath Ankylosing Spondylitis Functional Index

BASDAI = Bath Ankylosing Spondylitis Disease Activity Index

ASAS – IC = ASsessment in Ankylosing Spondylitis Improvement Criteria

Bath Ankylosing Spondylitis Functional Index (BASFI):

1.     Visual analog scale (VAS) – 10 cm

2.     Mean score of 10 questions

3.     Questions level of functional disability, including:

4.     Ability to bend at the waist and perform tasks

5.     Looking over your shoulder without turning your body

6.     Standing unsupported for 10 minutes without discomfort

7.     Rising from a seated position without the use of an aid

8.     Exercising and performing strenuous activity

9.     Performing daily activities of living

10.            Climbing 12 to 15 steps without aid

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI):

A self-administered instrument (using 10-cm horizontal visual analog scales) that comprises 6 questions.Over the last one week, how would you  describe the overall level of:

1.              Fatigue/tiredness

2.              AS spinal (back, neck) or hip pain

3.              Pain/swelling in joints other than above

4.              Level of discomfort from tender areas

5.              Morning stiffness from the time you awake

6.              How long does morning stiffness last?

Assessment in Ankylosing Spondylitis (ASAS):

An improvement of  > 20% and absolute improvement of > 10 units on a 0–100 scale in > 3 of the following 4 domains:

1.Patient global assessment (by VAS global assessment)

     2.Pain assessment (the average of VAS total and nocturnal        pain scores)         

     3.Function (represented by BASFI)

     4.Inflammation (the average of the BASDAI’s last two VAS concerning morning stiffness intensity and duration)

Absence of deterioration in the potential remaining domain

(deterioration is defined as > 20% worsening).

For early diagnostic ankylosing spondylitis can be used next scheme:

 

The diagnosis of AS is made based upon the modified New York Criteria

A. Diagnosis

1. Clinical criteria

            a. Low back pain and stiffness for more than 3 months which improves with exercise, but is not relieved by rest.

            b. Limitation of motion of the lumbar spine in both the sagital and  frontal planes.

             c. Limitation of chest expansion relative to normal values corrected for age and sex. (<5cm=Abnormal in young adult)

2. Radiologic criterion of sacroiliitis grade greater than or equal to 2 bilaterally

or sacroiliitis grade 3-4 unilaterally. Grades are as follows:

           a. 0 = normal

           b. 1 = suspicious changes

           c. 2 = minimum abnormality (small localized areas with erosions or sclerosis)

           d. 3 = unequivocal abnormality (moderate or advanced sacroiliitis with erosions, evidence of sclerosis, widening, narrowing or partial ankylosis)

          e. 4 = severe abnormality (total ankylosis)

B. Grading

1. Definite ankylosing spondylitis diagnosis if the radiologic criterion is associated with at least 1 clinical criterion.

2. Probable ankylosing spondylitis if:

          a. Three clinical criteria are present.

          b. The radiologic criterion is present without any signs or symptoms  satisfying the clinical criteria. (Other causes of sacroiliitis should be considered.)

Investigations
       An elevated ESR or CRP is seen in up to 75% of patients with ankylosing spondylitis, but this may lack correlation with clinical disease activity. A mild normochromic, normocytic anemia is present in 15% of patients.

Imaging

Imaging of the sacroiliac joints and the spine has an important role in the diagnosis, classification and monitoring for patients with SpA. However, radiographic sacroiliitis reflects structural changes which may appear late in the disease process at least in a subset of patients. Thus, it has low specificity especially for patients at the early stages

of the disease.

 

 

Radiograph of the lumbar spine in a patient with ankylosing spondylitis showing
reactive sclerosis and erosions at the corners of the vertebral bodies, or “shiny corners”(arrow).

 

Syndesmophytes

Syndesmophytes are generally seen only in the seronegative spondyloarthropathies. 

These are due to inflammation and ossification of the outer fibers of the annulus fibrosus, known as the Sharpey’s fibers. This is classically seen in ankylosing spondylitis. In the other seronegativespondyloarthropathies, one usually sees paravertebral ossification which forms in the paravertebral connective tissue at some distance from the spine. In practice, it may be very difficult to distinguish osteophytes from syndesmophytes or paravertebral ossification.

 

 

 

In someone with ankylosing spondylitis, inflammatory spondyloarthropathy, the pattern is not what we see with degeneration.

 

 Treatment

ASAS/EULAR recommendations for the management of AS.

The overarching principles of the management of patients with AS are:

▶ AS is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary treatment coordinated by the rheumatologist.

▶ The primary goal of treating the patient with AS is to maximise long term health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalisation of function and social participation.

▶ Treatment of AS should aim at the best care and must be based on a shared decision between the patient and the rheumatologist.

▶ The optimal management of patients with AS requires a combination of non-pharmacological and pharmacological treatment modalities.

1.General treatment:

The treatment of patients with AS should be tailored according to:

▶ The current manifestations of the disease (axial, peripheral, entheseal, extraarticular symptoms and signs).

▶ The level of current symptoms, clinical findings, and prognostic indicators.

▶ The general clinical status (age, gender, comorbidity, concomitant medications, psychosocial factors).

2. Disease monitoring

The disease monitoring of patients with AS should include:

▶ Patient history (questionnaires)

▶ Clinical parameters

▶ Laboratory tests

▶ Imaging

▶ All according to the clinical presentation as well as the ASAS core set

The frequency of monitoring should be decided on an individual basis depending on:

▶ Course of symptoms

▶ Severity

▶ Treatment

3. Non-pharmacological treatment

▶ The cornerstone of non-pharmacological treatment of patients with AS is patient education and regular exercise.

▶ Home exercises are effective. Physical therapy with supervised exercises, land or water based, individually or in a group, should be preferred as these are more effective than home exercises.

Physical therapy and exercise, along with medication, are at the heart of therapy for ankylosing spondylitis. Physiotherapy and physical exercises are clearly preceded by medical treatment in order to reduce the inflammation and pain, and commonly followed by a physician. This way the movements will help in diminishing pain and stiffness, while exercises in an active inflammatory state will just make the pain worse.

Patients who are able to do so, lie flat on their face or back on the floor for a prescribed cumulative period of time each week, to prevent the chronic stooping which may otherwise result.

▶ Patient associations and self-help groups may be useful.

4. Extra-articular manifestations and comorbidities.

▶ The frequently observed extra-articular manifestations, for example, psoriasis, uveitis and IBD, should be managed in collaboration with the respective specialists.

▶ Rheumatologists should be aware of the increased risk of cardiovascular disease and osteoporosis.

5. Non-steroidal anti-inflammatory drugs

▶ NSAID, including Coxibs, are recommended as first-line drug treatment for AS patients with pain and stiffness.

▶ Continuous treatment with NSAID is preferred for patients with persistently active, symptomatic disease.

▶ Cardiovascular, gastrointestinal and renal risks should be taken into account when prescribing NSAID.

NSAIDs such as aspirin, ibuprofen, indometacin, naproxen and COX-2 inhibitors, which reduce inflammation and pain. These drugs tend to have a personal response to the pain and inflammation, although commonly used anti-inflammatory drugs like nimesulide are less effective than others;

6. Analgesics

▶ Analgesics, such as paracetamol and opioid (like) drugs, might be considered for residual pain after previously recommended treatments have failed, are contraindicated, and/or poorly tolerated.

7. Glucocorticoids

▶ Corticosteroid injections directed to the local site of musculoskeletal inflammation may be considered.

▶ The use of systemic glucocorticoids for axial disease is not supported by evidence.

8. Disease-modifying antirheumatic drugs

DMARDs such as cyclosporin, methotrexate, sulfasalazine, and corticosteroids, used to reduce the immune system response through immunosuppression;

9. Anti-TNF therapy

▶ Anti-TNF therapy should be given to patients with persistently high disease activity despite conventional treatments according to the ASAS recommendations.

▶ There is no evidence to support the obligatory use of DMARD before or concomitant with anti-TNF therapy in patients with axial disease.

▶ There is no evidence to support a difference in efficacy of the various TNF inhibitors on the axial and articular/entheseal disease manifestations; but in the presence of IBD a difference in gastrointestinal efficacy needs to be taken into account.

▶ Switching to a second TNF blocker might be beneficial especially in patients with loss of response.

▶ There is no evidence to support the use of biological agents other than TNF inhibitors in AS.

TNFα antagonists such as etanercept, infliximab and adalimumab (also known as biologics), are indicated for the treatment of and are effective immunosuppressants in AS as in other autoimmune diseases;

 

 

Appropriate Patients for Anti-TNF Therapy:

1. Definitive AS according to Modified New York Criteria.

2. Active disease for ≥ 4 weeks.

·        BASDAI > 4 cm at two times, 1 month apart.

·        Physician Global Assessment ≥ 2 on Likert Scale.

3. Treatment Failures.

·        All types AS – lack of response/intolerability > 2 NSAIDs for ≥ 3 months.

·        Patients with peripheral arthritis – lack of response/intolerability to > 1 DMARD, sulfasalazine preferred.

Contraindications for Anti-TNF Therapy

·        Current or recurrent infections

·        Tuberculosis

·        Multiple sclerosis

·        Lupus

·        Malignancy

·        Pregnant or lactating

Monitoring and Discontinuing Treatment With Anti-TNF Agents:

1.ASAS core set of outcome parameters to monitor patients: Physical function, pain, spinal mobility, patient’s global assessment, stiffness, peripheral joints and entheses, acute phase reactant, fatigue.

2.Assess at 6 to 8 weeks and discontinue patients who do not meet response criteria.

·        BASDAI: Reduction of ≥ 2 units and.

·        Physician Global Assessment > 1.

Anti-TNF Agents

Etanercept

Approved in the United States and Europe for treatment of AS

Dose: 50 mg SC per week  as two 25 mg  injections administered on same day or 3 to 4 days apart

Infliximab

Approved in Europe for treatment of AS

Dose: 5 mg/kg IV at week 0, 2, and 6 and every 6  to 8 weeks thereafter.

TNFα blockers have been shown to be the best promising treatment, slowing the progress of AS in the majority of clinical cases. They have also been shown to be highly effective in treating not only the arthritis of the joints but the spinal arthritis associated with AS. A drawback is the fact that these drugs increase the risk of infections.

10. Surgery

▶ Total hip arthroplasty should be considered in patients with refractory pain or disability and radiographic evidence of structural damage, independent of age.

▶ Spinal corrective osteotomy may be considered in patients with severe disabling deformity.

▶ In patients with AS and an acute vertebral fracture a spinal surgeon should be consulted.

11. Changes in the disease course

 If a significant change in the course of the disease occurs, other causes than inflammation, such as a spinal fracture, should be considered and appropriate evaluation, including imaging, should be performed.

 

 

 

Rheumatoid arthritis.

 

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks the joints producing a inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints RA is the most common form of chronic inflammatory joint disease.

Etiology

The cause of RA is unknown. Genetic, environmental, hormonal, immunologic, and infectious factors may play significant roles. Socioeconomic, psychological, and lifestyle factors (eg, tobacco use, the main environmental risk ) may influence disease outcome.

Patogenesis

The pathology of RA is characterized by the infiltration of several inflammatory cells into both the pannus and the joint fluid, and by subsequent tissue destruction.  Chemokines, as well as other inflammatory mediators play key roles in the pathogenesis of RA, and the coordinated production of chemokines and proinflammatory cytokines is important in the orchestration of the inflammatory responses observed in patients with RA. Imbalance between pro- and anti-inflammatory cytokine activities favours the induction of autoimmunity, chronic inflammation and thereby joint damage. Monocytes that are attracted to the RA joint differentiate into macrophages and become activated. These macrophages play a pivotal role in RA because they are numerous in the inflamed synovial membrane and at the cartilage-pannus junction.

http://www.nyas.org/publications/ebriefings/Detail.aspx?cid=ec3e5958-700a-4a01-b237-221e138048f7

 

Autoreactive B cells can be driven by the T cells to produce IgG autoantibodies that may be directly involved in joint damage, and B cells are known to be critical in activating CD4+ T cells. As the B cell appears to play an important role in the RA process, it is appropriate to consider how B cell-mediated effects might be reduced or prevented in patients with this disease.

Classification

Clinical characteristics:

1. Rheumatoid arthritis:

– polyarthritis (5 and more)

– oligoarthritis (2-4 joints)

– monoarthritis ( 1 joint)

2. Rheumatoid arthritis with visceratis  and disorders of reticuloendothelial system of serous membranes, lungs, heart, blood vessels, eyes, kidneys Feltie’s syndrome .

3. Rheumatoid arthritis in combination with:

– Osteoarthrosis

– Diffuse connective tissue disorders

– Juvenile arthritis (including Still’s disease)

Immunological characteristics:

– Seropositive

– Seronegative

The course of the disease:

– Rapidly progressive

– Slowly progressive

– No significant progression

 

Disease Activity Score (DAS) is used in determination of stage activity. Its used to determine whether it is under control and if any treatment adjustments are required.  It can also assist in establishing a target score to aim for, to help inform treatment decisions and optimise disease management.       
DAS28 is a composite outcome measure that assesses:
•    How many joints in the hands, wrists, elbows, shoulders, and knees are swollen and/or tender.       
•    The erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) in the blood to measure the degree of inflammation.         
•    The patient’s Visual Analogue Score (a simple scale) to assess how they are feeling on that day from 0 (very good) to 10 (very bad).  
The results are combined to produce the DAS28 score, which correlates with the extent of disease activity:   
•    < 2.6: Disease remission   
•    2.6 – 3.2: Low disease activity   
•    3.2 – 5.1: Moderate disease activity     
•    > 5.1: High disease activity          
A score of less than 2.6, classified as ‘remission’, is the ultimate goal for patients with RA, though it’s important to recognise that not everyone can achieve this.  However, the vast majority of patients can, if treated early and appropriately, achieve DAS disease remission or low disease activity, which will bring about a great improvement, long-term, to their quality of life.

Stage activity calculator example you can download as phone program or find at this website:  http://www.4s-dawn.com/DAS28/.

 

Radiographic stage:

I periarticular osteoporosis

II Osteoporosis + joint space narrowing (can be 1-3 lesions)

III + The same + multiple lesions

IV The same + bony ankylosis

Functional capacity of the patient:

I   kept employability

II  employability lost

III lost the ability to self-service

Clinic

In the majority of patients the onset is insidious, with joint pain, stiffness and symmetrical swelling of a number of peripheral joints, but other disease patterns can occur. Initially, pain may be experienced only on movement of joints, but rest pain and prolonged early morning stiffness are characteristic features of all kinds of inflammatory arthritis.

While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur.

Joints

The arthritis of rheumatoid arthritis is due to synovitis, which is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness limits their movement. With time, RA nearly always affects multiple joints (it is a polyarthritis). Most commonly, small joints of the hands, feet and cervical spine are affected, but larger joints like the shoulder and knee can also be involved, differing per individual. Synovitis can lead to tethering of tissue with loss of movement and erosion of the joint surface, causing deformity and loss of function.

Rheumatoid arthritis typically manifests with signs of inflammation and the affected joints are swollen, warm, painful and stiff early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the inflammatory disease which the person may experience and may last for more than an hour. Gentle movements may relieve symptoms in early stages of the disease.

Hands

As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity. The fingers may suffer from almost any deformity, depending on which joints are most involved.

Specific deformities: like ulnar deviation, boutonniere deformity, swaeck deformity and “Z-thumb” but these are of no more significance to diagnosis or disability than other variants.

In the typical case the small joints of the fingers and toes are the first to be affected. Swelling of the proximal, but not the distal, interphalangeal joints gives the fingers a ‘spindled’ appearance, and swelling of the metatarsophalangeal joints results in ‘broadening’ of the forefoot. As the disease progresses with or without inter­vening remissions, it tends to spread to involve the wrists, elbows, shoulders, knees, ankles, subtalar and midtarsal joints.

In 10-15% of patients the disease starts as an acute polyarthritis with severe systemic symptoms. A systemic onset, with fever, weight loss, profound fatigue and malaise without joint symptoms, occurs less often, particularly in middle-aged men, and this can cause diagnostic confusion with malignant disease or chronic infections. The onset is palindromic in some patients, with recurrent acute episodes of joint pain and stiffness in individual joints lasting only a few hours or days. In about one-third of such cases the disease evolves into one more typical of arthritis.

RA: Proximal Interphalangeal Joints.

 

Involvement of the proximal interphalangeal (PIP) joints usually is easily recognized from the fusiform soft tissue swelling, often accompanied by regional osteopenia. Uniform cartilage loss occurs early at this site and erosion appears somewhat later. Erosive disease parallels the synovial and capsular anatomy, being extensive over the proximal phalangeal condyles and more limited over the base of the distal phalanges. Flexion or extension deformities are frequent in advanced disease; bony ankylosis is rare. Erosive artic­ular disease rarely is seen in the distal interphalangeal joints, although swelling and tenderness are common.

Metacarpophalangeal Joints.

Soft tissue swelling in the metacarpophalangeal (MCP) joints, although clinically prominent, is more difficult to evaluate than in the proximal interphalangeal joints, but in high-quality radiographs appears as discrete capsular distention. The cartilage at this site becomes narrow later, whereas erosion, particularly of the radial aspect of the metacarpal head, is an early and important sign of rheumatoid arthritis. Small, discrete, pocketed erosions develop at the proximal phalangeal base near the capsular insertion. As the erosive process evolves, narrowing ensues, and eventually complete destruction of the joint with “pencil in cup” deformity is seen, accompanied by palmar subluxation and ulnar deviation.

 

 

Complete subluxation with marked ulnar deviation at the metacarpophalangeal joints of a 90-year-old woman with rheumatoid arthritis (RA). Arrows mark the heads of the metacarpals, now in direct contact with the joint capsule instead of the proximal phalanges. 

Ulnar Deviation and Subluxation.

This left hand shows typical manifestations of end-stage erosive changes about the metacarpophalangeal (MP) joints, with volar dislocation and ulnar drift of the fingers.

 

Ulnar Deviation

Boutonniére Deformity

 

This is a right thumb demonstrating typical soft tissue imbalance found in rheumatoid arthritis. The metacarpophalangeal (MP) joint is hyperflexed, and the interphalangeal  joint is hyperextended.

 

Swaeck deformity with hyperextension of the proximal interphalangeal joints and flexion of the distal interphalangeal joints of the second, third, and fourth digits of the hand. The fifth digit displays the boutonniere deformity, with flexion at the proximal interphalangeal joint and hyperextension at the distal interphalangeal joint.

 

 

Wrist

In the wrist, soft tissue swelling is usually prominent and recognized relatively easily, particularly adjacent to the ulnar styloid, as a result of synovitis of the extensor carpi ulnaris tendon sheath. This involve­ment frequently leads to characteristic focal demin-eralization and surface erosion of the medial ulnar styloid. Additional erosion of the distal ulna results from synovitis of the prestyloid recess, eroding the tip of the styloid, and from synovitis in the inferior radio-ulnar compartment that erodes the foveal region.

 

The hand and wrist are common sites of synovitis in rheumatoid arthritis. Marked swelling in the wrist and metacarpophalangeal joints is caused by synovial proliferation. 

 

ACR/EULAR 2010 criteria RA

 

Diagnostics

Laboratory analysis :

Complete blood count: evidence of moderate normochromic anemia (hemoglobin level not lower than 90 g / L), high activity and long duration of the disease was more pronounced anemia (may be reduced to 35-40 g / l). WBC count and erythrocyte sedimentation rate value dependent on the degree of activity of the process. With long-term course of rheumatoid arthritis is possible leukopenia.

Radiographic stage of joint damage in RA:

Stage I – periarticular thickening and sealing of soft tissue + periarticular osteoporosis.

RA, I stage. XR of hands in a straight projection. Moderate periarticular osteoporosis. Single cystoid enlightenment bone. A slight narrowing of the gaps of individual metacarpophalangeal joints.

 

Stage – II –the  same + single erosions (1-4) indicates the progression of arthritis.

RA, II stage. XR of hands.

Expressed periarticular OP. Numerous cystoid enlightenment bone. Narrowing the slots most joints. Single erosion in the metacarpophalangeal joints.

 

Stage-III is characterized by the addition to the existing pattern of multiple erosions (> 5) in the typical joints.

RA, III stage. XR of hands in a straight projection. Common OP. Numerous erosion of the articular surfaces. The narrowing of the joint gaps of multiple joints. Deformation of the wrist bones.

 

 

Stage IV – is characterized by the appearance of a partial or complete ankylosis intercarpal joints or one of the carpal-metacarpal joints except I carpal-metacarpal joint.

RA, IV stage.  XR of hands. Expressed common OP.Mmultiple bone

ankylosis of the wrist joint.

Treatment of Rheumatoid arthritis

 

I. Disease-Modifying Antirheumatic Drugs (DMARD) decrease and prevent retard, retard the development of bone erosions or facilitate their healing, keep the function of joints, decrease expense for the treatment, keep economic activity of the patients with the RA:

a) cytotoxic immunosuppressive therapy:

1) methotrexate 7,5 mg (10-15 mg, sometimes 20 mg) once weekly 1-2 months, followed by a maintenance dose of  7,5 – 10 mg once weekly;

2) cyclophosphamide 100-200 mg/daily iv until a total dose – 1,5-2 g, followed by a maintenance dose of 50 mg daily;

3) azathioprine 100-150 mg daily 2-3 months, followed by a maintenance dose of 50 mg daily;

4) cyclosporine 2,53 mg/kg daily;

5) leflunomide initially 100 mg once a day for three days, followed by a maintenance dose of 20 mg a day;

6) gold salts (chrysotherapy):

– auranofin – 6 mg once a day or 3 mg twice a day;

– aurothioglucose (intramuscular injection) initial 10 mg the first week, 25 mg the second and third weeks, then 25 to 50 mg once a week until a total dose of 800 mg to 1 gram has been given, maintenance – intramuscular, 25 to 50 mg every two weeks for two to twenty weeks, then 25 to 50 mg every three to four weeks;

– gold sodium thiomalate (intramuscular injection)  initial 10 mg the first week, 25 mg the second week, then 25 to 50 mg once a week until the desired therapeutic response is obtained or until toxicity occurs, up to a total dose of 1 gram. Maintenance – intramuscular, 25 to 50 mg every two weeks for two to twenty weeks, then 25 to mg every three or four weeks.

7) sulfasalazine 1 gram 2-3 times a day 1-2 months;

8) D-penicillamine Oral, initially 125 or 250 mg once a day as a single dose, the dosage being increased, if necessary and tolerated, by adding 125 or 250 mg per day at two- to three-month intervals up to a maximum of 1.5 grams per day.

9) antimalarials – hydroxychloroquine sulphate 200-400 mg/d.

Combination therapy:

 methotrexate + hydroxychloroquine sulphate, methotrexate + sulfasalazine, gold salts + hydroxychloroquine sulphate;

methotrexate + hydroxychloroquine sulphate + sulfasalazine;

II. Antiinflammatory therapy:

Corticosteroids – prednisolone 10 mg/d (RA without complications), methylprednisolone or triamcinolone 8 mg/d (to patients with moderate activity of RA) with following gradually decrease of dose;

– Patients with severe activity of RA and involvement of internal organs can be treated with 3 days of 1000 mg intravenous “pulses” of methylprednisolone or

– first day – intravenous 1 g methylprednisolone and 1 g cyclophosphamide,

– second day – intravenous 1 g methylprednisolone,

– third day – intravenous 1 g methylprednisolone.

III. Local treatment:

– Intra-articular corticosteroids may be helpful if one or two joints are the chief source of difficulty. (diprospan (betamethasone) once two-three weeks, 10-40 mg depending on the size of the joint to be injected).

– ointment gel with NSAIDs;

– physiotherapy.

Perspectives of the treatment:

* Biological agents

Biological agents (biologics) are produced through genetic engineering, and include:

–                     tumor necrosis factor alpha (TNFα) blockers – etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira)

–                     Interleukin 1 (IL-1) blockers – anakinra (Kineret)

–                     monoclonal antibodies against B cells – rituximab (Rituxan)

–                     T cell costimulation blocker – abatacept (Orencia)

–                     Interleukin 6 (IL-6) blockers – tocilizumab (an anti-IL-6 receptor antibody) (RoActemra, Actemra)

* new immunomodulator:

– subreum – bacterial immunomodulator receiving by thermal processing of bacterials

 

 

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.

 

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.

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/

 

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.

 

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

 

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

 

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 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

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 (Heberdeodes)

·        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

 

 

 

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

 

 

 

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 in nerve 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 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. No other significant arthropathy is seen

 

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

 

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.

 

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 = symptomatic s

 

 

Gout

 

Gout is an inflammatory arthritis characterized by self-limiting  but excruciatingly painful acute attacks. These  are a consequence of monosodium urate (MSU) crystaldeposition within articular or periarticular tissue.

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.

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).

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:

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.

Classification

 

Etiopathogenetic

·        primary

·        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:

·        exacerbation

·        remission

Radiographic stage of joint damage:

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

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

·        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:

·        present

·        absent

The degree of functional insufficiency:

·        0 – function is maintained;

·        I – kept a professional capacity;

·        II – lost a professional capacity;

·        III – lost the capacity for self-care.

Type nephropathy:

·        Urolithiasis.

·        Interstitial nephritis.

·        Glomerulonephritis.

·        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

 

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.

The symptoms of gout usually appear at night and come on like a freight train.

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.

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

§        

 

§                                 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.

Radiographic signs of gout are:

·        swelling of soft tissues;

·        irregular calcification of soft tissues (tophi)

·        bone erosion with sclerotic border;

·        symptom a punch (stamped form erosions with sclerotic border)

 

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.

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.

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 .

 

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.

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 ieutrophils reducing phagocytosis and transport of MSU crystals. Dose: 0,5 mg every hour till reducing symptoms,  but not more then 4 mg per day.

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 .

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).

 

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.

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. Average dose is 100-300mg/day.

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.

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.

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

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.

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.

Polyethylene  glycol–uricase

Differs from most PEGylated proteins currently in clinical use as it does not closely resemble any human amino acid sequence. PEGylation forms a covalent link between a protein and PEG, and has the advantageous properties of prolonging half life and decreasing antigenicity.

 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.