Rheumatoid Arthritis diagnosis and management

Rheumatoid Arthritis


Preliminary
Rheumatic disease is a term for a group of diseases with clinical manifestations of chronic pain in the musculoskeletal system, joint stiffness and swelling of tissue around the joints and tendon. Although the disorder primarily occurs in the joints but arthritis can also be of extra-articular tissues.
Rheumatoid arthritis (RA) is a progressive autoimmune disease, characterized by inflammation of the joints. This inflammation causes a loss of form and function of joints, causing pain, stiffness and swelling, which leads to the occurrence of damage and permanent loss of joint function. In the more severe cases, RA can affect the eyes, lungs, or blood vessels. RA also shorten life expectancy by attacking the organ systems.
RA is a form of autoimmune disease is most common and affects more than 6 million people worldwide, and is usually found autoantibody one of which is rheumatoid factor (RF).
This disease can affect any joint, but most of the attacks the small joints of the hands and wrists. All people at risk of developing RA is usually middle age between 20-50 years, but women have a 2-4 times higher risk than men, and this risk will be increased according to age, especially at the age of 40 to 50 years.

Definition
Rheumatoid arthritis is a non-bacterial inflammatory disease that is systemic, progressive, chronic, and tends to joints and connective tissue of joints symmetrically. On the other ideas have also said RA is a chronic autoimmune disease with symptoms of pain, stiffness, impaired movement, joint erosion and various other inflammatory symptoms.



Etiology
The main cause of this incident is unknown. There are some theories put forward regarding the causes of rheumatoid arthritis, namely:
A. hemolytic streptococcal infections and non-hemolytic streptococcus
2. endocrine
3. autoimmune
4. metabolic
5. genetic factors and environmental triggers
At this time, suspected rheumatoid arthritis caused by immune factors and infections. This autoimmune reaction against collagen type II, factors may be caused by virus infections and mycoplasma organism that produces or difteroid antigen collagen type II of the joint cartilage of patients.

Pathophysiology
Syinovial membrane in rheumatoid arthritis patients had hyperplasia, increased vaskulariasi, and infiltration of inflammatory cells fuse, especially CD4 + T cells. CD4 + T cells is a very important role in the immune response. In the latest research in the field of genetics, rheumatoid arthritis is associated with major-histocompatibility-complex class II antigen HLA-DRB1 * 0404 and DRB1 * 0401. The main function of HLA class II molecules is to present antigenic peptides to CD4 + T cells showed that rheumatoid arthritis is caused by as yet unidentified arthritogenic. These antigens can be exogenous antigen, such as viral proteins or proteins endogenous antigen. More recently a number of endogenous antigen has been identified, such as citrullinated proteins and human cartilage glycoprotein 39.
Antigen activated CD4 + T cells stimulate monocytes, macrophages and syinovial fibroblasts to produce interleukin-1, interleukin-6 and TNF-α to secrete matrix metalloproteinases through a relationship between the cell with the help of CD69 and CD11 through the release of mediators of solvents such as interferon-γ and interleukin-17. Interleukin-1, interlukin-6 and TNF-α is the key to the occurrence of inflammation in rheumatoid arthritis.

Activation of CD4 + T cells also stimulate B cells through direct cell contact and bond with the α1β2 integrin, CD40 and CD28 ligand to produce immunoglobulins including rheumatoid factor. Actual function of these factors rhumetoid in the pathogenesis of rheumatoid process is not known for certain, but most likely rheumatoid factor mengaktiflkan various complement through the formation of immune complexes. Activation of CD4 + T cells also express the overall osteoclastogenesis causes of joint disorders. Activation of macrophages, lymphocytes and fibroblasts also stimulate angiogenesis resulting peninkatan found in synovial vascularity with rheumatoid arthritis.

Symptom
RA symptoms are generally characterized by multiple symptoms that last for at least 6 weeks, namely:
A. Stiffness in and around the joints that lasts approximately 30-60 minutes in the morning
2. Swelling of 3 or more joints at the same time
3. Swelling and pain usually occurs in the joints of the hand
4. Swelling and pain usually occurs with a symmetrical pattern (pain in the same joints on both sides of the body) and generally attack the wrist joint.
At a more advanced stage, the RA can be characterized also by the presence of rheumatoid nodules, rheumatoid factor concentration (RF) abnormalities and radiographic changes include the erosion of bone.

   
In addition to attacking the hands and feet, RA also attacks the wrists, elbows, ankles, knees and neck, usually affects both sides of the body (symmetrical, left and right) at the same time. In the more severe cases RA can also attack the eyes, lungs or blood vessels.
History and Examination
History of Rheumatoid arthritis Septic arthritis degenerative joint disease
Onset Month Daily Sunday
Morning stiffness + + -
Minutes duration of pain Constant Watches
Pain on the activity + + + + + + / -
Multiple the number of joints involved, symmetric one (usually more) Varies
Distal Proximal finger joints

Inspection
Fever + / - + + -
Muscle weakness + + - +
Synovial Perlunakan + + + + / -
Heat to the joint + / - + + -
Effusi + + + + / -
Joint ROM ↓ ↓ ↓ ↓ ↓
Abnormalities in the articular
Abnormalities in synovial, tendon and bone:

A. Stage I (stage synovitis)
In the early stages of vascular congestion, proliferation of synovial infiltration subsinovial accompanied by the cells of lymphocytes and plasma cells polymorph. Further thickening occurred with the establishment of joint structures on villi and synovial effusion in the joints and tendon wrapping.

2. Stage II (stage destruction)
Further progress to chronic inflammation and destruction of joints and tendons occur. Damage to the cartilage due to proteolytic enzymes and in the folds of synovial tissue and vascular granulation tissue that forms on the surface of the joints (Panus). Bone erosion occurs on the edges of the joints caused by invasion of granulation tissue and resorption caused by osteoclasts. On tendon collagen invasion occurred along tendosinovitis that can cause partial or total tendon rupture.

 

3. Stage III (stage deformity)
At this stage a combination of destruction of joints, tension membrane lining the joints and tendon rupture will lead to instability and deformity of the joint. Abnormalities that may be found at this stage is ankylosis of bone. Inflammation that occurs may be diminished and disorder that arises primarily due to mechanical and functional disorders in the joints.

 
Investigations
A. Radiological examination: Plain, X-rays, MRI
2. Blood: ESR, CRP, counts, uric acid, rheumatoid factor and antinuclear antibody.
3. Examination of joint fluid through a biopsy or arthroscopy.
Radiological examination
A. Plain
At this early stage no abnormality is found significant, but can be found at an advanced stage refractory diffuse cortical joints and bones accompanied trabekulasi. In the event of destruction of cartilage, it will show joint space narrowing with erosion in some places.
 
             
2. Examination of radio-isotopes
On examination of radio-isotopes, the concentration of radio-isotopes seen rising in areas of abnormality.


X-ray findings
Rheumatoid arthritis Septic arthritis degenerative joint disease
Initial
Periarticular soft tissue swelling of the joints effusi joint gap narrowing
Osteophytes periarticular osteoporosis, marginal
End
Narrowing of the gap joint articular cartilage destruction and subchondral bone sclerosis
Periarticular erosion Subcortical cysts
Destruction of bone and articular cartilage Osteofit marginal
Joint subluxation secondary to involvement of the ligament

Synovial Fluid Analysis
Finding Normal Septic arthritis Rheumatoid arthritis degenerative joint disease
Appearance Turbid Clear Clear Cloudy
Clinical High test viscosity (fluid SLOWLY Remains intact when pulled Between thumb and index finger) watery (fluid breaks into droplets easily) Very watery High
Glucose Within 60% or more of serum glucose Very low Low Normal
Cell count/mm3 200 2.000 to 50.000 2.000 50.000 Usually Greater Than
Differential cell count monos 50/50 polys monos

 

Diagnosis
RA diagnosis criteria established, and continues to grow today. RA diagnostic criteria developed for the first time by a special committee of the American Rheumatism Association (ARA) in 1956. Because the criteria are considered non-specific and too complex to be used in the clinic, the committee conducts a review of the classification criteria for RA was in 1958. Someone said to suffer from the classic RA 7 of 11 if they meet specified criteria, if they meet the five criteria of definite, probable if it meets three criteria and is only possible if it meets two criteria. Although in 1958 the criteria have been used for nearly 30 years, but with the rapid development of knowledge about the RA, it is known that by using these criteria, many found fault diagnosis, or may include other types of arthritis
By combining variables most sensitive and specific in 262 patients with RA and 262 control patients, the 1987 revision of the arrangement is successful ARA classification criteria for rheumatoid arthritis in a new traditional format. The composition of these criteria are as follows:
A.R.A. Criteria for Rheumatoid Arthritis:
A. Morning stiffness
2. Arthritis in three or more joint areas
3. Arthritis of hand joints
4. Symmetrical arthritis
5. Rheumatoid nodules
6. Serum rheumatoid factor positive
7. Changes in the radiological picture
It is currently said to be suffering from RA patients if they meet criteria of at least 1 to 4 which suffered at least 6 weeks. But in 2010 College of Rheumatology / European League Against Rheumatism classification criteria sets, which are used for RA because it has a lot of criticism about the lack of sensitivity to RA in the early stages of diseases associated with joint disease or persistent and erosive.
The 2010 American College of Rheumatology / European League Against Rheumatism classification criteria for rheumatoid arthritis
Score
Target population (who should be on the test?):
1) having at least one joint with synovitis real kinis symptoms (swelling) *
2) with no apparent synovitis with other disease †
Classification criteria for RA
A. § joint involvement
1 large joint 0
Joints 2-10 of 1
1-3 small joints (with or without the large joints) ** 2
4-10 small joints (with or without the large joints) 3
> 10 joints (small joints at least 1) 5
B. Serology (it takes a minimum of test results, with a ratio value of IU)
Negative RF and ACPA negative (less / equal to their normal values) 0
Low RF-positive or ACPA-positive low (<3 above the upper limit of normal value) 2
High RF-positive or ACPA-positive high (≥ 3 above the upper limit of normal value) 3
C. Acute-phase reactants (required at least one test) ‡
Normal CRP and normal ESR 0 0
Abnormal abnormal CRP or ESR 1 1
D. Duration of symptoms § §
<6 weeks 0
≥ 6 weeks 1
Note:
* The target of research is a new patient.
† differential diagnosis with other joint disorders, but may also be accompanied by systemic lupus erythematosus, psoriatic arthritis, and gout.
§ joint involvement is intended to any joint swelling or softening at pemerisaan, which can be confirmed by imaging with a picture of synovitis. Except for the finger joints.
¶ shoulder, elbow, hip, knee, and ankle.
** Finger joints (metacarpophalangeal, proximal interphalangeal, metatarso-phalangeal 2-5, and wrist)
‡ determined by local laboratory standards.
Yen set since the start of patient-reported symptoms of synovitis.

Classification criteria for RA based on the algorithm: add scores of AD: patients with a score of ≥ 6 means definite RA. And although patients with the score currently <6/10 are not classified as RA, these patients can still develop into RA over time.

In the more recent criteria established by the ARA in 2011 are as follows:

The differential diagnosis
Rheumatoid arthritis must be distinguished from other disorders that cause poly-arthritis are:
A. Seronegative poly-arthritis found in psoriatic arthritis, Still disease, systemic lupus erythematous.
2. Rheumatic fever
3. Rheumatic polymyalgia
4. Juvenile rheumatoid arthritis
5. Ankylosing spondylitis
6. Reiter's disease
7. Gouty arthritis
8. Calcium pyrophosphate deposition disease
9. Arthropathies Heberden
10. Sarcoidosis


Treatment
Although RA treatment concept has yet managed to obtain a means of prevention and treatment of RA is perfect, the current treatment in patients with AR is intended to:
A. Relieve pain
2. Eliminate the symptoms of inflammation both locally and systemically active
3. Prevent tissue destruction
4. Prevent deformity and maintaining function of the joints to keep them in good condition.
5. Restore the organ dysfunction and joints are involved wherever possible in order to become normal again.
In the treatment of RA is generally always takes a multidisciplinary approach. An ideal team consists of doctors, nurses, physiotherapists, occupational therapists, social workers, pharmacists, nutritionists, and psychologists, all of which have their own role in the management of patients with RA either in education or medical treatment of this disease. Regular periodic meetings between the patient and his family with medical teams generally will allow the management of patients get better and will also improve patient adherence to treatment.
Once the diagnosis of RA can be enforced, the first approach to do is immediately try to foster good relationships between patients and their families with a doctor or treatment team who cared for him. Without a good relationship is likely to be difficult for patients to maintain adherence to treatment within a fixed period of time.
Although there is no treatment that can cure or inhibit the growth of rheumatoid arthritis, a comprehensive approach to an aggressive disease that combines the use of medication, rest, exercise, lifestyle modification, and sometimes surgery can help many people with the disease lead very normal lives.
Drug
Many drugs used to treat RA have the potential for serious side effects. Doctors usually choose drugs with minimal side effects at first. It takes a stronger drug or combination of other drugs as increased severity of disease.
Non-steroidal antiinflammatory drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs (NSAIDs) can relieve pain and reduce inflammation. NSAIDs work by altering the synthesis of prostaglandins by inhibiting the specific isoform of cyclooxygenase 1 (COX-1) and 2 (COX-2). The main problem with routine NSAID therapy is a side effect on the gastrointestinal (GI), renal complications, and inhibition of normal platelet function. Thus, alternative therapy should be carefully considered, and therapy should be closely monitored.
Steroids
Corticosteroids produce dramatic effects in the treatment of Rheumatoid Arthritis. Although steroids can provide dramatic recovery, but if used carelessly can result in more harmful effects than benefits. Drugs such as prednisone and methylprednisolone inflammation (Medrol), reduce and the pain and slow joint damage. Side effects may include easy bruising, thinning of bones, cataracts, weight gain, round face, and diabetes. Doctors often prescribe corticosteroids to reduce acute symptoms, and then carried out to reduce medication tappering off. For the treatment of Rheumatoid Arthritis, starting with 10 and 20 mg to control symptoms, then subtract the 2-4 weeks to the lowest tolerated dose (usually no more than 510 mg / day) and try not to exceed 10 mg/24 hours.
Disease Modifying Anti-Rheumatic drugs (DMARDs)
These drugs can slow the progression of rheumatoid arthritis and keep joints and other tissues from permanent damage by suppressing the immune system. However, because of the way these drugs work is slow and does not immediately relieve the symptoms that drugs in combination with NSAIDs. Drugs DMARDs including methotrexate (Rheumatrex, Trexall), leflunomide (Arava), hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine), minocycline (Dynacin, Minocin), and gold salts. Side effects vary, but can include liver damage, bone marrow suppression, and severe lung infections.



Generic Name Trade Name Max Dose (mg) Part Time (h) Frequency of Gastrointestinal Toxicity Renal Toxicity Dose Platelet Effect (days) a toxicity Lainb
Diclofenac Voltaren 75 2 2x1 Medium Medium 1 Hepatitis
Etodolac Lodine 300 6 4x1 Medium Low NA -
Indomethacin Indocin 50 4 3x1 High Medium 1 Headache
Nabumetone Relafen 500 NA Low Medium 1x2 20-30 Hepatitis
Sulindac Clinoril 200 8-14 2x1 Medium Low 1 Dermatitis
Tolmetin Tolectin Medium 3x1 Medium 1-2 400 2 -
Meclofenamate Meclomen 100 2 3x1 Medium Medium 1 Diarrhea
Feldene piroxicam Medium 1x1 Medium 20 30-86 14 -
Fenoprofen Nalfon Medium 4x1 Medium 2-3 600 1 -
Flurbiprofen Ansaid 100 6 3x1 Medium Medium 1 -
Motrin Ibuprofen 800 2 4x1 Medium Medium 1 -
Ketoprofen Orudis Medium 3x1 Medium 75 3 2 -
Naproxen Naprosyn 500 14 2x1 Medium Medium 4 -
Daypro oxaprozin Medium 1x2 Medium 40-50 600 NA -
Ketorolac Toradol 10 5 High Medium 4x1 1 -
Salicylsalicylic acid Disalcid 4x1 750 1 no no no -
Sodium salicylate - 650 0.5 Every 4 hours no no no -
Aspirin - 325 tabs 00:25 2/4 hours of High Medium 10 Tinnitus
Diflunisal Dolo2x1 500 10 no 2x1 Low Low -
Celecoxib Celebrex 200 11 2x1 Low Low no Sulfa allergies
a time required to return to normal
b Other NSAIDs also have the same effect, but the drug is more prevalent
NA = no data

Immunosuppressants
These medications act to tame the immune system, which is controlled in rheumatoid arthritis. Examples include azathioprine (Imuran, Azasan), cyclosporine (Neoral, Sandimmune, Gengraf) and cyclophosphamide (Cytoxan). These medications may increase susceptibility to infection.

TNF-alpha inhibitor
Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory substances produced by your body. TNF-alpha inhibitors may help reduce pain, stiffness in the morning, and perlunakan joints or swollen joints - usually within 1 or 2 weeks after treatment began. Examples include etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira). Potential side effects may include injection site irritation, congestive heart failure, blood disorders, lymphoma, demyelinating disease, and increased risk of infection.

Other drugs
Some other arthritis medications arthritis targeting various inflammatory substances produced by the body. These medications include anakinra (Kineret), abatacept (ORENCIA) and rituximab (Rituxan). Potential side effects include injection site reactions, decreased white blood cell count, headache, and increased upper respiratory tract infections.

Therapy / rehabilitation
An occupational therapist can help find different ways to approach everyday tasks in reducing the stress resulting from joint pain. For example, if your fingers are sore, we can retrieve the object by using arms. Push the door / window with the body, rather than pushing it with a sore hand.
The tools can make life easier to live without pain. For example, use the tool to grip and reach objects that are designed specifically to be able to make working in the kitchen easier, especially if you have pain in the fingers. Doctor or occupational therapist may have ideas about what kind of tools that can help as needed. Shop tools and a catalog of medical assistance can also be the place to look for ideas.






Surgery
If drugs fail to prevent or slow joint damage, surgery may be considered for repair of damaged joints. Surgery can help restore joint function. It can also reduce pain and correct deformity. Rheumatoid arthritis surgery may involve one or more of the following procedures:
• Joint replacement (total arthroplasty / joint replacement)
During joint replacement surgery, surgeons remove the damaged part in the joint and inserting a prosthesis made of metal and plastic. The success of all arthroplasty depends on the skill of surgeons, surgeons understanding of the basic functions of the underlying joint biomechanics, prosthesis design, and technical equipment used to insert the prosthesis.
The most commonly replaced joints in patients with inflammatory arthritis are the knees and hips, followed by the shoulder, metacarpophalangeal, elbow, wrist, and ankle.

• Repair tendon / tendon repair / Joint debridement
Inflammation and joint damage may cause tendons around the joints become loose or rupture. Joint state can be restored by repairing tendons around the joint.

• The appointment of the joint lining (synovectomy)
Sinovektomi are actions that can extend the life of the joint surface through the removal of the hyaline proliferative synovitis, which destroys cartilage. Sinovektomi indicated for the chronic synovitis. Chronic synovitis is a clinical entity characterized by the proliferation of the synovium and may also monoartikular. The term is relatively non-specific synovitis, and disturbances are usually the result of irritation of the joint reaction.
Specific indication for sinovektomi include the following conditions:
A. Synovitis with disease confined to the synovial membrane with little or no involvement of other structures of the joints;
2. Hemarthroses Recurrent villonodular synovitis in conditions such as pigmented or hemophilia;
3. Joint damage around the lysosome enzymes derived from white blood cells from infection successfully treated;
4. Failure of adequate trial of conservative management.
Contraindications include the ROM is reduced, significant degenerative arthrosis of the joints or other joints are involved, or cartilage involvement.

Sinovektomi technique is most often performed on knees, ankles, elbows, and wrists. There are three main techniques:
A. Sinovektomi open
2. Sinovektomi using the arthroscope
3. Sinovektomi radiation

• joint fusion (arthrodesis / joint fusion)
Arthrodesis is the union of the bone through the joints. Formation of bone fibrous joint that is moving through the joints is called ankylosis. With the unification of the bones through joints, movement between the bones to one another to be absent, thus eliminating the pain caused by arthritis. Although surgical arthrodesis can be performed on almost any joint, including the spine, joints are most frequently united ankles, knees, shoulders, and hips. Techniques used in each joint to follow the same general pattern. Released from the articular surface of hyaline cartilage remaining and then put together the optimum position of function after formed in such a way as to achieve maximum contact between the two opposing surfaces. Bone graft and some form of fixation is also often used, either internal fixation (plates, rods, or screws) or external fixation (external fixators or casts). It is used for arthrodesis mengimobilisasi place at the optimal position, because if not in an optimal position, can cause pain to a minimum. Further rehabilitation begins after adequate healing process.










Optimal Position of Joints after arthrodesis

Joint Angle Length Other Consideration
Ankle dorsiflexion 0 ° Slight shortening Talus displaced posteriorly.
0-5 ° valgus of hindfoot
5-10 ° external rotation
Knee flexion 15 ° Slight shortening -
5-8 ° flexion
20-30 ° flexion Shoulder - Patient's hand should be Able to touch the head and face.
20-40 ° abduction (lateral border of scapula)
25-40 ° of internal rotation
Slight hip flexion 25 ° shortening Do not destroy abductor mechanism.
0-5 ° abduction (Measured Between the shaft and a line through the Ischia)
0-5 ° external rotation



Prognosis
Prognosis is highly variable course of the disease. Some people have mild symptoms of short-term, but in most the disease is progressive for life. Approximately 20% -30% will have subcutaneous nodules (known as rheumatoid nodules), is associated with poor prognosis.
Poor prognostic factors include persistent synovitis, early erosive disease, extra-articular findings (including subcutaneous rheumatoid nodules), RF positive serum findings, serum anti-CCP positive autoantibodies, carriership of HLA-DR4 allel "shared epitope", a family history of RA, poor functional status, socioeconomic factors, a high acute phase response (erythrocyte sedimentation rate [ESR], C - reactive protein [CRP]) and an increase in clinical severity.





REFERENCES
A. Apley's System of Orthopaedics and Fractures.
2. Aronson, L (1999). Autoimmune Disease. Htpp / / bccc.pair.com / articles.htm; October 2002.
3. Appleton & Lange. Current Diagnosis & Treatment in Orthopedics, Fourth Edition. Copyright © 2006 by The McGraw-Hill Companies, Inc.
4. Clifford R. Wheeless, III, MD. Wheeless' Textbook of Orthopaedics.
5. Swiontkowski, Marc F.; Stovitz, Steven D. Manual of Orthopaedics, 6th Edition, Copyright © 2001 Lippincott Williams & Wilkins.
6. Mansjoer, Arif et al. Selekta kodokteran capita volume 2. Faculty of medicine. Media Aesculapius. Jakarta. Of 2000.
7. Prof, Chairuddin Rasjad. Introduction to Orthopaedic Surgery. Publisher PT, Yarsif Watampoene. Jakarta. , 2009.
8. Sjamsuhidajat, R & Wim de Jong. Textbook of Surgery. ED. 2. Book Medical Publishers EGC. Jakarta, 2004.
9. Journal of the American College of Rheumatology. Arthritis & Rheumatism. 2010 Rheumatoid Arthritis Classification Criteria. Vol. 62, No. 9, September 2010, pp 2569-2581 DOI 10.1002/art.27584 © 2010, American College of Rheumatology.
10. http://en.wikipedia.org/wiki/Rheumatoid_arthritis
11. http://www.mayoclinic.com/health/rheumatoid-arthritis