Extra articular features of RA:
* RA is a systemic disease, the extra articular manifestations are more common in patient with long-standing, sero-positive i.e, RF+ve, erosive RA.
* Constitutional symptoms as anorexia, wt. loss, fatigue, are most common, which can occur at presentation or through out the course of the disease.
* Generalized osteoporosis, muscle wasting, due to systemic inflammation.
* The most common extra articular features of RA is secondary sjogren syndrome manifested by dry eye (keratoconjuctivitis sicca) and dry mouth (xerostomia).
* Cutaneous features:
- Subcutaneous rheumatoid nodules: Nodules may occur any where ( for .e.g lungs, heart and eye,), but most commonly occur subcutaneously on extensor surfaces over joints , pressure or friction points. Such as extensor surface of forearm, toes, sacrum and achillis tendon. It is firm non tender and usually adhere to underlying periosteium. It is almost exclusively present in sero-positive patients. Sometimes the nodule is complicated by ulceration and secondary infection.
- Vasculitis: usually occurring in sero-positive cases, varying from benign nail bed infract to large skin ulceration and necrosis.
Pyoderma gangrenosum occurs with increased frequency in patients with RA.
* Ocular features:
• Dry eye "Keratoconjuctivitis Sicca" in secondary sjogren disease. • Episcleritis.
• Scleritis (more serious), and can progress to thinning of the sclera, scleromalacia, and even to corneal melting and perforation, scleromalacia perforance.
* Cardiovascular features:
• Asymptomatic pericarditis.
• Pericardial effusion.
· Constrictive pericarditis [rare].
• Occasionally heart block, cardiomyopathy, aortic regurgitation, coronary occlusion. Patients with RA have higher cardiovascular event (MI, stroke) than general population, presumably due to accelerated atherosclerosis from chronic systemic and/or vascular inflammation.
* Pulmonary features:
• Fibrosing alveolitis (common manifestation).
• Localized upper lobe fibrosis and cavitation (rare).
• Pleural effusion (especially in men) in sero-positive cases, exudative in nature.
• Rheumatoid nodule (pulmonary): Usually multiple, subpleural. In solitary nodule can mimic bronchial carcinoma, sometimes cavitated with similar appearance to pulmonary TB, may be complicated to
pneumothorax.
· Rarely, Bronchiolitis Obliterans Organizing Pneumonia (BOOP) which carry a poor prognosis
• Caplan s syndrome mean presence of Rheumatoid nodule + pneumocomosis.
* Neurological manifestations:
• Entrapment neuropathies "the peripheral nerve can be compressed by hypertrophied synoviam, joint subluxation" may cause carpal tunnel syndrome (median nerve compression at wrist). Tarsal tunnel syndrome (ant. tibial nerve compression at ankle). Ulnar nerve compression, lateral popliteal nerve compression can occur.
• Diffuse peripheral neuropathy and mononeuritis multiplex (due to vasculitic neuropathy).
• Cervical spinal cord compression (from subluxation of atlantoaxial or at subaxial level).
* Hematological features:
• Microcytic iron deficiency anemia (NSAID-induced GIT blood loss).
• Normochromic normocytic anemia, (of chronic disease) this type of anemia is due to active disease with or without thrombocytosis, the degree of anemia is proportional to the activity of the disease.
• Felty s syndrome: constitute of RA , splenomegaly and neutropenia. It can occur in long standing erosive, sero-positive RA, usually at age of 50-70, F > M , associated with wt. loss, leg ulcer, recurrent infection, rheumatoid nodule, Sicca syndrome, anemia, thrombocytopenia and abnormal liver function.
• Lymphoadenpathy, sometimes generalized which requiring biopsy since the increment in the risk of lymphoma in long standing RA.
* Amyloidosis can be a complication of long standing disease.
Investigations:
The investigations are usually directed to assist or established the diagnosis, to monitor the disease activity and damage, to monitor drug safety and efficacy.
In addition to anemia of chronic active disease sometimes associated with thrombocytosis, the acute phase response is usually elevated in active disease "wide spread" but could be normal in small and isolated joint synovitis.
Rheumatoid factors only present in 60-80% of RA, and sometimes it may take several months to become positive, so its absence doesn t exclude the diagnosis. Conversely RF is present in about 10% of normal individual, also can be present in other diseases as in chronic bacterial infections [subacute bacterial endocarditis, leprosy, TB, syphilis], viral disease, sarcoidosis, pulmonary interstitial disease, liver disease, mixed cryoglobulinemia, hypergammaglobulinemia.
Anticyclic citrullinated peptide antibodies (anti-CCP) assay carry a sensitivity (about 65%) and specificity (about 95%) for RA. Patients with either RF or anti-CCP antibodies typically have a worse radiological and functional outcome compared with other patients.
RA is associated also with other auto antibodies like ANA and antineutrophil cytoplasmic antibodies (ANCA).
Synovial fluid examination: In RA, the synovial fluid is inflammatory in characters, WBC count in the range of 5000 to 50000 per microliter, there are no synovial fluid findings that are pathognomonic of RA.
Radio graphical features:
1- periarticular osteopenia.
2- marginal non-proliferative erosions. "Erosions are uncommon within the first year, therefore it is not appropriate to wait radiological features before making diagnosis, however; MRI and US are much more sensitive for detecting early sign of damage even in patients with normal findings in radiography”.
Approach To Diagnosis:
As, unfortunately, there is no one single finding on physical examination or lab. testing that is pathognomonic of RA, instead , the diagnosis usually done according to clinical back ground, by an accurate and careful history and physical examination.
The clinical hall mark of the disease is persistent "synovitis". So documentation of inflammatory synovitis is essential for a diagnosis and other causes of synovitis must be excluded.
As many extra articular features of RA, characteristic symmetry ,typical serological findings, may not be evident in the 1st or the 2nd month of the disease, therefore the diagnosis of RA in early weeks is presumptive and exclusion of other causes of synovitis.
Even the acute phase response correlate with the amount of inflammatory activity "synovitis bulk" , so in patients with isolated small joints synovitis, the acute phase response may be normal.
A set of classification criteria, although not designed specifically for the purpose of diagnosis, mainly attended for epidemiological purposes, but can be used as a diagnostic aid, these criteria are:
(1) Morning stiffness more than one hour.
(2) Arthritis of 3 or more joints area.
(3) Arthritis of hand joints.
(4) Symmetrical arthritis.
(5) Rheumatoid nodule.
(6) Rheumatoid factor.
(7) Radiographic findings.
{Duration of arthritis should be 6 weeks or more}. [diagnosis of RA is made with four or more criteria]
"6 weeks is essential to ensure that self limiting or viral arthritis is not labeled prematurely as RA".
It is useful in comparative epidemiological studies, but not attended in the diagnosis of individual cases, as failure to meet these criteria, however especially during the early stages of the disease, does not exclude the diagnosis, whereas, irreversible damage can occur in early RA, so the diagnosis & treatment should not be delayed.
Management: The major goals of therapy are:
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- Stop joint damage and prevent disability and morbidity by early effective control of synovitis.
- To relive the pain, swelling and fatigue.
- To improve joint function.
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* Ideally the therapy should be mediated through multi disciplinary team.
* Patient education is highly essential, include education on nature of the disease, prognosis, therapy, importance of regular visit and monitoring. The education involve the family member as well.
* Physical therapy is mediated by physiotherapist, should include joint protection, joint splinting, orthotic adaptive foot wear, adaptive advices home environment modification, exercises of range of motion, stretching, strengthening and conditioning exercises.
Physical rest (as in afternoon nap and night time) is an integral part for overcoming fatigue.
* Hospital admission is needed when there are life threatening extra-articular features, when multiple intra-articular injection or for joint splinting.
* Periodic assessment of the disease activity, progression and disability and drug efficacy or side effects.
Drug Therapy: Traditionally the drugs used for management of RA can be divided into:
- Those used primarily for control of joint pain, swelling & stiffness as NSAID, but have no major effect on the disease "Although in long axis studies showed that the addition of small dose of pridinisolon to NSAID and DMARD (Disease Modifying Anti-Rheumatic Drug) therapy may slow the rate of radiological progression over two years in patients with early RA".
- And those involved to limit joint damage and improve long term effect and modifying the disease course to varying degree "DMARD".
* Prompt introduction of DMARDs either singly or in combination.
They are likely to be most useful when started early before irreversible damage has occurred.
* The most common DMARD of choice is methotrixate (MTX) because of it s proven clinical benefit and well-understood long term efficacy and toxicity profile. It is used either alone or combined with sulfasalazine or with hydroxy chloroquine or with both. (sulfasalazine and hydroxy chloroquine alone may used for treatment of patient with milder form of RA).
If combined therapy (MTX, sulfasalazine and hydroxy chloroquine) fail to control disease or are not tolerated, other DMARDs or anti-TNF therapy, should be used, either sequentially or in combination. (Gold compound are seldom used now because of their frequent toxicity and availability of other agents of better tolerability).
* The development of biological agents, "anti cytokine therapy" "anti-TNF therapy" Etanrecept, Infliximab, Adalimumab that bind and neutralized TNF-? have become available for treatment of RA and are remarkably effective in controlling RA in patient who failed to DMARD, and can be more effective when combine with methotrixate.
Anakinra is a recombinant IL1 receptor antagonist can inhibit IL inflammatory activity, either given as mono therapy or in combination.
Abatacept and Rituximab are among the recent additions to the biologic agents available for treatment of active RA who have inadequate response to other DMARD and other anti-TNF agents.
* Symptomatic management with using of NSAIDs and analgesics may also be required.
* Although corticosteroid are potent suppressors of inflammation and effective in managing pain and stiffness, but often it s not possible to avoid their side effects. Because of the well-appreciated side effects of the drugs, so long term use, generally should be avoided.
Sometimes short and brief courses of corticosteroid use, tapering over one to three weeks may be effective for controlling the disease flare or as (bridge) of disease control until DMARD therapy become effective.
In systemic manifestation especially vasculitis, predinsolon of 40-60 mg/day needed, with tapering according to response.
Sometimes intra-articular injection of corticosteroid is an effective means for reducing pain and inflammation in individual joints with persistent synovitis despite the above measures "after exclusion of sepsis".
* Surgery: 1- Snovectomy. 2- Tendon repair. 3- Osteotomy. 4- Arthrodesis. 5- Arthroplasties.
* Prognosis: the following factors at presentation are associated with poor prognosis:
1- presence of extra-articular manifestations.
2- insidious onset.
3- female gender.
4- presence of rheumatoid nodules, positive Rheumatoid factor and anti-CCP antibodies.
5- positive family history of severe RA.
6- involvement of MTP.
7- disease duration of over three months.
8- higher base line disability.
Co-morbidities:
· Osteoporosis: can result from both the disease itself and the use of corticosteroid. Most patients are routinely advised to take Calcium and vitamin D. Regular bone densitometry should be performed to show the need for anti osteoporotic measures e.g Bisphosphinate.
· Cardiovascular events: is the number one cause of death in RA patients. Low dose of aspirin should be considered in patients over the age of 50. Cholesterol level should be regularly monitored and cholesterol-lowering medication should be prescribed as needed.
المادة المعروضة اعلاه هي مدخل الى المحاضرة المرفوعة بواسطة استاذ(ة) المادة . وقد تبدو لك غير متكاملة . حيث يضع استاذ المادة في بعض الاحيان فقط الجزء الاول من المحاضرة من اجل الاطلاع على ما ستقوم بتحميله لاحقا . في نظام التعليم الالكتروني نوفر هذه الخدمة لكي نبقيك على اطلاع حول محتوى الملف الذي ستقوم بتحميله .