Rheumatoid arthritis

Transcription

1 1 P a g e Rheumatoid arthritis Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints, and it's the most common persistent inflammatory arthritis, occurring throughout the world and in all ethnic groups. Generally, all rheumatic diseases can be local diseases but generally, they have systemic involvement and RA is one of the common rheumatic diseases; at least, 1% of people worldwide are affected by RA. So, RA is a systemic disease, primarily presents as Arthritis -affecting the joints- so the main problem is arthritis & Other Organs can be involved. Etiology is not clear, probably Multifactorial [both genetic and environmental factors appear to be involved], but we know the mechanism of the disease [RA is characterized by infiltration of the synovial membrane with lymphocytes, plasma cells, and macrophages. CD4+ T cells play a central role by interacting with other cells in the synovium. Activated T cells stimulate B cells to produce immunoglobulins including RF, and macrophages to produce pro-inflammatory cytokines. These act on endothelium, synovial fibroblasts, bone cells and chondrocytes to promote swelling and congestion of the synovial membrane and destruction of bone, cartilages and soft tissue.] and because of that, we have more options for treatment. (TNF, il-1, 6 are important so they create drugs that block them) Diagnosis: - Typical clinical presentation [joint pain, swelling and stiffness affecting the small joints of hand, feet and wrist (without swelling, no Dx of RA)] - Rheumatoid factor presence or absence does not make or exclude diagnosis but positive RF means more extra-articular manifestations and more severe manifestations [because RF can form immune complexes within the joint and extra articular tissues, leading to vasculitis.]. In old days, we said that 70% of affected are RF positive and it was part of the criteria and now it s more important in the criteria than before. -

2 - You have to exclude other diseases that may mimic RA or cause arthritis (other than RA). ACR 1987 classification criteria for RA, the old criteria: 1- Morning stiffness lasting at least for 1 hour.* 2- Swelling in 3 or more joints.* 3- Swelling in hand small joints.* *These 4 must be present at least 6 weeks. 4- Symmetric joint swelling.* 5- Erosions or decalcification on X-ray of the hand [radiological changes]. 6- Rheumatoid nodules. 7- Abnormal serum rheumatoid factor. << This is the old criteria in the new one, the only 2 differences are: rheumatoid nodules are not present any more in the new criteria and they added anti-citrullinated protein antibody (ACPA). >> This is a normal joint, the joint is surrounded by a synovium, and it s the site of the inflammation; normally it consists of 1-2 cells thickness. With synovial inflammation, the thickness becomes hundreds of cells. In this case, the synovium will act as a tumor, it will invade the bone and the cartilage and destruct them and for that reason, the erosions in RA are lateral on the sides while the inside damage will be later. 2 P a g e

3 Constitutional Signs and symptoms of systemic RA: Fatigue, tiredness, weakness, weight loss, myalgia, excessive sweating, low grade fever, morning stiffness, lymphadenopathy. Those are general vague symptoms due to the generalized systemic inflammation. Laboratory features in RA: 1) Anemia*. 2) Eosinophilia*. 3) Thrombocytosis*. 4) Increased levels of alkaline phosphatase, Aspartate amino-transferase, and gammaglutamyl-transferase. 5) Decreased albumin and pre-albumin. 6) Elevated erythrocyte sedimentation rate [ESR]*. 7) Elevated C-reactive protein [CRP]* 8) Increase ferritin* (ferritin is considered as acute phase reactant; any patient with anemia & increased ferritin then think of chronic inflammatory disease). Now, the dr. had moved on to show us different pictures to patients with RA: 3 P a g e This looks normal once you look at it, but if you look more carefully, you see early changes in the MCPs & PIPs with symmetrical synovitis, no deformity Early RA with soft tissue swelling, involving PIPs Joints. Note that DIPs are spared and this is typical for RA.

4 This is severe disease, synovitis & Subluxation of MCPs, RA nodules. Again; DIPs are relatively spared. This is swan neck deformity (arrow) & boutonniere deformity (arrowhead). Maybe, you ll never see these deformities because of better treatment than before. This is ulnar deviation, damage of MCPs & PIPs & rheumatoid nodules & muscle atrophy. Ruptured tendon in RA patients The DIPs still relatively spared. 4 P a g e

5 This is metatarso-phalygeal [MTP] joint, it can be also affected. RA patient with carpal tunnel syndrome [CTS] There is distal involvement and it could be part of osteoarthritis. Deformity, subluxation, osteoporosis, erosions (MCP). This is a typical X-Ray where the carpal bones affected and damaged and soft tissue swelling around the MCPs (are damaged) and PIPs, osteoporosis. 5 P a g e

6 The dr. said that he ll not comment that much on the X-Ray but if you see X-Ray in the exam that shows ulnar deviation and damage on the MCP joint, it will be rheumatic Arthritis, there will be no another question about it. Here ulna styloid erosion, as I said it starts as erosion from sides, later on, it will be inside. Metatarsal joint, there could be damage or erosion (in 5 th MTP) and fibular deviation rather than ulnar deviation in the upper extremities. MTP joints with erosions, subluxation, osteopenia [a condition where bone mineral density is lower than normal. It is considered by many doctors to be a precursor to osteoporosis] Bone uptake in RA; carpal bones, MCPs and PIPs 6 P a g e

7 Differential Diagnosis: - Viral syndromes. - Post Streptococcal/other infections. - Psoriatic arthritis, reactive arthritis, and other systemic rheumatological diseases. - Crystal arthropathy like Gout. - Septic arthritis also may coexist. Here is Subcutaneous nodules. the typical site for it is the elbows, extensors, hands. * Rheumatoid nodules occur almost exclusively in seropositive patients, usually at sites of pressure or friction such as the extensor surfaces of the forearm [elbows], sacrum, Achilles tendon and toes. They may be complicated by ulceration and secondary infection. Similar nodules may occur in the pleura, lung, pericardium, and sclera. This slide is just to show you that this is a systemic disease that can affect even the heart, the lungs, kidneys (although it is not common), joint, skin and everywhere. 7 P a g e

8 Here we see lung nodules which is part of the disease. ILD [interstitial lung disease], Cavitation, TB, abscess, fungi, tumor, Nodule Major ocular manifestations: - Keratoconjunctivitis sicca. - Scleritis:painful and serious - Episcleritis; an inflammatory condition affecting the episcleral tissue that lies between the conjunctiva and the sclera, it's painful and may cause perforation. - Uveitis Episcleritis is common in RA, Superficial but cause irritation. Scleromalacia: degeneration and thinning (softening) of the sclera, occurring in rheumatoid arthritis, a potential serious complication is the perforation. Some patients got perforation and they lose vision (in the old days) but nowadays because of the immunosupression, this doesn t happen. 8 P a g e

9 Scleromalacia perforance: In this condition rheumatoid nodules may develop in the sclera and cause perforation And some patients their cornea may melt and they need corneal transplant [Marginal corneal disease, and perforation]. Rheumatoid vasculitis usually occurs in older seropositive patients in the context of systemic symptoms and multiple extra articular features. Vasculitis can vary from relatively benign nail-fold infarcts to widespread cutaneous ulceration and skin necrosis. Involvement of medium sized arteries can lead to mesenteric, renal or coronary artery occlusion. Vasculitis; blood vessels inflammation (here affecting small vessels) Vasculitis causes gangrene like this 9 P a g e

10 The spinal cord may affected because it has synovioum around the odontoid process and this synovioum may cause damage to the transverse ligament or to the odontoid, if it causes damage to the ligament, it will cut & cause compression on the spinal cord. Signs of SC damage: - Severe neck pain radiating to Occiput - Tingling or numbness in fingers and feet - Motor weakness - Urinary bladder dysfunction - Jumping legs <<< When the spinal cord is affected the patient may die! They take him to the surgery and the anesthetic resident don t know that he has RA and he push the patient backward with force so the patient has trans-sectional cord and he die on the table! >>> 10 P a g e

11 This is the new criteria, and you don t have to remember it. If you have more than 10 joints involvement then you have at least 1 small joint because this is a poly-articular arthritis affecting small and large joints, so if you have more than 10 joints and one of them is small joint then you say yes and go to the next step; the serology, if the serology is positive then this is definitely RA (serology means RF OR ACPC). If serology is negative then you look to the duration; if it is 6 weeks and more then it is RA. If it is shorter than 6 weeks then you go to APR (Acute Phase Reactant, CRP & ESR), If the APR positive then it is RA, if it is negative still not diagnosed. Most of the patient, the APR is positive and the serology: 75% is positive. 11 P a g e

12 The dr. didn t explain this table and it s not for memorization. The dr. said that the treatment is very complicated but the main action of drugs is that they block the inflammatory mediators (TNF, il 6, 2). And the earlier we diagnose and the earlier we treat, the higher percentage the person will go to remission. NAIDs are not good, they don t decrease the progression of the disease & nobody goes into remission. Prednisolone by itself don t make a difference (it increase CVS mortality) but if combined with disease modifying drugs [DMARDs], there s some evidence about increase the probability of remission. 12 P a g e

13 Systemic lupus erythromatosus SLE: is an Autoimmune multisystem disease characterized by widespread inflammation and production of autoantibodies (or autoimmune connective tissue disease) that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage. It is a Type III hypersensitivity reaction in which antibody-immune complexes precipitate and cause a further immune response. Even the RF will be positive in SLE (30% or more in SLE patients have RF positive and can present with RA and then you misdiagnose SLE as RA.). SLE is a systemic disease rather than local as RA, the difference is that: RA is a disease of joints with systemic manifestations while SLE is a true systemic disease and can mimic any disease including RA. So, this disease is associated with wide spectrum of presentation. Epidemiology: SLE is the most common connective tissue disease, the risk increases according to: 1) AGE: the peak of the age onset is between years old [20-30 in the book] because of complications as pregnancy, but it can affect any age. 2) SEX: around 90% of affected individuals are females. During the childbearing age, the ratio is 10:1. 3) RACE: high prevalence in African in US and UK 1: ,also in high prevalence in Latino and Asian.While rare in Africa. Caucasian prevalence 1:2000. The overall 5 years survival of SLE is 90%. And the mortality within 5 years of diagnosis occurs due to organ failure or overwhelming sepsis, both of which are modifiable by early effective intervention. >> The dr. said that he don t know the prevalence in Jordan and how much the problem is but this disease is a bad disease, there s no one year without losing few patients with lupus so it s associated with high mortality (young females) and morbidity. 13 P a g e

14 Clinical features 1) General Features: - Nonspecific symptoms: Severe fatigue, Fever, Weight loss, Anorexia, Lymphadenopathy. >> those are similar to the RA symptoms with 2 differences: - The fever is much higher in SLE while in RA; it s low-grade fever. - The typical presentation of SLE is much more than RA, where in RA (joint pain & swelling with morning stiffness), while in SLE (extreme fatigue, febrile, dyspnea, typical rashes on the face, etc). 2) Raynaud syndrome (secondary Raynaud's): is a vaso-spastic disorder causing discoloration of the fingers, toes, and occasionally other areas where it is caused by other instigating factor [ other than the ones causing primary Raynaud's], most commonly connective tissue disorders such as systemic lupus erythematous. 14 P a g e

15 3) Dermatological features: Malar rash: in 30-60%, it s an erythematous butterfly rash occurs over nasal bridge and malar bones [cheeks] and sparing the naso-labial fold. - It's erythematous, raised and painful or itchy. - When taking medication, it becomes faint. - It s superficial rash. Photosensitivity: rash over the sun exposed areas; [face, neck and V shaped area of chest]. - Rash varies in severity depending on exposure, Less under the orbit protected areas. - After they re exposed to sun for minutes, they come with sloughed skin - like rash Discoid rash: with erythematous hyper-pigmented margins and flat scarred hypo-pigmented centers. - This can be seen in SLE and pure cutaneous lupus. - It s a deep rash with scarring mainly on the face and neck. - Characterized by hyperkeratosis and follicular plugging and may cause scarring alopecia if presented on the scalp. 4) Gastrointestinal features: Oral ulcers: Oral or nasopharyngeal ulceration, usually painless, observed by physician Oral lesions in SLE: Erythema of hard and soft palate. Also you see papules, vesicles and petechiae. Also erythematous rash of the tongue. 15 P a g e

16 Mesenteric vacuities: is a serious complication which can present with abdominal pain, bowel infraction or perforation. 5) Arthritis and Arthralgia: Arthritis: Non-erosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion Symmetrical, but can be asymmetrical, affect large and small joints, it can be anything!! SLE arthropathy: Non erosive arthritis, Hand may show diffuse soft tissue swelling, ulnar deviation, swan neck deformity, MCP subluxation. In old days; 20 years ago, the rheumatology was only an observational specialty, there was no medications except methotrexate. So they was saying that the difference between RA & SLE arthritis that SLE is non-erosive (but not 100%!!) with deformities. Arthralgia: migratory arthralgia with early morning stiffness. tenosynovitis and small joint synovitis that can mimic RA. 6) Pulmonary features:: Pleuritis: the most common [30%] in life time of SLE patient. Pneumonitis, pulmonary embolism, pulmonary hypertension, pulmonary fibrosis & nodules Pulmonary hemorrhage: the most dreadful with 50 % mortality with treatment. Usually, males with SLE die because of pulmonary hemorrhage. < It can cause any disease in the lung > 16 P a g e

17 7) Cardiovascular features: Pericarditis: the most common. Aortic insufficiency: the most common valvular lesion (it damages the valves) Endocarditis, aortitis, myocarditis, valvulitis and antibiotic prophylaxis indicated for dental and surgical procedures Accelerated atherosclerosis & damage to the coronaries (CAD) with 10 times higher mortality from myocardial infarction from age and sex matched. Serositis: it includes: - Pleuritis: convincing history of pleuritic pain, pleural rub heard by a physician or evidence of pleural effusion, with dyspnea. OR - Pericarditis: documented by ECG, pericardial rub or evidence of pericardial effusion. < So, SLE can affect the pleura or inside the pleura > 8) Hematological features: Hemolytic anemia with reticulocytosis & mild jaundice & LDH >> usually, in hemorrhage, if the bone marrow still working, reticulocyte count will increase but if the bone marrow isn t working (aplastic crisis bcz of lupus), reticulocyte count will decrease. But in normal person, reticulocyte count will increase bcz the bone marrow will push more reticulocytes to the blood. Leukopenia: less than 4,000/mm total on 2 or more occasions OR Lymphopenia: less than 1,500/mm on 2 or more occasions OR Thrombocytopenia: less than 100,000/mm, in the absence of offending drugs. 9) Renal features: Lupus glomerulonephritis: presented as Persistent proteinuria (due to inflammation) greater than 0.5 grams per day or grater than 3+ or Cellular casts (due to glomerulonephritis as in children); may be red cell, hemoglobin, granular, tubular, or mixed. Impaired kidney function, as if creatinine level increases, then you should treat or the patient will develop renal failure. 17 P a g e

18 ** Lupus nephritis predict out come (prognosis); the kidneys are the target of lupus, if the kidney function is normal then the outcome is acceptable -except if there s other serious organ involvement- ** Major cause of mortality & morbidity. 10) Neurological features: Seizures OR psychosis: in the absence of offending drugs or known metabolic derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance < So, the global function of the brain will be impaired > 11) Immunological disorders: 95% of lupus patients are Anti-Nuclear Antibody (ANA) positive, but this antibody isn t specific for SLE since many diseases can be ANA positive. (so ANA test is sensitive but not specific). More specific tests: 1- Anti-DsDNA antibody. or 2- Anti smith antibody. And/Or 3- An abnormal serum level of IgG or IgM anticardiolipin antibodies. Or 4- A positive test result for lupus anticoagulant using a standard method. ACR criteria; 1982 classification criteria: The diagnosis of SLE is based on a combination of clinical features and laboratory abnormalities. To fulfill the classical criteria of SLE, You must have 4 criteria of 11 [simultaneously or serially] from the flowing: Malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurological disorder, hematologic disorder, immunologic disorder, antinuclear antibody. 18 P a g e

19 Anti-phospholipid antibody syndrome [APS] It is an autoimmune, hyper-coagulable state caused by antibodies against cellmembrane phospholipids that provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, or severe preeclampsia. Can be: - Primary (50%) without underlying disease. - Secondary (50%) to SLE, malignancy or infection. For diagnosis, you need 1 clinical & 1 lab criteria; - Clinically: 1) Recurrent venous and arterial thrombosis. 2) OR/AND Recurrent fetal loss. - Labs: 1) Lupus anticoagulant test by mixing studies: those which interfere with phospholipid dependent coagulation tests. 2) OR Anti-Cardiolipin antibodies test: antibodies which bind to negatively chared phospholipids on an ELISA plate. Thrombocytopenia & prolonoged PTT are clinical findings but not part of the criteria. Labs in SLE >> ANA: 95% positive, sensitive but not specific. 5-10% positive general population, also positive in other auto immune diseases (eg. thyroiditis) >> Anti-DNA antibody: specific but not sensitive, increase with active disease % of patients are positive. >> Anti-smith antibody: specific for SLE. 30% are positive. >> Rheumatoid factor: can be positive in 30%. 19 P a g e

20 Depend on organ involved Leukopenia and lymphopenia are common Thrombocytopenia Anemia of chronic disease Hemolytic anemia with high reticulocyte count, coombs positive Proteinurea, casts Abnormal liver and kidney function RA (as polyarticular arthritis) Vs. SLE (as arthritis in a connective tissue disorder): - CBC: white count & platelets are increased & Hb in decreased in RA while in SLE, Hb, white count & platelets are down. - Hemolytic anemia: not significant in RA but common in SLE. Anemia in RA is mainly due to GI hemorrhage, due to medications as NSAID & steroids. - C-reactive protein: negative in lupus (except in infections) & positive in RA. Always remember that pregnancy & SLE are not friends!! Familial Mediterranean fever - This is the most common of the familial periodic fever, predominantly affecting the Middle East, south Europe. - Autosomal recessive (so you need 2 mutations) disease characterized by attacks of serositis and fever, attacks are acute and sudden (last from 6-96 hrs; few hours to days); it come and resolve alone or by NSAID. - First attack occur before age 20 in 90%. - Symptoms: Abdominal pain in 95%, mostly as acute abdomen and peritonitis but some times mild, Mono-arthritis with effusion in 75%, mostly knees, ankles or wrists, Chest pain/ pleuritis (unilateral)in 30%, Pericarditis (rare 1%) WITH fever - or may be fever alone-. - The main complication of this disease is amyloidosis; any chronic inflammation can end with amyloidosis as RA. So it s a chronic recurrent inflammation that ends with amyloidosis and the most sensitive organ to amyloidosis is the kidneys so they end up with dialysis. 20 P a g e

21 Genetics: the responsible gene has been located in short arm of chromosome 16, MEFV gene encodes protein (pyrin, marenostrin), Pyrin mostly in cytoplasm of neutrophils or monocytes /regulates inflammation [regulates neutrophil mediated inflammation by indirectly suppressing the production of IL-1]. >> mutations: 28 mutation (most common), M694V and V726A. >> M694V associated with more severe disease and higher risk of amyloidosis Treatment: Colchicine (1-2 mg QD); decrease 60% of attacks and modifies 20-30% & prevents amyloidosis. It arrests cell division in the microtubules so decrease the inflammation. NSAIDs may help abort attack. THE END Best of luck ALL da3watkom :D Done by: Sara AL-Zu'bi & Hadeel Al-Kofahi. 21 P a g e