ICL 8.7: Rheumatoid Arthritis

Question 1

what’s the hallmark of RA?

Answer 1

symmetric synovial proliferation and tenderness in multiple joints, particularly the small joints of the hands and feet

most patients experience joint stiffness or gelling for more than an hour in the morning

Question 2

what marker is related to RA?

Answer 2

the blood of approximately 80% of patients with RA contains rheumatoidfactor (RF)

this is an immunoglobulin that binds the Fc region of the IgG molecule, anti–citrullinated peptide antibodies (ACPAs), or both RF and ACPAs

Question 3

what is the strongest environment risk factor for RA?

Answer 3

Cigarette smoking remains the strongest environmental risk factor for RA

other lifestyle factors and exposures such as alcohol use may be inversely associated with RA

Question 4

what is RA?

Answer 4

a systemic autoimmune disease characterized by the presence of autoantibodies in peripheral blood and synovial fluid. Most autoantibodies are not directed to joint-specific antigens

a common autoimmune disease that is associated with progressive disability, systemic complications, early death, and socioeconomic costs

RA involves a complex interplay among genotype, environmental triggers, and chance

localization of the inflammatory response occurs in the joint by virtue of poorly understood mechanisms that probably involve microvascular, neurologic, biomechanical, or other tissue-specific pathways

Question 5

what is the genetic role in RA?

Answer 5

twin studies implicate genetic factors in rheumatoid arthritis,with concordance rates of 15 to 30% among monozygotic twins and 5% among dizygotic twins

Question 6

what is the environmental role in RA?

Answer 6

gene interactions described in the text promote loss of tolerance to self-proteins that contain a citrulline residue, which is generated by post-translational modification

this anticitrulline response can be detected in T-cell and B-cell compartments and is probably initiated in secondary lymphoid tissues or bone marrow

these events generate an autoimmune response to citrulline-containing self-proteins

the localization of the inflammatory response occurs in the joint by virtue of poorly understood mechanisms that probably involve microvascular, neurologic, biomechanical, or other tissue-specific pathways.

Question 7

what is the pathogenesis of RA?

Answer 7

synovitis is initiated and perpetuated by positive feedback loops and in turn promotes systemic disorders that make up the syndrome of rheumatoid arthritis

it’s a combination of environmental factors, epigenetic modifications and susceptibility genes that lead to altered post-transcriptional regulation and loss of tolerance that leads to autoimmune disease and arthritis

Question 8

what is synovitis?

Answer 8

inflammation of a synovial membrane that lines the joints

this is the hallmark of RA!!

synovial tissue in joints with RA is markedly expanded by the recruitment and retention of inflammatory cells along with the formation of villus projections and the generation of pannus tissue that invades and destroys cartilage and bone

Question 9

45 year old female with history of Rheumatoid Arthritis came to her Rheumatologist for follow up. She is maintained on methotrexate 15 mg and folic acid. She denies any joint pain or stiffness. Her vitals are stable. On exam, she has no joint tenderness or swelling. On her elbow, she has firm mobile nodule which is painless. It does not interfere with her activity. Nodule was biopsied.

What will you see in pathology?

Answer 9

focal central fibrinoid necrosis with surrounding fibroblasts

aka a rheumatoid nodule!

Question 10

what are the stages of RA?

Answer 10

genetic risk –> preclinical autoimmunity –> initial signs/symptoms –> classifiable clinical disease

the clinical course of RA follows an onset of disease that may be abrupt and acute, gradual and insidious, or subacute between these extremes

a gradual onset is most common (at least 50% of cases), whereas a sudden onset is much less common (10% to 25%)

RA begins predominantly as an articular disease, and one or many joints may be affected.

Question 11

what happens during the preclinical stage of RA?

Answer 11

the preclinical period is present for a substantial time before the onset of clinically apparent inflammatory arthritis

it’s characterized by the evolution of multiple autoimmune and inflammatory processes that are measured by a number of specific biomarkers

it’s when a patient with susceptibility gene is exposed to environmental factors which leads to the development of autoimmunity and antibody production

when this is exposed to risk factors will lead to damage of cartilage and inflammation

Question 12

which joints are most often effected by RA?

Answer 12

1. PIP
2. MCP
3. wrist
4. elbow
5. shoulder
6. hip
7. knee
8. ankle

Question 13

how do you assess TA?

Answer 13

4 point technique

Question 14

what aerate 2 deformities you can see with RA?

Answer 14

1. boutonnere = PIP flexing

2. swan neck deformity = PIP extension and DIP flexion

Question 15

which joints are effected with osteoarthritis?

Answer 15

1. neck
2. lumbar spine
3. hips
4. knees
5. DIP and PIP

MCP and MTP joints are NOT involved like in RA

go look at diagram

Question 16

what are the extra-articular manifestations of RA?

Answer 16

these are poor prognostic factors; especially vasculitis and rheumatoid lung disease

1. pericarditis
2. pleuritis
3. vasculitis
4. Sojern syndrom
5. RA nodules

although the onset of RA is predominantly articular, it is frequently associated with a variety of extraarticular features, including generalized weakness, anorexia, weight loss, or fever

Question 17

what are rheumatoid nodules?

Answer 17

they develop on pressure areas like elbows, finger joints, occipital scalp, achilles tendon

they are firm and can be seen on tendons and frequently adherent to the underlying periosteum

Question 18

what is Sweet syndrome?

Answer 18

spots on the skin from RA

its main signs include fever and painful skin lesions that appear mostly on your arms, neck, head and trunk

Question 19

what is pyoderma gangrenosum?

Answer 19

not limited to RA but it’s a skin condition where

Question 20

what are the hematological manifestations of RA?

Answer 20

1. anemia

due to reduced EPO and blunted response to EPO; usually correlates to disease stage

2. thrombocytosis

may correlate with the number of joints involved

3. lymphadenopathy

Question 21

60 year old male with history of seropositive [ RF and CCP] Rheumatoid Arthritis came with ℅ fever and fatigue. He has long standing Rheumatoid Arthritis for which he is non compliant to medication. He has left lower extremity ulcer which is non healing. He has Rheumatoid nodule on his right elbow. Temp: 100.5 Pulse 90, BP- 120/70. On Physical Exam he has symmetrical synovitis of his b/l MCP and MTP. Respiratory: clear. Abdomen: Non tender, BS+, Fullness in LUQ.

Labs:
WBC: 1800 , Hb : 11.5 GM, Platelets: 450

what’s the diagnosis?

Answer 21

felty’s syndrome

Question 22

what is felty’s syndrome?

Answer 22

RA + splenomegaly + leukopenia

it occurs in patients with long standing, seropositive, nodular, deforming RA

bacteria infections are common in Felty syndrome and correlated with a polymorphonuclear leukocyte count lower than 100 = high mortality

increase in number of large granular lymphocytes in blood and bone marrow

SANTA = splenomegaly – anemia — neutropenia – thrombocytopenia — arthritis

Question 23

what are the lung manifestation of RA?

Answer 23

1. pleural effusion

the presence of multinucleated giant cells is highly specific for rheumatoid pleuritis

2. pulmonary nodules
3. RA interstitial lung disease

generally takes the form of nonspecific interstitial pneumonitis or usual interstitial pneumonitis

Question 24

what is Caplan’s syndrome?

Answer 24

pulmonary nodulosis and pneumoconiosis in patients with RA

it’s characterized by several nodules greater than 1 cm in diameter and scattered throughout peripheral lungs

seen in patients exposed to coal dust

Question 25

what are the ocular manifestations of RA?

Answer 25

1. keratoconjunctivitis sicca
2. episcleritis and scleritis
3. scleromalacia
4. ulcerative keratitis

Question 26

what is rheumatoid vasculitis?

Answer 26

small-vessel vasculitis commonly involves the skin and causes nail fold infarcts, digital gangrene and leg ulcers

the rapid, progressive, and widespread appearance of new areas of involvement, including clinical cutaneous vasculitis and multiple neuropathies, is indicative of systemic arterial disease and portends a worse outcome

poor prognosis

Question 27

what is the neurological manifestation of RA?

Answer 27

1. peripheral entrapment neuropathy
2. atlantoaxial subluxation
3. a diffuse, granulomatous pachymeningitis (rare)

Question 28

what are some of the long term complications of RA?

Answer 28

1. arteriosclerosis
2. low bone density
3. depression
4. insulin resistance
5. acute phase response (CRP)

Question 29

what is the survival rate of RA with extra-articular manifestations?

Answer 29

lower….

all patients with RA have a lower life expectancy but if there’s also extra-articular manifestations it’s even lower

Question 30

30 year old female comes to her physician with c/o progressive joint pain over the past few months. it started with her right hand and now she has pain in both hands and feet. she also complains that morning are difficult. she works as a secretary and notices that she has difficulty getting up from sitting position.

On examination she is afebrile with normal vitals.She has 2nd and 3rd MCP tenderness with swelling in both hands. She has right knee swelling.Her left wrist is also swollen.

what’s the best diagnostic test?

Answer 30

ESR and CRP

Question 31

how do you diagnose RA?

Answer 31

RA is a clinical diagnosis for which no single physical finding or laboratory test result is pathognomonic

if patients has >6 points of the qualifications, you get diagnosed with RA

1. joint distribution
2. serology for RF and ACPA
3. symptom duration
4. acute phase reactants

Question 32

what are the goals of treatment for an RA patient?

Answer 32

1. reduce pain, stiffness and fatigue
2. improve quality of life
3. prevent joint destruction
4. maintain full function
5. reduce CV events
6. prolong lifespan

“treat early and treat hard”

Question 33

what is biosimilar?

Answer 33

it’s like a biologic agent but they’re made some changes in the structure so now it can be used to treat RA

Question 34

what is RF?

Answer 34

autoantibodies to the Fc portion of IgG

they are the longest-known marker antibodies in RA

high-titer IgM-RF and also IgA-RF are of high diagnostic and prognostic value because they are associated with erosive and more severe disease

IgM-RF can be detected in 60% to 80% of RA patients with established disease, whereas its prevalence in patients with early RA ranges between 50% and 60%

Question 35

60 year old female came to her primary care physician with ℅ nodes. She has noticed bump in her finger. In the morning she has morning stiffness lasting for about 30 mins. Her husband has h/o gout and her mother had similar hand. DIP and PIP are swollen.

Answer 35

Heberden’s and Bouchard’s

that’s because this joint swelling is typical for hand OA and it has a hereditary components

Question 36

what do you see in the x-rays of someone with RA?

Answer 36

1. Periarticular Osteopenia
2. Soft tissue swelling
3. Joint space narrowing
4. Bone erosion
5. Subluxation

Question 37

with what drug do you treat RA?

Answer 37

treat with combination of DMARDs = disease-modifying anti-rheumatic drugs

start DMARD within six weeks of diagnosis or symptoms at the maximal efficacious dose that is tolerated by the patient

aim for remission of disease activity

Question 38

which drugs are DMARDs?

Answer 38

1. methotrexate
2. sulfasalazine
3. hydroxychloroquine
4. leflunomide

Question 39

what is CCP?

Answer 39

CCP = cyclic citrullinated peptides

Citrullinated antigens expressed in the inflamed joint include fibrinogen, vimentin, α-enolase, and collagen

so then there are anti–citrullinated protein/peptide antibodies (ACPAs) which are directed to antigens containing the unusual amino acid citrulline. They are the most specific marker antibodies for RA and, like high-titer RF, are linked to erosive RA

it is associated with the severity of RA, such as erosiveness, more rapid disease progression, worse outcome, and extra-articular manifestations

super high sensitivity and specificity; considered the gold standard diagnostic test for RA