Rheumatoid Arthritis Flashcards
A 37 y/o day care attendant is seen by a nurse practitioner after 4 weeks of polyarthritis of the wrists MCPs and knees. RA latex is positive. She is diagnosed with RA and started on low dose MTX. Which is true?
- A positive anti- CCP will confirm the diagnosis.
- X-ray or ultrasound may confirm the diagnosis.
- Treatment should always start with NSAIDs.
- CRP should be done before starting MTX.
- She probably has an alternative diagnosis.
She probably has an alternate Dx - parvovirus B19
What causes carpal tunnel?
“MEDIAN TRAP”
Myxedema
Edema
Diabetes
Infiltration (sarcoid, leukemia, fibrosis)
Amyloid
Neoplasms
Trauma
RA
Acromegaly
Pregnancy
What infections should be expected for a gardner with septic joint?
Sporotrichosis
Nocardiosis
Blastomycosis* - decomposed wood in north central or southern US
Pantoea (Enterobacter) agglomerans - Opportunistic infection from plants and animal feces.
What are the ocular manifestations of RA?
Scleritis and potential scleromalacia perforans as isolated complication of RA or part of the Sicca Syndrome with keratoconjunctivitis sicca.
Dry eye
Sicca syndrome includes dry mouth with potential caries, test with Shermer test
scleromalacia perforans is when eye is flat, humor has run out
What are the cervical manifestations of RA?
A-A Subluxation
Erosion of odontoid process
C-spine ankylosis
With subluxation, patients tend to have C2 radiculitis and myelopathic symptoms, including extremity weakness, gait and balance problems.
+ Romberg test, with numbness in extremities
Important to measure displacement and amt of cord compression
- anesthesia and hyperflexion of the neck indicates complete cord compression
What are the pulmonary manifestations of RA?
Cough
Dyspnea
“Cellophane crackles” – close to the ear crackles
Pulmonary fibrosis
Caplan’s syndrome (RA nodules in lungs)
What is Caplan’s syndrome?
rheumatoid pneumoconiosis, also known as Caplan’s syndrome, can occur in workers exposed to silica, as well as in patients with silicosis, coal workers’ pneumoconiosis or asbestosis.
It was originally described in coal workers with pneumoconiosis.
Where can rheumatoid nodules present? What do they mean, and are more likely to have?
Rheumatoid nodules
- in skin, sclera, lungs
Often mean RF seropositivity
- more likely to have vasculitis and anti-CCP Ab
In addition to rheumatoid nodules, what skin changes are often present in RA?
Neutrophilic dermatosis/Sweet’s Syndrome
(Type IV/IL-8 &GM-CSF neutrophilia, overproduction of IL-8 in Th1 pathway inducing neutrophilia)
Pyoderma gangrenosum (all WBCs infiltrating skin, part of RA but also seen in CML, Crohn’s, UC, IgA myeloma)
Livedo reticularis - rheumatoid med vessel vasculitis, also seen in polyarteritis nodosa of anti-phospholipid Ab syndrome)
Small vessel vasculitis - circular purpura, RA vasculitis is most often small vessel vasculitis
What will many people with RA have on abdominal exam?
Felty’s Syndrome, complication of long-standing RA
SANTA:
Splenomegaly
Anemia (pale, hypochromic red cells)
Neutropenia Nodules
Thrombocytopenia
Arthritis - RA
Explain the classification criteria for Dx of RA.
2010 Classification criteria for RA diagnosis:
6 out of 10 = RA
- Number and site of involved joints: 1-5 points
2 to 10 large joints = 1 point
1 to 3 small joints = 2 points
4-10 small joints = 3 points
> 10 joints (including at least one small joint) = 5 points
- Serological abnormality (RF or Anti-CCP): 2-3 points
Low positive (above the upper limit of normal, ULN) = 2 points
High positive (greater than 3 times the ULN) = 3 points
- Elevated acute phase response (ESR, C-RP): 1 point (above the ULN = 1 point)
- Symptom duration: 1 point
(at least six weeks = 1 point)
What are the newer biomarkers in RA?
14-3-3η (eta)
Multibiomarker Disease Acticity (MBDA)
What is 14-3-3η? What is the usefulness when Dx’ing RA?
14-3-3η involved in the regulation of protein phosphorylation and mitogen-activated protein kinase pathways. It can help to diagnose early RA when CRP is negative, most specific test.
What is the MBDA biomarker in RA Dx? What is it helpful with?
Multibiomarker Disease Acticity (MBDA). Includes IL-6, TNKr type 1, VCAM 1, EGF, VEGF-A, etc*.
ie.YKL-40, matrix metalloproteinase-1, MMP-3, CRP, SAA, leptin, resistin
High MBDA > 44 is associated with rapid radiologic progression, and response to TNFi ove triple therapy.
What are the rheumatic diseases with a positive RF?
Rheumatic diseases with positive (> 50%) RF:
Cryoglobulinemia*
Sjogrens
RA
MCTD
What are the non-rheumatic diseases with positve RF?
Non-rheumatic diseases with positive RF:
Infections – parasites, leprosy, SBE*, virus (Hep C)
Lung diseases – silicosis, IPF
Miscellaneous - PBC
*High titer RF without rheumatic disease, Subacute Bacterial Endocarditis
What is RF?
Rheumatoid Factor:
anti-IgG IgG
or
anti-IgG IgM
IgM is more troublesome b/c its larger
What is anti-CCP Ab from?
anti-cyclic citrullinated protein
- inflamed joints produce cyclic citrullinated proteins from breakdown of arginine
anti-CCP Ab are initially produced against bacterial by-products
- Porphyromonas gingivalis from oral plaque, Proteus from GU, Prevotella and Leptotrichia from GI tract
Which individuals develop anti-CCP Ab?
APCs pick up CCP Ag
presented to T-cells
T-cells in HLA-DRB1 SE carriers activate B-cells and create anti-CCP Ab
epitope spreading causes Ab to attack CCPs in human joints
What is the use of X-ray in dx of RA?
show erosions on lateral/marginal signs
- difference between gouty (lateral extension of the spur) and OA signs/erosions
- shows early erosion at tip of ulnar styloid
What does US show in RA?
joint synovitis, with erosions and joint spaces
What does MRI show in RA?
MRI is gold standard
early signs picked up as edema of the bone
Erosions
What is the pathology of RA?
- Synovial cell hyperplasia and endothelial cell activation are seen in early RA.
- CD4 T cells, mononuclear phagocytes, fibroblasts, osteoclasts, and neutrophils, and B cells (RF) play major roles. Cytokines, chemokines, and other inflammatory mediators (eg, TNF-a, interleukin IL-1, IL-6, IL-8, TGF-ß, FGF, PDGF) are all active.
- Ultimately, inflammation and exuberant proliferation of the synovium (ie, pannus) leads to destruction of cartilage, bone, tendons, ligaments, and blood vessels.
- Destruction of the cartilage and erosion of the underlying bone with pannus from a patient with rheumatoid arthritis.
What are some other forms of arthritis that are DDXs for RA?
Osteoarthritis
Gout
Spondyloarthropathies
Lyme arthritis
FMF
What infections are DDXs for RA?
Infections
Parvo B 19
Hepatitis C
What collagen vascular diseases are DDXs for RA?
SLE
Polymyalgia rheumatica
Wegeners granulomatosis
RF
What are some cancers that are part of the DDX for RA?
Hypertrophic pulmonary osteoarthropathies – lung and GI cancers
Palmar fasciitis – ovarian carcinoma
What are the SSXs of FMF? What causes it, and how is it treated?
Familial Mediterranean Fever
caused by lack of “pyrin”, a neutrophil protein that keeps them from mobbing body spaces
eventually causes a deadly secondary amyloidosis
Treated with colchicine
episodic fever
arthritis
pleuritis
peritonitis
hot ankle rash
What are the SSXs and complications of vasculitis throughout the body?
CNS - stroke
Eye - reduced visual acuity
Nose- epistaxis
Heart - MI, HTN
Lungs - bloody cough, lung infiltrates
GI - bloody stools, abdominal pain
Kidneys - glomerular nephritis
MM pain
Joints - pain, arthritis
Skin - palpable purpura, livedo reticularis
General SSXs: fever, HA, weight loss
What is the DSA-28?
Disease Activity Score 28 (used for staging and prognosis, determines Tx)
- count the number of tender joints
- count the number of swollen joints
- measure the ESR
- Ask the patient to rate global activity of arthritis during the past week from 0 (no symptoms) to 100 (very severe)
- enter data into calculator or work out
What is the Vectra test?
Some rheumatologist use the Vectra test (12 biomarkers with emphasis on CRP, Il6, and SAA) to evaluate disease activity
What are the major structures/features of a joint affected by RA? What are the major cell types involved?
Inflamed synovial membrane
Pannus:
mostly T-cells and macrophages
also has fibroblasts, plasma cells, endothelium, dendritic cells
Synovial fluid (mostly neutrophils)
What are the major classes of drugs to Tx RA?
NSAIDs
Steroids
DMARDs (nonspecific)
Biologic DMARDs (specific)
What are the DMARDs for RA?
MTX
Sulfasalazine
Hydroxychloroquine
Leflunamide - pyrimidine synthesis inhibitor
Minocycline
What are the biological DMARDs for RA, and what do they do?
Biologic DMARDs (specific)
TNFi - adalimumab, etanercept, infliximab, certolizumab, golimumab
Abatacept – blocks T cell costimulation
Rituximab – depletes B cells
Tocilizumab - blocks IL6 receptor
Tofacitinib – inhibits Janus Kinase 3
Which biologics do what in RA and disease progression?
Abatacept - downregulates APC presentation to T-cells, downregulates T-cells stimulating B-cells to make RF/ACPA
Rituximab - downregulates B cells making RF/ACPA
Anti-TNFs - works on APCs; stops synovial inflammation, destructive joint changes, systemic inflammation
Anakinra - works on APCs, anti-IL-1 that reduces destructive changes and systemic inflammation
Tocilizumab - works on APCs, reduces IL-6 and reduces synovial inflammation, destructive changes, systemic inflammation
32 y/o female with 3 year of RA. AM stiffness > 30 minutes. Slight wrist, with some MCP and PIP swelling (synovitis). X-rays normal.
Treatment:
NSAIDs and prednisone?
MTX + folic acid– reevaluate in 2-3 months
36 y/o female with 1 year RA. AM stiffness > 90 minutes. Prominent synovitis. US shows early erosions.
Treatment:
1.MTX sulfasalazine, hydroxychloroquine (or MTX/lefluonamide)
30 year old female with 2 years of RA. Marked synovitis. Some joint deformity. Bilateral erosions. On MTX, HCQ, Sulfa.
Treatment:
MTX with etanercept – advantage to totally arrest joint damage
Consider other biologics if TNFs fail
What are the long term complications of RA?
MI – decreased with response to anti- TNF therapy*!
Osteoporosis
NSAID bleeds and perforations
Lymphoma and GU malignancies
A 52 y/o female with RA has been on MTX and etanercept for 4 months with little response. What is the next step?
A.Continue the program.
B.Change to tofacitinib
C.Add tofacitinib
D.Change to rituximab
E.Switch to MTX with adalimumab
Continue the program as it may take 6 – 12 months for a response.
