Title: A 60YearOld Woman With Generalized Weakness and Stiff Knees Chapter 21
1A 60-Year-Old Woman With Generalized Weakness and
Stiff Knees Chapter 21
Daphne Ang, M.D. Pathology Resident Eugene G.
Martin, Ph.D. Associate Professor of Pathology
Laboratory Medicine
- Based upon LABORATORY MEDICINE CASEBOOK. An
introduction to clinical reasoning - Jana Raskova, MD Professor of Pathology
Laboratory MedicineStephen Shea, MD
Professor of Pathology Laboratory
MedicineFrederick Skvara, MD Associate
Professor of Pathology Laboratory MedicineNagy
Mikhail, MD Assistant Professor of Pathology
Laboratory MedicineUMDNJ-Robert Wood Johnson
Medical SchoolPiscataway, NJ
2History and Presentation
- A 60-year-old woman admitted to hospital with
complaints of - Generalized weakness of two weeks duration
- Morning stiffness of both knees aggravated by
movement - Mild fever
- Ten pound weight loss in previous month
- Two similar episodes reported in the previous
year involving joints of wrist and hands
responded to anti-inflammatory medications - She has been taking aspirin to relieve the pain
- Physical Exam
- Alert ?, mild distress
- Temp. 100 oF
- BP 120/80
- HR 85 bpm and regular
- Respiratory rate 20 per minute
- Abdomen soft with mild splenomegaly
- Knees swollen, warm and painful.
- Mild atrophy of the muscles of the forearm
- Small subcutaneous nodues in the back of the
forearms - Swelling noted metacarpal-phalangeal joints
Whats In Your Differential? What Do You Do
Next?
3Distinction between rheumatoid arthritis and
osteoarthritis
4Differential Diagnosis
5Differential Diagnosis
6Scleroderma
Malar rash and Oral mucositis Systemic lupus
erythematosus
Pseudogout vs Gout
7Gottrons papule
Podagra - Gout
Uveitis, Urethritis, Arthritis Reiters syndrome
8HEMATOLOGY
9Erythrocyte Sedimentation Rate
- PRINCIPLE The distance the erythrocytes will
fall is a function of weight, surface area and
charge - Erythrocytes have a negative potential charge
(the zeta potential) which normally repels rbcs - Plasma proteins have a positive charge and
promote erythrocyte aggregation. particularly
fibrinogen - LIMITATIONS OF TEST
- Very non-specific
- Sometimes normal where usually it is abnormal
- Very technique specific eg tilt of the tube is
CRITICAL. Must be perfectly vertical. - ESR falsely elevated in
- Anemia
- Macrocytosis
- Concentration of anti-coagulant too high
- ESR falsely reduced in
- Polycythemia
- Microcytosis
- Marked poikilocytosis (sickle cells,
acanthocytes) - Any delay in running the test (rbcs become less
spherical and less readily form a rouleaux
10Erythrocyte Sedimentation Rate (2)
- Conditions resulting in increased ESR
- Acute or chronic infection
- Tissue necrosis and/or infarction
- Well-established malignancy
- Rheumatoid-collagen diseases
- Temporal arteritis
- Polymyalgia rheumatica
- Rheumatoid arthritis
- Collagen disease
- Abnormal serum proteins
- Changes in serum proteins that alter plasma
viscosity influence RBC sedimentation eg.
Myeloma proteins - Physiologic stress pregnancy obesity chronic
renal failure (75) - MARKED ELEVATIONS IN ESR (100mm/hour)
- Multiple myeloma
- macroglobulinemia
- polyclonal hypergammaglobulinemia
- hyperfibrinogenemia
- PROGNOSTIC in Hodgkins
- Poor - ESR 60 mm/hour in asymptomatic Hodgkins
patient (as bad as a symptomatic patient)
11Erythrocyte Sedimentation Rate (3)
- 3 main uses
- As an aid in detecting an inflammatory process
- As a monitor of disease course or activity
- As a screen for occult inflammatory or neoplastic
conditions
12C-Reactive Protein
- Produced by the liver - present during episodes
of acute inflammation. - Elevations in
- Rheumatoid arthritis
- Rheumatic fever
- Cancer
- Tuberculosis
- Pneumococcal pneumonia
- Myocardial infarction
- SLE
- Connective tissue disease
- Bacterial, viral, fungal, or parastic infection
- Other causes of ongoing inflammation
- Positive CRP results also occur during the last
half of pregnancy or with the use of oral
contraceptives
Acute Phase Reactants Plasma proteins elevated
acutely in reponse to illness, infection, trauma,
tissue necrosis cerulplasmin, haptoglobin,
fibrinogen, CRP, a-1 antitrypsin
13CHEMISTRY
14Rheumatoid Arthritis Lab Studies
- Anemia in approximately 80 of patients with RA.
The anemia is normocytic and normochromic. - Thrombocytosis may be present.
- Erythrocyte sedimentation rate (ESR) is elevated
in approximately 90 of patients with RA. - Serum RF result is positive in approximately 70
of patients with RA. - Antinuclear antibodies (ANA) are present in
approximately 30 of patients with RA. - Can identify autoantibodies against DNA, histones
or soluble nuclear antigens - Felty syndrome is a triad of RA, neutropenia, and
splenomegaly. Patients with Felty syndrome are
prone to serious bacterial infections that result
in higher rates of morbidity and mortality than
for other patients with RA. This requires prompt
diagnosis and initiation of antibiotic therapy
15Hypoalbuminemia
- Causes of decreased plasma albumin
- Decreased synthesis.
- Increased catabolism very slow
- Increased loss
- Nephrotic syndrome
- Exudative loss in burns
- Haemorrhage
- Gut loss
- Redistribution
- Haemodilution
- Increased capillary permeability (leakage into
the interstitium) - Decreased lymph clearance.
- Stress response
- Overall, the picture in the stress response is
- Initial decrease in albumin associated with
increase in acute phase proteins. - Subsequent global increase in hepatic protein
synthesis including albumin.
16Patient Summary
- Hematology
- Anemia normochromic, normocytic
- Thrombocytosis
- Slightly elevated WBC
- Increased ESR
- Chemistry
- Uric Acid is a little low
- Albumin is a little low
- Cholesterol is a little high
17Immunology Tests
Rheumatoid Factor (RF) usually an IgM
auto-antibody to IgG. Occasionally the antibody
is against IgA or IgE. Produced by activated B
cells and forms an immune complex by binding to
the Fc fraction of IgG molecules.
18Rheumatoid Arthritis
- DESCRIPTION
- Chronic, systemic inflammatory disorder effecting
many tissues and organs principally joints - Cause unknown, but autoimmunity plays a pivotal
role - 1 of the worlds population
- PATHOGENESIS
- RA is triggered by exposure to an arthritogenic
microbial antigen ? acute arthritis FOLLOWED by a
runaway autoimmune reaction - Four elements
- Genetic susceptibility
- Concordance monozygotic twins
- 70 are HLA-DR4
- Microbial antigens
- Autoimmunity
- Mediators of joint damage (cytokines, IL, TNF,
proteases, elastases, etc.
- MORPHOLOGY
- Joints
- Perivascular inflammatory infiltrate
- Increased vascularity
- Organizing fibrin
- Osteoclastic acitivity ?Juxta-articular erosions
- Subchondral cysts
- Osteoporosis
- Skin
- Rheumatoid nodules (25 of patients) at areas
subject to pressure (elbows, lumbosacral) - Blood Vessels
- Complication of severe RA
- Vasculitic syndromes potentially catastrophic
- Medium Small arteries
- Similar to Polyarteritis Nodosa EXCEPT kidneys
ARE NOT involved - Peripheral neuropathy, ulcers and gangrene
19- Ulnar deviation of fingers
- Periarticular osteoporosis clearing at the ends
of the bones - Phalangeal-metacarpal joints are destroyed with
resultant joint narrowing
20Joint aspiration Papanicolaou stain. Mag x78.
- Knee joint aspirate
- Predominant cells -neutrophils, but scattered
macrophages also present - Early involvement associated with neutrophil rich
aspirate
21Rheumatoid Arthritis
- Joint capsule - lined with synovium, ? produces
synovial fluid that lubricates and nourishes
joint tissues. - In rheumatoid arthritis, the synovium becomes
inflamed, causing warmth, redness, swelling, and
pain. - The inflamed synovium invades and damages the
cartilage and bone of the joint. - Rheumatoid arthritis also can cause more
generalized bone loss that may lead to
osteoporosis
http//www.niams.nih.gov/hi/topics/arthritis/rahan
dout.htm
22Features of Rheumatoid Arthritis
- Onset 20-45
- Females males (31)
- Tender, warm, swollen joints
- Symmetrical pattern of affected joints
- Joint inflammation
- Primary - the wrist and finger joints closest to
the hand - Secondary - sometimes g other joints, including
the neck, shoulders, elbows, hips, knees, ankles,
and feet - Fatigue, occasional fevers, a general sense of
not feeling well - Pain and stiffness lasting for more than 30
minutes in the morning or after a long rest
23Rheumatoid Arthritis
- Onset 20-45
- Females males (31)
- Associated laboratory findings
- Anemia.
- Osteoporosis
- Particularly if using corticosteroid drugs, such
as prednisone. - Sjogrens syndrome
- Systemic inflammatory disorder that affects the
mucous membranes - causing dry mouth,
- decreased tear production, and other dry
conditions of the bodys membranes. - Felty syndrome
- Felty's Syndrome
- Rheumatoid arthritis, Splenomegaly, Leucopoenia
(weight loss, skin pigmentation and ulceration,
lymphadenopathy and anaemia)
24Normal synovial lining HE x78
Synovial Lining
- Lining epithelium is thin and lies on top of a
loose connective tissue layer. - Scattered lymphocytes and plasma cells are present
Loose connective tissue
25Portion of synovium from patient. HE x 12.
- Synovial villi are thickened with a heavy
inflammatory cell infiltrate and increased
vascularity (granulation tissue) - Superficial areas of necrosis are present and
masses of inflammatory cells can be seen free
above the synovial surface
26Portion of synovium from patient. HE x78.
- Neutrophils, lymphocytes, plasma cells,
macrophages, and fibroblasts are responsible for
increased cellularity. - Capillaries are increased in number, synovial
lining cells are hypertophic and hyperplastic.
Hyperplastic, hypertrophic synovial lining cells
27Material from subcutaneous nodules Unstained
DIC microscopy. Orig. mag x150
- Numerous flat, notched plates consistent with a
cholesterol crystals. - Common in rheumatoid nodules
- Not generally found in joint aspirates
28Subcutaneous nodules in rheumatoid arthritis. HE
x20.
- 20-30 of patients with rheumatoid arthritis have
rheumatoid nodules - Most common pressure areas such as elbow
- Other locations
- Lung, spleen, myocardium, cardiac valves,
pericardium and aorta. - Eosinophilic center of fibrinoid necrosis
surrounded by palisading histocytes. - Note inflammatory cell infiltrate of lymphocytes
and plasma cells, as well as some fibrosis.
29Case Summary
- Final Diagnosis
- Active rheumatoid arthritis
- Symmetrical joint pain, swelling and morning
stiffness typically
30Sequelae of Rheumatoid Arthritis
- Higher risk of coronary heart disease
- More silent heart attacks (5X ?) and sudden
cardiac deaths (3X ?) - Not explained by risk factors such as elevated
cholesterol, blood pressure and body mass index,
diabetes, and/or alcohol abuse
31American Rheumatism Association revised criteria
for rheumatoid arthritis classification
32Therapeutic Options
- Patient education and counseling
- Pharmacologic treatment
- Analgesics, NSAIDS
- Glucocorticoids, SAARDS/MARDS (slow-acting
antirheumatic drugs disease-modifying
antirheumatic drugs) - Surgery for functional abnormalities caused by
proliferative synovitis (eg. Tendon rupture) or
by bone and joint destruction