rheumatic disease lab med

what specimens can we use to evaluate rheumatic disease

whole blood/serum/plasma/ synovial fluid drawn straight from joints

inflammatory musculoskeletal problem on 1 or 2 joints

septic or crystals in joints

non-nflammatory musculoskeletal problem on 1 or 2 joints

osteoarthritis, trauma

non-articular musculoskeletal problem on 1 or 2 joints

bursitis, tendonitis

inflammatory musculoskeletal problem on many joints

rheumatic arthritis

non-inflammatory musculoskeletal problem on many joints

osteoartiritis

non-articular musculoskeletal problem on many joints

fibromyalgia

what is the most common non-inflammatory musculoskeletal problem

fibromyalgia

what is the most common inflammatory musculoskeletal problem

rheumatoid arthritis

nonspecific lab tests for rheumatic disease

erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to measure inflammation, esp acute

uric acid

synovial fluid analysis

CBC/BMP/LFT/TSH/urinalysis

specific lab tests for rheumatic disease

rheumatoid factor

anticitrullinated protein antibodies (ACPAs)/ anti-CCP

antinuclear antibodies (ANAs)

antineutrophil cytoplasmic antibodies (ANCAs)

HLA B27

complement levels

a group of proteins made in the liver that inc or dec in concentration in response to inflammation/infection/injury

acute phase reactants

what do we use acute phase reactant measurements for

best used to assess ACUTE response in the blood (if it goes up and then drops its acute, if it goes up and stays high its a chronic problem)

can evaluate severity, monitor changes over time, assess prognosis

nonspecific and not diagnostic

tells if pt is having inflammatory or non-inflammatory issue

what kind of measurements are best for acute phase reactants

serial measurements most valuable

an indirect measurement of acute phase proteins

erythrocyte sedimentation rate

what does it mean if your pt has an elevated erythrocyte sedimentation rate

inflammation (inflammation causes RBCs to stick together and sink faster)

infection (bacterial), connective tissue disease (giant cell arteritis/polymyalgia rheumatica, lupus, cancer)

(if acute should see rapid decline in days/wks)

what is the gold standard method for erythrocyte sedimentation rate

westergreen method

what does a low erythrocyte sedimentation rate mean (takes a loooong time for RBCs to sink)

afibrinogenemia, agammaglobulinemia, extreme polycythemia, inc plasma viscosity, sickle cell anemia, basically that changes RBC shape or inc amount of RBCs

a direct measure of acute phase proteins that is less sensitive to non-inflammatory factors that has a rapid response to stimulus (rises fast and drops fast if stimuli removed) and peaks 2-3 dats at levels that reflect the extent of tissue injury

C-reactive protein (CRP)

a plasma protein made by hepatocytes thats active in the complement pathway and cellular immune response (most healthy ppl have some of this in their system)

CRP

things that may falsely raise erythrocyte sedimentation rate

age, female, preg, bleeding, alc, exercise, cancer, renal failure, DM, meds, supplements

limitations of C-reactive protein

no uniformity in reporting conc and variability in interpretation (dont know how to interpret)

what amount of CRP indicates significant inflammatory process

over 1mg/dL

persistently elevated C-reactive proteins means what

chronic inflammatory states (rheumatoid arthritis, TB, cancer, autoimmune things)

usually with a concomitant elevation of ESR

a more sensitive measure of acute phase proteins that can reflect incidence of cardio/vascular events (MI, stroke, etc)

high-sensitivity CRP (should be measured twice in 2wks and averaged when used for cardiovasc stuff)

a test that looks for rheumatoid factors in blood (aka immunoglobulins aka autoantibodies) that is most stable and easiest to quantify due to multiple binding sites

rheumatoid factor (RF)

if you have an acute problem what antibodies will you see more of

IgM

if you have an chronic problem what antibodies will you see more of

IgG

test methods to measure rheumatiod factor and how is it reported

latex agglutination and ELISA (most sensitive and can detect other isotypes)

reported as qualitative (pos/neg) results

reported as a dilutional titer (over 1:16 is high) or concentration (over 15IU/mL is high)

Rheumatoid factor titers over 50 is most commonly associated with what (but NOT diagnostic)

rheumatoid arthritis (80% sensitivity and specificity)

pos results for rheumatiod factor could mean what (besides rheumatoid arthritis)

autoimmune disorders, inflammatory disease, infection, cancer, smoker, old

RA pts w rheumatiod factor titers in normal range

seronegative

RF+ rheumatic disorders

rheumatoid arthritis

lupus

scleroderma (systemic sclerosis)

sarcoidosis

vasculitis (polyarteritis nodosa)

mixed connective tissue disease

sjogren syndrome

RF+ nonrheumatic disorders

hepatits, cirrhosis

infections (malaria/TB/syphilis/mononucleosis/bacterial endocarditis/parasitic or viral infn)

cancers after chemo/radiation

over 65yo

smoker

what does rheumatiod factor correlate with

severe articular disease (but may remain positive lifelong w/o getting sx of rheumatoid arthritis) (can have RF w/o RA and vise versa)

do we do serial tests for rheumatiod factor

no (once positive, no value in re-testing bc doesnt change w disease activity0

IgG autoantibodies against citrullinated proteins

anticitrullinated protein antibodies (ACPA/ ACCP)

gold standard test for rheumatoid arthritis

anticitrullinated protein antibodies (ACPA/ ACCP)

what does a positive test on anticitrullinated protein antibodies (ACPA/ ACCP) mean

clinical feature of RHEUMATOID ARTHRITIS

associated w more erosive forms and worse long term prognosis but also used as an early indicvator of RA in asymptomatic/undifferentiated arthritis pts

do we do serial measurements for anticitrullinated protein antibodies (ACPA/ ACCP)

no (doesnt correlate w disease activity)

how do we measure anticitrullinated protein antibodies (ACPA/ ACCP)

qualitative and quantitative tests by ELISA (neg = less than 20)

autoantibodies directed against cellular nuclear or cytoplasmic antigens, highly sensitive but non specific (DONT use for screening if asymptomatic)

antinuclear antibodies (ANA)

what is the gold standard for LUPUS or related autoimmune disease dx

antinuclear antibodies (ANA) (quantitative assay by immunofluoroescense (IFA))

what is a high titer for antinuclear antibodies (ANA) and what does that indicate

over 1:640, suspicious for autoimmune disorder

once you get a positive antinuclear antibodies (ANA) test what should you do

consider more specific tests for definitive dx

speckled antinuclear antibodies (ANA) means what

lupus

homogenous antinuclear antibodies (ANA) means what

Rheumatoid arthritis

nucleolar antinuclear antibodies (ANA) means what

scleroderma

peripheral antinuclear antibodies (ANA) means what

lupus or crest disorder (autoimmune)

conditions that are antinuclear antibodies (ANA) positive

relative of pt has autoimmune disease, preg, hepatitis, idiopathic fibrosis, chronic infections, malignancy (lymphoma, leukemia, melanoma), immune thrombocytopenic purpura, autoimmune hemolytic anemia, med induced (procainamide, hydralazine, quinidine, tetracycline, TNF inhibitors), autoimmune thyroid disease, T1D, IBS, celiac, MS, chrohns, ulcerative collitis

when do we test for ANA

used for screening (PRETEST PROBABILITY IMPORTANT)

most helpful in establishing a dx when pts sx, physical findings, and other lab results suggest a moderate to high suspicion of systemic autoimmune disease

DONT use to screen pts w/o specific sx

autoantibodies specific for SLE (lupus) that rise during flare up and fall when it subsides so we can use it for disease management

anti-dsDNA (double stranded DNA)

autoantibody specific for SLE (lupus) but not sensitive, bind to nuclear proteins complexed w small nuclear RNAs and remain positive after disease has subsided and other antibodies normaliezed (good diagnostic tool)

anti-Sm (smith)

autoantibody that targets the protein portion of nucleosomes in DNA, is present in all cases of drug-induced lupus (caused by hydralazine, isoniazid, procainamide)

anti-histone (nucleosome)

autoantibody whose presence strongly supports the dx of sjogren’s, usually seen in pair but may be seen alone, and may be ANA neg

anti-Ro/SSA and anti-La/SSB

autoantibodies directed against neutrophil cytoplasmic antigens with a high specificity in active disease (90%) but not diagnostic alone

antineutrophil cytoplasmic antibodies (ANCA)

what does a positive antineutrophil cytoplasmic antibodies (ANCA) test indicate

vasculitis syndromes (i.e granulomatosis w polyangitis (GPA), microscopic polyangitis, eosinophilic granulomatosis w polyangitis, IBD, liver/renal disease, drug induced syndromes)

what are the two types of assays to measure antineutrophil cytoplasmic antibodies (ANCA)

immunofluorescence (IF) and confirmed by enzyme immunoassay

measures the amount of complement proteins (C1-C9) in the blood and their activity to identify and fight off disease (NOT an antibody test). most commonly just test C3 and C4

complement (C3 and C4)

what is the most abundant complement protein

C3

what complement protein is the most sensitive and specific to smaller changes

C4

what do we use C3 and C4 measurements for

dx, monitor and determine prognosis for autoimmune stuff like lupus

what do high levels of C3 and C4 indicate

inflammatory process

sarcoma, cancer, viral infxn, non-alcoholic liver disease, obesity, DM, heart disease, autoimmunity, psoriasis, ulcerative colitis

what do low levels of C3 and C4 indicate

hypercatabolism due to immune system activation

LUPUS/ RHEUMATOID ARTHRITIS

vasculitis, alcoholic liver disease

antigen on the surface of WBCs encoded by thr B locus that helps to differentiate “self” from “foreign material”

human leukocyte antigen B27 (HLA-B27)

what does a positive human leukocyte antigen B27 (HLA-B27) test indicate

ANKYLOSING SPONDYLITIS (young ppl w back pain), reiter syndrome, anterior uveitis

do all pts w ankylosing spondylitis have HLA-B27

no, if asymptomatic/ no family hx then positive test NOT clinically significant

is human leukocyte antigen B27 (HLA-B27) definitive alone

NO, must include clinical features and imaging (MRI or xray) for confirmation

final breakdown product of purine metabolism, circulates in the plasma as sodium urate and excreted by kidneys

uric acid

uric acid over 7, due to increased formation or dec excretion (can cause renal stones leading to neuroapthy)

hyperuricemia

deposition of uric acid crystals in the joints

gout