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باطنية
د. وميض العمري

عدد الاوراق (11)

12/2/2013

Polyarthritis

Definitions
Polyarthritis : more than 4 joints .
Oligoarthritis : 2-4 joints .
Monoarthritis : one joint .
Chronic polyarthritis : more than 2 months .
Acute , recent … within 2 or few months .
Early R.A : ? Few months to 2 years

Causes of Polyarthritis

Chronic inflammatory joint disorders (immune related) e.g rheumatoid arthritis , chronic juvenile arthritis , SLE , seronegative arthropathies , systemic vasculitis and Behcets disease .
Acute rheumatic fever .
Crystal induced arthritis (gout and psedugout) .
Generlized osteoarthritis .
Infective arthritis : viral , bacterial and lyme disease .
Others : malignancies , henoch-schonlein purpura , erythema nodosum related arthritis and serum sickness like arthritis (drug reactions)

Chronic polyarthritis: selected causes
Rheumatoid arthritis and other immune related disorders such as juvenile rheumatoid arthritis , spondylarthropathies , systemic lupus and other connective tissue diseases .
Generlized osteoarthritis .
Gout .
Pseudogout .
Sarcoidosis .


Rheumatoid Arthritis: Ulnar Deviation and MCP Swelling

 SHAPE \* MERGEFORMAT 


Migratory polyarthritis: causes

Rheumatic feverTypical (classical) ( patternGonococcal arthritis
Viral arthritis
SLE
Idiopathic juvenile arthritis
Poly articular gout
Lyme disease
Acute reactive arthritis
othersMigratory element (
Polyarticular Coarse / Progression
Simultaneous .
Additive .
Migratory .
Episodic (e.g Whipples disease arthritis , atypical R.A. , episodic reactive arthritis ) .

Prominent Features of some migratory arthritides 1

Acute Rheumatic Fever :
- Typical (classic) migratory pattern , new joints are affected during decreasing activity of the previously affected joint , occurring within 2-3 & up to 5 weeks of streptococcal pharyngitis . Activity does not remain in a single joint more than 5-10 days .

- Cardiac involvement is common during the acute phase , though may be missed . Rheumatic valvular disease may be found without a past history of arthritis .


Prominent Features of some migratory arthritides 2
Neisserial arthritis :
- Can be polyarticular & may be migratory .
- Gonococcal skin lesions may appear as scattered crops of vesiculopastular on erythematous base .
- Meningococcal skin lesions are more likely to be petechial .
- Tenosynovitis .
- More in females . Many do not report lower abdominal pain or vaginal discharge .
- Most frequent age is 16-25 .

Diagnostic Problems in acute & early chronic polyarthritis
Infection (viral etc) is an important cause in acute polyarthrits , while a non-infective cause is the usual setting in chronic polyarthritis .
Specific diagnosis is a frequent challenge in acute polyarthritis and even in early chronic polyarthritis .
Infective cause should be excluded before labelling a case as unclassified arthritis specially if steroids &/or immunosuppression is to be used .
Specific diagnosis may need a rather long time ( a lag period ) .
Before specific diagnosis is possible and if infection is excluded we may use the term unclassified inflammatory joint disease , the treatment of which is rather similar to treatment of early rheumatoid arthritis but with certain precautions .

Early RA: First few months of symptoms , frequently a challenging diagnosis



Rheumatoid Arthritis: Hands



Several Months of Disease 5 Years of Disease a very clear diagnosis

Rheumatoid Arthritis: 10 Years Later


Rheumatoid Arthritis: Feet



Systemic Manifestation

Such as fever , weight loss , reduced appetite and general weakness .
Mild to moderate severity systemic features can occur in most causes of polyarthritis but not polyarticular O.A.
Severe systemic features :
- Arthritis of infective disorders e.g infective endocarditis
- Stills disease .
- SLE .
- Acute reactive arthritis .
- Bacterial arthritis (about 10-19% polyarthritis) .
Joints Distribution : Selected Examples
Gout of the DIPs



Special Joints Features 1
Red overlying skin :
- Acute gout .
- Septic arthritis .
- Skin infection .
- Flare of Heberdens nodules .
Multilating small joints arthritis :
- Severe R.A.
- Severe psoriatic arthritis .
Prominent soft tissue swelling (synovial thickening) :
- R.A. : The usual cause .
- Other inflammatory joint diseases .
- Some infilterative arthropathies e.g amyloidosis .

Acute Gout Red Joints



Special Joints Features 2

Arthritis + tenderness of adjacent bones :
- Dactilities (swollen digits) of psoriatic arthritis .
- Hypertrophic pulmonary osteodystrophy .
Boney swelling (palpable osteophytes) : O.A.
Yellowish chalky material : Gout .
Peripheral joint bone remodeling : O.A.

Hypertrophic osteoarthropathy: clubbing , periostitis and arhtritis



Gouty Tophi

Chronic polyarticular gouty tophi

Can occur in various joints, bursa & tendons



Tophi

Solid urate deposits in tissues

Reactive Features

Reaction to infection :
- Reactive arthritis :
* Diarrhea 1-3 weeks before arthritis .
* Urinary infection .
* Urethritis .
- Rheumatic fever :
* Post streptococcal infection specially pharyngitis / Tonsillitis .
* About a third do not recall pharyngitis .
- ? Some cases of gonococcal arthritis .
- Controversial in many other cases of seronegative spondarthritis .
Reaction to non infective environmental factors :
- U.V. light in SLE .
- Drugs : drugs lupus and serum sickness like illness .
- Hormons .
- Smoking as a risk factor in R.A.
- Diet ,Alcohol , exersion in Gout .


Drug-induced ANAs
Some drugs that cause positive ANAs :
Procainamide
Hydralazine
Phenothiazines
Diphenylhydantoin
Isoniazid
Quinidine
Some biological antirheumatic agents .

Clues to a primary disorder 1

Chronic / recurrent diarrhea , tenesmus or blood in stool : suggest inflammatory bowel disease (IBD) , namely : alcerative colitis , chrons disease and non specific colitis .
Look for easily missed lesions or family history of psoriasis .
Any suspicion of malignancy : specially acute leukemia & others e.g lung cancer / Lymphoma / Myeloma etc .
Suspicion of viral disorders :
- Preicteric polyarthritis of virus B hepatitis :
* History of injection , blood or blood products transfusion .
* Raised liver enzymes .
* Rheumatoid factor is sometimes positive .

Clues to a primary disorder 2

- Rubella & Parvovirus B19 acute polyarthritis . Most oftenly in female . About half recall a rash . The acute phase rarely lasts more than 2 weeks . Serology confirms the diagnosis .
-AIDS- associated arthritis / polyarthritis .
Lyme disease (spirochetal infection) in endemic areas .
Others e.g Amyloidosis .
 Clues to a primary disorder 3 :
Arthritis as a paraneoplastic syndrome :
Hypertrophic osteoarthropathy
Amyloidosis
Secondary gout
Carcinoma polyarthritis


Extraarticular & Internal Organ Manifestation 1


Extraarticular & Internal Organ Manifestation 2

Investigating polyarthritis :General principles
Possible investigations
- Inflammatory markers
- Autoantibodies .
- Serum uric acid .
- Bacterial studies .
- Viral serology .
- Imaging .
- Synovial fluid .
- Synovial biopsy .
- Organ related tests .
Investigations should be directed by the clinical suspicions .
Late chronic polyarthritis is generally less challenging than acute and early chronic polyarthritis

Investigating polyarthritis : inflammatory markers

Non-inflammatory conditions with elevated ESR
Aging
Female sex
Obesity
Pregnancy
Age-adjusted upper limit normal for ESR
Male: age/2
Female: (age + 10)/2


Causes of markedly elevated ESR
ESR >100
Infection, bacterial (35%)
CTD (GCA, PMR, SLE, vasculitides (25%)
Malignancy: lymphomas, myeloma, etc (15%)
Other causes (25%)

Causes of extremely low ESR

ESR ~ 0mm/hr
Agammaglobulinemia
Afibrinogenemia/dysfibrinogemia
Extreme polycythemia (Hematocrit >65%)
Increased plasma viscosity

Investigating polyarthritis :CRP

Acute phase reactant produced by liver
Response to IL-6, other cytokines
Rises and falls quickly
Elevation within 4 hr of tissue injury
Peak at 24-72 hr
Half-life ~18 hr
CRP <0.2 mg/dL: normal
CRP 0.2-1.0 mg/dL: indeterminate (may be seen in smoking, DM)
CRP >1.0 mg/dL: inflammatory
Levels > 10mg/dL suggest bacterial infection (up to 85%), or possibly systemic vasculitis, metastatic cancer


Investigations of Polyarthritis :Bacterial studies
Synovial fluid WBC count over 50000/cu mm strongly suggests a bacterial infection though is occasionally seen in rheumatoid , crystal induced and reactive arthritis .
synovial fluid Grams stain identifies bacteria in 50-75% of cases while cultures are positive in over 90% of cases .
If genococcal arthritis is suspected swabs should be taken from potential mucosal portals of entry . In some studies blood and synovial fluid cultures are negative in the majority of these patients .
In arthritis of infective endocanditis synovial fluid cultures are usually ve .

Investigations of Polyarthritis : viral suspicion

If viral polyarthritis is suspected
- Rubella antibodies ( German measles ) :
- Hepatitis B surface antibody + liver functions .
- Tests for AIDS .

Investigation of Polyarthritis :ANA Serology

ANA: Interpretation
Is the ANA a good screening test for SLE?
If >5% of normal U.S. population has positive ANA, then over 12.5 million normal people in U.S. are ANA positive . Prevalence of SLE is only ~1/1000, so only 250,000 individuals with SLE and positive ANA .

Clinical value of ordering an ANA test can be dramatically enhanced when there is a reasonable pre-test probability of an autoimmune disease .

ANA patterns 1

Homogeneous (diffuse)
SLE, drug-induced SLE, other diseases


ANA patterns 2
Rim (peripheral)
SLE, autoimmune hepatitis



ANA patterns 3

Speckled
SLE, MCTD, Sjogrens, Scleroderma, other dz


ANA patterns 4
Nucleolar
Scleroderma, hepatocellular carcinoma

ANA patterns 4

Centromere
Limited scleroderma (CREST)

Rheumatoid factor 1

Autoantibody directed against the Fc (constant) region of an IgG molecule .
Multiple isotypes, including IgM, IgG, IgA, and IgE .
IgM RF is routinely measured using latex agglutination titers, nephelometry, and ELISA .
Very low levels normal, but higher production secondary to chronic immune stimulation .
RF positive in ~80% of patients with RA .
Multiple other causes of positive RF .


Conditions associated with a positive rheumatoid factor
Rheumatologic diseases
RA (80-85%)
Sjogrens (75-95%)
MCTD (50-60%)
Scleroderma (20-30%)
Sarcoidosis (15%)
Polymyositis (5-10%)

Frequency of RF positivity in normal population

AGE
20-60 years
60-70 years
>70 years

Frequency of +RF

2-4%
5%
10-25%

Anti-CCP antibodiesAnti citrullinated protein antibody

Sensitivity 68% for RA .
Specificity 98% for RA .
Can be seen in active TB, other CTD .
Clinical implications .
Predictive of more aggressive disease with more progressive joint damage .
Useful in early diagnosis .


Antiphospholipid antibodies
Heterogeneous group of Ab that bind to plasma proteins, have affinity for phospholipid surfaces .
Anticardiolipin Ab (ACL) .
Lupus anticoagulant (LAC) .
Beta 2-glycoprotein I .

Antiphospholipid antibodies

Conditions with positive aPL .
~8% normal population.
chronic infections e.g., HIV, Hep C.
Medications e.g., phenothiazines, hydralazine, phenytoin, procainamide, quinidine.
~20% pts. with systemic vasculitis.
~15% pts. with recurrent miscarriage.
~50% pts. with SLE.

Anti-neutrophil cytoplasmic Antibodies (ANCA)

C-ANCA
Most commonly seen in Wegeners granulomatosis, microscopic polyarteritis, rarely Churg-Strauss vasculitis .




ANCA
P-ANCA
seen in multiple diseases as well as vasculitis .

Anti streptolysine O antibody ASO

A high titre simply means a recent streptococcal infection .
It doesnt diagnose rheumatic fever specially where streptococcal infection is common .

Serum uric acid levels

Hyperuricemia
> 7.0 mg/dL in males
>6.0 mg/dL in females
24 hour urine collection
Urate >800 mg/24 hrs suggests overproduction
Urate <800 mg/24 hrs suggests underexcretion
Important considerations
Only 15% of pts. with hyperuricemia develop gout
If uric acid level>10mg/dL, risk increases to 30-50%
In ~10% of patients with acute gout, serum uric acid levels are normal
Need joint aspiration and polarized light microscopy to diagnose with certainty


Asymptomatic hyperuricemia
Treatment indications
Acute overproduction e.g., tumor lysis syndrome
Severe hyperuricemia e.g., uric acid levels >12mg/dL
Risk of uric acid nephrolithiasis is ~50%

Investigations of Polyarthritis : Imaging

In chronic polyarthritis : characteristic features do occur in rheumatoid arthritis , Gout , O.A. , Psoriatic arthritis and others .
In acute polyarthritis : even in bacterial arthritis characteristic XR finding ( rarefaction & subchondral bone erosion ) may not be noted for 2-4 weeks after onset .
MRI & isotope scanning may identify early juxtaarticular osteomyelities & deeply located effusions e.g hip effusion .

Chondrocalcinosis: knee radiograph


Gout: toe (radiograph) massive erosions

Investigations of Polyarthritis : Synovial fluid basic analysis

Gout vs CPPD
Synovial fluid polarized microscopy
Bright needle shaped negatively birefringent crystals .



Rhomboid shaped crystals weakly positive birefringent .


Beautiful Urate Crystals : Synovial fluid



pyrophosphate crystals (ordinary, polarized, and compensated polarized light microscopy)










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Non-rheumatologic conditions

Chronic hepatitis
Pulmonary disease
Neoplasms
Aging
Cryoglobulinemia
(40-100%)
Infections
AIDS, Mono, TB, syphilis, parasites, endocarditis

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