Arthralgias / Arthritis (focus on bilateral polyarthralgias)

Joint Pain.  A true purview of the Rheumatologist, because the majority of joint diseases have imperfect gold standards.  There are no tissue diagnoses, and only occasional conditions like gout or septic joint are definitively identified by aspiration.  Most are diagnosed clinically, based on a research criteria reviewed regularly by the American College of Rheumatology and its European counterparts.

Initially, call it “arthritis” if there’s objective synovitis, i.e. joint inflammation (red, hot, swollen, tender, with limited passive ROM).  Say “arthralgias” if the joints are normal on exam.  Arthralgias can easily be due to a type of arthritis, destructive or not, and not every objectively-appearing arthritis is eventually destructive.  So the distinction isn’t that relevant to diagnosis.

FIRST STEP — Determine that the patient is complaining of joints (where bone meets bone), and not muscles (like fibromyalgia).  Exclude periarticular conditions like bursitis & tendonitis  (though enthesitis, tendon & ligament attachment points, can also be rheumatologic, esp. at the heel).  Be sure you’re not dealing with bone disease or neuropathic pain syndromes.  See our posting on distinguishing among “Musculoskeletal Disorders.”

NEXT  —  Let’s say, from now on, we’re dealing with bona fide arthralgias / arthritis.  Identify the pattern of involvement.  This includes:

• Monoarticular:  One joint
• Oligoarticular:  A few joints
• Polyarticular:  Many joints (focus of today’s posting)

•  Small joint: Wrists-hands-fingers / Ankles-feet-toes
• Medium joint:  Elbows-wrists / knees-ankles
• Large joint: Shoulders-elbows / Hips-knees
• Spine

• Symmetric vs. Asymmetric
• Migratory (leaves one joint, moves to another)

In terms of size, hard to say if wrists are small or medium, if knees are medium or large.

OBVIOUSLY  —  Define chronology (prior occurrences, relapses remissions) and duration.

KEY QUESTION  —  Does the pain or stiffness hurt worse when you wake up in the morning, or worse with use as the day goes on?

• Early morning pain or stiffness for >30-60 minutes, that’s relieved with use, practically guarantees a rheumatologic disease of one sort or another.

Let’s start with the common complaint of relatively symmetric (i.e. bilateral)…

POLYARTICULAR SMALL JOINT ARTHRALGIAS.

Fingers, toes, hands & feet (maybe wrists & ankles too).  One frequent etiology: non-specific viral infections (prototype is Rubella) that cause arthralgias or even arthritis.  Symptoms all resolve on their own within 4-6 weeks.

Many people in the general population are antibody-positive for the various rheumatologic serologies, but will never develop any illness.  If you rush to obtain these tests, you’ll set yourself up for misdiagnoses (& be setting patients up for a life-long label).

So, during the first 6 weeks of arthralgias:

1.  DON’T WORK-UP intrinsic rheumatologic causes of symmetric polyarthritis

2. If the patient has fevers, address serious possibilities [click for brief summary]:

• Endocarditis
• Primary (Acute) HIV
• Rheumatic Fever
• Disseminated Gonorrhea
• Adult Still’s Disease [not so emergent]

3.  Also for fevers, or associated systemic symptoms like malaise or nausea, order LFTs:

• Hep A
• Acute Hep B

4.  Lyme Disease: For a person who has been in forests of an endemic area during tick season [June to August] within the past few months:

• Perform a skin exam for unnoticed Erythema Migrans
• Generalized arthralgias occur with Early Lyme (serology Neg!!!)
• Migratory arthralgias may occur with Early Disseminated Lyme
• DO NOT order Lyme Disease serology unless other manifestations of Early Disseminated Lyme [meningitis, cranial or peripheral neuropathy, carditis, multiple EM lesions]
• Click on the above link for a summary of arthritis & Lyme Disease (with pictures)

5.  Immunocompromised patient: R/O  B19 Parvovirus

• order a nucleic acid amplification test (PCR) [more sensitive than IgM antibody]
• Diagnosis not so important for the arthralgias per se, but to then monitor for life-threatening aplastic anemia with CBC and reticulocyte counts.

Once arthralgias have continued unabated for 6 weeks, with morning stiffness a key component, it’s time to focus on rheumatologic disorders.  These are summarized in the following table; click an entity for distinguishing symptoms & main diagnostics (some brief, some long).  But DON’T order shotgun panels to rule out everything.  We’ll summarize a logical strategy below.

 MAIN CAUSES OF BILATERAL SMALL-JOINT POLYARTHRALGIAS

Most Common   * Rheumatoid Arthritis * Lupus (SLE) * Hepatitis B * Hepatitis C   Usually Oligoarthritis (but Possibly Small Joint Polyarthritis)   * Psoriatic Arthritis * Gout (when chronic) * Sarcoidosis

Uncommon Diseases   * Sjögren’s Syndrome (not-so-uncommon) * Inflammatory Osteoarthritis * Scleroderma * Mixed Connective Tissue Disease * Relapsing Polychondritis * Vasculitis (various types) * Paraneoplastic Syndrome

So, as you can see, most bilateral small-joint arthritis is going to wind up as:

• Rheumatoid Arthritis (RA)
• Systemic Lupus Erythematosus (Lupus, SLE)
• Hepatitis B (chronic)
• Hepatitis C (chronic)

Therefore, order the following tests to start:

• Rheumatoid Factor (RF)  —  for RA
• Cyclic Citrulinated Peptide (CCP)  —  for RA
• Antinuclear Antibody (ANA)  —  for SLE
• Hepatitis B surface Antigen (HBsAg)  —  for chronic Hep B
• Hepatitis C Antibody (HepC AB)  —  for Hep C

Also order some general tests:

**  CBC for Anemia  —  a normocytic Anemia of Chronic Disease raises index of suspicion for a rheumatologic disorder

**  Erythrocyte Sedimentation Rate (ESR)  —  if elevated, also raises suspicion.  Though one lecturer I heard opined, “A high Sed Rate only proves the lab was open that day.”  Extremely high ESRs (near 100 mm) point to a handful of illnesses like endocarditis, multiple myeloma, giant cell arteritis, HIV.

Note that an ESR normally rises with age.  A neat formula for normal ESR:

• ½ the Age (+5 in women)

**  C-Reactive Protein (CRP)  —  Substitute for the Sed Rate.  I prefer the ESR simply because I’m more used to it (function of my age).  Some interesting differences in use:

• No equivalent “extremely high CRP” as for ESR
• CRP may be more useful for monitoring Tx (responds sooner)
• CRP may be normal in Lupus, while ESR is elevated
• CRP may be easier for lab tech
• Don’t rely on either to rule-in or -out inflammatory disease

**  Creatinine & BUN  —  Renal insufficiency raises an index of suspicion for vasculitic component.  And discourages NSAID palliation.

**  Urinalysis  —  Proteinuria points renal, often SLE.

A word [or more] about the Serologies:

Rheumatoid Factor positivity is common in the general population.  Its usefulness for diagnosing RA depends on how high the titer.

CCP is very specific for RA, but only 70% sensitive.

ANA is extremely sensitive for SLE (around 95%).  Be very reluctant to diagnose Lupus with a negative ANA.  Conversely, low-titer ANA’s are extremely common in the general population & thus non-specific.  In general:

• Titer ≥1:320 very specific for a rheumatologic disorder of one sort or another
• Titer ≥1:160 very sensitive for Lupus
• Titer ≤1:80 not useful [consider it almost a “negative”]
• Staining patterns (e.g. speckled, homogeneous) less useful than thought.  Very operator-dependent, variable, many extraneous confounders.
• Some Non-Rheumatologic autoimmune disorders give a high ANA, like Autoimmune Hepatitis, Graves’, Hashimoto’s, Primary Biliary Cirrhosis, etc.

Hepatitis serologies (HBsAg and HepC AB) are virtually 100% sensitive & specific for chronic Hep B & C.

 SUMMARY

 So we have a patient with persistent arthralgias, maybe or maybe not  signs of frank arthritis, and we’ve ordered serologies:

**  HBsAg or HepC AB positive:  Yes, we’ve got a diagnosis!!!  See our post on Chronic Hepatitis.  (of course, they could have both the chronic hepatitis & something else too, so don’t stop reading yet).

**  RF and/or CCP elevated:  Dx Rheumatoid Arthritis

• Send to Rheumatology unless you’re quite good at management
• Give NSAIDs if renal function normal (anti-inflammatory component very helpful with pain relief, but NO effect on preventing joint destruction)
• If joints hot, start Prednisone 40 mg/day pending Rheum appt, but taper down to 10 mg within 2 weeks.  Can call Rheum to discuss [when the primary wants to use Prednisone, Rheum sometimes expedites the appointment].
• Screen for Latent TB (before, or same time as, you give any Prednisone Rx)

**  ANA elevated ≥1:160  (RF negative or low titer, CCP negative):  Think Lupus to begin with (esp. if ANA ≥1:640):

• Order additional Antibodies: double-stranded DNA (dsDNA), anti-Smith (“Sm”), and anti-Phospholipid, which are very specific for SLE
• Order Complement studies (C3 and C4 are low in SLE) and RPR (false-positive very common in SLE)
• Be sure you’ve obtained other lab tests for SLE:  CBC (for cytopenias), U/A (for protein)
• Get a good history: clinical findings just as important as lab tests [click in Table or here for diagnostic parameters for SLE.]

As you can see, we’ve covered the major diagnostic parameters for the most common causes of bilateral small-joint polyarthralgias.  What if they’re non-diagnostic?

We can eliminate Hep B and C if serologies are negative.  But our patient could still have RA or SLE (statistically the best likelihood).

**  ANA low / negative, but ESR/CRP High /  maybe there’s a Normocytic Anemia.  Sero-Negative Rheumatoid Arthritis is found in up to one-third of RA patients, and bony erosions are very specific.  For bilateral arthralgias, order X-Rays of wrists, hands, and feet.

• Send to Rheumatology no matter what the X-rays!  Because if they’re normal, you’d like Rheum to Dx and Tx Sero-Neg RA before erosions occur.
• In an older patient like this, have a certain index of suspicion for a paraneoplastic syndrome.  Still, unless there’s clinical suspicion, no tests other than standard cancer screening (e.g. mammogram >40, colon CA >50) give a yield.  Certainly DON’T order a whole host of tumor markers

**  ANA elevated, but NO suggestion of SLE (by above labs & history).  Also warrants a Rheum referral, since they’re best at diagnosing both Lupus when classical criteria are missing, as well as the less likely rheumatologic disorders.  If you have or want to do your own work-up, seek key clinical findings for the diseases (see also TABLE above, with links):

»  Dry Eyes and/or Dry Mouth  —  Think Sjogren’s.  Quite common.

• Order key Antibodies: Anti-Ro (SSA), Anti-La (SSB).

»  Tight Skin, with subcut. nodules, Raynaud’s, or telangiectasias  — 

Think Scleroderma.  Rare.

• Order key Antibodies:  Anti-Centromere, Anti-Topoisomerase 1 (SCL 70).

»  Any / All / None of Above?  Might also think Mixed Connective Tissue Disease.  An elevated ANA is 100% sensitive by definition.  Even rarer.

• Order main Antibody:  Anti-RNP (a.k.a. Anti-U1 RNP).

 Other Connective Tissue Diseases

Various conditions may occasionally feature prominent small-joint arthralgias, but usually present with other more typical complaints.  The ANA is often normal.  Might inquire about symptoms such as:

 »  Psoriasis  — 

think Psoriatic Arthritis  [not uncommonly causes small joint disease]

 

 »  Recurrent monoarticular arthritis of toe, ankle, knee, wrist  — 

think Chronic Gout

 

»  Blood: eccyhymoses, petichiae, hemoptysis, epistaxis, hematuria  — 

think Vasculitis

 

»  Mononeuritis multiplex (asymmetric polyneuropathy)  — 

think Vasculitis

 

 »  Hilar adenopathy on CXR  — 

think Sarcoidosis

 

»  Recurrent inflammation external ear  —

? Relapsing Polychondritis  [very rare]

 

**  All Labs Normal, No Key Findings, arthralgias persist.  It’s OK to send this patient to Rheum, but first be very sure that you are in fact dealing with bona fide arthralgias, and not repetitive motion injury (tendons), carpal tunnel syndrome, other neuropathic pain syndromes, or fibromyalgia (muscles, not joints).

Next time — Mono- / Oligoarticular Arthritis.