Joint Pain: Many Joints — Full Text

Introduction (to all types of Joint Disease)

[Scroll down a little for this specific topic: Pain in Many Joints]

Joint Disease.  We say “arthritis” when there’s evidence of inflammation, like joints are red, hot, & swollen, OR if we see destruction on x-ray.  We say “arthralgia” if there’s only joint pain.  Arthralgias can be due to a type of arthritis, destructive or not, but they may also (even more commonly) be due to viruses or other conditions which will go away without consequence. Even diseases with inflammatory arthritis don’t always cause permanent damage.

FIRST STEP — We determine that the patient’s pain is coming from joints (where bone meets bone), and not muscles (like Fibromyalgia).  We also rule out conditions around the joint, like bursitis, tendonitis, bone disease, or conditions caused by nerve damage.  See our topic on distinguishing among Musculoskeletal Disorders.

NEXT  —  Let’s say, from now on, we’re dealing with the actual joints.  We identify the pattern of involvement, which includes:

• One Joint: (Monoarticular: “mono” = “one”, “articular” = joint)
• A Few Joints: (Oligoarticular: “oligo-” = “few,” like oligarchy)
• Many Joints:   (Polyarticular:  “poly” = “many”)

• Small joints:   Wrists-hands-fingers / Ankles-feet-toes
• Large joints:   Shoulders-elbows / Hips-knees
• Spine

• Symmetric  (pretty much similar pattern on right & left)  vs.  Asymmetric
• Migratory   (leaves one joint, moves to another)

Overall, there are 2 broad types of arthritis:

• Inflammatory auto-immune diseases (rheumatoid arthritis, lupus, scleroderma, etc.), which can occur at any age & affect a variety of organs besides the joints
• Degenerative arthritis, a.k.a. Osteoarthritis, due to wearing out of joints with age (usually occurs >60 y.o.).  There are no other complications apart from the affected joint itself. By the way, inflammatory arthritis can cause complete destruction of a joint that it becomes osteoarthritic.

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

• Early morning pain or stiffness lasting >30-60 minutes, that gets better with use as the joints loosen up, practically guarantees an inflammatory disease of one sort or another

No such pain in the morning, pain begins gradually during the day:  NOT an inflammatory joint disease (most likely muscle pain, tendon strain, bursitis, etc.).  See Musculoskeletal Disorders.

Now choose from the following common types of Joint Pains:

xxx• Polyarthritis  (many joints hurt, including wrists, hands, ankles, and/or toes) — read on below
xxx• Monoarticular Arthritis  (just one joint / just a few joints)
xxx• Oligoarthritis (just a few joints hurt, usually larger ones like shoulder, elbow, hip, knee)
xxx• Spine Pain  —  see topics Back Pain and Neck Pain

POLYARTHRITIS (Pain in Many Small Joints)

One frequent cause are various viral infections that we never wind up identifying exactly, but which get better on their own.  Symptoms all get better within 4-6 weeks.  This time frame is important, because…

Many people in the general population have antibodies in their blood that are positive for the various inflammatory diseases, but they will never develop any illness.  If we rush to get these tests, we set patients up for misdiagnoses of life-long diseases, when all the person really had was a simple virus that goes away on its own.

QUICK NOTE: If Fever + Joint pains for <10 days  →  test for Covid-19, self-isolate (see Covid Tests)

1. So, during the first 4-6 weeks of pain in many small joints:

1.  We DON’T TRY TO DIAGNOSE life-long chronic diseases like rheumatoid arthritis, etc., unless we see actual red, hot, swollen joints, and the patient is very uncomfortable (even then, we have to be careful, because some simple viruses can cause this).

2. If the patient has fevers along with joint pains, they probably have a virus, but we consider some rather rare but more serious possibilities:

• Endocarditis  —  Damaged or artificial heart valves; IV drug users 
• Acute HIV  —  Recent risks for HIV (unprotected sex or injection drug use the past month); maybe sore throat; swollen glands all over (joints may hurt, but usually aren’t red, hot, & swollen)
• Rheumatic Fever —  Age <30 (usually <15); pain moves daily from joint to joint; sore throat 2-4 wks ago
• Disseminated Gonorrhea  —  Pain in tendons; small spots with pus on arms / legs; recent new sex partner (without using protection)
• Acute Hepatitis (Hepatitis A / B / C) — Poor appetite, nausea, upper right abdominal pain, yellow eyes (jaundice)

3.  Lyme Disease: For a patient who has been in a high-risk area during tick season [June to August] within the past few months:

• We examine the skin for unsuspected Lyme rash (see Lyme Disease Rash)
• We DO NOT order Lyme Disease tests unless there are other symptoms or findings of Early Disseminated Lyme (heart or nervous system abnormalities) [see purple link above].
• Click for a summary of Arthritis in Lyme Disease

4.  Very Immunocompromised patients can have serious complications of  B19 Parvovirus (harmless for most people):

• We order a nucleic acid amplification test (PCR)
• Diagnosis is not so important for the joint pains, but to then monitor for life-threatening anemia, by checking blood counts (especially “reticulocyte” counts)

5. BUT, let’s say we’re not dealing with any of the uncommon conditions above. So…

Once pain has gone on 4-6 weeks in many small joints

Once joint pain has continued for 4-6 weeks, and not getting better, especially if there’s significant morning stiffness, it’s time to focus on inflammatory diseases.  These are summarized in the following table; click an entity for distinguishing symptoms & main diagnostic tests.  But we DON’T order all sorts of tests to rule out everything.  Our strategy is summarized below.

2.  Joint Pains going on over 4-6 weeks, with stiffness lasting at least 30-60 min. in early morning:

Work-Up

We begin by ordering blood tests for the most common causes (see explanations below):

• Rheumatoid Factor (RF) Antibody  —  for Rheumatoid Arthritis
• Cyclic Citrullinated Peptide (CCP) Antibody  —  for Rheumatoid Arthritis
• Antinuclear Antibody (ANA)  —  for Lupus
• Hepatitis B surface Antigen (HBsAg)  —  for Chronic Hepatitis B
• Hepatitis C Antibody (HepC Ab)  —  for Hepatitis C

We also order some general tests:

• Complete Blood Count (CBC) for Anemia  —  Specifically Anemia of Chronic Disease with normal-sized blood cells (not small pale ones we see with low iron). This suggests the presence of an inflammatory arthritis
• Erythrocyte Sedimentation Rate (ESR, “Sed Rate”) and C-Reactive Protein (CRP) —  If the results are high, it may suggest inflammatory arthritis
• Blood Tests for Kidney Function  —  Mainly the Creatinine and BUN. If the kidneys aren’t working 100%, we think more of certain inflammatory conditions, but we also especially avoid using NSAID medications for pain.
• Urinalysis  —  Protein in the urine may point to Lupus.

A word [or more] about the first group of tests above:  Tests for any disease have their own different levels of “sensitivity” and “specificity,” which relate to false-positive & false-negative results:

• Sensitive means a negative test helps rule out a disease.  “Not Sensitive” means many false-negatives
• Specific means a positive test helps identify a disease.  “Not Specific” means many false-positives

Interpreting the Lab Results

** Rheumatoid Factor (RF) — Used to diagnose Rheumatoid Arthritis.

• Not very specific, because a fair number of random people test positive.  The result is reported as a the numerical titer; high titer is more specific (the more sure a person has the disease)
• Many people (maybe up to 30%) with Rheumatoid Arthritis are “sero-negative”: lab tests for antibodies (serologic tests) are negative, even though they have the disease.

** CCP is very specific for Rheumatoid Arthritis, but not so sensitive, since only 70% of people with the disease test positive.

** ANA is extremely sensitive for Lupus (>95%).  We’re very reluctant to diagnose it with a negative ANA.  Conversely, we can tell if the test is “strongly-positive” or not by a numerical “titer.” ANA’s with low titers are very common in the general population & thus non-specific (don’t count).  In general:

• Titer ≥1:320 very specific for an inflammatory disease of one sort or another
• Titer ≥1:160 very sensitive for Lupus (but maybe false-positive, not specific)
• Titer ≤1:80 not useful [consider it almost a “negative”]
• There are different ANA staining patterns, which aren’t as helpful as we used to think.  They depend on ability of lab techs, & many outside factors can interfere.
• Many non-rheumatologic auto-immune diseases give a high ANA, like Autoimmune Hepatitis, Hyperthyroidism, Hypothyroidism, Primary Biliary Cirrhosis, etc.
• Main way of diagnosing Lupus is by its symptoms (see link)

** Hepatitis Serologic Tests (HBsAg and HepC Ab) are virtually 100% sensitive & specific (no false-positives or false-negatives) for Chronic Hepatitis B & C

Making the Diagnosis

So we have a patient with persistent joint pains, but the joints look normal to us, and we’ve ordered lab tests:

**  HBsAg or HepC Ab positive:  Yes, we’ve got a diagnosis  —  Chronic Hepatitis !!!  But they could have both chronic hepatitis & something else too, so don’t stop reading yet

**  Rheumatoid Factor and/or CCP elevated:  We diagnose Rheumatoid Arthritis

• We usually refer to a Rheumatologist, because treatment can be complicated.  In the meantime, we give some sort of anti-inflammatory medication
• We test for Latent Tuberculosis, because many medications can make the germ reactivate (but not NSAIDs, and steroids only at high doses for longer periods of time)

**  ANA elevated ≥1:160  (and Rheumatoid Factor is negative or low titer, CCP negative):  We think Lupus to begin with (especially if ANA ≥1:640):

• We order additional blood Antibody tests: double-stranded DNA (dsDNA), anti-Smith (“Sm”), and anti-Phospholipid, which are very specific for Lupus (no false-positives)
• We order blood tests for C3 & C4 Complement (low in Lupus) and a syphilis test (the RPR / VDRL) which is often positive in Lupus (“false-positive” for syphilis)
• We make sure we’ve obtained other general lab tests:  CBC (for low blood cell counts), Urinalysis (for protein), BUN and Creatinine (for kidney function)
• MOST IMPORTANT  —  we take a careful Medical History: symptoms are just as important as lab tests [see Lupus].

As you can see, we’ve obtained the major tests and information for the most common causes of symmetrical small-joint polyarthralgias.  BUT, what if we still don’t have a diagnosis?

We can eliminate Hepatitis B and C if tests are negative.  But our patient could still have Rheumatoid Arthritis or Lupus.  So we consider other information.

**  Blood Tests for Inflammation: (ESR / CRP are high, or there’s an Anemia of Chronic Disease).  These general tests suggest that some sort of inflammation is going on, & our patient has joint pains.  Up to 30% of Rheumatoid Arthritis patients are what we call “Sero-Negative,” meaning that the two main antibody tests are negative.  So we order X-rays.

**  X-Rays of wrists, hands, ankles, and feet:  if they show evidence of joint destruction (“bony erosions”), that’s very specific for Rheumatoid Arthritis

• We refer to Rheumatology no matter what the X-rays show!  Because if they’re normal, we’d like a solid diagnosis of Sero-Negative Rheumatoid Arthritis (RA with negative blood test) before erosions occur.
• In an older patient, we may wonder about a possible Paraneoplastic Syndrome (unusual symptoms due to a yet-to-be-found cancer).  Still, unless there’s other reason to think of cancer (like family history), we don’t do extensive tests, because some are invasive (potentially dangerous), & positive results are rare.  We would order standard screening (e.g. mammogram >40 y.o., colonoscopy >50 y.o.).

**  ANA elevated, but NO suggestion of Lupus (by additional lab tests & Lupus symptoms):  We refer to Rheumatology, since they’re best at diagnosing Lupus when classical criteria are missing, & also the more obscure & uncommon rheumatologic disorders.  They might obtain the following tests, depending on what they think likely:

• Dry Eyes and/or Dry Mouth  —  Think Sjögren’s Syndrome (fairly common).  Order key antibody lab tests:  Anti-Ro (SSA), Anti-La (SSB).
• Tight Skin, with nodules under skin, Raynaud phenomenon (cold-sensitive fingers turn red, white, and blue), or telangiectasias (clusters of tiny veins)  —  Think Scleroderma (rare).  Order key Antibody tests:  Anti-Centromere, Anti-Topoisomerase 1 (SCL 70).
• Any / All / None of Above?  Might also think Mixed Connective Tissue Disease (very rare).  A high ANA is 100% sensitive by definition (normal ANA rules out the diagnosis).  Order main Antibody blood test:  Anti-RNP (a.k.a. Anti-U1 RNP).

Other Connective Tissue Diseases

Various diseases may occasionally include small-joint arthralgias, but usually cause other more typical symptoms.  The ANA is often normal.  So we might inquire about symptoms such as:

• Psoriasis  —  think Psoriatic Arthritis  [usually large-joint arthritis, but small-joint possible]
• Recurrent pain in just one toe, ankle, knee, or wrist  —  think Chronic Gout
• Blood:  purple rashes, coughing or urinating blood, bloody nose  —  think Vasculitis
• Tingling (constant) or Weakness in just one arm or leg  —  think Vasculitis
• “Hilar adenopathy” found on Chest X-Ray  —  think Sarcoidosis
• Recurrent inflammation of the external ear  — Relapsing Polychondritis  [very rare]

All Labs Normal, No Key Findings, joints still hurt  —  We’d probably refer this patient to Rheumatology, but first we’d want to be very sure that we are in fact dealing with actual arthralgias (joint pains), and not repetitive motion injury (tendons), carpal tunnel syndrome or other neurological types of pain, or Fibromyalgia (muscles, not joints).  See Musculoskeletal Disorders.

And that’s it for Arthritis in many small joints (or “Arthur-itis,” as some folks say).

See also Joint Pain — Many Joints for the clinician’s condensed thought-process when face-to-face with a patient.