24 Osteopathic Family Physician (2018) 24 - 31 Osteopathic Family Physician | Volume 10, No.

5 | September / October, 2018

REVIEW ARTICLE

Approach to Polyarthritis for the Primary Care Physician

Arielle Freilich, DO, PGY2 & Helaine Larsen, DO
Good Samaritan Hospital Medical Center, West Islip, New York

KEYWORDS: Complaints of joint pain are commonly seen in clinical practice. Primary care physicians are frequently
the first practitioners to work up these complaints. Polyarthritis can be seen in a multitude of diseases. It
Polyarthritis can be a challenging diagnostic process. In this article, we review the approach to diagnosing polyarthritis
Synovitis joint pain in the primary care setting. Starting with history and physical, we outline the defining
characteristics of various causes of arthralgia. We discuss the use of certain laboratory studies including
Joint Pain sedimentation rate, antinuclear antibody, and rheumatoid factor. Aspiration of synovial fluid is often
required for diagnosis, and we discuss the interpretation of possible results. Primary care physicians can
Rheumatic Disease
initiate the evaluation of polyarthralgia, and this article outlines a diagnostic approach.
Rheumatology

INTRODUCTION PATIENT HISTORY

Polyarticular joint pain is a common complaint seen Although laboratory studies can shed much light on a possible diagnosis, a
in primary care practices. The differential diagnosis detailed history and physical examination remain crucial in the evaluation
is extensive, thus making the diagnostic process of polyarticular symptoms. The vast differential for polyarticular pain can
difficult. A comprehensive history and physical exam be greatly narrowed using a thorough history.
can help point towards the more likely etiology of the
complaint. The physician must first ensure that there
are no symptoms pointing towards a more serious Emergencies
diagnosis, which may require urgent management or During the initial evaluation, the physician must first exclude any life-
referral. It is then important to differentiate between threatening conditions, which may present with arthritic-type symptoms.
true articular pain versus pain which arises from outside Urgent orthopedic evaluation should be considered in the setting of
the joint. Distinguishing whether the arthritis has an significant injury to a joint. A warm, swollen joint should raise concern
inflammatory component can further narrow down for infection before a diagnosis of gout or pseudogout is given. While
the differential diagnosis. Inflammatory conditions constitutional symptoms such as fever, weight change, or fatigue may
will often cause synovitis with warmth and swelling, as indicate a systemic rheumatic disease, sepsis from infection must be ruled
well as prolonged morning stiffness. These conditions out. Weakness may be a sign of muscle dysfunction, such as myositis or a
also cause constitutional symptoms, and patients may degenerative neuromuscular disorder. Radiculopathy must be considered
report other associated complaints such as rash or in the presence of neurogenic pain. Once we have ruled out these serious
ocular involvement. Physical exam of a patient with diagnoses, we may further focus on the patient’s symptoms.1
osteoarthritis, a non-inflammatory condition, will often
reveal osteophytes and crepitus, as opposed to an
inflammatory arthritis, which will demonstrate findings Joint Involvement
of synovitis. Laboratory and imaging studies are often Characterizing the joint symptoms a patient is experiencing is an important
nonspecific, but may help rule in or rule out certain aspect of the diagnostic approach. The physician must determine whether
diagnoses. Much of the initial workup for polyarthritis the patient is experiencing true joint inflammation as opposed to
can be done in the primary care setting using proper periarticular pain as seen with tendonitis or bursitis. Usually, joint swelling
clinical investigation and appropriate diagnostic studies will not be seen in non-arthritic conditions.2 Arthritis is defined as joint
(See Figure 1). inflammation alongside joint pain. This is in contrast to arthralgia, which
lacks the inflammatory component. It is important to make this distinction.
Markers of inflammation include surrounding erythema, warmth,
tenderness, and swelling of the joint.3
CORRESPONDENCE:
Arielle Freilich, DO PGY2 | [email protected] The quality of pain a patient reports can help guide the physician. True
articular pain would be expected to improve with rest of the joint and
Copyright© 2018 by the American College of Osteopathic worsen with movement or stress. Neurogenic pain would cause feelings of
Family Physicians. All rights reserved. Print ISSN: 1877-573X
Freilich, Larsen Approach to Polyarthritis for the Primary Care Physician 25

FIGURE 1:
General approach for evaluation of polyarthritis symptoms1

Polyarthralgia




History/Physical


Consider:
- Tender + Fibromyalgia
Synovitis
points Bursitis

Tendinitis

+

Consider: - Symptoms lasting Consider:
Early Systemic Rheumatic > 6 weeks Viral arthralgia
Osteoarthritis
Condition
+ Hypothyroidism
Viral arthritis
Neuropathic
Consider:
Bone disease
Systemic Rheumatic Condition
Soft tissue
Work-up: Depression
CBC
Work-up:
LFTs
CBC
Consider: Consider:
ESR
Hepatitis serology LFTs
RF
Parvovirus Hepatitis serology
ANA
XR
Renal function
Thyroid studies
UA
Calcium
Joint aspiration (see
Albumin
figure 2)
Alkaline Phosphatase

numbness, burning, or a “pins and needles” sensation. This type of pain will not worsen with joint movement and is often more severe
at night. Claudication, or pain from arterial insufficiency, will promptly improve with rest. Inflammatory arthritis would cause pain which
persists even with rest.1,4

The timeframe of symptoms must be established. Acute symptoms persist anywhere from hours to two weeks. Symptoms lasting more
than two weeks are considered chronic. Chronic symptoms may be constant or intermittent. Investigating these patterns may help
identify certain triggers or associated conditions.4

Rheumatoid arthritis (RA) classically affects multiple joints in a bilateral and symmetrical pattern. Patients will present with pain, stiffness,
and swelling of joints. Morning stiffness is a common complaint and often lasts more than one hour after awakening.5 Other systemic
rheumatic diseases, such as systemic lupus erythematosus (SLE) and polymyalgia rheumatica, may present with similar patterns.
Spondyloarthropathies, including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and arthritis associated with inflammatory
bowel disease are characterized by the presence of the HLA-B27 gene. Joint involvement with these conditions is typically asymmetric and
commonly involves inflammation of the sacroiliac joints and spine. Enthesitis, inflammation of the insertion site of tendons or ligaments,
is the hallmark of the spondyloarthropathies.6
26 Osteopathic Family Physician | Volume 10, No. 5 | September / October, 2018

The joints involved can provide important clues. Rheumatoid TABLE 1:

arthritis will usually affect the proximal interphalangeal joints Differential Diagnosis of Polyarthritis 2,3
(PIP), as well as the metacarpophalangeal joints (MCP), but will not
involve the distal interphalangeal joints (DIP). This differentiates
between osteoarthritis which will involve the DIP and PIP, but Rheumatoid arthritis
spares the MCP.7 SLE affects similar joints as RA, however there Systemic lupus erythematosus
is rarely bone destruction.2 Any of these joints can be affected
with psoriatic arthritis, gout, pseudogout, and sarcoid. Lyme Scleroderma
disease differs as inflammation of the hand is not commonly Polymyalgia rheumatica
seen.3 Early Lyme often causes a migratory arthralgia, later SYSTEMIC RHEUMATIC
CONDITIONS Polymyositis
progressing to arthritis of mainly large joints.8 In one study, 51
percent of patients developed arthritis weeks to months after
Still’s Disease
being diagnosed with Lyme disease. The majority of patients
experienced knee effusions, but other large and small joints, such Sjӧgren’s syndrome
as temporomandibular joint, were also involved. Many patients
Sarcoidosis
experienced recurrent attacks, with some progressing to chronic
arthritis.9
Viral
Bacterial arthritis from a nongonococcal source classically occurs
in one joint, with only 10 to 19 percent of cases having polyarticular Bacterial
INFECTIOUS
involvement. Gonococcal arthritis is typically polyarticular and (gonococcal vs nongonococcal)
may have a migratory pattern. Systemic signs such as fevers, Other (Lyme, tuberculosis)
chills, and a vesicular rash are common.8

Various viral infections may cause arthritic symptoms. An

Gout
episode of polyarthritis may be the early signs of a fulminant CRYSTAL-INDUCED
hepatitis B infection, causing joint pain and fevers during a Pseudogout
prodromal phase.8 HIV must be considered, as early disease
may cause various forms of arthralgia. Patients may experience
episodes of oligoarthritis as well as symmetrical polyarthritis.2,8 Ankylosing spondylitis
Parvovirus B19 may not cause the frequently classic “slapped- Psoriatic arthritis
cheek” rash in adults. While most adults with parvovirus infection
are asymptomatic, approximately 60 percent of women who are SPONDYLOARTHROPATHIES Inflammatory bowel disease
symptomatic will develop arthropathy. These patients will often Reactive arthritis
complain of polyarthritis which is symmetric and affects small
joints such as hands, knees, wrists, and ankles. While most see Juvenile idiopathic arthritis
resolution of symptoms in one to three weeks, 20 percent of
women will continue to have pain which could last years. In one
study on parvovirus B19, 48 percent of adults studied described Henoch-Schönlein purpura
a symmetrical polyarthropathy. Most complained of pain and Polyarteritis nodosa
SYSTEMIC VASCULITIS
stiffness. Several women experienced recurrent episodes of joint
symptoms after resolution of the infection.10 Children are less Granulomatosis with
polyangiitis
likely than adults to experience parvovirus-related arthropathy.
As opposed to adults, children usually have involvement of large
joints in an asymmetric pattern.11 Hyperthyroidism
If a patient experiences joint tenderness and swelling which fully ENDOCRINE DISORDERS Hypothyroidism
resolves, followed by recurrent attacks, crystal-induced arthritis,
such as gout, must be considered. Generally, one joint is affected Hyperparathyroidism
with each attack. The initial presentation may involve multiple
joints along with fever. Episodes may last one to two weeks, while Osteoarthritis
symptom-free periods could last years early on in the course2
(See Table 1). Fibromyalgia
OTHER
Amyloidosis
Fibromyalgia is a condition associated with arthralgia that may
be confused for polyarthritis. Patients will complain of pain of Malignancy
the back, elbow, trochanter, medial knee, and anterior chest.
This pain can be localized to specific tender points. Symptoms
are often symmetric. It is often associated with stiffness which is
worse in the morning.12
Freilich, Larsen Approach to Polyarthritis for the Primary Care Physician 27

TABLE 2:
Patterns of Joint Symptoms 2

SYMPTOM PATTERN DEFINITION EXAMPLES

Gout
Episodes of polyarthritis symptoms with complete resolution
INTERMITTENT Pseudogout
between attacks
Reactive arthritis

Lyme disease
MIGRATORY Joint symptoms resolve and then reappear in different joints
Gonococcal arthritis

Systemic lupus erythematosus

Symptoms in joints persist, with addition of further
ADDITIVE Rheumatoid arthritis
joint involvement over time
Osteoarthritis

A possible sequelae to certain urogenital and enteric infections is reactive arthritis. The most common causes are Chlamydia trachomatis,
Salmonella, Shigella, Campylobacter, and Yersinia. Patients with this condition will experience an additive polyarthritis usually affecting
large joints in an asymmetric pattern. Joint symptoms typically present one or two weeks following the infection6 (See Table 2).

Extra-articular Manifestations
Many rheumatologic causes of polyarthritis will also present with constitutional and systemic signs. Fever, weight loss, and fatigue may be
seen. Multisystem involvement of diseases like RA and SLE may present with rash, adenopathy, mucosal ulcers, Raynaud’s, xerostomia,
and keratoconjunctivitis sicca.1 Psoriatic arthritis may be suspected in the setting of a history of psoriasis and the classic nail findings such
as hyperkeratosis and pitting.13 The spondyloarthropathies may feature ocular involvement and mucosal lesions.6

The inflammation associated with RA stretches way beyond the boundaries of the joints. Subcutaneous and pulmonary nodules may
develop. Vasculitis and peripheral neuropathy are also associated with the disease. Patients may develop pericarditis with associated
effusions. Some potential ocular findings include episcleritis or scleritis.7

Similarly to RA, gout can result in cutaneous nodules referred to as tophi. These crystal deposits can distort the joint space as well as
cause pain. Differentiating between RA nodules and tophaceous nodules involves aspiration and analyses of the fluid.2

In addition to the synovitis seen with rheumatoid arthritis, the spondyloarthropathies also feature enthesitis. These conditions also
present with spinal inflammation and dactylitis, or “sausage digits.”14

Fever may be seen in conditions other than rheumatic causes. Infection must always be entertained in the setting of fever. Gout and
pseudogout are also known to cause fevers during attacks. As previously mentioned, SLE may involve fever. Spiking fevers preceding joint
symptoms may be a sign of Still’s disease.15

Identifying certain rashes can aid in diagnosis. As discussed earlier, history of a “slapped-cheek” rash can indicate parvovirus B19. This
classic rash is described as lacy, erythematous, and maculopapular in appearance.16 SLE often involves a light-sensitive rash which
classically involves the face but can also be seen between joints. History of a target-shaped rash can point towards a diagnosis of Lyme
disease, although the rash is usually resolved prior to the onset of joint symptoms.15

PHYSICAL EXAM
During the exam, it is important to assess joint motion, joint integrity, and exact location of pain to help determine whether a patient
is experiencing a mechanical abnormality, soft tissue disease, or true joint disease. Synovitis will present with effusion, warmth, and
joint pain with movement. Further analysis will be required, as noninflammatory conditions may also present with joint swelling and
effusion.1,2

Soft tissue abnormalities, such as bursitis, tendinitis, or injury to a muscle will usually present in a predictable manner. Patients will
usually have intact passive range of motion but will experience decreased active range of motion secondary to pain. Point tenderness
28 Osteopathic Family Physician | Volume 10, No. 5 | September / October, 2018

to the affected area will often be seen. Decreased active as well diagnosis, so it is important to consider clinical presentation
as passive range of motion should raise concern for synovitis or alongside the laboratory testing. Positive ANA without the clinical
structural joint damage. Stability of the joint must be assessed, features of a rheumatic condition should not drive a diagnosis.3
as laxity may indicate ligament damage.1 Osteoarthritis should Although it cannot provide a definite diagnosis as discussed, the
be considered if crepitation is observed without erythema or higher the ANA titer is, the more likely a patient is to have SLE.1
warmth.4 Septic arthritis can present with a painful, warm,
erythematous joint. Based on patient history, a diagnosis of
Rheumatoid Factor & Anti-Citrullinated Peptide
crystal-induced arthritis may be more likely.8
Antibodies
Rheumatoid factor (RF) is a nonspecific marker. It may be identified
LABORATORY STUDIES in not only rheumatoid arthritis, but also Sjӧgren’s syndrome,
After a thorough history and physical, laboratory investigations SLE, vasculitis, and chronic infections such as hepatitis C and
should be ordered when appropriate. It is unnecessary to do tuberculosis.1 RF should only be ordered in the setting of moderate
further testing once a mechanical or extraarticular problem is suspicion for rheumatoid arthritis.1 The test has poor sensitivity
identified. There are a variety of tests that may help further guide and specificity. Approximately 20 percent of rheumatoid arthritis
diagnosis. patients lack RF, while five to ten percent of patients without the
disease will have positive rheumatoid factor.17

Erythrocyte Sedimentation Rate &

C-Reactive Protein Serum Uric Acid
Both erythrocyte sedimentation rate (ESR) and C-reactive protein While uric acid in excess can predispose individuals for developing
(CRP) are nonspecific markers of inflammation. They are useful gout, hyperuricemia alone is not diagnostic for the condition.18
in differentiating between inflammatory and noninflammatory Measuring serum uric acid during a suspected attack does not
processes. ESR can be elevated in many diseases, and is therefore aid with diagnosis, as uric acid levels may be normal or even low
not diagnostic on its own. For example, levels will be increased in during this time. Uric acid levels become useful for monitoring
the setting of rheumatic conditions, malignancy, and infection. In chronic gout.1
the acute phase of inflammation, CRP is more reliable than ESR.
Non-inflammatory conditions such as diabetes, renal disease, and Synovial Fluid
dysproteinemia can increase ESR, as ESR can be affected in the
Analysis of synovial fluid becomes a very important diagnostic
setting of abnormal red blood cells. While ESR is not diagnostic,
modality when a crystal-induced arthritis or infection is suspected.
an elevated ESR level alongside a classic history and physical
In order to confirm these diagnoses, the joint must be aspirated.
can further support a diagnosis of rheumatic disease or other
It is important to send the fluid for Gram stain and culture, cell
inflammatory process.1,4
count, and microscopy to identify crystals.4 Gout is diagnosed with
the presence of monosodium urate crystals which are negatively
Antinuclear Antibody birefringent on microscopy.4,18 Synovial fluid containing at least
Antinuclear antibody (ANA) may be useful when considering a 2,000 per mm3 of white blood cells is considered inflammatory in
diagnosis of SLE. It is highly unlikely a patient with negative ANA nature. If the sample contains over 50,000 per mm3, infection is
results will have a diagnosis of SLE.1 Five to ten percent of the likely (Table 3).19 Fluid culture will confirm the presence of bacteria
population will have positive ANA testing without a rheumatologic and guide the proper antibiotic treatment. While cell counts and
culture are pending, any patient with fever and joint effusion
should be treated with concern for septic arthritis4 (See Table 3,
TABLE 3: Figure 2).
Synovial Fluid Analysis3

CLASSIFICATION WBC count Polymorphonuclear leukocyte count Examples

NORMAL FLUID 0-200 per mm3 <25%

NONINFLAMMATORY <2,000 per mm3 <25% Osteoarthritis

Rheumatoid arthritis
INFLAMMATORY 2,000-50,000 per mm3 >75% Psoriatic arthritis
Gout

Septic arthritis
SEPTIC JOINT >50,000 per mm3 >90% Gout
Reactive arthritis
Freilich, Larsen Approach to Polyarthritis for the Primary Care Physician 29

FIGURE 2:
Interpretation of synovial fluid aspirate1

Polyarthralgia with
effusion/inflammation

Joint aspiration

+Bone marrow
>2,000 WBCs - Osteoarthritis
Bloody fluid OR Soft tissue injury
elements
>75% PMNs Viral infection

+
Consider: Intra-articular
Coagulopathy fracture
Culture Sterile
Pseudogout +Crystals
positive fluid
Tumor
Trauma

Gout Infectious Consider:

Check: Pseudogout arthritis RA
PT/INR Viral infection
Platelets SLE
Lyme disease

Sarcoid
Spondyloarthropathy

Check:
CBC
ESR
IMAGING RF
During the initial investigation, imaging should be used to support a diagnosis. Conditions like Consider:
RA, osteoarthritis, gout, and psoriatic arthritis can eventually cause very obvious features on film, LFTs
but early in the disease course there may only be subtle, or even absent, radiographic findings.20 HLA- B27
Imaging is not always necessary, and may not offer any insight in the setting of newly suspected RA, ANA
SLE, gout, or tendonitis. Radiologic studies can be helpful in the setting of injury, compromised joint Lyme serology
function, possible infection, history of malignancy, or poor response to conservative treatment.1

On plain films, joint space narrowing is often used as a marker for potential articular cartilage
damage in early osteoarthritis (OA), but studies show there is not a clear correlation, and this
finding cannot accurately diagnose or rule out OA.21 In early RA, conventional radiography may
show nonspecific signs such as soft tissue swelling.1 Identification of erosions early on has been
shown to indicate likely progression of structural joint damage. As prompt treatment is required
for good prognosis in RA, it is crucial to identify these early erosions. Ultrasound and MRI are
found to better detect bone erosions than plain films, and can be very important in monitoring
RA progression.22 Conventional radiography is the first line in detecting structural damage from
seronegative spondyloarthropathies such as ankylosing spondylitis, but MRI can be useful in
detecting early inflammatory changes.23
30 Osteopathic Family Physician | Volume 10, No. 5 | September / October, 2018

OSTEOPATHIC PRINCIPLES AUTHOR DISCLOSURES:

No relevant financial affiliations.
Although there is no definitive evidence regarding the benefit of
osteopathic manipulative treatment (OMT) in treating arthritic
pain, some studies have shown that including OMT in the
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