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Acute Nontraumatic Joint Conditions

By admin Last updated Dec 9, 2022

Ovid: Manual of Orthopaedics

Editors: Swiontkowski, Marc F.; Stovitz, Steven D.

Title: Manual of Orthopaedics, 6th Edition

> Table of Contents > 4 – Acute Nontraumatic Joint Conditions

Acute Nontraumatic Joint Conditions

I. History

Document the onset of the symptoms: Did the joint pain
begin days, weeks, or months ago? Morning stiffness is important to
differentiate inflammatory forms of arthritis (rheumatoid arthritis and
ankylosing spondylitis) from noninflammatory forms (degenerative joint
disease). The character and duration of the pain are more important. Is
the pain only associated with activity or is it present even at rest?
Is only one joint involved or are multiple joints affected? Are they
symmetrically involved? In the hands, the proximal finger joints are
often involved with rheumatoid arthritis and the distal finger joints
are more often involved in osteoarthritis (1) (Table 4-1).
A thorough history of past medical problems and social issues and a
current review of systems is essential. One must consider possible
exposure to infectious diseases and current systemic symptoms of
illness when differentiating the possibilities.

II. Examination

Check for fever because the temperature may be elevated
with septic arthritis. Muscle wasting occurs more often with rheumatoid
arthritis. Tenderness about the joint and increased warmth are more
indicative of inflammatory conditions. The examination should determine
the presence of an effusion (fluid in the joint). Severe guarding
against joint motion associated with pain usually is indicative of a
septic condition (Table 4-1).

III. Roentgenographic and Laboratory Data

Roentgenographic findings.
Look for evidence of periarticular soft-tissue swelling, joint
effusion, osteopenia, joint space narrowing, periarticular erosions,
joint subluxation, and articular cartilage or bone destruction (1). All of these

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findings are evidence of inflammatory (rheumatoid or septic) arthritis.
In contrast, marginal osteophytes, subchondral cysts, joint space
narrowing, and sclerosis are associated with osteoarthritis (Table 4-2). In the lower extremity, weight-bearing radiographs increase the diagnostic value of the study.

TABLE 4-1 History and Examination

History	Rheumatoid arthritis	Septic arthritis	Degenerative joint disease
Onset	Weeks	Day(s)	Months
Morning stiffness	+ +		–
Pain duration	Hours	Constant	Minutes
Pain with activity	+ +	+ + +	±
Number of joints involved	Multiple, symmetric	One (occasionally more)	Variable
Finger joint	Proximal		Distal
Examination
Febrile	±	+ +	0
Muscle wasting	+ +	0	+
Synovial tenderness	+	+ +	±
Increased warmth	±	+ +	0
Effusion	+	+ +	±
Joint range of motion	↓	↓↓↓	↓
+ + +, extremely important symptom or sign; + +, very important symptom or sign; +, important symptom or sign; ±, symptom or sign might or might not be present; 0, symptom or sign is not present; ↓, decreased; ↓↓↓, markedly decreased.

TABLE 4-2 Roentgenographic Findings

Rheumatoid arthritis	Septic arthritis	Degenerative joint disease
Early
Periarticular soft-tissue swelling	Joint effusion	Joint space narrowing
Periarticular osteoporosis		Marginal osteophytes
Late
Joint space narrowing	Articular cartilage and bone destruction	Subchondral sclerosis
Periarticular erosions		Subcortical cysts
Articular cartilage and bone destruction		Marginal osteophytes
Joint subluxation secondary to ligamentous involvement

Laboratory data (Table 4-3)

Synovial fluid analysis involves assessing the following:

Appearance (color)
Clot (presence or absence)
Viscosity
Glucose (compare with simultaneous serum glucose)
Cell count per cubic millimeter
Differential cell count
The type of crystals that might be present in the joint fluid aspirate as evaluated under a polarizing light microscope

Gram stain and synovial fluid culture: aerobic, fungal, acid fast baccilus (AFB)

TABLE 4-3 Synovial Fluid Analysis

Finding	Normal	Rheumatoid arthritis	Septic arthritis	Degenerative joint disease
Appearance	Clear	Cloudy	Turbid	Clear
Clinical viscosity test	High (fluid remains intact when slowly pulled between thumb and index finger)	Watery (fluid breaks into droplets easily)	Very watery	High
Glucose	Within 60% or more of serum glucose	Low	Very low	Normal
Cell count/mm³	200	2,000–50,000	Usually greater than 50,000	2,000
Differential cell count	Monos	50/50	Polys	Monos

TABLE 4-4 Differential Diagnosis of Inflammatory Polyarthritis

Rheumatoid arthritis (RA)
1. Seropositive—female, symmetric joint and tendon involvement,
  synovial thickening, joint inflammation in phase, nodules, weakness,
  systemic reaction, erosions on radiogram, rheumatoid factor present, C′H₅₀ level depressed in joint fluid that has 5,000–30,000 WBCs/mm³, approximately 50%–80% polymorphs.
2. Seronegative—either sex, symmetric joint and tendon involvement,
  joint inflammation in phase, little or no systemic reaction, usually no
  erosions radiographically, rheumatoid factor absent, C′H₅₀ not depressed in joint fluid that has 3,000–20,000 WBCs/mm³, approximately 20%–60% polymorphs.
Collagen-vascular
1. Systemic lupus erythematosus—female, symmetric joint distribution
  identical to RA, hair loss, mucosal lesions, rash, systemic reaction,
  visceral organ or brain involvement, leukopenia, (false-) positive
  serologic test for syphilis, no erosions radiographically,
  noninflammatory joint fluid with good viscosity and mucin clot and
  1,000–2,000 WBCs/mm³, mostly small lymphocytes. Serum C′H₅₀ often depressed, antinuclear antibody (ANA) titer elevated, anti–native-human DNA antibody titer increased.
2. Scleroderma—tight skin, Raynaud phenomenon, resorption of digits,
  dysphagia, constipation, lung, heart, or kidney involvement, symmetric
  tendon contractures, little or no synovial thickening, radiographic
  calcinosis circumscripta, positive ANA with speckled or nucleolar
  pattern.
3. Polymyositis (dermatomyositis)—proximal muscle weakness, pelvic and
  pectoral girdles, tender muscles, skin changes, typical nail and
  knuckle pad erythema, symmetric joint involvement, electromyographic
  evidence of combined myopathic and denervation pattern, muscle biopsy
  abnormal, elevated creatine phosphokinase.
4. Mixed connective tissue disease—swollen hands, Raynaud phenomenon,
  tight skin, symmetric joint and tendon involvement, may be joint
  erosions radiographically, positive ANA speckled pattern,
  antiribonucleoprotein antibody increased, good response to
  corticosteroid therapy given in antiinflammatory doses.
5. Polyarteritis nodosa—symmetric involvement, diverse clinical picture of systemic disease, histologic diagnosis.
Rheumatic fever
Young (2–40 yr), sore throat, group A streptococci, migratory
arthritis, rash, heart or pericardial involvement, elevated
antistreptolysin O titers. Migratory joint inflammation responds
dramatically to aspirin treatment.
Juvenile rheumatoid arthritis
Symmetric joint involvement, rash, fever, no rheumatoid factor,
radiographic periostitis, erosions late, can begin or recur in adult.
Psoriatic arthritis
Asymmetric boggy joint and tendon swelling, skin or nail lesions may
not be prominent or may follow arthritis, distal interphalangeal joints
might be prominently involved, radiologic periostitis or erosions, no
rheumatoid factor. C′H₅₀ usually not depressed in inflammatory joint fluid with polymorph predominance.
Reiter’s syndrome
Male, urethritis, iritis, conjunctivitis, asymmetric joints, lower
extremity, nonpainful mucous membrane ulcerative lesion, balanitis
circinata, keratosis blennorrhagica, weight loss. C′H₅₀ increased in serum and in joint fluid with 5,000–30,000 leukocytes/mm³. Macrophages in joint fluid with 3–5 phagocytosed polymorphs (Reiter’s cell).
Gonorrheal arthritis
Migratory arthritis or tenosynovitis fully settling in one or more
joints or tendons, either sex, primary focus urethra, female
genitourinary tract, rectum, or oropharynx, skin lesions, vesicles,
gram-negative diplococci on smear but not on culture of vesicular
fluid, positive culture at primary site, blood, or joint fluid.
Polymyalgia rheumatica
Elderly patient (>50 yr), symmetric pelvic or pectoral girdle
complaints without loss of strength, morning stiffness of long
duration, fatigue prominent, weight loss, joints can be involved,
especially shoulders, sternoclavicular joints, knees, sedimentation
rate markedly elevated, fibrinogen always elevated, alpha 2 and gamma
globulin elevation, anemia, response to low-dose (10–20 mg) prednisone,
serum creatine phosphokinase normal, elevated alkaline phosphatase
(liver).
Crystal-induced
1. Gout—symmetric arthritis, flexion contractures, prior history of
  acute attacks, tophi, joint inflammation out of phase, systemic
  corticosteroid treatment for RA, hyperuricemia, monosodium urate
  monohydrate crystals in joint fluid.
2. Pseudogout—symmetric arthritis, flexion contractures,
  metacarpophalangeal, wrist, elbow, shoulder, hips, knees, and ankles,
  prior acute attacks (sometimes), joint inflammation out of phase,
  calcium pyrophosphate dihydrate crystals in joint fluid.
Other
Amyloid arthropathy, peripheral arthritis of inflammatory bowel
disease, tuberculosis, subacute bacterial endocarditis, viral arthritis.

Modified from McCarty DJ. Differential diagnosis of arthritis: analysis of signs and symptoms. In: McCarty, DJ, ed. Arthritis and allied conditions, 10th ed. Philadelphia, PA: Lea & Febiger, 1985:51–52.

TABLE 4-5 Rheumatoid Arthritis Diagnostic Criteria

Morning stiffness
Pain on motion or tenderness in at least one join^a
Swelling (soft tissue thickening or fluid, not bony overgrowth alone) in at least one join^a
Swelling of at least one other join^a^,^b
Symmetric joint swelling with simultaneous involvement of the same joint on both sides of the bod^a^,^b; terminal phalangeal joint involvement will not satisfy the criterion
Subcutaneous nodules over bony prominences, on extensor surfaces, or in juxtaarticular region^a
Roentgenographic changes typical of rheumatoid arthritis (which
must include at least bony decalcification localized to or greatest
around the involved joints and not just degenerative change^b)
Positive tests for rheumatoid factor in serum^b
Poor mucin precipitate from synovial fluid (with shreds and cloudy solution)
Characteristic histologic changes in synovial membran^b
Characteristic histologic changes in nodules^b

Categories	Number of criteria required	Minimum duration of continuous symptoms	Exclusions^c
Classic	7 of 11	6 wk (No. 1–5)	Any of listed
Definite	5 of 11	6 wk (No. 1–5)	Any of listed
Probable	3 of 11	6 wk (one of No. 1–5)	Any of listed

^aObserved by a physician.
^bRefer to original reference for further specifications.
^cRefer to original reference for listing of exclusions.
From Medsger TA Jr, Masi AT. Epidemiology of the rheumatic diseases. In: McCarty DJ, ed. Arthritis and allied conditions, 10th ed. Philadelphia, PA: Lea & Febiger, 1985:11.

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Helpful blood tests
include a complete blood count, erythrocyte sedimentation rate (ESR),
C-reactive protein (CRP), uric acid, rheumatoid factor, and antinuclear
antibody.

IV. Differential Diagnosis of Acute Nontraumatic Joint Conditions (Table 4-4) (1, 2, 3)

Rheumatoid arthritis (Table 4-5)
- History often reveals symmetric joint and tendon involvement, typically in a younger female patient (4).
- Examination
  shows synovial thickening, joint tenderness, subcutaneous nodules,
  weakness associated with muscle wasting, and, often, systemic disease.
- Roentgenograms and
  laboratory data show that erosions are usually present, but rheumatoid
  factor is present in only 75% of patients. Roentgenograms are
  often normal in acute forms of rheumatoid arthritis except for signs of
  swelling or periarticular osteopenia. Joint fluid contains 2,000 to
  50,000 white blood cells (WBCs)/mm³, approximately 40% to 80% of which are polymorphonuclear leukocytes.
Septic arthritis
- Bacterial
  - The history may indicate drug or alcohol abuse, systemic illness (e.g., diabetes, chronic renal failure, or poor nutrition).
  - Examination
    can reveal severe inflammation and often a primary septic focus. Severe
    splinting (autoprotection by muscle spasm) of the joint is present, and
    pain is associated with passive motion.
  - Laboratory tests show a purulent joint fluid with polymorphonuclear leukocytes predominating (WBCs: 50,000–300,000/mm³).
    The infectious agent may be identified on smear or culture. Synovial
    glucose is less than 60% of a concurrent serum glucose. The ESR and CRP
    are elevated. Serial blood cultures obtained before antibiotic therapy
    often grow the infecting organism.
- Tubercular and fungal
  - History may
    reveal a focus, chronic immunodeficiency [human immunodeficiency virus
    (HIV) or acquired immunodeficiency syndrome (AIDS)], drug or alcohol
    abuse, or poor nutrition.
  - Examination shows marked chronic joint swelling.
  - Laboratory tests reveal predominating polymorphonuclear leukocytes with acid-fast organisms present on smear and culture.
- Viral
  - History often indicates antecedent or concomitant systemic viral illness.
  - Laboratory analysis
    of joint fluid can mimic inflammatory or noninflammatory conditions.
    Either mononuclear or polymorphonuclear leukocytes can predominate.
Osteoarthritis (nonerosive degenerative joint disease)
- History reveals a middle-aged or elderly patient unless the condition follows trauma.
- Examination reveals that angulatory deformities and osteophytes are frequently present in the later stages of disease (1,5,6).
- Roentgenograms
  show narrowing of the cartilage space associated with marginal
  osteophytes. There is often subchondral bone sclerosis and occasionally
  subchondral cysts, which accompany these findings in the weight-bearing
  joints.

Crystal-induced arthritis (Table 4-6) (5)

Gouty arthritis

The patient may report a history of similar attacks.
Examination
can show redness and warmth over the affected joint, typically the
first metatarsal-phalangeal joint. Later, symmetric arthritis with
contractures and tophi (subcutaneous crystal deposits) may develop.

Laboratory findings include hyperuricemia and synovial fluid containing monosodium urate monohydrate crystals. The crystals, which are seen by

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compensated polarized light microscopy (sometimes by ordinary light
microscopy), are negatively birefringent, needle-shaped rods.

TABLE 4-6 Differential Diagnosis of Inflammatory Monarthritis

Crystal-induced
1. Gout—male, lower extremity, previous attack, nocturnal
  onset, precipitated by medical illness or surgery, response to
  colchicine, hyperuricemia, sodium urate crystals in joint fluid with
  polymorphs predominating, and WBCs 10,000–60,000/mm³.
2. Pseudogout—elderly, knee or other large joint, previous
  attack, precipitated by medical illness or surgery, flexion
  contractures, chondrocalcinosis on radiography, calcium pyrophosphate
  dihydrate crystals in joint fluid with polymorphs predominating, and
  WBCs 5,000–60,000/mm³.
3. Calcific tendonitis or equivalent—extraarticular, tendon or
  capsule of larger joints, previous attack same or other area,
  calcification on radiography, chalky or milky material aspirated from
  area, polymorphs with phagocytosed ovoid bodies microscopically.
Palindromic rheumatism
Middle-aged or elderly male, very sudden onset, little systemic
reaction, previous attacks, positive rheumatoid factors, little or no
residual chronic joint inflammation, olecranon bursal enlargement.
Infectious arthritis
1. Septic—severe inflammation, primary septic focus, drug or
  alcohol abuse, joint fluid with polymorphs predominating, WBCs
  50,000–300,000/mm³ (pus), infectious agents identified on
  smear and culture, or bacterial antigens identified in joint fluid.
  Lyme disease must be considered in the differential where possible
  exposure to tick vector is possible.
2. Tubercular—primary focus, drug or alcohol abuse, marked
  joint swelling for long period, joint fluid with polymorphs
  predominating, acid-fast organisms on smear and culture.
3. Fungal—similar to tuberculosis.
4. Viral—antecedent or concomitant systemic viral illness,
  joint fluid can be of inflammatory or noninflammatory type, either
  mononuclear or polymorphonuclear leukocytes may predominate.
Other
1. Tendonitis—as in A.3 but without radiologic calcification, antecedent trauma, including repetitive motion.
2. Bursitis—as above, but inflamed area more diffuse, antecedent trauma.
3. Juvenile rheumatoid arthritis—one or both knees swollen in
  preteenager or teenager without systemic reaction, no erosions, mildly
  inflammatory joint fluid with some polymorphs, and no depression in
  synovial fluid C′H₅₀ levels.

From McCarty DJ. Differential diagnosis of arthritis: analysis of symptoms. In: McCarty DJ, ed. Arthritis and allied conditions, 10th ed. Philadelphia, PA: Lea & Febiger, 1985:50.

Pseudogout
- History sometimes reveals previous acute attacks.
- Examination
  discloses a symmetric arthritis with frequent contractures of the
  metacarpophalangeal, wrist, elbow, shoulder, hip, knee, and ankle
  joints. Roentgenograms may reveal the presence of calcium deposits in
  cartilage or, less often, in ligaments, meniscus, and joint capsules
  (chondrocalcinosis). The knee is the most common site.
  Chondrocalcinosis has been classically associated with pseudogout, but
  this condition is also seen with a high frequency in
  hyperparathyroidism, hemochromatosis, hemosiderosis, hypophosphatasia,
  hypomagnesemia, hypothyroidism, gout, neuropathic joints, and aging (1,5,6).
- Laboratory
  analysis of the synovial fluid reveals calcium pyrophosphate dihydrate
  crystals that are regularly shaped and weakly positively birefringent,
  but have a different extinction angle compared to that of urate
  crystals (6).

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Inflammatory polyarthritis other than rheumatoid arthritis (Table 4-4)
- Reiter syndrome
  - History often
    reveals a sexually active man (chlamydia is the most common organism
    identified) with urethritis and conjunctivitis accompanying the
    arthritis. Patients have an equivocal response to antiinflammatory
    drugs.
  - Examination
    often reveals urethritis, iritis, conjunctivitis, and nonpainful mucous
    membrane ulcerative lesions, with asymmetric arthritis of the joints in
    the lower extremities or back. Roentgenograms may show an asymmetric
    sacroiliitis as well as isolated involvement of the spine (“skip”
    areas). Heel pain can be a common associated feature of the
    presentation.
  - Laboratory data. The joint fluid has 5,000 to 30,000 leukocytes/mm³
    with macrophages that contain three to five phagocytosed
    polymorphonuclear leukocytes (so-called Reiter cell). Measurement of
    HLA-B27 antigen is not very useful.
- Psoriatic arthritis
  - Examination
    shows asymmetric boggy joint and tendon sheath swelling. Skin or nail
    (pitting) lesions are generally present. The distal interphalangeal
    (DIP) joints of the hand are frequently involved (1,5).
  - Roentgenographic
    periostitis, cortical erosions, or both can be seen along with spinal
    asymmetric sacroiliitis and isolated vertebral ankylosis (skip areas).
    The “pencil-in-cup” deformity is typically seen in the DIP joints of
    the hand. No rheumatoid factor is found. There is polymorphonuclear
    leukocytic predominance in the joint field.
- Systemic lupus erythematosus (SLE)
  - History most
    commonly reveals symmetric joint distribution identical to rheumatoid
    arthritis in a female patient. Hair loss and Raynaud symptoms
    (vasospasm of digital arteries) are common.
  - Examination may disclose rash (facial erythema), mucosal lesions, serositis, renal or brain involvement, and a systemic reaction.
  - Laboratory evaluation
    shows leukopenia, prolonged partial thromboplastin time (lupus
    inhibitor) with anticardiolipin antibodies, a noninflammatory joint
    fluid with good viscosity* and mucin⁺, and 1,000 to 2,000 WBCs/mm³, which are mostly lymphocytes. A depressed serum C′H₅₀, elevated antinuclear antibody and an increased anti–native-human DNA antibody titer are found.
- Rheumatic fever
  - History
    reveals a sore throat, fever, rash, and migratory joint pain that
    responds dramatically to aspirin treatment in younger individuals (that
    are beyond the ages of Reye syndrome).
  - Examination shows a rash as well as heart (murmur) or pericardial (friction rub) involvement.
  - Laboratory tests result in group A streptococci isolated on throat cultures and an elevated antistreptolysin O titer.
- Juvenile rheumatoid arthritis (JRA)
  - History shows
    symmetric joint involvement. The illness can begin or recur in the
    adult. Short stature and limb length irregularity generally accompany
    the most severe forms because the physes are affected by the
    inflammatory process. Patients with systemic onset (10% of children
    with JRA) have intermittent
    
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    fever
    with rash. Those patients (40% of total) who have involvement of five
    or more joints are characterized as polyarticular onset and are
    differentiated from pauciarticular-onset patients (7).
    There is a very high proportion of cervical spine involvement in the
    patients with JRA. The prevalence of JRA has been estimated to be
    between 57 and 113 per 100,000 children younger than 16 years of age in
    the United States (7).
  - Examination
    may reveal a rash and fever. Cardiac, renal, and ocular abnormalities
    may be present. Eye involvement occurs in 30% to 50% of early onset JRA
    patients (7).
  - Laboratory tests
    show roentgenographic periostitis with erosions later in the course of
    disease. Rheumatoid factor or FANA may be present. Other causes of
    arthritis in the child or adolescent must be excluded.
- HIV infection.
  Migratory arthralgia and myalgia with accompanying muscle weakness are
  features of this disease. Radiographic changes are nonspecific.
Inflammatory spondyloarthropathy (Table 4-7)
- Ankylosing spondylitis
  - History
    usually reveals clinical sacroiliitis in a male patient. A positive
    family history often is present. A good response to antiinflammatory
    agents is common.
  - Examination
    reveals limitation of spinal motion, uveitis, and diminished chest
    expansion. A positive Patrick’s test indicative of sacroiliac
    involvement is typically present (1,5,6).
  - There is laboratory evidence
    of roentgenographic sacroiliitis and smooth, symmetric spinal
    ligamentous calcification, often with complete ankylosis (the “bamboo
    spine”) and no skip areas. The HLA-B27 antigen should be present.
- Reiter syndrome (see IV.E.1)
- Psoriatic arthritis (see IV.E.2)
- Spondyloarthropathy secondary to inflammatory bowel disease
  - The history may not reveal bowel disease as a prominent feature; it can be subclinical.
  - Bowel disease is found on examination.
  - Laboratory tests show roentgenographic evidence of sacroiliitis that is often symmetric and ankylosing.

TABLE 4-7 Differential Diagnosis of Inflammatory Spondyloarthropathy^a

Ankylosing spondylitis—male, symmetric sacroiliitis
clinically and radiologically, limitation of spinal motion, uveitis,
smooth symmetric spinal ligamentous calcification, ankylosis often
complete, no skip areas, family history, HLA-B27 antigen often present,
good response to antiinflammatory drugs.
Reiter syndrome—male with urethritis, skin-eye-heel,
asymmetric peripheral joint involvement, sacroiliitis often asymmetric
and skip areas of involvement in spine, coarse asymmetric
syndesmophytes in spine, ankylosis incomplete and asymmetric, HLA-B27
often positive, equivocal response to antiinflammatory drugs.
Psoriatic spondylitis—skin or peripheral joints involved, asymmetric sacroiliitis, skip areas, may be ankylosing, HLA-B27 often present.
Inflammatory bowel disease—sacroiliitis, often symmetric,
ankylosing, bowel disease may be silent, spinal inflammation, unlike
peripheral arthritis, does not vary with and is not responsive to
treatment directed at bowel inflammation, HLA-B27 often present.
Other—infection (bacterial tuberculous, fungal), osteochondritis, multiple epiphysitis in young adult.

^aJuvenile
rheumatoid arthritis spondyloarthropathy occurs almost entirely in
HLA-B27–positive boys and is regarded as juvenile ankylosing
spondylitis.
From McCarty DJ. Differential diagnosis of arthritis: analysis of symptoms. In: McCarty DJ, ed. Arthritis and allied conditions, 10th ed. Philadelphia, PA: Lea & Febiger, 1985:52.

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V. Treatment (Table 4-8)

Rheumatoid arthritis (8,9,10,11)

Aspirin
is inexpensive but inconvenient to take because most authorities
recommend a range of 10 to 16 five-grain tablets per day to reach an
antiinflammatory level. Some patients simply cannot tolerate the
medication because of gastrointestinal side effects. Enteric-coated or
time-release preparations, 650 mg PO t.i.d or q.i.d, may be taken with
meals but not with antacids. These preparations may limit the dyspepsia
but do not alter the risk of gastrointestinal bleeding. Tinnitus must
be monitored in all patients receiving aspirin-containing compounds; it
is an early sign of salicylate toxicity. This therapy is sufficient
only for mild, nonerosive forms of rheumatoid arthritis.

Other nonsteroidal, non-aspirin antiinflammatory medications
are much more convenient, but more expensive. Patients who take these
medications long term should have biannual laboratory work to look for
adverse hepatic, renal, hematopoietic, and other reactions. Physicians
should educate their patients as to the potential adverse effects of
any medication. One easy education tool is the patient medication
instruction sheet. The treating physician may need to experiment with
various antiinflammatory medications before finding which preparation
is the best suited for the individual patient. Many different
preparations are now marketed (4). Physicians
prescribing these medications should know their cost. For example, a
1-month supply (120 tablets) of generic ibuprofen, 600 mg,
(prescription or over-the-counter) costs between $15 and $20, whereas a
1-month supply (360 tablets) of an over-the-counter brand name form of
the same drug (e.g., Advil, Medipren, Anaprox),

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200
mg, costs the patient between $35 and $36. The dosage of any
antiinflammatory drug should be the lowest possible that is effective
in relieving symptoms. There are several classes of these drugs, the
latest being the COX II inhibitors, which have a decreased incidence of
gastrointestinal ulceration and are equally effective (10,12). This therapy is sufficient only for mild arthritis.

TABLE 4-8 Treatment

Rheumatoid arthritis	Septic arthritis	Degenerative joint disease
Drugs Acetylsalicylic acid (first) Other antiinflammatory prescription medications Gold or D-penicillamine Methotrexate Sulfasalozine Chloroquine Steroids Synovectomy. If done, usually should follow 6 months of medical management. (Do not do a prophylactic synovectomy if there is roentgenographic evidence of joint destruction manifested by a severe loss of cartilaginous space.) Joint debridement and synovectomy (for pain relief only) Partial or complete joint replacement Arthrodesis	Antibiotics. Cefazolin (Kefzoi) or nafcillin (Nafcil or Unipen) with gentamicin (Garamycin) or tobramycin (Nebcin) until the culture and sensitivity results are obtained; then specific antibiotic therapy Surgery. Operative debridement and irrigation of the joint, followed by appropriate drainage	Antiinflammatory agents Support by bracing and other means Physical therapy Heat Exercises Surgery Debridement Osteotomy Partial or complete joint replacement Occasionally, arthrodesis

Gold is often
effective for treatment of rheumatoid and psoriatic arthritis; however,
it is no longer considered to be first-line therapy. Three forms of
gold are available. Two are injectable in the form of water-soluble,
gold sodium thiomalate (Myochrysine) and an oil-based aurothioglucose
(Solganal). The usual treatment required is two test doses of 10 to 25
mg each, followed by weekly doses of 50 mg IM for 20 weeks. A
maintenance dosage of 50 mg every 4 weeks may be given for life, but
dosage is empirical and smaller doses may be effective. The third form,
Auranofin, is administered orally, 3 mg PO b.i.d. The most common toxic
reaction to gold is dermatitis or albuminuria. Almost any condition can
occur, and gold should be withheld if any unusual symptoms develop. Do
not persist with gold if results are doubtful (9).
D-Penicillamine
(Cuprimine), a derivative of penicillin, may be substituted for gold in
the treatment of rheumatoid arthritis; it is also no longer considered
to be first-line therapy. The drug is marketed in 125- and 250-mg
capsules. The starting dosage is 250 mg/day, and it can be increased by
250 mg every 3 months to a maximum of 1 g/day. This slow approach
appears to lessen toxicity but retains efficacy. Because the drug is
toxic, the patient must be carefully monitored, particularly for bone
marrow depression, thrombocytopenia, and albuminuria (9).
Methotrexate. First-line therapy.
Sulfasalazine. First-line therapy.
Chloroquine is available as 250-mg chloroquine phosphate tablets. Hydroxychloroquine
(Plaquenil), which is available in 200-mg tablets, is more commonly
used because it is less toxic, but it is not as effective as
chloroquine phosphate (9).
- Dosage
  - Chloroquine phosphate is given in doses of 250 mg/day PO.
  - Hydroxychloroquine is given in doses of 200 mg PO b.i.d.
  - It may take up to 6 months to achieve a result. Attempt a dose reduction every 6 months.
- Precautions
  - Do not exceed the recommended dose. This dosage schedule does not apply to children.
  - Inform the patient of toxicity.
  - Have an ophthalmologist follow up with the patient.
  - Do not refill a prescription over the telephone; examine the patient first.
  - Stop therapy whenever there are any complaints of visual disturbance or a question of eye toxicity.
- Side effects
  - The major side effect is blindness resulting from chloroquine combining with retinal pigment.
  - Other effects are gastrointestinal upset, skin rash, weight loss, peripheral neuritis, and convulsions.
Azathioprine,
a purine analog with immunosuppressive activity, has been shown to be
effective in rheumatoid arthritis; it should be prescribed by
rheumatologists (8).
Leflunomide (Aravan)
Etanercept (Enbrel), a tumor necrosis
factor alpha (TNF-α) inhibitor, is the first “biologic” agent for use
in rheumatoid arthritis. It has been proven to be effective in
controlled trials and is generally well tolerated. Rarely, there have
been cases of serious infections, and the cost (over $10,000 per year)
must be

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considered.
It has also been shown to be useful in combination therapy with
methotrexate. It should be prescribed by rheumatologists (13,14,15).
Corticosteroids
yield a dramatic effect in the treatment of rheumatic disease. Although
steroids can offer dramatic relief, indiscriminate use may actually
produce more harm than good. In the treatment of rheumatoid arthritis,
steroids do not alter the course of the disease, and in subsequent
years, the relief will probably deteriorate because patients may have
more than one disease.
- Usage
  - Establish a specific diagnosis before treatment with steroids.
  - Adjust the dosage
    to the situation. For rheumatoid arthritis, start with 10 to 20 mg to
    control symptoms, then taper over 2 to 4 weeks to the lowest tolerated
    dose (usually no more than 510 mg/day) and try not to exceed 10 mg/24
    hours. For SLE crisis, one might start with 60 mg in a 24-hour period.
  - Although more than 20 generic glucocorticosteroids are available, most rheumatologists have settled on prednisone as the standard.
  - Monitor serum electrolytes and glucose because steroids cause increased excretion of sodium and potassium.
  - Administer the steroid once each morning
    to minimize the effect on the pituitary–adrenal axis. If there is good
    control of the inflammatory process, use alternate-day therapy.
  - Obtain a baseline eye examination before starting long-term therapy. Steroids can cause cataracts and increased intraocular pressure.
  - Beware of suppressed reaction to infection as a complicating factor, especially if the patient’s general condition is deteriorating while he or she is taking steroids.
  - With long-term therapy, be sure to recognize and manage complications of the systemic rheumatic disease as opposed to the iatrogenic complications of long-term steroid use, which are managed differently.
  - Patients should always carry information that they are on steroids.
  - Supplemental increased doses are necessary when stress occurs, even minor stress such as a tooth extraction.
- Undesirable effects
  - Steroid diabetes that is insulin-resistant, but without ketosis or acidosis
  - Muscle wasting secondary to a negative nitrogen balance
  - Buffalo hump and round face
  - Sodium retention that results in edema (especially important for patients with heart disease)
  - Hirsutism and occasional alterations in menstrual function in women secondary to adrenal atrophy
  - Peptic ulcer disease with possible perforation and abscess
  - Suppressed wound healing
  - Osteoporosis and avascular necrosis of the femoral or humeral head. Pathologic fractures are often associated.
  - Lymphocytosis and occasionally a leukemoid reaction
  - Subcutaneous hemorrhages and acne
  - Central nervous system changes such as psychosis, seizures, and insomnia at higher dose
  - Immunosuppression with increased risk of infections, candida, herpes zoster, and so on
Surgical treatment
- Synovectomy,
  if done, should follow at least 6 months of nonoperative management.
  This prophylactic procedure should not be performed if roentgenographic
  evidence of joint destruction manifested by a severe loss of
  cartilaginous space exists.
- There is still a place for joint debridement and synovectomy (open or arthroscopic) in patients with significant joint pain, but not enough joint destruction
  
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  to justify surgical joint knee replacement. Recently, arthroscopic
  synovectomy in the knee and shoulder has been shown to be effective.
- Joint replacement
  may be necessary. The most common joints replaced in the patient with
  inflammatory arthritis are knee and hip, followed by shoulder,
  metacarpophalangeal, elbow, wrist, and ankle.
- Very rarely, arthrodesis is indicated, especially with ankle involvement.
- Forefoot surgery
  is frequently required and most commonly consists of first
  metatarsophalangeal joint arthrodesis combined with lesser
  metatarsophalangeal joint resection with claw toe release.

Septic arthritis
- Antibiotics (see Chap. 3, Table 3-2).
  Proper cultures must be obtained before initiating antibiotic therapy.
  These are obtained either as an aspirate or intraoperatively.
- Drainage of the joint is usually necessary.
  - Needle aspiration and irrigation
    are sometimes sufficient if the joint can be easily inspected for an
    effusion. The joint may need decompression more than once daily. The
    hip joint always requires open drainage. A knee joint infection can be
    handled by needle decompression if the exudate is not loculated and if
    aspiration clearly decompresses the joint. If marked improvement is not
    noted within 48 hours, then the open (or arthroscopic) irrigation and
    debridement should be performed.
  - Operative irrigation and drainage
    of the joint are often necessary with or without debridement.
    Postoperatively, wounds are usually closed over drains and judicious
    immobilization is used. Increasingly, arthroscopic lavage is being used
    for knee and shoulder joint involvement.
Osteoarthritis
- Medical treatment consists of acetaminophen or nonsteroidal antiinflammatory preparations. Due to safety concerns, acetaminophen is considered the first-line agent (2,16).
  There is some evidence that the “nutricuticals” glucosamine and
  chondroitin sulfate have some efficacy in treating the symptoms of
  osteoarthritis (17). See V.A.1 and V.A.2 for a more complete discussion.
- Various braces are available to offer joint support (see also Chap. 6).
  Simple neoprene sleeves for the knee or elbow are useful. For
  unicompartmental knee arthritis, braces that “unload” the diseased
  compartment are proven to be effective (3).
- Physical therapy
  can be helpful, especially in providing exercises to maintain muscle
  tone. Deep heat treatments provide symptomatic relief. The most
  effective therapy is patient-directed home therapy, which emphasizes
  maintaining strength and motion with low-impact exercise routines.
  Prolonged outpatient therapy is expensive and of limited value.
- Weight loss
  is extremely useful for overweight patients with osteoarthritis. This
  may seem obvious in the weight-bearing joints of the lower extremity
  due to excessive force on the joints. Still, it is often neglected.
  Additionally, there is increasing evidence that obesity is associated
  with an increase in osteoarthritis of the upper extremity, suggesting a
  systemic effect such as through inflammatory mediators.
- Intraarticular steroid injections are helpful. The options available are listed in D.2.b.
  (pseudogout treatment). Recently, injection of hyaluronic acid
  compounds (Synvisc or Hyalgan) has been proven to be efficacious. This
  requires serial injections given 1 week apart over either 3 or 5 weeks.
  The therapy has the same effectiveness as oral antiinflammatory therapy.
- Various surgical procedures offer relief of joint pain and improved function. These include the following:
  - Debridement, generally arthroscopic
  - Osteotomy for varus malalignment of the knee to move the weight-bearing axis into the lateral, more normal compartment
  - Partial or complete joint resurfacing or replacement
  - Occasionally, joint arthrodesis. This is generally reserved for use in the previously septic joint.
  - Autologous chondrocyte transplantation is
    a technique that may be used selectively for the management of focal
    traumatic articular cartilage defects. It is not indicated for diffuse
    osteoarthritis of the knee (18,19).
Crystal-induced arthritis (9)
- Gouty arthritis
  - Acute attacks may be provoked by surgery or trauma or other systemic illness. They generally respond to the following agents:
    - Colchicine,
      one 0.6-mg tablet initially followed by one tablet per hour until
      gastrointestinal upset occurs, joint symptoms resolve, or a maximum of
      ten tablets has been ingested in a 24-hour period; or 2 mg
      intravenously (IV) initially (avoid injecting outside the vein by
      injecting into a functioning IV) followed by 1 mg q6h until the flare
      symptoms resolve or a maximum of 5 mg has been injected in a 24-hour
      period. A suppository formulation is available for patients who cannot
      take oral medications. IV colchicine should be avoided in elderly
      patients and patients with renal disease.
    - Indomethacin (Indocin), 50 mg PO q.i.d for the first day, followed by 25 mg q.i.d.
    - Other antiinflammatory drugs, which can be tried if indomethacin is ineffective or not well tolerated.
  - The authors suggest treatment with colchicine, 0.6 mg PO b.i.d, between acute attacks until the patient is symptom free for 1 year. Consultation with a rheumatologist is advised.
  - A xanthine oxidase inhibitor such as allopurinol
    (Zyloprim), 100 to 300 mg/day PO, works by lowering the uric acid pool
    of the body. The physician should be aware of the serious and possibly
    fatal adverse reactions to allopurinol, including agranulocytosis,
    exfoliative dermatitis, acute vasculitis, and hepatotoxicity. These
    agents should not be initiated during an acute attack, rather after
    resolution.
  - Uricosuric agents:
    probenecid and sulfinpyrazone. These agents increase the amount of uric
    acid excreted in the urine, so their use can be associated with uric
    acid renal calculi. As with allopurinol, the therapy should be
    initiated after resolution of the acute attack.
    - Probenecid (Benemid), 0.5 mg PO q.i.d up to 2 or 3 g/day.
    - Sulfinpyrazone (Anturane), 100 mg PO b.i.d up to q.i.d.
  - Recommendations for managing hyperuricemia
    - Confirm the elevated serum uric acid by repeating the test.
    - Determine whether the condition is secondary
      to drugs or blood dyscrasia. One should rule out renal disease with a
      serum creatinine in a 24-hour serum uric acid excretion test. If uric
      acid excretion is greater than 1 g per 24 hours, consider treating the
      hyperuricemia. If renal disease is present, then allopurinol may be the
      drug of choice.
    - Discuss dietary recommendation to limit foods rich in purines, such as certain beef and fish.
    - Generally withhold therapy unless there has been one acute attack of gouty arthritis.
    - Rule out hyperuricemia secondary to a lymphoproliferative or myeloproliferative disease.
    - Do not treat hyperuricemia secondary to thiazide diuretics.
- Pseudogout
  - Differentiate pseudogout from acute gouty arthritis by joint fluid examination for specific crystals.
  - Consider aspirating the joint fluid or injecting
    insoluble steroids intraarticularly, using 0.1 mL for small joints and
    up to 1 to 2 mL for most large joints. The types of steroids useful for
    this application are as follows:
    - Hydrocortisone acetate, 25 to 50 mg/mL
    - Prednisone tertiary butyl acetate, 20 mg/mL
    - Triamcinolone hexacetonide (Aristospan), 5 and 20 mg/mL
    - Betamethasone acetate and sodium phosphate (Celestone), 6 mg/mL
    - Methylprednisolone acetate (Depo-Medrol), 20 and 40 mg/mL
  - Colchicine may provide dramatic relief.
  - Many patients respond to antiinflammatory agents such as indomethacin.
Inflammatory polyarthritis (assuming no coexisting chlamydia infection)
- Reiter syndrome
  treatment is symptomatic. The prognosis is guarded because chronic
  arthritis develops in many people. Sulfasalazine, MTX may be considered
  for chronic moderate-to-severe disease.
- Psoriatic arthritis. Immunosuppressive drugs,
  such as methotrexate, are useful when administered in doses of 7.5 to
  25.0 mg PO or IM once weekly. Methotrexate can induce hair loss, cause
  oral ulcers, promote teratogenesis, and cause hepatitis and cirrhosis
  of the liver.
- Systemic lupus erythematosus
  - Do not treat until the diagnosis is established.
  - Do not overtreat.
    Mild cases can be handled with reassurance, aspirin, indomethacin, or
    one of the many nonsteroidal antiinflammatory drugs that are available.
  - An occult infection
    sometimes is difficult to diagnose and differentiate from an
    exacerbation of SLE. In these situations, be sure to rule out
    infections of the genitourinary tract, heart, and lungs.
  - Advise the patient to rest as necessary.
  - Avoid excessive exposure to the sun.
  - Chloroquine, hydroxychloroquine, and mepacrine
    (Atabrine) usually control the skin manifestations and arthralgia.
    Mepacrine should be administered 100 mg per day PO. This medication can
    cause yellow staining of the skin, but this effect is not considered a
    reason to discontinue its use.
  - Prednisone, less than 10 mg/day PO, may be added to the regimen if the patient does not respond to the preceding measures.
  - Immunosuppressive agents are indicated as steroid-sparing agents for treatment for SLE.
  - The treatment of this disease is
    empirical and must be individualized and monitored by the
    rheumatologist. There are no absolutes.
Inflammatory spondyloarthropathy
- Ankylosing spondylitis
  - The most important part of the initial therapy is an educational effort
    by the physician or physical therapist that should cover proper
    sleeping position, gait, posture, breathing exercises, and “measuring
    up” every morning (i.e., straightening the spine every day to reach a
    mark placed on the wall to help prevent kyphosis or at least identify
    its development).
  - Nonsteroidal antiinflammatory drugs
    are the drugs of choice for milder cases. As with treatment for
    osteoarthritis, trial and error to identify the optimum drug is the
    rule. After relief is obtained, decrease the dose to the lowest
    possible effective dose (6).
  - Ophthalmologic evaluation is indicated because anterior uveitis occurs in 10% to 60% of patients.
  - Sulfasalazine or methotrexate may be useful in aggressive cases.
  - Radiation therapy has been abandoned because of late malignancy reports.
- Treatment of Reiter syndrome is discussed in V.E.1.
- Treatment of psoriatic arthritis is discussed in V.E.2.
- Rheumatic fever
  - Rest is recommended according to the degree of cardiac involvement (8).
  - Aspirin is used for mild arthritis.
  - Prednisone is
    used for patients with carditis and heart failure. Start with 40 to 60
    mg per day, and adjust the dosage according to patient response.
  - Diuretics and digitalis are often needed.
  - Penicillin is indicated for the initial treatment as well as continued prophylaxis. See Chap. 3 for the appropriate parenteral dose.
  - Throat culture family contacts.
- Juvenile rheumatoid arthritis (1,6)
  - Salicylates
    or nonsteroidal antiinflammatory drugs are the mainstay of therapy; one
    third of patients can be managed with these drugs alone (7).
    - For children weighing less than 25 kg, use 100 mg/kg body weight per day in four to six divided doses.
    - For adults a total daily dose of 2.4 to 3.6 g of aspirin usually is sufficient.
  - Methotrexate is effective in 70% to 80% of patients with JRA.
  - Gold is used
    if, after 6 months of adequate salicylate and physical therapy, loss of
    joint function is progressive owing to active synovitis. See V.A.3
    for a discussion of gold therapy. For children, use 1 mg/kg body weight
    per week to a maximum of 25 mg/kg body weight per week; injectable
    therapy is effective in 50% of patients; oral gold therapy is
    ineffective.
  - Antimalarial drugs such as hydroxychloroquine are used as an alternative to gold. Do not exceed 200 mg/m² body surface per day. Ophthalmologic examinations are recommended every 3 months. See V.A.7 for a more complete discussion of antimalarial drugs.
  - D-Penicillamine is not recommended for routine use in JRA.
  - Corticosteroids
    are rarely warranted for joint disease alone. If given, they should be
    administered at the lowest effective dose, preferably on alternate days
    for very short periods. Steroid injections into troublesome joints for
    synovitis may be helpful if multiple injections into the same joint are
    avoided.
  - Physical and occupational therapy
    are helpful to maintain function, prevent contracture, and optimize
    motion and muscle strength. Therapeutic maneuvers should be performed
    twice daily at home. Night splints to prevent deformity are usually
    essential.
  - Orthopaedic surgery
    - Synovectomy plays a limited role in the early treatment of JRA.
    - Reconstructive surgery (e.g., soft-tissue releases, osteotomies, and total joint replacement) can be indicated.
    - Ophthalmologic evaluation is necessary for early diagnostic treatment of any iridocyclitis.
    - Amyloidosis is seen in 5% of patients and can be fatal if kidneys fail.
    - Do not forget the whole child, the effects of this disease on other organ systems, and the child’s mental health.

Footnotes

*The
clinical viscosity test is considered good or high if the fluid remains
intact when slowly stretched between the examiner’s thumb and index
finger.

⁺A
good mucin clot is one that occurs after a few drops of glacial acetic
acid are added to a supernatant of centrifuged joint fluid and a dense,
white precipitate forms.

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