Chapter 3: Rheumatology

Although over 100 different causes of arthritis exist, there is none more important to the emergency physician than the diagnosis of septic (bacterial) arthritis. If septic arthritis goes undiagnosed or untreated, mortality may result and at the least, rapid destruction of articular tissue is inevitable. Some infections, if untreated, can destroy cartilage in as little as 2 days. Depending on the study, the mortality of septic arthritis is around 11%.¹

Evaluation begins with a thorough history. The physician should first determine when the pain started. An acute onset (hours to 1 week) suggests trauma, infection, or crystal-induced arthritis. A history of similar attacks might support a diagnosis of crystal-induced arthritis, although this cannot completely rule out an infectious etiology. Chronic joint pain usually suggests a chronic problem, but the clinician should be careful to note any new features that are unusual to the patient and might signify a concomitant condition (i.e., a septic joint in a patient with rheumatoid arthritis [RA] or gout).

The distribution of affected joints and pattern is determined next. Monoarthritis involves one joint, oligoarthritis involves two to three joints, and polyarthritis occurs in more than three joints.² Symmetric involvement that is additive and initially involves the small joints is found in RA. Migratory arthritis, especially if it occurs in conjunction with a fever, is consistent with rheumatic fever and/or gonococcal arthritis. Further discussion of the differential diagnoses of monoarthritis and polyarthritis are provided below.

Next, the patient should be questioned about constitutional symptoms (e.g., fever), previous episodes, and trauma. Fever and weight loss are important signs because they signify systemic illness. A history of similar previous episodes suggests crystal-induced or other noninfectious causes. If a patient states that he/she has a fever, the physician should think of septic arthritis. Patients who have a history of trauma should be thought of as possibly having a fracture, which may not be seen on the initial x-ray, particularly in the lower extremity where fractures may be occult. Diarrhea, urethritis, or uveitis suggests a reactive type of arthritis. Obtaining a history of a rash or skin lesion may also provide an important clue to the proper diagnosis.

Stiffness is usually an indication of synovitis, but worsening stiffness after sleep that gradually improves (i.e., gelling) with movement suggests RA.³ If the patient complains of weakness, the clinician must differentiate generalized weakness from a focal deficit. Paresthesias may indicate a compressive neuropathy or radiculopathy. Significant muscle pain suggests the possibility of myositis.

When approaching a patient with joint pain, the emergency physician should first remember that the source of the pain may be articular or periarticular (i.e., bursitis, tendonitis, cellulitis). This can best be determined on examination. Some distinguishing features are listed in Table 3–1. In patients with cellulitis, the involvement is usually not isolated to the joint alone. If it is, however, then palpating the area where one normally performs an arthrocentesis will reveal this to be more tender than any other location in the patient with arthritis. Even with the most detailed examination, however, cellulitis in the area of the wrist, knee, and sometimes the ankle can mimic arthritis. Painful limitation of motion usually indicates joint involvement.

After it has been determined that the joint itself is the likely source of pain, ascertain whether the joint pain is inflammatory (i.e., arthritis) or noninflammatory (i.e., arthralgia). Inflammatory conditions, such as septic arthritis and gout, will cause swelling, erythema, and warmth. Tenderness to palpation is noted. Range of motion, which is typically decreased, and the presence of an effusion should be noted and documented. Compare the affected joints to the unaffected side to get a better sense of the abnormalities in the affected joint.

A helpful way to classify arthritis is based on the number of joints involved—as monoarticular or polyarticular. There is overlap within these classifications that the clinician should be aware of. For instance, infectious arthritis is generally considered monoarticular, but in 10% to 20% of cases, more than one joint is affected.^4–7 Gonococcal arthritis may present with either monoarticular or polyarticular involvement. In addition, a patient with arthritis of only one joint may be presenting with the first symptom of what will eventually manifest as a polyarticular condition.

Acute Monoarthritis

The three most common causes of acute monoarthritis in adults are infections, crystals, and trauma.⁸ Table 3–2 lists the differential diagnosis for patients who present with acute monoarthritis.

Approximately 80% to 90% of nongonococcal bacterial infections are monoarticular, often affecting the large joints such as the knees and hips.⁹ Other pathogens also infect the joints in a monoarticular pattern. Fungal arthritis is usually insidious in onset and may be seen in an immunocompromised host. Viral arthritis is common, can be monoarticular, and is frequently associated with herpes simplex virus. Human immunodeficiency virus (HIV) may be seen in patients presenting with monoarticular (or oligoarticular) arthritis involving the lower-extremity joints, heralding the onset of HIV infection. These patients may have a nonreactive synovial fluid or one that is only minimally reactive. Infection with human immunodeficiency virus does also increase one’s risk for infections but it is unclear to what extent.¹⁰

Acute monoarticular arthritis in patients with prosthetic joints is a significant concern as it may indicate infection. Having a prosthetic joint (especially a knee or hip) puts patients at a higher risk for having an infectious etiology. The two most common ways that a prosthetic joint gets infected is from the surgery itself or from hematogenous spread (which is the most common).¹¹ Patients with hip prostheses who present with a monoarthritis may have loosening of their hardware, which is the most common cause of long-term failure of arthroplasties.

Hemarthrosis is most commonly seen after trauma; however, it may be caused by acquired or congenital clotting abnormalities such as hemophilia.

Many systemic diseases can initially present with a monoarthritis. This is clearly an uncommon presentation of systemic diseases; however, it should be considered when the other conditions listed earlier and discussed later in the chapter have been ruled out. Systemic diseases that can present with a monoarthritis include systemic lupus erythematosus (SLE), RA, arthritis of inflammatory bowel, Behçet disease, and Reiter syndrome.

Polyarthritis

In polyarthritis, four or more joints are involved. Three patterns of polyarthritis exist:

1. Additive. Examples include RA, SLE, and psoriatic arthritis, all of which have joint involvement that progresses to include additional joints over time.

2. Migratory. With gonococcal arthritis or acute rheumatic fever, symptomatic joints subside and then different joints become involved. A migratory pattern may also be seen in viral arthritis, Lyme arthritis, and SLE.

3. Intermittent. In gout, pseudogout, and familial Mediterranean fever, one sees a picture of arthritis with signs and symptoms that come, last a few days, and then remit.

A differential diagnosis and diagnostic features of some common causes of polyarthritis are listed in Table 3–3.¹² Other less common causes of polyarthritis include endocarditis, vasculitis, and occult malignancy. In one large series, 44% of patients with bacterial endocarditis had a polyarthritis. Some of the joints have an asymptomatic effusion whereas others are warm, red, and painful.⁹ Systemic vasculitis can present with polyarthritis and fever. In addition, patients usually have concurrent skin lesions (purpura, petechiae), neuropathy, or microscopic hematuria.

Polyarthritis associated with fever must trigger the clinician to think of infection first and foremost. In patients with polyarthritis, synovial fluid examination is extraordinarily useful, especially when one is considering bacterial infection as a possibility. Leukocyte counts over 50,000/mm³ suggest bacterial infection but can be seen in RA and crystal-induced arthritis. Unfortunately, an elevated erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) is of minimal diagnostic value. Studies looking at ESR and CRP showed that they had a sensitivity and a specificity of 95% and 29% for ESR and 77% and 53% for CRP, respectively, when evaluating for infection.^13–16

Arthrocentesis

The clinician ought to have a low threshold to perform an arthrocentesis on joints where the diagnosis of septic arthritis is a possibility because of the morbidity and mortality risk associated. Sterile technique and local anesthetic should be utilized in all cases. The patient should be consented for the procedure. The general principles of arthrocentesis include using the extensor surface, distraction, and approximately 20 to 30 degrees of flexion (Video 3–1). Because the synovial fluid is frequently thick and in the case of inflammatory arthritis, full of cellular debris, a large needle should be used. In larger joints such as the shoulder and knee, an 18- or 20-gauge needle is appropriate (Table 3–4). Poor technique or a large amount of movement of the needle during the procedure can damage the articular cartilage. The infection rate secondary to arthrocentesis is 1:10,000 aspirations.¹⁷ Videos 3–2 to 3–10 illustrate the recommended technique for performing arthrocentesis on the joints most commonly requiring the procedure.

Arthrocentesis of the knee is a common procedure in the emergency department. In this procedure, the needle should be inserted approximately 1 cm medial to the medial/superior aspect of the patella and directed just posterior to the posterior surface of the patella. The angle of the needle should be directed toward the center of the patella. You may push medially on the lateral aspect of the patella to better define the patellar boundaries.

Synovial Fluid Analysis

Table 3–5 presents some of the common findings of synovial fluid analysis in patients with arthritis. Fluid is sent for differential leukocyte count, culture, Gram stain, and examination for crystals. If only a few drops of synovial fluid are obtained, then one should send these for a culture, Gram stain, and crystal determination, in order of importance. Because a septic joint must be ruled out, the culture is vital. Differential leukocyte counts can assist in making a diagnosis of infection, as a finding of 90% polymorphonuclear neutrophils (PMNs) suggests either infection or crystal-induced disease, even if the total leukocyte count is low. A definitive diagnosis from analysis of the joint aspirate is obtained in only 44% of cases.¹⁷ However, differentiating between inflammatory and noninflammatory arthritis is possible.

The presence of crystals does not exclude infection.⁴ Chronic joint injury in patients with crystal-induced arthropathy makes these patients more susceptible to septic arthritis. The likelihood of concomitant crystal disease and septic arthritis does seem to be low, as demonstrated by an abstract presented at the 2004 Society of Academic Emergency Medicine Annual Meeting. Of 265 aspirates containing crystals, only 4 (1.5% [95% CI, 0–3%]) subsequently grew positive cultures. However, when doubt about the diagnosis exists, antibiotics should be administered until culture results have returned.

Inflammation of a joint caused by the presence of a microorganism is uncommon but, perhaps, the most serious arthritic condition presenting to the emergency department. If it is not recognized, septic arthritis will lead to rapid joint destruction and irreversible loss of function. More than 30% of patients with septic arthritis develop residual joint damage and mortality rates are approximately 10%.^5–7

The most common agents are gram-positive aerobes, usually Staphylococcus aureus (S. aureus), which accounts for approximately 50% of these infections.⁶ Most of these bacteria are resistant to penicillin. In patients with RA, diabetes, or polyarticular septic arthritis, the percentage of cases due to S. aureus increases to 80%. Streptococci account for approximately 25% of infections, with Streptococcus pneumonia and group A β-hemolytic Streptococcus being the most common. Gram-negative bacteria are found in 20% of cases and Neisseria gonorrhoeae account for the remaining 5%. Gonococcal arthritis is more common in young, otherwise healthy, sexually active individuals. Gram-negative septic arthritis is more common in immunocompromised hosts, the elderly, intravenous drug users, and patients with open wounds.^6,18

A prerequisite for the development of septic arthritis is that bacteria must reach the synovial membrane. This may occur in any of the following ways:

1. Hematogenous spread

   • Occurs as a result of implantation of the organism within the perivascular synovium or rich vascular beds at the articular surfaces. Hematogenous spread often occurs in the sacroiliac (SI) joints of intravenous drug users.¹⁹

2. Contiguous spread

   • A route that is particularly common in small children is dissemination of bacteria from an acute osteomyelitic focus in the metaphysis or epiphysis.

   • An infection in the vicinity of the joint can progress to the joint or spread through the lymphogenic route. This is most often seen in nonpenetrating traumatic and postoperative wound infections and skin and softtissue infections around the joint, particularly the knee.

3. Direct joint penetration

   • Iatrogenic infections caused by joint puncture for a diagnostic or therapeutic purpose (rare, incidence of 1:10,000).

   • Penetrating trauma that is caused by dirty objects or by animal or human bites often gives rise to a severe infection because of the high inoculate of bacteria and lacerated tissue.

Risk Factors

Although it is true that septic arthritis may occur in any joint and in any individual, there are some clinical situations in which it is more likely. Identified risk factors include age older than 80, diabetes mellitus, RA, joint prosthesis, joint surgery, HIV, and a skin infection.^{4,10–12,17–19} Fifty-nine percent of all cases of septic arthritis occur in patients with a previous joint disorder.^20,21 This is significant because of the potential misdiagnoses that can occur if the clinician falsely attributes new joint pain to a “rheumatoid flare” when it is secondary to bacterial infection. Local factors that predispose to the development of septic arthritis include direct trauma, recent joint surgery, osteoarthritis (OA), repeated intra-articular steroid injection, and prosthetic joints. In one study, synthetic joint material existed in 29% of infected joints.²¹ Systemic conditions associated with bacterial arthritis include liver disease, alcoholism, renal failure, malignancies, acquired immunodeficiency syndrome (AIDS), and immunosuppression. Intravenous drug use predisposes to septic arthritis, often in an unusual location (sternoclavicular joint). Adverse prognostic factors include older age, preexisting joint disease, and synthetic joint material.

Clinical Presentation

Although septic arthritis usually presents as a monoarthritis, 10% to 20% of patients have polyarthritis at the onset, involving several large joints. When the condition presents in this fashion, it presents as an additive type of arthritis. The lower extremities are most often affected, particularly the hip and knee joints.²² The knee is involved in 50% of cases. The hip is more commonly infected in children. Ten percent of infections involve the SI joint and these are difficult to detect on physical examination.

A septic joint is, by definition, inflammatory in nature, and therefore is erythematous, warm, and tender. Distention of the joint capsule and increased intra-articular pressure contribute to pain. Patients are reluctant to move and put weight on the joint. Range of motion is severely limited due to pain and joint effusion. Joint effusion is present in 90% of these patients, but is less apparent in joints like the shoulder. Rarely, these findings are less evident if the patient presents early in the clinical course. Multiple studies have looked at the sensitivity of the physical exam findings with pain (sensitivity 85%) and swelling (sensitivity 78%) being the most common. Fever is also less helpful than one would think—in one study less than half of the patients had a fever with culture-proven septic arthritis. There are little to no studies on specificity of physical examination findings in the diagnosis of septic arthritis.¹⁴ The absence of fever and peripheral leukocytosis, although often present in septic arthritis, should not be used to exclude the diagnosis. In fact, only half of patients with bacterial arthritis will have fever or leukocytosis.⁵

In infants, the symptoms are usually systemic rather than local. Small children develop high fevers and are usually ill-appearing. The clinical features are more often characteristic of sepsis than local arthritis. This is a key point to remember if one is considering this diagnosis in children. Older children are also febrile and unwell, but the local signs are more prominent.

Gonococcal arthritis possesses some unique characteristics and is therefore mentioned separately. It is part of a clinical triad of disseminated gonococcal infection (DGI) that also includes dermatitis and tenosynovitis. DGI occurs in 0.5% to 3% of cases of mucosal infection.²³ The arthritis of DGI is polyarticular in 40% to 70% of cases and is usually migratory.⁶ It is most common in young, sexually active adults, with a female to male ratio of 3:1.²⁴ A possible explanation for this is that women who have a gonococcal infection tend to be less symptomatic and therefore might not get treatment immediately thereby allowing the infection to spread.²³ The most common joints involved are the knees and wrists. Characteristic skin lesions are present in two-thirds of cases and include multiple, painless macules, papules, and pustules on an erythematous base.¹⁶ Typically, the rash occurs on the arms, palms, soles, legs, or trunk. Tenosynovitis of the tendons of the wrist and ankle may be associated, and is also present in two-thirds of patients.

Laboratory Analysis

A clinical suspicion of infectious arthritis should be followed up by an arthrocentesis of the joint in question. Arthrocentesis is performed by the emergency physician unless prosthetic material is present within the joint (see Videos 3–1 to 3–10). Hip arthrocentesis is difficult and is best performed with either ultrasound or fluoroscopy. In these cases, orthopedic consultation is appropriate.

Synovial fluid should be sent for Gram stain, culture, leukocyte and differential counts, and crystal examination. Blood cultures should be obtained as they are positive in 50% of cases of nongonococcal septic arthritis.²⁵ The peripheral white blood cell count is elevated in only half of the patients and therefore cannot be relied on to exclude the diagnosis.²⁶ As noted in Table 3–4, the synovial fluid leukocyte count is usually >50,000 cells/mm³ with a predominance of polymorphonuclear cells. One recent study noted, however, that this “cutoff” is not sensitive enough to use to exclude the diagnosis.²⁶ In their patients with culture-proven septic arthritis, more than one-third of patients with septic arthritis had synovial leukocyte counts <50,000 cells/mm³ and 10% had counts <10,000 cells/mm³.

As stated previously, the finding of crystals does not exclude the diagnosis of septic arthritis as these two entities can coexist.²⁷ Diagnosis is further confounded by the fact that both conditions may present with fever, an inflammatory arthritis, and high synovial leukocyte counts. In many cases, the Gram stain and good clinical judgment must guide the emergency physician until the culture result is available 2 days later. It is our recommendation that a patient with a history of gout with similar attacks in the past, crystals in the synovial fluid, low clinical suspicion, and a negative Gram stain can be treated for gout alone with close follow-up of the culture results. However, when doubt about the diagnosis exists, the patient should be treated for septic arthritis with antibiotics and an orthopedic consultation.

Bacteria are identified by a Gram stain of the synovial fluid in 50% of cases and on culture in more than 90% of cases.²⁸ Previous administration of antibiotics will create a significant increase in false-negative Gram stains and cultures. Conversely, the use of blood culture bottles and a higher volume of synovial fluid may increase the chance of a true positive culture, although this has not been shown universally.^29,30 Diluting the synovial fluid in a blood culture bottle inhibits the bactericidal components of the synovial fluid and increases the yield.

Laboratory results unique to gonococcal arthritis include a lower yield from synovial fluid cultures (50%). A much higher yield is obtained from mucosal culture (80%). Blood cultures are positive in only 20% to 30% of cases.²³

Although radiographs are frequently not helpful in making the diagnosis of septic arthritis, they typically show symmetric soft-tissue swelling around the involved joint; marginal erosion or erosions of the bone occur later. The hallmark of septic arthritis is the loss of the white cortical line over a long contiguous segment. Unfortunately, radiographs have limited diagnostic value in the early stages of this disease. Radionuclide scanning and magnetic resonance imaging (MRI) may identify juxta-articular osteomyelitis and effusions in deep locations such as the hip and SI joint.

The difficulty in making this diagnosis is that the WBC count and Gram stain are not sensitive enough to rule out septic arthritis in patients with a high clinical suspicion. If the WBC count and Gram stain are consistent with septic arthritis, then the patient should be started on appropriate antibiotics and admitted with an orthopedics consult. If the WBC count and gram stain are equivocal and the patient’s clinical picture is worrisome for septic arthritis, antibiotics should be started along with an orthopedic consult. If the WBC count and gram stain are normal, and the concern for septic arthritis is low, the patient may be discharged with close follow-up awaiting the culture results. The emergency physician should have a low threshold to perform arthrocentesis, initiating antibiotics, and admitting these patients as morbidity and mortality is many times directly correlated with the delay in treatment initiation. Delay in treatment is the best predictor of an unfavorable outcome.

Treatment

Therapy consists of systemic antibiotics, splinting, closed or open drainage of the septic joint, and later rehabilitation. Initiate antibiotic treatment as soon as possible after arthrocentesis and a set of blood cultures are obtained. Empiric antibiotic treatment for nongonococcal septic arthritis in the era of methicillin-resistant S. aureus (MRSA) consists of vancomycin plus ceftazidime. Antibiotic selection should be tailored to the Gram stain. These treatment regimens do not cover IV drug users or prosthetic joints, and an infectious disease specialist should be consulted for these patient populations.

Orthopedic consultation and admission is warranted for all patients. Currently, the mainstay of treatment is repeated daily closed drainage. If fluid cannot be obtained from the joint, or there is a poor response to antibiotic therapy, then open drainage or arthroscopy is required. Open drainage is usually necessary when the hip is affected. Arthroscopy is preferred in the knee and shoulder because of easier irrigation. Prosthetic material should be removed operatively. Rarely, early infections of prosthetic joints can be treated with debridement and a long course of antibiotics.

Gonococcal arthritis is treated with intravenous antibiotics for 24 to 48 hours after improvement begins. The agent of choice is a third-generation cephalosporin, typically, ceftriaxone 1 g intravenously every 24 hours. Oral therapy is initiated with ciprofloxacin 500 mg twice a day. Synovial effusions may require repeat aspiration, but open drainage is rarely necessary.

Gout and pseudogout are inflammatory syndromes caused by crystal deposition in the joints and soft tissues. Features of these two syndromes are compared in Table 3–6.

Gout

Gout is caused by the precipitation of uric acid crystals in the joints and soft tissues. Uric acid precipitates from solution at approximately 7 mg/dL, so a slight rise in the serum concentration of urate from the normal range of 4 to 5 mg/dL may lead to gouty arthritis. Levels of uric acid are normally higher in men than in premenopausal women, and rise with age in both sexes. Hence, the typical patient afflicted with gout is a middle-aged man. Gout is unusual in men younger than 30 years of age and in premenopausal women. People with diets high in meats and seafood tend to have higher levels of uric acid. Patients with diets rich in dairy tend to have lower uric acid levels.³¹

Although up to 5% of adults have some degree of hyperuricemia, only one-fifth of these (1% overall) will ever develop gout. Among patients with serum uric acid levels of 9 mg/dL, 5% will develop acute gout per year.³² Hyperuricemia may be caused by either overproduction of uric acid, or decreased excretion in the urine. Although a discussion of disorders of urate metabolism is beyond the scope of this text, the emergency physician should be familiar with a few causes of decreased urate excretion as they may precipitate an attack of gouty arthritis: loop diuretics (furosemide, thiazides), salicylates, the antimicrobials pyrazinamide and ethambutol, and ethanol.²² Because uric acid solubility is temperature dependent, environmental cold or poor circulation can lead to precipitation.

Clinical Presentation

The presentation of gout is divided into four stages:

• Stage 1 (asymptomatic hyperuricemia). Symptoms are usually not present, although a small percentage of patients develop urinary calculi.

• Stage 2 (acute gouty arthritis). This stage is heralded by the rapid onset of severe pain and swelling of the affected joints. The first metatarsophalangeal (MTP) joints are affected in over half of initial attacks and eventually in up to 90% of patients with gout. Other sites commonly affected are other joints in the foot, the ankle, and the knee. When the hand is affected, the swelling may be quite significant (Fig. 3–1). Almost 90% of initial attacks are monoarticular. The affected joints are markedly erythematous, more so than in other types of noninfectious arthritis. Tendons and bursae may be affected. Although mild attacks resolve within a few days, more severe attacks require several weeks to resolve completely. Patients are occasionally systemically ill, and may even appear septic.³³

• Stage 3 (intercritical gout). Between attacks of gouty arthritis, the patient is asymptomatic but may still have urate crystals present in both previously affected and unaffected joints.

• Stage 4 (chronic gout). Approximately half of patients who have had attacks of gout for a period of 10 years or more develop tophi, nodules in the skin and soft tissues containing precipitated uric acid crystals (Fig. 3–2). Tophi and the associated inflammatory reaction to urate crystals can damage cartilage, subchondral bone, tendons, and skin, leading to cosmetic and functional deformities.

Diagnosis

Serum uric acid levels are usually elevated between attacks in patients with gout. However, during an acute attack, uric acid precipitates into the affected tissues and the serum uric acid level may normalize. Thus, serum uric acid levels are of no use during an acute attack of gout.³⁴

There have been proposals for using clinical criteria only as the diagnostic modality of making the diagnosis. This is an attractive method, because it would obviate the need for arthrocentesis. One review article looked at three of these methods and illustrated that none had a sensitivity or a specificity of greater than 70% and 88%, respectively.³⁵ Although these are attractive it is important that we differentiate crystal-induced arthropathy from septic arthritis and therefore arthrocentesis remains the cornerstone of the diagnosis.

Aspiration of the inflamed joint is the key to the diagnosis of gout. Synovial fluid from a gouty joint reveals:

• Needle-shaped urate crystals. If polarized light microscopy is available, they will appear yellow when oriented parallel to the axis of slow vibration marked on the microscope’s compensator (i.e., negatively birefringent). The crystals are found intracellularly (within neutrophils) during an acute attack of gout.³⁶

• Low viscosity.

• High leukocyte count, often >50,000/mm³. Seventy percent or more will be neutrophils.

• An absence of bacteria on Gram stain and culture.

Because little fluid is usually obtained from aspiration, especially from the small joints of the foot, a few guidelines for the use of synovial fluid are in order:

• Often, only two drops of fluid, one for microscopy and one for culture, are necessary.

• Do not discard the small amount of fluid remaining in the needle or its hub. This may be enough to make the diagnosis.

• If only a small amount of fluid is available, the preferred order of analysis is culture, and then crystal examination, Gram stain, and cell count. Any other studies can then be performed if sufficient fluid has been obtained.

Radiographic changes, such as joint erosion, occur long after the diagnosis of gout is made and therefore may not help in diagnosis of the acute gout attack (Figs. 3–3 to 3–6).³⁷

Treatment

Strategies for managing gout vary, depending on the acuity of the disease. For the patient who has had three or fewer attacks, with recovery between attacks, treatment is aimed at decreasing the pain and inflammation during the acute attacks. Plasma urate concentrations are not treated at this point in the disease as most patients do not go on to develop chronic gout. The American College of Rheumatology (ACR) recently released guidelines for the treatment of gout and the following recommendations are based on these guidelines.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment. Indomethacin at the dose of 50 mg every 6 to 8 hours is usually effective. This dose is maintained until the pain and swelling decrease, and is then reduced to 25 mg every 6 to 8 hours until the attack resolves completely. Ibuprofen, initially 800 mg every 6 to 8 hours, or naproxen, initially 500 mg twice a day, are alternatives. The ACR guidelines do not recommend one particular NSAID as first line therapy, but did propose that the NSAID chosen should be continued until complete resolution of the gout attack. The provider should also be cautious in aggressive NSAID use in people with renal impairment, people who have gastrointestinal (GI) side effects, or other contraindications.

Colchicine has been used since the early 1800s to treat gout. Although it is effective, the side effects of vomiting and diarrhea limit its utility. Intravenous rather than oral administration decreases the GI side effects, but may lead to local tissue necrosis if the medication extravasates. Now that effective NSAID therapy is available, the use of colchicine in the acute care setting should be reserved for patients who do not respond to or cannot tolerate NSAIDs. Colchicine is administered orally, 1.2 mg dose initially with 0.6 mg given 1 hour later. Subsequent dosing of 0.6 mg daily or two times a day is prescribed until the attack resolves. Decrease the dose in patients with renal insufficiency. Intravenous colchicine should be given only in conjunction with a consultant.

Intra-articular steroid injection may be performed, but the clinician should avoid its use if there is any doubt about the diagnosis, especially if septic arthritis is a consideration. The ACR panel recommended a minimal starting dose of oral prednisone at 0.5 mg/kg per day for a duration of 5 to 10 days.

Other analgesics, such as acetaminophen and opiates, may further alleviate pain, and should not be forgotten. Finally, eliminate any medications such as diuretics that precipitated the attack. The sooner treatment is initiated after an attack begins, the better the response.

The management of chronic gout is beyond the scope of this chapter; however, the emergency physician should be familiar with the medications used to treat this condition, and their side effects.

Allopurinol decreases serum urate concentration. Approximately 5% to 10% of patients develop hypersensitivity reactions, usually a pruritic maculopapular rash. A full-blown systemic hypersensitivity syndrome, including fever, eosinophilia, erythema multiforme, and multiorgan–system dysfunction, occurs occasionally and may be fatal. Any patient suspected of having such a reaction should be admitted to the hospital, and the patient’s rheumatologist notified.

Probenecid decreases the serum urate concentration. It decreases the renal excretion of other drugs, such as penicillins, NSAIDs, and dapsone. Aspirin completely blocks the therapeutic effect of probenecid.²² GI side effects and hypersensitivity reactions may occur in patients receiving probenecid. Probenecid should not be started during an acute attack, as it increases urate precipitation during the initiation of treatment, worsening acute gout.

Colchicine may be given prophylactically for up to 9 months following normalization of serum urate levels in a patient with chronic or recurrent gout. Long-term colchicine therapy should only be undertaken by a consultant.

Complications

Patients with long-standing gout have a higher incidence of nephrolithiasis, proteinuria, and hypertension.

Septic arthritis may occur in the same joint as crystal-induced arthritis.^17,38 In these cases, the inflammatory response caused by the joint infection probably leads to precipitation of urate or calcium pyrophosphate crystals and thus an attack of gout or pseudogout. Because the synovial fluid cell counts of patients with crystal-induced arthritis and infectious arthritis are similar, synovial fluid obtained from patients with acute arthritis should always be cultured, even if crystals are seen. Any patient with gout who is systemically ill in the setting of an acute attack of arthritis, or whose arthritis seems worse or different than usual, should have his/her joint fluid cultured and empiric antibiotic treatment started.

Finally, RA and gout rarely occur together, so if a patient with RA presents with what appears clinically to be an acute case of gout, an infected joint should be strongly suspected and arthrocentesis performed.³⁸

Pseudogout

Calcium pyrophosphate dihydrate (CPPD) crystal deposition in joints occurs primarily in elderly patients.³⁹ Although historically this has been called pseudogout, many rheumatologists now refer to this entity as acute calcium pyrophosphate crystal arthritis (alternatively, acute CPP crystal arthritis). It may present as acute monoarticular arthritis or as chronic arthritis (usually complicating underlying OA). CPPD crystals are found incidentally at arthrocentesis in over 40% of patients with OA.⁴⁰

For simplicity, one may want to think of this as gout with only the real difference being in the synovial fluid results. The clinical presentation, diagnostic approach and treatment modalities are the same as gout. The difference is that the synovial fluid will have positive birefringent rhomboid or rod-shaped crystals as opposed to the negative birefringent rod-shaped crystals of gout.

Radiographic studies may be normal, may show changes of OA, or may reveal calcification of cartilage, synovial tissues, and tendons. Calcification of joint cartilage, chondrocalcinosis, occurs most commonly in the hand and knee (Fig. 3–7).

Although any joint may be involved, the knee is most commonly affected, followed by the wrist, shoulder, ankle, and elbow joints. Pain and inflammation are severe, and develop rapidly over 6 to 24 hours. As with gout, overlying erythema is common, and the patient may be febrile. Patients with subclinical cognitive impairment may become confused, and sepsis must be ruled out in such cases.

Over 90% of cases affect a single joint and involvement of more than a few joints is rare and should prompt a search for another etiology for the patient’s arthritis.²² Joint trauma, concurrent severe illness, surgery, initiation of thyroid replacement therapy, or other systemic diseases such as Wilson disease, hemochromatosis, and hyperparathyroidism may precipitate attacks. Most attacks, however, are idiopathic.

Diagnosis is made by joint aspiration, which reveals:

• Rhomboidal or rod-shaped CPPD crystals, which are weakly positively birefringent and appear blue when oriented parallel to the axis of slow vibration marked on a polarizing microscope’s compensator. As with gout, the presence of crystals does not rule out infection, and all synovial fluid specimens must be sent for a culture and Gram stain.

• Bloodstained or cloudy synovial fluid.

• Decreased viscosity.

• Elevated leukocyte count, occasionally WBC counts >50,000/mm³, primarily neutrophils. However, cell counts vary more than in gout and may be much lower.

Treatment

Treatment of acute pseudogout is similar to treatment of acute gout. NSAIDs are effective, but may have gastric and renal toxicities. Dosage is as noted previously for gout. Other analgesics, such as acetaminophen and opiates may be necessary.

Complete joint drainage by aspiration is therapeutic as well as diagnostic, and may resolve the attack of pseudogout. Intra-articular steroid injection may be performed after infection is ruled out.

Any underlying illnesses that triggered the attack should be treated. The affected joint is mobilized as soon as the patient can tolerate. Ice has been found to relieve the symptoms of acute gouty arthritis significantly better than warm packs used for other forms of arthritis.³⁶ Because patients are usually elderly and have preexisting OA, prolonged immobility can rapidly lead to permanent functional disability.

Hydroxyapatite Crystal Arthropathy

In addition to urate and calcium pyrophosphate crystals, hydroxyapatite crystals can also provoke an acute arthritis. Apatite crystals are found in nearly half of osteoarthritic joints, usually in combination with CPPD crystals.

Although hydroxyapatite crystals usually are incidental findings at arthrocentesis, they can occasionally provoke an acute inflammatory reaction resembling gout or pseudogout. The apatite crystals may also lead to rapid erosion of joint cartilage in the setting of OA, with pain and loss of joint function.

The crystals may be needle-shaped or may coalesce into larger irregular clumps or rods; they may be difficult to identify on microscopy. Apatite crystals are often found with CPPD and urate crystals in the setting of gout or pseudogout. In these cases, the role of the apatite crystals is unclear.

NSAIDs, analgesics, and referral to an orthopedic or rheumatologic specialist are indicated if apatite arthropathy is suspected. Joint aspiration may be therapeutic as well as diagnostic. A consultant may perform intra-articular steroid injection once infection is ruled out.

OA is the most common form of arthritis in older patients, causing pain that can significantly reduce function and the quality of life. It is more commonly found in women than men. OA is such a common condition at midlife and in elderly patients that it is almost safe to say that it is ubiquitous.

Pathologic Features

The pathologic features of OA include the sum of a dysregulation of tissue turnover in weight-bearing joints. The cartilage is broken down over time due to mechanical forces and because if its avascular nature, is difficult to repair. Focal areas of damage to articular cartilage occur, and there is an increased activity of subchondral bone. Although historically it has been thought of as a solely cartilage repair problem, recent research suggests that there are a host of factors involved including biomechanical, genetic, and immunologic components that contribute to the formation or OA.

Risk Factors

Risk factors for OA include age, family history, obesity, joint trauma, abnormal joint shape, occupational activity, and the female gender. Obesity is a major risk factor, particularly for OA of the knee in women. Weight loss can prevent the onset of symptomatic OA, delay radiographic progression, and lessen symptoms.

Reproductive and hormonal variables also predispose to generalized OA in women. Genetic factors contribute, as there is a strong familial link, particularly in women. Trauma and overuse are other major causes of joint involvement, particularly in the knee and in the hand. Repeated minor trauma may cause increased OA with occupational overuse. Recreational overuse or habitual physical activity is not associated with symptomatic knee OA; however, there is an increased risk of this disorder in elite athletes.

Clinical Presentation

Pain is undoubtedly the most prominent and important symptom of OA. This pain typically gets worse with the duration and intensity of activity. The most commonly affected joints include the thumb base, distal interphalangeal (DIP), knee, hip, first metatarsal phalangeal, and the spinal apophyseal. Joints may be affected in isolation or as part of primary generalized OA. Symptoms of OA include use-related exacerbations of pain, stiffness with inactivity (gelling) that improves in minutes, loss of movement, feelings of instability, and functional handicaps.⁴¹ The difference between the stiffness in OA and RA is that the stiffness in OA gets better in a few minutes, whereas the stiffness in RA can sometimes take up to an hour to show any improvement. Ultimately, joint deformity results as the disease progresses. The severity of radiographic changes is associated with an increased likelihood of pain, although severe joint damage can be asymptomatic.

On examination, the patient has tender spots around the joint margin, and there is firm swelling of the joint margin. The patient has course crepitus most easily identified during passive movements and signs of mild inflammation. Movements are painful and restricted, and there is tightness in the joint. The hip joint is most likely to be painful, and the hand is least likely.

Hand Osteoarthritis

The first carpometacarpal joint and the distal and proximal interphalangeal (PIP) joints are the most commonly affected joints. Patients have pain and bony swelling at the base of the thumb with Heberden nodes (small bony growths found at the DIP joints). Loss of function in the hands may be quite marked in the beginning, as the joints go through phases of inflammation, perhaps lasting for months. The long-term outlook for function, however, is generally good despite residual bony deformities.

Knee Osteoarthritis

Symptoms tend to have a gradual onset and deteriorate with time. Mechanical abnormalities, obesity, and poor quadriceps muscle strength contribute to progression and associated disability. The knee may be affected in any or all of its three compartments (medial and lateral tibiofemoral and patellofemoral), but the medial compartment is more frequently affected than the lateral. Joint-line pain, tenderness, and loss of articular cartilage lead to joint-space narrowing and gradual varus deformity. OA of the patellofemoral joint contributes to retropatellar crepitus and pain, particularly when going up and down stairs and slopes. In approximately 15% to 20% of patients with knee OA, there are effusions that may be long-standing and result in synovial cyst development, particularly in the popliteal fossa (Baker cyst). Medial extension along the anserine bursa is also common. Baker cyst may occasionally rupture and mimic deep vein thrombosis, with pain, swelling, and inflammation in the calf and lower leg.

Hip Osteoarthritis

Hip OA often occurs in the elderly population and tends to be more common in men. Pain is characteristically present in the groin. Involvement may be unilateral or bilateral. Symptoms of pain or tenderness around the pelvic girdle region (e.g., in the buttocks or lateral aspect of the thigh) may indicate OA of the hip, but other possibly coexisting conditions should be considered, such as referred pain from the spine or trochanteric bursitis. In the early stages, patients may experience pain with extremes of motion, with internal rotation usually being the earliest movement affected. Patients with advanced disease may experience referred pain in the knee.

Diagnosis

The diagnosis is largely clinical, but is supported by the findings on radiographs (Figs. 3–8 and 3–9). Radiographs are normal early in the disease, but narrowing of the joint space develops as the disease progresses. Ninety percent of individuals older than 40 years have radiographic changes characteristic of OA; however, only 30% have symptoms. Other x-ray features include subchondral sclerosis, marginal osteophytes, and joint narrowing. Laboratory features in arthritis are nonspecific and are generally not helpful in making the diagnosis. If arthrocentesis is performed, the fluid results should be noninflammatory in nature. There should be a low WBC count (<2000), without crystals, and it should appear as transparent (not cloudy) yellow.

Treatment

The aim of treatment in OA is to relieve pain and allow the patient to be as active and independent as possible. The drugs used in the management of OA are simple analgesics to relieve pain and NSAIDs to reduce symptoms. The ACR recently released treatment guidelines based on location of the arthritic joint. In hand OA they recommend thermal modalities, topical and oral NSAIDs, and tramadol. For knee and hip the recommendations are the same but also include aerobic exercise and for patients who are obese, weight loss.⁴² Intra-articular corticosteroids provide local relief of symptoms and also can be added to the treatment regimen of patients with knee and hip OA. Exercise therapy, hydrotherapy, and walking aids and appliances are all adjuncts that are used in this disease process.⁴¹ Oral glucosamine and chondroitin may possess some degree of efficacy.⁴³ A Cochrane Review of glucosamine treatment for OA showed that patients may get a small reduction in pain and improvement in function, but that the results were marginal at best. The ACR did not recommend the use of either glucosamine or chondroitin for knee OA. Ultimately, many patients need joint replacement surgery, particularly in cases of advanced hip and knee OA. Indications for surgery include the presence of significant night pain or rest pain, but must be individualized.

RA is an autoimmune disease that affects approximately 1% of the world’s population. It is characterized by a symmetric, progressive polyarthritis. Unlike OA, RA often has systemic manifestations. Although the cause of RA is unclear, and its course in each patient can be unpredictable, the symptoms can range from mild to tremendous pain, suffering, and disability.^44,45

RA has widely varying onset, severity, and progression. It is twice as common in women as in men, and has its usual onset in the fourth and fifth decades of life. It is thought that there is a genetic predisposition to RA. Prevalence of RA increases with age. (Note: Juvenile rheumatoid arthritis [JRA] is a distinct syndrome and is discussed separately.)

RA is characterized by an autoimmune attack on synovial tissue, leading to marked (up to 100-fold) proliferation of synovium. Adjoining tissues are affected by this synovial neoplasia, including cartilage, bone, ligaments, tendons, and bursae. This inflammation, combined with physical stress, destroys joint structure and function. In addition, extra synovial manifestations may affect almost any organ.

A basic understanding of the pathophysiology of RA allows the emergency physician to suspect the disease in the undiagnosed patient, and to tailor treatment and detect systemic complications in all patients with RA.

The emergency physician will encounter two main groups of patients with RA: (1) those who have not yet been diagnosed as having RA and present with polyarticular arthritis; and (2) those who have been previously diagnosed and present with an acute flare, systemic manifestations of the disease, or an unrelated medical problem.

New-Onset Rheumatoid Arthritis

Although etiology of RA is unclear the current thinking is that it is a combination of environmental and genetic factors. Onset is usually, but not always, articular, symmetric, and gradual. The variability of symptoms and progression in RA often makes initial diagnosis difficult: onset may be over weeks to months, duration of illness may last weeks or decades, and severity may vary from mild arthritis to crippling deformity. It should be noted that the initiation of RA probably begins years before any clinical symptoms are apparent.⁴⁶ This is important to realize, because early referral to a rheumatologist and initiation of therapy can greatly improve long-term outcomes.

RA is an autoimmune disease, and 70% to 80% of patients have rheumatoid factor (RF), an immune complex, circulating in their serum. RF is not specific for RA, and may be found in other diseases. A new test for anti-citrullinated protein antibodies (ACPA) shares the same sensitivity as rheumatoid factor, but has improved specificity. In patients with a positive RF and ACPA, the sensitivity of making a laboratory diagnosis is further improved.⁴⁷

The diagnosis of RA is still based primarily on clinical criteria. The ACR has a scoring system that includes number of joints involved, RF and ACPA, CRP and ESR, and duration of symptoms. The higher the score the more likely the patient has RA. The classification system requires observation of the patient over time (at least 6 weeks), so the initial diagnosis of RA is unlikely to be made in the acute care setting. The goal in the acute care setting is, therefore, to suspect rheumatologic disease, alleviate any acute symptoms, rule out other urgent/emergent conditions, and then refer the patient to the appropriate provider for definitive diagnosis and long-term management. The emergency physician should:

• Rule out joint infection with mono- or oligoarticular involvement (see later discussion).

• Attempt to differentiate RA from other polyarthropathies, such as OA and gonococcal arthritis.

• Arrange for baseline laboratory studies, including ESR, complete blood count (CBC), and creatinine level. RF and ANA tests may also be requested.

• Rule out serious extra-articular disease.

• Treat symptoms of pain and inflammation.

Any patient suspected of having RA should have a primary care provider, as many of these patients will develop systemic comorbidities, such as pulmonary or renal disease. Specialty referral may be deferred to the primary care provider if the patient is not severely ill. Studies suggest that patients with RA have less morbidity when a rheumatologist is involved in their care.

Treatment

A variety of agents with varying therapeutic and side effects are used, and must often be combined for optimal results (Table 3–7). A treatment regimen should be tailored for each individual patient. Therapy with agents other than NSAIDs, and perhaps a brief course of steroids, should only be undertaken after consultation with the physician who will be following the patient.

Nonsteroidal Anti-inflammatory Drugs

NSAIDs are used to treat symptomatic pain and inflammation of RA, and should be used if they are not contraindicated. They can adversely affect renal function and may exacerbate or cause peptic ulcer disease. Numerous agents are available, with variable dosage and cost. Unfortunately, a given patient’s therapeutic response to each drug is not predictable, and neither are the exact side effects the patient will experience. If a patient with known RA presents with pain, the physician should ask whether the patient already knows which agent is most effective.

Corticosteroids

These drugs may be given systemically or by local injection. Systemic corticosteroids (e.g., methylprednisolone, 100–1000 mg/d for 3 days) can improve the symptoms of an acute RA flare. However, systemic corticosteroids do not prevent joint destruction and thus have no sustained benefit for patients with RA. They also have serious side effects on many organ systems. Chronic use of systemic corticosteroids (e.g., prednisone, 5–7.5 mg/d) should be limited to severe, unremitting disease; and should be discussed with a consultant before initiation.

Local corticosteroid injection decreases symptoms of acute inflammatory synovitis. Joint infection must be ruled out prior to administration, particularly if the flare is mono- or polyarticular.

Disease-Modifying Antirheumatic Drugs (DMARDs)

DMARDs are the mainstay of treatment in RA. Unlike corticosteroids, DMARDs may alter the destructive course of RA. For this reason, and despite the potential for toxicity, these agents are recommended early in the course of RA. The most commonly used DMARD in the initial phase of treatment is methotrexate. DMARDs are expensive, and require several weeks of use for maximal benefit. They are usually combined with NSAID therapy, and sometimes with corticosteroids. One-third of patients take more than one DMARD (Table 3–8).⁴⁴

DMARDs have the potential for severe side effects, and their use requires close follow-up and careful dose titration. Initiation of DMARD treatment without consultation is beyond the acute care scope of practice. Because patients may present with iatrogenic complications, the emergency physician should have some familiarity with the major agents used and their side effects.

Other Therapeutic Modalities

Other therapeutic modalities for the treatment of RA include:

• Joint immobilization or bed rest, or both; these may be useful for patients with an acute flare, but joint rest must be weighed against the effects of deconditioning.

• Physical therapy.

• Reconstructive surgery; this is sometimes necessary to correct deformities, particularly in the hand.

Preexisting Rheumatoid Arthritis

The goals in the acute care setting are to treat the patient’s pain and inflammation, limit tissue destruction, and improve daily functioning. These patients are often on immunosuppressive drugs, which predispose them to infections and may obscure signs of serious infection. Both RA and the medications used to treat it may cause systemic complications.

Articular Disease

Usually, symmetric and progressive joint deterioration are seen, with exacerbations and remissions over the course of the disease (Table 3–9, Figs. 3–10 and 3–11). Function is worse after immobility or sleep and improves with activity during the day. Patients report morning stiffness, usually lasting more than 30 minutes, with a median duration of 1.5 hours.

Clinical findings include pain in the affected joints, both at rest and with motion, along with joint swelling, warmth, and tenderness. Erythema may be present with acute onset or flare; if present, the physician should consider infection. Pain, inflammation, and disuse atrophy of muscles lead to progressive functional impairment and loss of range of motion. Radiologic signs of soft-tissue swelling, symmetric joint-space narrowing, and osteopenia of adjoining bones are present.

The “rheumatic hand” is characteristic: the (PIP), metacarpophalangeal (MCP), and wrist joints are inflamed, whereas the DIP joints are spared.

Initial treatment is with NSAIDs and modification of activity. Rest, splinting, and preferential use of large rather than small joints (e.g., carrying a bag on the shoulder rather than in the hand) can delay joint destruction. DMARDs are added, with consultation, for progressive disease.

Acute Rheumatoid Arthritis Flare

In this presentation, the patient has acutely increased synovial inflammation with variable systemic and constitutional symptoms. Joint involvement is symmetric, usually with six or more painful, tender, swollen joints. Morning stiffness worsens, typically lasting over 1 hour. ESR >30 mm/h and elevated CRP levels are often present.⁴⁸

The immediate goal of treatment is alleviation of the acute pain and inflammation, followed by prompt referral to the patient’s primary care provider or rheumatologist. Joint infection must always be considered, particularly with mono- or pauciarticular flares (see later discussion).

Bed rest may be sufficient in some patients. NSAIDs are prescribed unless contraindicated. The patient should be referred promptly to a specialist for DMARD treatment.

A systemic steroid bolus (e.g., methylprednisolone, 100–1000 mg/d for 3 days), given after consultation, can help control a severe, generalized flare. Some patients may require up to 1 month of daily, low-dose systemic steroid therapy. Local steroid injection into the most acute joints, after infection is ruled out, can decrease local inflammation. The patient’s rheumatologist or primary care provider generally performs injection.

Finally, the emergency physician should be alert for signs of new systemic disease, either rheumatic or iatrogenic.

Septic Rheumatic Joint

Patients with RA are at increased risk of joint infection as a result of inflammation and immunosuppression. Furthermore, anti-inflammatory and immunosuppressive medications may suppress clinical signs of infection and delay the diagnosis.

There is no definitive test or finding, other than a positive synovial fluid Gram stain or culture, which can diagnose a septic joint in the setting of rheumatic inflammation. Unfortunately these two entities can present in very similar ways, and given the high morbidity of septic arthritis, the clinician should have a low threshold for performing arthrocentesis when septic arthritis is a possibility. A number of findings can guide the clinician’s diagnosis and treatment decisions.

Joint infection is usually monoarticular. Diagnosis is much more difficult if the infection is polyarticular. Infection may be indicated by pain greater than the patient’s usual flare, fever, and systemic toxicity. Polyarticular infection is usually asymmetric, because of hematogenous spread.

Diagnosis necessitates joint aspiration for culture, Gram stain, and cell count. The physician must ensure that a specimen of synovial fluid is obtained for culture before starting antibiotic therapy.

Empiric antibiotic treatment should be started if clinical suspicion is high, or if the aspirate demonstrates positive Gram stain; leukocyte count >50,000 mm³ (unusual in RA, but possible); or PMNs >90%. Blood and other specimens, such as urine, should be cultured to increase the yield of any infecting organism, and to search for a site of initial infection.

Antibiotic selection should be based on Gram stain results. Empirically, vancomycin and a third generation cephalosporin like ceftriaxone would be good initial choices. This will not cover special cases as in prosthetic joints or pseudomonal infections. Because of the high rate of morbidity of septic arthritis, consultation with an infectious disease specialist is highly recommended in these instances. Empiric treatment without the proper diagnostic workup may commit the patient to an unnecessary course of antibiotics and may delay initiation of appropriate anti-inflammatory therapy.

Popliteal (Baker’s) Cyst

Popliteal cysts are common because of the synovial proliferation that characterizes RA. A cyst may rupture spontaneously or as a result of physical activity, leading to acute calf pain and swelling. The most difficult task facing the emergency physician is ruling out an acute deep venous thrombosis (DVT). Heparinization following a misdiagnosis of DVT can lead to continuing hemorrhage into the calf, with subsequent compartment syndrome.

Ultrasound is the least invasive test and is widely available. Venography or a contrast arthrogram is rarely necessary. Note that a crescent-shaped hemorrhage below either malleolus is characteristic of a ruptured cyst and not a DVT.

Rest, elevation, and analgesia are usually all that is required. Intra-articular corticosteroid injection (after consultation) may help alleviate symptoms before and after rupture. Actual compartment syndrome is rare, but must be treated immediately to prevent permanent disability. Residual calf swelling usually lasts several weeks, but may persist over 3 years.

Atlanto-Axial Subluxation

Although spinal arthritis is common in RA, actual C1-C2 subluxation is uncommon, with an incidence of approximately 5%, overall, in RA. The incidence increases with increasing severity of the patient’s overall disease. Actual cord or vascular compromise is rare, but it does occur and can be iatrogenic, resulting from manipulation, such as intubation.

Symptoms and signs of cord compression include severe neck pain, usually radiating to the occiput; extremity weakness, which may be upper or lower, or both (often difficult to assess because of the patient’s severe and long-standing arthritis); numbness or tingling in the fingers or feet; loss of vibration sense, with preservation of proprioception; “jumping legs,” caused by spinal reflex disinhibition; and bladder dysfunction. Patients may also have vertebral artery insufficiency, including syncope or vertigo.

An atlanto-dens interval >2.5 mm in adults and >5 mm in children is diagnostic. Although an emergent computed tomography (CT) can help if cord compression is suspected, an MRI will give much more information and is the test of choice.

Apply a hard cervical collar and refer the patient for traction and fusion if there are signs of neurologic or vascular compromise. Treatment is generally medical until there are signs of cord compression, at which point surgical options become the mainstay of therapy. For the emergency physician, emergent airway management is of particular importance. The clinician should avoid any aggressive airway maneuvers in patients with signs of RA, or a history of RA, if at all possible.

Systemic Disease

RA may affect nearly any organ. Systemic disease is common, and may be life threatening. Systemic complications may be caused by the primary rheumatic disease process, a medication, or a combination of both. Signs of serious systemic disease may be missed, particularly in the patient in whom the diagnosis of RA has not yet been made. The organs that are most often affected include the lungs, heart, liver, and spleen. Blood vessel involvement is also common.

Pulmonary Disease

Mild and asymptomatic pulmonary disease is common in RA. Patients may have pulmonary nodules, pleural effusion, or fibrosis. They occasionally present with restrictive, chronic obstructive pulmonary disease-like symptoms. Acute obliterative bronchiolitis is uncommon, but may be fatal; it is unclear if it is caused by the RA itself, or by the medications (DMARDs) used to treat RA.

Cardiac Disease

Pericarditis is the most common cardiac disorder. Usually, asymptomatic chronic inflammation is detected only at autopsy, but inflammation may be acute and constrictive. Rheumatic myocarditis and endocarditis occasionally occur. With endocarditis, the physician must rule out bacterial endocarditis; these patients are predisposed to bacteremia as a result of open wounds and immunosuppression.

Hepatic Disease

Hepatitis is often subclinical but may be overt. Liver abnormalities often occur as a result of drug side effects.

Spleen

Felty’s disease is defined as RA that occurs in association with an enlarged spleen and leukopenia. It usually occurs in a patient with long-standing RA, including rheumatoid nodules and marked joint deformity. Patients are subject to neutropenia and severe bacterial infections, as well as thrombocytopenia. Any patient suspected of having Felty’s disease requires emergent consultation, admission, and aggressive treatment of any suspected bacterial infections. Treatment of RA may improve the manifestations of Felty’s disease, but plasmapheresis or splenectomy may be required.

Blood Vessel Disease

Small vessel inflammation is integral to the pathophysiology of RA. Clinically diagnosable vasculitis may be chronic or acute. With chronic vasculitis, leg ulcers and nail fold infarcts are common. Distal sensory neuropathy may also be seen. Acute systemic vasculitis is rare and usually occurs in patients with long-standing disease.

Juvenile idiopathic arthritis (JIA) is the current terminology for JRA (or Still disease). It may develop at any age, and is characterized as a chronic synovial inflammation without a known cause. No laboratory tests are diagnostic of this condition. The clinical manifestations include spiking fever for 3 days or greater, a salmon-pink rash, generalized lymphadenopathy, and hepatomegaly and/or splenomegaly.⁴⁹ In 50% of patients, the temperature is over 40°C and there is polyarticular involvement. The evanescent pink rash blanches with compression and may be pruritic, and thus confused with a drug-sensitivity reaction. The polyarthritis seen initially is a migratory arthritis that eventually becomes a persistent arthritis (Fig. 3–12). This is a very difficult diagnosis to make, and the emergency clinician—rather than trying to make the diagnosis—should focus on excluding more emergent causes of arthritis (i.e., Lyme disease, infection, avascular necrosis, osteomyelitis, tumors, Kawasaki disease, etc.) and then refer the patient to a rheumatologist.⁴⁹

In a similar fashion to adult RA, the treatment of JIA has made many advances.^50–53 Methotrexate, intra-articular corticosteroid injections, and the biologic-modifier etanercept (Enbrel) are all being used to treat JIA. Table 3–8 delineates the side effects of these agents. In the acute setting NSAIDs may be used while awaiting rheumatology follow-up. These patients should be referred to a rheumatologist early in the disease course.

Although SLE is not usually thought of as a joint disorder, inflammatory arthritis occurs in most patients. SLE is, like RA, an autoimmune disorder that has a variable expression in each individual patient. SLE may also be triggered by medications, such as procainamide.

Clinical Presentation

SLE follows a relapsing and remitting course. It typically affects multiple organ systems, with different systems affected at different times over the course of the disease. Onset early in life is associated with more severe disease than is late onset.

Arthralgias and arthritis are commonly present at the onset of SLE in 75% and 50% of patients, respectively. Over the course of their disease, over 90% of patients suffer musculoskeletal involvement. Symmetric synovitis affecting the hands, wrists, and knees is typical and may be difficult to differentiate clinically from RA. The arthritis can vary greatly in duration from days to months.⁵⁴ Bone destruction is not usually present in SLE, unlike RA. The combination of synovial inflammation and tendonitis along with chronic corticosteroid usage can result in tendon and ligament damage. Other musculoskeletal structures are often affected. Typical musculoskeletal deformities are summarized in Tables 3–10 and 3–11.

Although musculoskeletal involvement in SLE is generally symmetric, it is not always the case. However, if only a single joint is involved, or if one joint is much more acutely inflamed than others, intra-articular infection should be ruled out. The clinician should also be on the lookout for avascular necrosis, because it can occur with SLE.

SLE can affect any organ in the body. Although a complete discussion is beyond the scope of this chapter, the provider should be alert for signs of systemic illness in any patient presenting with inflammatory arthritis (Table 3–12).

A number of laboratory abnormalities can occur in patients with SLE, including autoantibodies, but most tests are not available emergently and no single antibody is completely sensitive or specific for SLE. If an arthrocentesis is performed, the fluid should be consistent with inflammatory results. The ESR is usually elevated, but unfortunately does not correlate with clinical disease activity. Serum IgM-RF is present in up to half of patients with SLE.

Treatment

Systemic corticosteroids are the mainstay of treatment for SLE. Both low-dose (<0.5 mg/kg/d) and high-dose (1.0 mg/kg/d) regimens of prednisone are used, depending on the lupus manifestation being treated. Unlike RA treatment, chronic corticosteroid usage is often necessary for SLE. The authors prefer alternate day therapy as it has less side effects. In the acute care setting, NSAIDs are also used. As with RA, antimalarials and immunosuppressive drugs are commonly prescribed, but this should be done by the specialist. The physician should remember that all these agents are immunosuppressive, and that patients are therefore more susceptible to serious infections. Furthermore, the immunosuppressive medications may mask signs of infection.⁵⁵

Arthritis is a sequela to several common viral infections. The following is a discussion of arthritis secondary to viral hepatitis, HIV, rubella, and parvovirus.

Hepatitis

In hepatitis B virus infection, during the 1- to 3-week prodromal phase, polyarthritis may be accompanied by moderate fever and, sometimes, by an urticarial or a maculopapular rash. Usually, the small joints are affected symmetrically with arthralgias or arthritis. Aminotransferase levels are usually elevated at this stage, and hepatitis B surface antigen is detectable. Hepatitis C virus may also induce rheumatologic symptoms. In one study, arthralgias were found in 9% of patients, whereas arthritis was found in 4%.⁵⁶ The arthritis presents as either a symmetric polyarthritis (very similar to RA) or a mono-oligoarthritis.⁵⁷

Treatment remains controversial. Corticosteroids and NSAIDs are usually avoided due to their potential to worsen the infection or cause hepatotoxicity. In some cases of persistent arthritis, it may be helpful to treat hepatitis B and C virus infection with interferon.

Human Immunodeficiency Virus

Several patterns of arthropathy have been described in patients infected with HIV, including brief episodes of severe arthralgia, acute episodic oligoarthritis, and persistent symmetric polyarthritis. Arthritis may be an early feature of AIDS. Arthritis associated with AIDS infrequently presents with a fever, but the picture may be confounded by coincidental infection and the clinician should have a low threshold for arthrocentesis in this immunocompromised patient population. Both a Reiter-like syndrome and a Sjögren-like syndrome occur with increased frequency in this disease.

Most patients with HIV who exhibit rheumatic complaints are severely ill as a consequence of other clinical features of HIV. These patients may not tolerate many of the conventional medications used for arthritis. In general, most patients exhibit a mild-to-severe rheumatic disorder that is self-limiting and experience a good response to a combination of analgesics and NSAIDs.

Rubella

Arthralgias and arthritis are reported to occur in up to 50% of infected women as compared with up to 6% of men with this disease. This is an uncommon presentation in children with rubella. Rubella vaccine may cause symptoms in 15% or more of recipients. Joint symptoms usually start within 1 week of the skin rash in natural infection or within 10 to 28 days after immunization. Finger, wrist, elbow, hip, and knee as well as toe joints are most frequently affected, usually asymmetrically. Sudden onset of symptoms is characteristic. Arthralgia and joint stiffness, as well as arthritis, may be accompanied by tenosynovitis and even carpal tunnel syndrome. Usually, both the natural and the vaccine-induced arthritis resolve without residua within 30 days; however, some patients experience recurrent arthralgias and episodes of arthritis for up to 2 years and sometimes even longer. There are no abnormal laboratory findings in analysis of synovial fluid.

Parvovirus

Parvovirus B19 is most commonly associated with erythema infectiosum (fifth disease) in children or aplastic anemia.⁵⁸ Arthropathy occurs in up to 5% of children infected with parvovirus B19; however, less than 50% of patients have evident joint swelling.

In adults, a rheumatoid-like polyarthritis that is occasionally persistent may occur. The arthropathy is more common in adults than children, occurring in 60% of patients. It is characterized by a symmetric polyarthropathy with pain, swelling, and morning stiffness in the affected joints. The finger joints, wrists, and knees are most often affected. It presents very similarly to RA. Although the median duration of joint symptoms is approximately 10 days and most resolve by this time; rarely, the pain and stiffness may persist longer.

A patient with acute parvovirus arthritis exhibits significant levels of IgM and IgG antibodies to parvovirus B19. Treatments with immunoglobulin preparations have been reported to be successful in patients with parvovirus B19-induced red cell aplasia. NSAIDs have been used to treat myalgias and arthralgias.

Lyme disease is caused by the spirochete Borrelia burgdorferi (B. burgdorferi) and is transmitted by the Ixodes tick.⁵⁹ Lyme disease is endemic in the northern Atlantic states, the upper Midwest, and the Pacific Northwest. Lyme arthritis is differentiated from other forms of arthritis due to the characteristic joint involvement and nearly universal correlation with an immune response.⁶⁰

Clinical Presentation

The clinical progression of Lyme disease is generally described in three stages. Dissemination of B. burgdorferi, the causative agent, is accompanied by fever and migratory arthralgia, with little or no joint swelling, but frank arthritis appears weeks or months later. Arthritis is usually episodic, affecting primarily large, but also some small joints.

Stage 1 (Early Infection)

The first sign of infection occurs within 3 to 30 days of the tick bite. It is characterized by erythema chronicum migrans. This rash occurs in 60% to 80% of patients and usually fades within 3 to 4 weeks regardless of the treatment, although the lesions may recur.⁵⁹ Other signs and symptoms include fatigue, malaise, fever, arthralgia, headache, sore throat, and lymphadenopathy.

Stage 2 (Disseminated Infection)

This stage of infection begins weeks to months later and is associated with cardiac, neurologic, skin, and musculoskeletal abnormalities. Predominant symptoms in stage 2 are debilitating fatigue and malaise. Fluctuating symptoms of meningitis accompanied by facial palsy and peripheral radiculopathy are the usual pattern. At this stage, musculoskeletal pain is common and migratory in joints, bursae, tendons, muscles, and bones. Pain usually occurs without joint swelling and lasts hours or days at a given location. Secondary skin lesions resembling erythema chronicum migrans occur in approximately 50% of patients.

During stage 2, approximately 70% of patients develop brief attacks of asymmetric monoarticular or oligoarticular arthritis, primarily in large joints.⁶¹ The knee joint is affected in approximately 80% of these patients. These attacks occur within 2 weeks to 2 years (average 6 months) after the onset of the disease, and usually follow intermittent episodes of arthralgia or migratory musculoskeletal pain. Attacks involving the periarticular structures, including the peripheral enthesitis (i.e., tendons insertion into bone), have been reported.

Stage 3 (Late Infection)

This stage occurs in approximately 60% of untreated patients. Of the patients that reach this stage, only 10% will suffer with arthritis.⁶¹ In patients who do have arthritis, the duration of attacks increases to months, but individual attacks may be separated by remission of months or even years. Synovial lesions may show villous hypertrophy and mononuclear infiltrate. Chronic arthritis leads to loss of cartilage, subchondral sclerosis, periarticular soft-tissue ossification, bony erosion, osteopenia, osteophyte formation, and even permanent joint disability. In this stage, spirochetes have been found in joint fluid, synovial tissue, and in blood vessels, mimicking endarteritis obliterans.

Diagnosis

The diagnosis may be difficult in early, disseminated stages before seroconversion, unless one identifies the characteristic erythema migrans lesion. The majority of patients (80%) have joint involvement of some type usually after the skin lesion of erythema migrans.⁶⁰ The diagnosis is largely based on the clinical picture, including exposure to an area of endemic disease and a prompt response to antibiotic therapy. Serological testing is often times unreliable; and therefore, if the ELISA test is positive, then the clinician should proceed to the Western blot because it is more specific. If the clinical suspicion is high and the serological tests are negative then treatment should be initiated and the serological testing repeated at a later date. IgG antibodies are almost always present when synovitis is a prominent feature of late Lyme infection and often persist in cases of successfully treated inactive disease. The Western blot method should be used to confirm the presence of antibodies to B. burgdorferi.

Treatment

Prompt treatment of the disease in its early stages is successful in relieving the arthritis process in 90% of patients.⁶² Unfortunately, although these agents cure the underlying infection, Lyme arthritis does not respond to antibiotics. Prophylaxis to Lyme disease can be done in selected groups of patients with a single dose of doxycycline 200 mg. Because the antibiotic choice and duration of treatment depends on the particular patient as well as appropriate disease staging, consultation with an infectious disease specialist is highly recommended (Table 3–13).

The seronegative spondyloarthropathies (SNS) are a group of related disorders that lead to inflammation and fusion of the SI joint and, in some cases, of peripheral joints.^29,63,64 The term seronegative refers to the lack of IgM-RF in the patient’s serum. Most patients with SNS possess the HLA-B27 antigen, and males are generally affected more often and more severely than females.

This group of disorders is, like RA, characterized by morning stiffness, owing to the inflammatory nature of the disease. Unlike RA, these disorders lack serum RF and rheumatoid nodules, and tend to affect predominantly the axial skeleton rather than the small joints of the distal extremities. These diseases are compared in Table 3–14.

Although each disease has its own characteristics, there is significant overlap between them. As in RA, patients present to the emergency department either with an exacerbation of previously diagnosed disease or with new or undiagnosed disease. With the exception of Reiter syndrome, patients with SNS usually have a subacute presentation. As long as the emergency physician suspects the diagnosis of SNS and refers the patient for timely follow-up, a definite diagnosis of a specific SNS need not be made in the emergency department.

Ankylosing Spondylitis

Ankylosing spondylitis is characterized by inflammation of the SI and intervertebral joints. Inflammation at the sites of ligamentous insertion (enthesopathy) leads to calcification and loss of motion of the joints. It is helpful to differentiate between an inflammatory back pain presentation and mechanical back pain presentation. Inflammatory back pain has no improvement with rest and pain is better with exercise, whereas, mechanical back pain is improved with rest and worse with exercise.

Clinical Presentation

The presence of ankylosing spondylitis is suggested by gradual onset of back discomfort (often dull and difficult to localize), onset before 40 years of age, persistence of discomfort for 3 months or longer, and morning stiffness that improves with exercise. If there is no evidence of Reiter syndrome, psoriasis, or inflammatory bowel disease (IBD, see later discussion), ankylosing spondylitis is the likely diagnosis. Radiographs of the SI joints should show at least some evidence of sacroiliitis. Spinal films show progressive syndesmophytes and kyphosis.

The symptoms of inflammatory back disease are particularly characteristic of ankylosing spondylitis. Some patients continue to have only low back pain related to sacroiliitis, whereas others show progressively more widespread back pain and limitation of motion as a result of involvement of the lumbar, dorsal, and cervical spine. Few patients progress to develop the classic rigid “bamboo” spine. Patients may, however, have involvement to a lesser degree of the dorsal spine and costosternal and costovertebral muscle insertion, causing ill-defined dorsal spine pain and pleuritic-type chest pain. Peripheral joint involvement frequently accompanies the back disease, with hips and shoulders being affected most frequently. Other joints affected are the wrist, MCP, and the MTP joints. Most typically, involvement is in an asymmetric pattern, but in some patients, the polyarthritis is symmetric, making it clinically indistinguishable from RA. Patients may experience a single episode of peripheral arthritis or have recurrent flares.

Other manifestations of ankylosing spondylitis include fatigue, weight loss, and iritis in up to 25% of patients. Acute iritis is more common in HLA-B27–positive than in HLA-B27–negative individuals. Pulmonary fibrosis, particularly of the upper lobe, is associated with cough, dyspnea, and sputum production. Aortic insufficiency caused by fibrosis involving the aortic ring and valve has been recognized for many years. HLA-B27–positive spondyloarthropathies are associated with severe bradyarrhythmias, and these patients may present with symptomatic complete heart block.

Physical examination may initially be unremarkable. With progressive disease, the normal lumbar lordosis is lost, and marked kyphosis of the spine may develop. In advanced disease, the patient develops severe flexion deformities of the lumbar spine, with compensatory (and occasionally primary) flexion of the hips and knees.

Laboratory studies are nonspecific. The ESR is elevated in up to 75% of patients with ankylosing spondylitis, but this does not correlate with disease activity. The HLA-B27 marker is usually present, but it is not readily tested in acute care settings.

Systemic involvement is less common and less severe than in RA. Acute iritis requires ophthalmologic referral for possible corticosteroid treatment. Patients with severe disease may develop restrictive pulmonary disease because of their stooped posture, and occasionally pulmonary fibrosis and cavitation with Aspergillus colonization are seen. Less than 10% of patients with severe ankylosing spondylitis will develop cardiac disease (i.e., aortic incompetence and conduction defects).

The diagnosis of ankylosing spondylitis is based primarily on the history, with typical features of inflammatory back disease and other manifestations, as previously described. Standard criteria for the diagnosis of ankylosing spondylitis include the presence of sacroiliitis. Radiographic changes range from vague loss of definition of the edge of the SI joint with some sclerosis to more definite sclerosis, indistinct margins, erosions, and subsequent fusion. Additional techniques such as radionuclide bone scan, CT scan, and MRI are occasionally helpful in clarifying an uncertain picture.

Treatment

The most effective treatment for ankylosing spondylitis is physical therapy, which attempts to reduce pain, improve function, and prevent the progressive spinal kyphosis that characterizes the disease. Analgesic and anti-inflammatory medications are used to allow the patient to participate actively in physical therapy. NSAIDs, including indomethacin and naproxen, can be effective in decreasing morning stiffness and increasing physical activity. NSAIDs without physical therapy are of little benefit, and any patient seen in the emergency department who is using NSAIDs alone should be informed of this fact and referred to the appropriate provider. Some of these patients will be placed on high-dose steroids but these should not be started without guidance by a rheumatologist. Since the advent of antitumor necrosis factor therapy, the treatment has improved substantially in this condition.⁶⁵

Patients with ankylosing spondylitis should also be knowledgeable about the potential systemic complications, especially uveitis, so that they can recognize them and seek treatment before permanent disability results. Some patients may go on to require surgical options such as joint replacement or fusion.

Reactive Arthritis

Reactive arthritis is triggered by an infection at a distant site.^66,67 The arthritis occurs several weeks after the initial infection, and the infecting organism is not present in the joints at the time arthritis develops. Hence, the arthritis is reactive rather than infectious (e.g., disseminated gonorrhea). It may occur in a previously healthy patient following an episode of infectious enteritis, cervicitis, urethritis, or less commonly, pneumonia or bronchitis.

The original description of reactive arthritis linked this condition entirely to Reiter syndrome, with the presence of arthritis, urethritis, and conjunctivitis. We now realize that Reiter syndrome is only one cause of reactive arthritis.⁶⁷

The mechanism of reactive arthritis remains unclear. Organisms that may cause reactive arthritis include Chlamydia trachomatis, Streptococcus pneumoniae, Salmonella, Shigella, Campylobacter, and Yersinia enterocolitica. HIV has also been implicated. The association of gonococcus and other organisms with HLA-B27–associated reactive arthritis is unclear.

Men are affected more often than women. Approximately 75% of patients with reactive arthritis have HLA-B27. Although rheumatic fever is, in a sense, a reactive arthritis, it is not associated with HLA-B27 and is not included in the group of SNS. The incidence of reactive arthritis following infection with a responsible organism varies but is on the order of 1% to 2% or less.

Clinical Presentation

Reactive arthritis should be high on the list of differential diagnoses whenever a young adult presents with acute arthritis affecting the knees and ankles. It is accompanied by malaise, fever, and weight loss. Another feature is that it is unusual for the upper extremity to be involved.

Acute onset of arthritis occurs 2 to 6 weeks after the inciting infection. Distribution of arthritis is asymmetric, primarily affecting the knees and ankles. Inflammation is centered about the sites of ligament and tendon insertion (enthesopathy), including the Achilles tendon and plantar fascia insertions.

Entire fingers or toes are often swollen, leading to dactylitis, or “sausage digits.” As with the other SNS disorders, low back pain associated with sacroiliitis may occur.

Nonmusculoskeletal manifestations include sterile conjunctivitis, which occurs in approximately 40% of patients. Iritis occurs in up to 5% of patients and may lead to permanent visual impairment and mucous membrane involvement with oral and genital ulcers. These ulcers occur early in the course of the disease and are usually painless; painful ulcers are most often the result of other disorders or superinfection. Cardiac (conduction system and aortic valve) and neurologic (central or peripheral) involvement occurs, but is uncommon.

Diagnosis

The diagnosis of reactive arthritis is mostly clinical. Synovial fluid analysis shows inflammatory cell counts, with leukocyte counts of 500 to 75,000/mm³, mostly neutrophils. HLA testing is useful in making a definitive diagnosis, but is not available on an emergent basis. Radiographs show bony erosion at sites of tendon and fascia insertion. Radiologic sacroiliitis tends to be asymmetric, but may be indistinguishable from the lesions of ankylosing spondylitis.

Treatment

Antibiotics have little effect on established disease process, and this in itself is suggestive that it is triggered by a self-perpetuating inflammatory response.^57,66,67 The arthritis is treated with NSAIDs. Steroids are used in this condition when there is a poor response to NSAIDs. Disease-modifying antirheumatic drugs such as azathioprine and methotrexate have been used in some patients with good results.⁶⁸ Corticosteroid injection of a particularly symptomatic joint may also be performed by a specialist after infection is ruled out. Patients often relapse; however, relapses are not related to recurrent infection. Treatment of a relapse, as described earlier, is primarily with NSAIDs.

Enteropathic Spondyloarthropathy

Up to 20% of patients with IBD (which includes ulcerative colitis or Crohn disease) will develop arthritis.⁶⁷ This arthritis may be peripheral, affecting primarily the ankles and knees, or central, affecting the SI joints. Peripheral arthritis symptoms tend to occur late in the course of IBD, and tend to follow the course of the underlying IBD.

IBD-associated spondylitis is unrelated to the stage or course of the patient’s IBD and may occur before the onset of IBD symptoms. The joints involved are large and small joints, predominantly in the lower limbs. Frequently, there is a tendonitis with inflammation at the insertion of the tendon, which is the hallmark of this disorder. A peripheral arthritis, mainly asymmetric, appears in 17% to 20% of cases of IBD. Although GI inflammation usually occurs first, articular symptoms may precede the intestinal symptoms by months or even years. This is seen especially in Crohn disease. The type of arthritis seen in IBD is an asymmetric additive polyarthritis. Erythema nodosum can be seen in the pretibial area, with the lesions varying from 1 to 5 cm in diameter. One of the key findings in all of the IBDs is that the effusion is disproportionately greater than the pain. Rarely, no bowel signs are present, only fever, arthritis, malaise, and anemia.

The prevalence of Crohn disease has increased during the past three decades to approximately 75 per 100,000 population. The classic triad of Crohn disease is diarrhea, abdominal pain, and weight loss. Peripheral arthritis, mainly articular and asymmetric, appears with an equal gender ratio, as previously indicated. The peak age of this disease is between 25 and 45 years. Large and small joints are involved, predominantly those of the lower limb (most commonly, the knees and the ankles but also the MCP and MTP joints). The arthritis is mainly migratory and transient and usually subsides within 6 weeks, but it may become chronic and destructive. Colonic involvement increases the susceptibility of peripheral arthritis in Crohn disease. Attacks of arthritis may be related temporarily to flares of bowel disease, although this is less pronounced than in ulcerative colitis.

In ulcerative colitis, the prevalence is 50 to 100 per 100,000. Abdominal manifestations of ulcerative colitis are diarrhea and blood loss. The pattern of peripheral arthritis is identical to those seen in Crohn disease, but its prevalence is much lower (5%–10%). The disease onset usually precedes the joint symptoms, but a coincidental onset of joint and abdominal symptoms is not uncommon. In the course of the disease, the temporal relationship between attacks of arthritis and the flares of bowel disease is more marked than in Crohn disease. Joint symptoms are more common in total than in partial colon involvement. Surgical removal of the inflamed colon has a therapeutic effect on joint symptoms.

Treatment of enteropathic spondyloarthropathy should be undertaken after consultation with a rheumatologist or gastroenterologist. Systemic glucocorticoids and sulfasalazine may be indicated, but initiation of treatment of IBD is beyond the scope of acute care practice.

Psoriatic Arthropathy

Fewer than 10% of patients with psoriasis will develop an associated arthritis. Approximately 5% of these patients will have exclusively spinal involvement, another 40% will have both peripheral and axial arthritis, and 20% of the remaining patients have sacroiliitis. Some patients have a symmetric polyarthritis resembling RA; if serum RF is present, the patient is considered to have both RA and psoriasis.

Initial treatment of psoriatic arthritis utilizes NSAIDs. After a firm diagnosis is made, a consultant may initiate methotrexate and antimalarials.

Fibromyalgia is an idiopathic disorder that causes chronic pain and manifests few objective clinical features. The basic pathophysiologic abnormalities in fibromyalgia are unknown, but some evidence suggests a role for abnormalities of the neurotransmitters serotonin, norepinephrine, and substance P. Fibromyalgia is 10 times more common in women than in men, with the typical age at onset between 35 and 60 years.⁶⁹ Clinical features include “pain all over,” paravertebral muscular tightness, and fatigue. Sleep disturbances are present in 75% of patients. Other characteristic features include morning stiffness, nondermatomal paresthesias, subjective swelling, anxiety, and headaches. A significant functional disability is often present.⁷⁰

Diagnosis

The diagnosis is based on clinical presentation and the results of standard laboratory tests are normal. The criteria for classification of fibromyalgia are widespread pain for a period of at least 3 months in combination with tenderness at 11 or more of 18 specific tender point sites.⁷⁰

Treatment

The treatment of fibromyalgia is challenging with less than half of the patients experiencing symptom relief and only 3% undergoing complete remission.⁷¹ Pharmacologic treatment includes tricyclic antidepressants, selective serotonin reuptake inhibitor, and tramadol.^72,73 NSAIDs and steroids have not been shown to be effective. Nonpharmacologic treatment options include exercise, biofeedback, hypnotherapy, and acupuncture.⁷⁴

Sarcoidosis is a chronic systemic inflammatory condition that is characterized by the presence of noncaseating granulomas. Although pulmonary manifestations are most common, acute arthritis may be the initial presentation and may mimic other forms of arthritis. Rheumatologic symptoms are present in 4% to 38% of patients with sarcoidosis.⁷⁵

Arthritis secondary to sarcoidosis is usually an oligoarthritis, but may be polyarticular, and rarely is monoarticular. The ankle and knee joints are most frequently involved in acute sarcoidosis. Symmetric ankle arthritis at onset is very sensitive and specific for the diagnosis of acute sarcoid arthritis. Acute sarcoid arthritis is associated with erythema nodosum in 71% of cases (Fig. 3–13). The patient generally has an atraumatic, tender, warm, erythematous swelling that often is clearly periarticular rather than synovial. Chronic arthritis is uncommon as this condition usually remits after a few weeks to months.

Diagnosis

Radiographs show only soft-tissue swelling. Joint aspiration often yields no synovial fluid. When effusion is aspirated from the joint, leukocyte counts are <1000/mm³. Cultures are negative and crystals are not identified by microscopy. A serum measurement of angiotensin-converting enzyme (ACE) level is elevated in 40% to 90% of patients, but is not specific.

Treatment

Acute sarcoid arthritis may respond to NSAIDs and these are used as the initial treatment of choice. Refractory disease is treated with steroids. Other options include antimalarials, methotrexate, azathioprine, cyclosporine, cyclophosphamide, and a tumor necrosis factor inhibitor.

Polymyalgia rheumatica and temporal arteritis represent different manifestations of the same disease process. To this end, many of the symptoms of these conditions overlap. Over half of patients with temporal arteritis have signs of polymyalgia rheumatica and, conversely, one-third of patients with polymyalgia rheumatica have evidence of temporal arteritis on biopsy. Both conditions occur in women twice as frequently as men. Age at onset is above 50 years and the conditions are more common in White people of northern European ancestry. The most common systemic symptom is fever. Other nonspecific complaints include fatigue, anorexia, and weight loss. ESRs are >50 mm/h with normal values being present in only 4% to 13% of patients.⁷⁶

Diagnosis

Polymyalgia rheumatica is distinguished by pain and stiffness in the shoulder, neck, and pelvic girdle. Polymyalgia rheumatica is more common than temporal arteritis and is present in approximately 0.5% of those above 50 years of age. Patients may report difficulty getting out of bed, getting dressed, or combing their hair. Affected muscles are tender to palpation. The diagnosis is largely clinical.

Temporal arteritis (giant cell arteritis) is diagnosed in (1) individuals older than 50 years with (2) new headache, (3) temporal artery tenderness or decreased pulse, (4) ESR >50 mm/h, and (5) an abnormal biopsy showing vasculitis. Possessing three of these five criteria is 93% sensitive and 91% specific for the diagnosis.⁷⁷ The most common complaint is headache, often localized to the temporal region. Headache is the presenting symptom in 32% of cases and is present by the time of diagnosis in 68% of patients. Jaw claudication is present in 45% of patients at diagnosis. Temporal artery tenderness is present in one-fourth of patients. Permanent loss of vision, the most dreaded complication, occurs when inflammation occludes the arteries of the eye, leading to ischemic optic neuropathy. Ocular symptoms are initially unilateral, but the second eye becomes affected within a period of 1 to 10 days.

Treatment

Fortunately, treatment of polymyalgia rheumatica and temporal arteritis results in dramatic improvement within a period of 48 to 72 hours. Prednisone in an oral dose of 40 to 60 mg is given initially. Weight-based dosing also exists. For temporal arteritis, treatment should be instituted immediately to avoid potential visual loss. Confirmation biopsies can then be scheduled within the following week. In patients with visual symptoms, there are treatment variations, but therapy should be given in the form of intravenous methylprednisolone 250 mg every 6 hours. Steroids are tapered gradually over a period of months to years. Both conditions tend to have self-limited courses, but relapse may occur in up to 25%.⁷⁸

Hemorrhagic joint fluid is most commonly caused by trauma. In the absence of trauma, acute joint hemorrhage suggests the presence of a bleeding diathesis (e.g., hemophilia) or coagulopathy (e.g., warfarin). Other rare entities to be considered include a joint neoplasm or a pigmented villonodular synovitis.

Hemophilia

Acute hemarthroses are frequently seen in male patients with severe hemophilia of either the classic type (hemophilia A, factor VIII deficiency) or Christmas disease (hemophilia B, factor IX deficiency). The knee is most commonly affected, followed by the elbow and the ankle, but any large joint may be involved. Some degree of joint trauma usually initiates the bleeding, although it may be quite insignificant, particularly in patients with recurrent hemarthrosis.

Three stages of hemophilic arthropathy are recognized. The first is an acute bleeding phase into the joint that occurs in childhood after the child has begun to walk. The joints become warm and often are held at approximately 30 degrees flexion. This allows maximal volume of fluid. The second stage is a chronic synovitis that occurs in response to repeated hemorrhages within the joint. The third and final stage is a destructive arthropathy.

In hemophilic arthritis, larger joints are affected more commonly than smaller joints. Radiographic changes include subchondral bone cysts as well as broad osteophytes, which appear late in the disease and are similar to those seen in severe OA. Findings on x-ray that are specific to hemophilic arthropathy include widening of the intercondylar notch of the femur, squaring of the distal patella, and enlargement of the proximal radius.

Before the availability of specific therapy to replace the deficient clotting factor, the recurrent hemarthroses of hemophilia lead inexorably to chronic degenerative arthropathy. The repeated presence of blood in the joint space leads to pigmentation, hypertrophy, and ultimately to fibrosis of the synovium. Cartilage deteriorates and range of motion is decreased. The final result is clinically similar to severe OA, with chronic pain, swelling, and loss of mobility. Osteophyte formation, diminished joint space, and periarticular osteopenia may be seen on radiographs in advanced cases.

Treatment

Therapy for acute hemarthrosis in hemophiliacs involves replacement of the deficient clotting factor, aspiration of the hemarthrosis in selected cases, analgesia, and immobilization. In severe hemorrhage, repeat doses of clotting factor may be necessary. Patients must be referred for close follow-up and physical therapy to minimize long-term disability.

Replacement of the clotting factor may be accomplished with a number of blood products and concentrates. Factor concentrates include both recombinant factor and purified plasma-derived factor, which have eliminated or significantly reduced the rate of viral transmission.^79,80 Hemophilia A may be treated with fresh frozen plasma (FFP), cryoprecipitate, or factor VIII concentrates. The large volume of FFP needed to adequately restore clotting activity, however, usually precludes its use.

To calculate the amount of concentrate needed, the classic hemophiliac presenting with a bleeding emergency is first assumed to have a native factor VIII activity of 0%. It is recommended that the activity be raised acutely to 30% to 50% of normal in the treatment of hemarthrosis. One unit of factor VIII per kilogram of body weight raises the plasma level by 2%. To calculate the number of units of factor VIII to administer, use the following formula:

Factor VIII required = 0.5 × (weight in kg) × (% change in factor activity needed)

Therefore, to raise the levels to the desired 30% to 50% of normal for treating acute hemarthrosis, 15 to 25 units per kilogram of factor VIII are administered as an initial dose. If cryoprecipitate is used, each bag contains a volume of approximately 10 mL with 5 to 10 units of factor VIII activity per milliliter, or approximately 80 units of activity per bag. If, FFP is used, each milliliter contains one unit of factor VIII activity, so 15 to 25 mL/kg must be given.

To summarize, a 70-kg patient with classic hemophilia and an acute hemarthrosis should receive 25 units per kilogram to raise the factor VIII level to 50% of normal. This requires 1750 units of factor VIII, 180 millilter of cryoprecipitate (18 bags), or 1750 milliliter of FFP (8 units).

Patients with factor IX deficiency (hemophilia B) are treated with purified factor IX products in an analogous fashion with the same goal of raising the factor IX level to 30% to 50% of normal. The major difference is that one unit of factor IX per kilogram will raise the plasma level by 1%. To calculate the amount of factor IX required, use the following formula:

Factor IX required = 1.0 × (weight in kg) × (% change in factor activity needed)

The duration of treatment of hemophilic hemarthrosis depends on the severity of the bleeding and the persistence or resolution of symptoms. Minor bleeding that is accompanied by little or no swelling may be treated with a single infusion of clotting factors. Because the half-life of exogenous factor VIII is 12 hours, any significant bleeding requires repeated doses until symptoms resolve. Consultation with the patient’s physician should be sought in these cases. Factor IX has a half-life of approximately 16 hours.

Large, tense hemarthroses seen in the first few hours after the onset of symptoms should be aspirated to prevent persistent pain and the development of chronic joint dysfunction. This is particularly true if the patient has had few or no previous bleeding episodes in the affected joint. Hemarthroses more than 24 hours old are usually clotted and cannot be aspirated. Aspiration must be performed during the infusion of factor VIII to avoid excessive bleeding or performed immediately after to avoid the early coagulation of the hemarthrosis. After aspiration, plasma factor VIII levels of 25% to 50% should be maintained for several days.

Whether or not a joint is aspirated, immobilization should be instituted and maintained until all symptoms have resolved. The patient must be referred to a consultant who will be able to immediately start a program of physical therapy to limit muscle wasting and restore joint mobility as early as possible. Ice and analgesics are important adjuncts in the treatment of hemarthrosis, but care must be taken to avoid salicylates and nonsteroidal agents that may aggravate the bleeding diathesis by inhibiting platelet function.

A small percentage of hemophiliacs fail to respond to factor replacement because of high levels of circulating antibodies to factor VIII. A number of treatment modalities are available to circumvent the problem and the emergency physician should seek consultation if the patient has a history of high antibody levels. Joint aspiration should not be attempted in patients with antibodies.

Coagulopathy

Hemarthrosis is associated with oral anticoagulants and occurs spontaneously at a rate of approximately 1.5%.⁸¹ This rate seems to be higher in patients with higher prothrombin times and those with underlying joint disease. Management of a patient who takes warfarin and is found to have a hemarthrosis consists of bed rest, splinting, and analgesic administration. If possible, the anticoagulant should be discontinued and vitamin K should be administered to reduce bleeding. Arthrocentesis should be performed to remove blood and avoid chronic joint damage. Joint aspirations are not contraindicated in patients taking warfarin and are associated with a low risk of hemorrhage.⁸²

Other

Joint neoplasms are rare, but they should be suspected in acute hemarthroses without trauma or bleeding diathesis. Symptomatic treatment and referral for biopsy are indicated. Pigmented villonodular synovitis is a rare disorder of unknown etiology that may be present with acute hemorrhagic monoarthritis.

Traumatic arthritis may arise as an early sequela of joint injury or much later as a reaction to mechanical derangement of the joint such as a meniscal injury in the knee. There may or may not be a discreet history of injury to the joint, as occasionally the original insult is trivial enough to pass unnoticed by the patient. Joint effusions after trauma may be small or large. The fluid indices range from normal to frankly hemorrhagic. The rapid development of hemarthrosis after trauma suggests a major ligamentous injury or intra-articular fracture. The presence of fat globules in the joint aspirate is diagnostic of a cortical fracture. A symptomatic joint effusion should be aspirated completely to avoid damage to cartilage from elevated pressures and to allow adequate examination for ligamentous injuries. In the absence of joint instability, which requires early surgical intervention, immobilization, rest, and referral are usually adequate therapy. Repeat evaluation for a ligament or a cartilage injury after recovery is necessary.

Neuropathic (Charcot’s) arthropathy is a progressive deterioration of joints in patients with a neuropathy.^83–85 Charcot described the condition in 1868 in patients with tabes dorsalis. Other associated neurologic conditions include cerebral palsy, leprosy, syringomyelia, meningomyelocele, and alcoholic neuropathy. Today, diabetic neuropathy is by far the leading cause.⁸⁶ The reported prevalence of the condition in diabetic populations ranges from 0.1% to 0.4%.⁸³ The foot and ankle are the most common location for the development of neuropathic arthropathy, with the tarsometatarsal joint being the most common joint affected.

Controversy exists as to the true mechanism. The condition seems to be triggered by trauma, which triggers autonomic dysfunction with an increase in bone blood flow. Abnormal healing processes occur with osteoclastic bone destruction. Injury to bone progresses due to abnormal weight bearing.⁸³

Early in the course of this condition, the joint is usually warm and erythematous with hyperemia. With time, the foot becomes swollen, deformed, and unstable. Sensory loss and the absence of deep tendon reflexes are common in this condition.

Two types of neuropathic joints are noted on radiographs—atrophic and hypertrophic.⁸⁵ In the atrophic variety, there is rapid destruction and resorption of the joint. It is generally localized to the forefoot and causes osteolysis of the distal metatarsals. A hypertrophic joint develops over a longer period of time and appears in the midfoot, hindfoot, or ankle. In the hypertrophic variety, there is massive juxta-articular joint inflammation with very large osseous debris accompanied by deformity and subluxation of the joint. The atrophic or acute variety poses a diagnostic problem in that it has been associated with rampant infection or tumor.

Treatment of this condition basically involves immobilization of the affected joint and restriction of weight bearing in order to avoid further injury. Mechanical devices fitted to prevent accelerated bone destruction have been used. Experimental studies suggest that electrical bone stimulation and the use of pamidronate show some promise for treatment.⁸⁵ When possible, surgical arthroplasty can be tried, but it often fails. The emergency physician is primarily functioning as a diagnostician in this condition.

Special thanks to James Peter Redmond, Jr for his assistance in the revision of this chapter.