A 49-year-old African American man was referred to rheumatology with        a positive antinuclear antibodies (ANA) test result, constitutional symptoms,        and lymphadenopathy. He presented with unintentional weight loss, low-grade        fever, night sweats, and malaise. The patient also complained of pain in        several joints and a history of minimal sun exposure that caused a painful        rash.

The physical examination revealed that the patient had a low-grade        fever, with a temperature of 37.7ºC (99.9ºF). His weight was 205 lb, down        from 235 lb 6 months earlier. Widespread lymphadenopathy was found in the        cervical, supraclavicular, axillary, and inguinal regions. Findings from        the remainder of the examination were unremarkable, with no synovitis or        rash. Laboratory findings included positive results for ANA (1:640, speckled        pattern), anti-Smith antibodies, and anti-ribonucleoprotein antibodies;        hypocomplementemia; polyclonal hypergammopathy; leukopenia; anemia; and        elevated levels of inflammatory markers.

A whole-body positron emission tomography (PET) survey scan (top) demonstrated        the diffuse nature of the patient’s lymphadenopathy. A right-sided supraclavicular        lymph node excisional biopsy specimen revealed follicular hyperplasia and        regressed follicles that were atretic with hyaline-vascular change, with        sheets of plasma cells in the interfollicular zones (middle and bottom).

Learn the cause of this lymphadenopathy, malaise, and rash by clicking here.

Articles

A 49-year-old African American man was referred to rheumatology with a positive antinuclear antibodies (ANA) test result, constitutional symptoms, and lymphadenopathy.

Lymphadenopathy and Constitutional Symptoms in a 49-Year-Old Man

ABSTRACT: Initial treatment of patients with plantar fasciitis is based on an understanding of the functions of the plantar fascia and the methods for reducing stress applied to it. The differential diagnosis of heel pain may be narrowed by carefully identifying the area of tenderness. There is little scientific evidence to indicate that traditional approaches to treatment substantially improve patients’ long-term outcome, but spontaneous improvement and resolution are common. A rational approach to treatment begins with identifying the possible causes of connective tissue irritation. If specific problems can be identified, a strategy designed to correct these factors should be planned. Surgical release is indicated for severe plantar fascial pain after prolonged attempts at nonoperative treatment. Many intriguing new approaches to treatment-resistant plantar fasciitis are under investigation. (

Heel pain, including that caused by plantar fasciitis, is a common reason why patients seek evaluation from a doctor. The impairment that results from heel pain often is a nuisance, and the pain can be so exquisite and disabling that it interferes with the patient’s recreational, work, and social activities. Initial treatment may be instituted by a variety of doctors, including family physicians, internists, physiatrists, orthopedists, and podiatrists.

Plantar fasciitis is a common and painful heel disorder. Initial treatment is centered on an understanding of the important functions of the plantar fascia and the methods for reducing the stress that is applied to it with daily activities. Exciting new treatment methods are on the horizon. In many cases, however, the high-grade scientific evaluation that is necessary for widespread application of these methods is not yet available. In this article, I provide an update on the latest approaches to the diagnosis and management of plantar fasciitis.

Arch mechanics are centered on the plantar fascia.

The architecture of the midfoot bones has no inherent stability. Pressure applied to the forefoot in the absence of connective tissue support leads to shearing and displacement of the joints. The intrinsic plantar ligaments closely line the inferior surface of the midfoot (

). Although the integrity of the intrinsic ligaments is crucial to the posture of the arch, these ligaments do not have sufficient leverage or size to stabilize the midfoot against the magnitude of body weight.

 described the windlass model of arch stability. The plantar fascia inserts onto the forefoot into the plantar plates of the metatarsophalangeal joints and by extension into the base of the proximal phalanx of each toe. This causes the plantar fascia to tighten when the toes are dorsiflexed. The tightness accentuates and stiffens the arch at the end of the step (

). Because the first metatarsal head is the largest in diameter, the plantar fascia attached to the hallux tightens more; thus, the arch is more accentuated on the medial foot, causing the foot to invert.

When combined with the force of forefoot pressure, the tension within the plantar fascia redirects the force along the axis of the bones. This redirection reduces shear stresses across the foot that would otherwise lead to stress fractures and premature arthritis in the midfoot.

This function is shared by the foot’s intrinsic muscles, which, like the plantar fascia, stabilize the arch by linking the heel to the toes. One study that evaluated arch function demonstrated a 3.2-mm drop in the height of the navicular from the floor when the intrinsic muscles were paralyzed in vivo.

 The health and conditioning of these muscles may be a factor responsible for the development of arch pathology and plantar fasciitis that is not well recognized.

Although plantar fasciitis is the predominant source of heel pain, a few of the less common reasons for heel pain also should be kept in mind (

). The differential diagnosis of heel pain may be narrowed by carefully identifying the area of tenderness. Tenderness with stress fractures of the calcaneus usually is palpable circumferentially around the tuberosity of the calcaneus.

Pain resulting from neuritis of branches of the posterior tibial nerve occurs medially and along the superior border of the intrinsic musculature or along the posteromedial aspect of the ankle. A percussion sign may elicit pain that radiates into the sensory distribution of the nerve, the plantar forefoot, or the heel.

Connective tissue damage in the plantar fascia usually is located somewhat discretely at the insertion of this structure along the anterior and medial aspect of the weight-bearing portion of the heel. The tenderness also may be appreciated at the central or lateral portion of the heel. In some cases, it may extend distally along the medial band into the longitudinal arch.

The diagnostic value of plain radiographs of the heel has been questioned.

 In practice, these studies rarely change treatment decisions. However, the use of radiographs in the management of musculoskeletal disorders has become so routine that some discussion with the patient about their appropriate use may be necessary to explain their omission. If the pain is not improving progressively or if invasive treatment is planned, radiographs certainly should be obtained to rule out extremely rare abnormalities that may alter the treatment plan, although the finding of a heel spur provides little help in selecting the best management of this disorder.

More advanced radiographic studies, such as MRI, CT, ultrasonography, and nuclear medicine, are rarely necessary and their use should be confined to cases in which there is confusion in the diagnosis. For example, fibromyalgia syndrome (FMS) is common in patients who present with heel pain,

 possibly making the physical examination results less reliable. Although surgery may be helpful for patients with FMS, a more aggressive radiological evaluation may be prudent in the selection of patients for surgical treatment.

Deterioration of the plantar fascia occurs for many reasons. Connective tissue deterioration is associated with many systemic factors that alter microcirculation within tissue, such as the patient’s age, arteriosclerosis, lipid abnormalities, tobacco abuse, and diabetes mellitus. Rheumatoid arthritis, ankylosing spondylitis, and other seronegative arthropathies can be associated with plantar fasciitis and other enthesopathies.

Some predisposing factors relate to the biomechanical environment of the ligament. Mechanical overload of the plantar fascia has been suspected to play a significant role in the development of plantar fasciitis. Several studies have identified associations of plantar fasciitis with obesity and poor ankle flexibility; both of these factors would be expected to add to the mechanical load of the forefoot.

The plantar fascia also may be damaged by direct impact on the heel through gait or repetitive trauma to or overloading of the front of the foot through gait abnormalities, posture, and other tendon contractures (eg, hamstring tendon contractures). Damage to other supporting structures that assist in arch stabilization may increase the stress on the plantar fascia; this may include injuries to the posterior tibial tendon or intrinsic plantar ligaments, resulting in acquired flatfoot deformity, or “fallen arches,” and instability caused by midfoot arthritis. The intrinsic musculature may be compromised in many ways, including weakness resulting from compressive or peripheral neuropathy and deconditioning because of the patient’s age or the use of overprotective footwear or arch supports.

There is little scientific evidence to indicate that traditional approaches to treatment substantially improve patients’ long-term outcome. The natural history of plantar fasciitis is unknown. Nearly all accepted conservative therapies yield a high success rate. As a result, large study sizes are necessary to identify statistically significant differences in effectiveness. However, studies of this size and quality are rare in clinical medicine.

A rational approach to management of plantar fasciitis begins with identification of the possible causes of the connective tissue irritation. If specific problems can be identified, a strategy designed to correct these factors should be planned.

If the discomfort from the plantar fasciitis is not severe, a good starting point is a program that includes weight loss, simple stretching exercises, and mechanical protection of the plantar fascia. Casting has been shown to be highly effective for severe pain.

 Although immobilization leads to deconditioning of the musculature and mechanical weakening of the plantar fascia, it seems to help resolve severe, acute pain.

Exercise therapy is an effective approach. Hamstring and Achilles contractures have been associated with the development of plantar fasciitis, and stretching programs have been a mainstay of treatment. Most programs focus on improving the flexibility of these muscles. Stretches that concentrate on the plantar fascia seem to increase the effectiveness of standard stretching programs over the short term.

Conditioning exercises for the foot help relieve stress on the plantar fascia by strengthening supporting structures. Although deep tissue massage techniques are used frequently, they have not been proved to be effective. Therapeutic ultrasound and other modalities have not been shown to be useful.

There has been a lot of experience with braces that maintain the ankle in a neutral or slightly dorsiflexed position at night, and several prospective trials have shown improvement with their use over several weeks.

 However, patients often do not tolerate these braces well while sleeping, especially in cases in which there is bilateral involvement.

NSAIDs are prescribed frequently for plantar fasciitis. Although they are ef-fective as a pain medication, they do little to accelerate recovery from plantar fasciitis.

 Pathology studies of surgical specimens show degeneration, fragmentation, and revascularization but little evidence of acute or long-term inflammatory changes.

Corticosteroid injections are effective for relieving acute pain in patients with plantar fasciitis. Corticosteroids work by modulating the production of inflammatory and anti-inflammatory proteins within the cell. The long-term effect of these injections on plantar fascia is less well understood, and no or incomplete relief often is seen several days or weeks after the procedure. The injections are associated with rupture of the plantar fascia and atrophy of the fat pad of the heel and, thus, should be used judiciously.

Rocker-soled shoes reduce pressure on the forefoot and often help reduce plantar fascial pain. However, this comes at the expense of increased ankle motion, shoe weight, and instability. Arch supports are another effective method of treatment, but no clear increase in satisfaction is demonstrated with custom arch supports compared with less expensive prefabricated inserts. Whether these types of footwear changes are helpful preventive measures in otherwise healthy feet is uncertain.

Surgical release of the plantar fascia is indicated for severe plantar fascial pain after prolonged attempts at nonoperative treatment have been made. Usually, a portion (one-third to one-half) of the fascia is cut. The American Orthopedic Foot and Ankle Society and the American College of Foot and Ankle Surgeons have recommended 6 months of nonoperative management before this step is considered. The connective tissue may be released endoscopically (using a fiberoptic scope) or through an open approach. The ultimate results are comparable. In patients who have undergone excessive (more than 50%) fasciotomy, results have been poor.

 The progressive loss of the windlass effect may lead to a risk of midfoot pain and stress fractures in these patients.

Many intriguing new approaches to treatment-resistant plantar fasciitis are under investigation. Although their effectiveness is questionable, many physicians are incorporating them into their practices. Because traditional treatment is time-tested and cost-efficient, evidence of clear superiority of these newer techniques is necessary before they should be accepted as mainstream treatments.

The machine used for managing musculoskeletal disorders with extracorporeal shock wave therapy (ESWT)-the application of high-intensity pulses of ultrasonic energy-was modified from designs that were used successfully to break up kidney stones. The FDA approved ESWT in 2000 for the treatment of patients with plantar fasciitis who did not improve with conservative therapy. The initial results of controlled studies indicated that such treatment is moderately effective and has few adverse effects, although it did require general or local anesthesia.

A later, well-publicized study disputed the findings of a beneficial effect with this treatment.

 Criticism of this report included patient selection (many of the subjects had pain for a brief period) and the low-energy technique used. Many well-controlled, blinded, randomized studies have since reported encouraging results.

The results achieved with this procedure probably vary greatly with the device used and the amount of energy delivered. Interest in this treatment seems to be waning.

Botulism toxin injection has been used frequently for cosmetic purposes and in the management of neuromuscular disorders. Such injection also has been used off-label for musculoskeletal disorders, including lateral epicondylitis, low back pain, and plantar fasciitis. Injection into the plantar fascia has been shown to provide significant pain relief.

 Whether the mechanism of the pain relief involves paralysis of the irritated intrinsic muscles near the heel or a direct analgesic effect is not clear. Because the studies evaluating botulism toxin injection have been small and uncontrolled, endorsement awaits validation from larger, higher-quality investigations.

The use of autograft whole-blood injections has fallen out of favor, but currently there is considerable interest in the use of platelet-rich plasma (PRP) in the management of a wide variety of musculoskeletal complaints. This preparation is separated from whole blood after it has been centrifuged. The buffy coat layer, which contains the platelets, is isolated from the serum and red blood cells. However, there have been no good published studies to support the use of PRP.

Despite the lack of clear proven indications for PRP, its use in the community seems to be increasing. Some of the demand may be fueled by reports of high-profile athletes with various musculoskeletal injuries having received successful treatment with PRP. This treatment can be quite expensive and often is not covered by insurances. Although no published studies are available in peer-reviewed journals supporting the use of PRP in plantar fasciitis, one placebo-controlled study showed no significant effect in patients with Achilles tendinopathy.

With radiofrequency microtenotomy-the perforation of tissue with a radiofrequency probe during surgical, percutaneous, or endoscopic exposure-the mechanical disruption is less than that with the use of plantar fasciotomy. This may reduce the possibility of midfoot pain, or “lateral column syndrome,” which complicates plantar fasciotomy postoperatively. Although radiofrequency microtenotomy has been available on the market for more than 10 years, the literature currently evaluating it consists of only small case series. Studies comparing the results of this procedure with those of more conventional surgical fasciotomy procedures are necessary before it can be recommended as an alternative. None are currently available.

Although plantar fasciitis may lead to considerable and prolonged pain in a few cases, it often improves spontaneously. Therefore, large, well-controlled trials are necessary before new therapies should be adopted as standard practice. Although many promising treatments for plantar fasciitis are on the horizon, widespread use of these modalities should be reserved to controlled clinical trials until their usefulness is proved definitively.

 Huang CK, Kitaoka HB, An KN, Chao EY. Biomechanical evaluation of longitudinal arch stability. 

 Hicks JH. The mechanics of the foot, part II: the plantar aponeurosis and the arch. 

 Fiolkowski P, Brunt D, Bishop M, et al. Intrinsic pedal musculature support of the medial longitudinal arch: an electromyography study. 

 Levy JC, Mizel MS, Clifford PD, Temple HT. Value of radiographs in the initial evaluation of nontraumatic adult heel pain. 

Initial treatment of plantar fasciitis is based on finding ways to reduce stress applied to the plantar fascia. Surgery for plantar fasciitis may be indicated if prolonged attempts at nonoperative correction are unsuccessful.

Management of Plantar Fasciitis Evolving

 Joint pain and joint damage resulting from rheumatoid arthritis (RA) lead to functional limitations that reduce patients’ quality of life and make activities of daily living difficult. Recent guidelines have emphasized treat to target strategies for minimizing joint destruction in patients with RA and maximizing their functional well-being, but these strategies have not been tested in usual-care settings and have not focused on the functional improvements that occur when disease activity is reduced by medication. The Routine Assessment of Patient Index Data 3, a composite of patient self-reported measures, includes a multidimensional HAQ (MDHAQ). The MDHAQ provides questions to determine patients’ ability to perform activities related to function. Additional treatment strategies that focus on directly addressing functional disabilities may be needed. (

Rheumatoid arthritis (RA), which affects an estimated 1.3 million Americans, is a complex inflammatory disorder associated with synovitis and joint destruction.

Both joint pain and joint damage resulting from RA lead to functional limitations that reduce patients’ quality of life and make activities of daily living difficult.

For example, RA is associated with significant morbidity, a reduced life span, and lost work productivity,

 and it ranks among the common chronic illnesses with the worst quality of life.

 Within 10 years of diagnosis, 35% of patients with RA will be work-disabled.

 In addition to its toll on patients’ physical and emotional health, RA is associated with losses to the US economy that were estimated at $58 billion in 2008.

New RA management strategies have “treat to target” objectives, but determining which measure to use to assess disease activity and response to therapy has been a challenge. In the past, clinical assessment of joint swelling and tenderness, along with imaging and laboratory studies, formed the basis of decision making. However, these tools offered limited information about the impact of synovitis on a patient’s function.

This is the first article in a 5-part series designed to provide a practical approach to better understanding of function in RA. An update on treat to target is offered in this introductory article. Upcoming articles will discuss the importance of function in RA, how function is assessed in RA, how functional assessment may be incorporated into clinical practice, and the role of the nurse in multidisciplinary RA care.

Treat to Target Strategies in Patients With RA

The importance of treat to target strategies for minimizing joint destruction in patients with RA and maximizing their functional well-being has been emphasized in recent guidelines from the American College of Rheumatology (ACR), the European League Against Rheumatism (EULAR), and an international task force.

 These recommendations are based on several studies that have shown improved outcomes for patients with RA based on quantitative measures of disease activity and treatment with intensive predetermined regimens of oral disease-modifying antirheumatic drugs (DMARDs) and biologic agents.

 An incentive to perform quantitative clinical disease activity measures in the routine care of patients with RA also is driven by quality of care initiatives that require quantitative measures of disease activity.

RA Disease Activity and Functional Assessments

Treat to target studies have shown that patients with RA achieve lower levels of disease activity and a better quality of life with intensive therapy and quantitative monitoring of disease activity. However, treat to target strategies have not been tested in usual-care settings and have not focused on the functional improvements that occur when disease activity is reduced by medication.

This highlights important differences between RA disease activity as measured by instruments such as the 28-joint Disease Activity Score (DAS 28) and the Clinical Disease Activity Index (CDAI) and the functional ability of patients with RA as measured by instruments such as a Health Assessment Questionnaire (HAQ) and the Routine Assessment of Patient Index Data 3 (RAPID3).

 The RAPID3 is a composite of patient self-reported measures that includes a multidimensional HAQ (MDHAQ), and the DAS 28 and CDAI are primarily physician-reported measures that rely on physician assessments of tender and swollen joints. Techniques for assessing tender and swollen joints are demonstrated in an instructional video, “Performing a Standardized Joint Count in Rheumatoid Arthritis,” and in an article.

The 2010 criteria for the diagnosis of RA established by the ACR and the EULAR were developed to promote the diagnosis of early disease.

 The original 1987 ACR criteria for a diagnosis of RA included radiographic signs that typically occur with chronic disease.

 The differences between the old and new criteria for a diagnosis of RA highlight an important distinction between reversible synovial inflammation as emphasized by the new ACR/EULAR criteria and irreversible structural joint changes that are part of the 1987 ACR criteria. With reversible inflammation of the joint, there is a greater probability that medications will lead to functional improvements. In contrast, when irreversible structural changes have occurred, occupational therapy probably is the best way to improve function for these patients with RA.

Some authors have proposed that the RAPID3 may be used as a measure of RA disease activity for targeted treatment decisions.

 In addition to the patient-reported MDHAQ functional questions, the RAPID3 is a composite score that also includes visual analog scales (VAS) of patient pain and patient global arthritis disease.

The MDHAQ consists of a set of questions that patients answer to determine their ability to perform activities related to function. Several functional domains are assessed by the MDHAQ; questions for each domain include dressing and grooming, arising, eating, walking, hygiene, grip, and reach (Figure). For example, the MDHAQ asks patients whether they have no, some, or much difficulty in getting in and out of bed. The functional domains of the MDHAQ will be demonstrated in a new video program, “A Practical Understanding of Function in Rheumatoid Arthritis” (see Box, “Video Demonstrates In-Office Assessment of Function in Patients With RA”). 

Video Demonstrates In-Office Assessment of Function in Patients With RA 

“A Practical Understanding of Function in Rheumatoid Arthritis,” a new video program, demonstrates in-office assessment of function in patients with the condition. The video provides relevant information for determining more targeted and individualized treatment and emphasizes the various roles of medications and occupational therapy in those treatment strategies.

The VAS that are part of the RAPID3 ask patients to rate their pain and arthritis disease on a scale of 0 to 10 (10 being the worst). There is a moderately good correlation between the RAPID3 and DAS 28 measures, although they have important differences. While there may be a good correlation between joint pain and swelling and a patient’s functional ability as measured by tools such as the MDHAQ, some patients with good DAS 28 scores clearly have poor scores on the RAPID3. Our own research findings suggest that among patients with RA in DAS 28 remission, as many as 40% report moderate or severe functional disabilities as assessed by the RAPID3.

The Tight Control for Rheumatoid Arthritis study, which used a treat to target strategy, and other studies have demonstrated that adjusting DMARD therapy to improve disease activity using the DAS 28 improves patient disease activity and quality of life.

 However, oral DMARDs and biologic agents probably will not improve the functional abilities of patients with RA in DAS 28 remission who also have high RAPID3 scores and chronic damage resulting from RA and other diseases. Therefore, additional treatment strategies that focus on directly addressing functional disabilities, such as evaluation and treatment by an occupational therapist, may be needed to treat patients with RA who have good DAS 28 scores but poor scores on assessments such as the RAPID3, which emphasize functional abilities.

The MDHAQ is a validated tool that provides important information for assessing the functional abilities of patients with RA. This tool can be incorporated into routine clinical practice easily and provides information that differs from that provided by quantitative disease activity measurements such as the DAS 28 and CDAI. Next in the series: a discussion of the importance of function in RA.

 Lee DM, Weinblatt ME. Rheumatoid arthritis. 

 Smolen JS, Aletaha D, Koeller M, et al. New therapies for treatment of rheumatoid arthritis. 

 Helmick CG, Felson DT, Lawrence RC, et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States, part I. 

 Wong JB, Ramey DR, Singh G. Long-term morbidity, mortality, and economics of rheumatoid arthritis. 

 Lundkvist J, Kastng F, Kobelt G. The burden of rheumatoid arthritis and access to treatment: health burden and costs. 

 Currie CJ, McEwan P, Peters JR, et al. The routine collation of health outcomes data from hospital treated subjects in the Health Outcomes Data Repository (HODaR): descriptive analysis from the first 20,000 subjects. 

Allaire S, Wolfe F, Niu J, Lavalley MP. Contemporary prevalence and incidence of work disability associated with rheumatoid arthritis in the US. 

 Saag KG, Teng GG, Patkar NM, et al; American College of Rheumatology. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. 

 Smolen JS, LandewÃ© R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs [published correction appears in 

 Smolen JS, Aletaha D, Bijlsma JW, et al; T2T Expert Committee. Treating rheumatoid arthritis to target: recommendations of an international task force [published corrections appear in 

 Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. 

 Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. 

 Bakker MF, Jacobs JW, Verstappen SM, Bijlsma JW. Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility [published correction in 

 Verstappen SM, Jacobs JW, van der Veen MJ, et al; Utrecht Rheumatoid Arthritis Cohort Study Group. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). 

 van Tuyl LH, Lems WF, Voskuyl AE, et al. Tight control and intensified COBRA combination treatment in early rheumatoid arthritis: 90% remission in a pilot trial. 

 Tanaka E, Mannalithara A, Inoue E, et al. Efficient management of rheumatoid arthritis significantly reduces long-term functional disability. 

 van der Heijde DM, van’t Hof M, van Riel PL, van de Putte LB. Development of a disease activity score based on judgment in clinical practice by rheumatologists. 

 Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. 

 Bruce B, Fries JF. The Health Assessment Questionnaire (HAQ). 

 Pincus T, Swearingen CJ, Bergman M, Yazici Y. RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without formal joint counts for routine care: proposed severity categories compared to disease activity score and clinical disease activity index categories. 

 Pincus T, Yazici Y, Bergman MJ. RAPID3, an index to assess and monitor patients with rheumatoid arthritis, without formal joint counts: similar results to DAS28 and CDAI in clinical trials and clinical care. 

 Pincus T, Furer V, Keystone E, et al. RAPID3 (Routine Assessment of Patient Index Data 3) severity categories and response criteria: similar results to DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) in the RAPID 1 (Rheumatoid Arthritis Prevention of Structural Damage) clinical trial of certolizumab pegol. 

 Starz TW, Moreland LW, Levesque MC. Quantitative joint assessment to improve RA outcomes. 

 Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 

 Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. 

 Lupash DM, Patel AM, Amity CL, et al. Comparison of the patient-based routine assessment of patient index 3 in usual care of rheumatoid arthritis to the physician-based disease activity score-28 joint count and clinical disease activity index. 

RA ranks among the common chronic illnesses with the worst quality of life.

Understanding Function in RA: An Update on “Treat to Target”

ABSTRACT: Fibromyalgia syndrome (FMS) has been fraught with ambiguity in diagnosis, uncertainty in understanding of its pathophysiology, and difficulties for physicians in managing it competently. In 1990, classification criteria were published that emphasized a tender point examination requiring evaluation by specialists. Also, an erroneous impression that FMS is a “peripheral musculoskeletal disease” was created. Since then, there has been increasing recognition of central pain sensitization as the underlying neurobiological basis that explains most of the cardinal systemic symptoms. In 2010, the American College of Rheumatology (ACR) published new FMS diagnostic criteria suitable for the primary care setting that incorporated both peripheral pain and somatic symptoms. More recently, the ACR 2010 criteria have been further simplified to a survey format for use in epidemiological studies. (

Fibromyalgia syndrome (FMS)-a chronic pain condition that affects at least 2% of the adult population in the United States and other regions

-has been fraught with ambiguity in diagnosis, uncertainty in understanding of the pathophysiology behind its myriad symptoms, and difficulties that physicians face in managing it competently. Chronic widespread pain used to be its defining feature, but patients also may exhibit a range of other symptoms, including sleep disturbance, fatigue, irritable bowel syndrome, headache, and mood disorders.

The American College of Rheumatology (ACR) classification criteria, developed in 1990, helped galvanize research on FMS. The criteria required the presence of widespread pain in combination with 11 or more of 18 specific tender point sites. Widespread pain was defined as “3 out of 4 quadrant” pain, including left- and right-sided and upper- and lower-segment pain, and axial pain.

The 1990 ACR criteria required tender point examination-found to be a barrier in the primary care setting. Also, they created the erroneous impression that FMS is a peripheral musculoskeletal disease with the pathology centered on the tender points. Since then, understanding about the underlying pathophysiology of this complex pain syndrome has evolved and the need to develop new diagnostic criteria has grown.

This is the third in a series of articles that describe new or modified classification and diagnostic criteria for various rheumatologic conditions. The first article (“New Classification Criteria for RA,” 

 November 2011, page 422) discussed recent revisions in rheumatoid arthritis classification criteria. The second article (“New Axial and Peripheral Spondyloarthritis Classification Criteria,” 

 December 2011, page 454) reviewed the new classification criteria for the spondyloarthropathies. In this article, we discuss the new ACR diagnostic criteria for FMS and their modification as survey criteria.

Diagnosis of FMS is performed mostly in the primary care setting. However, tender point examination rarely is performed in this setting, and when it is performed, it often is done incorrectly.

The 2010 ACR criteria were aimed at simplifying the diagnosis of FMS and being suitable for use in primary care practice without requiring a tender point examination. Another objective was to recognize the importance of the numerous nonpain symptoms of FMS, such as perceived cognitive impairment (“fibrofog”), fatigue, and sleep disturbance, in making the diagnosis.

Also, the new diagnostic criteria were meant to objectively assess disease severity and to develop a method of longitudinally monitoring patients who subsequently may not satisfy classification criteria. These goals were not achievable with the older classification criteria.

The Process of Developing New Diagnostic Criteria

To develop the new criteria, Wolfe and colleagues

 conducted a 2-phase, case-control, multicenter study that involved more than 600 and 300 patients in phases 1 and 2, respectively. Cases were defined as patients with a previous diagnosis of FMS. Diagnosis could be made on clinical grounds by a physician or by the 1990 classification criteria or both. Controls were age- and sex-matched patients with noninflammatory painful disorders, such as degenerative back pain and other regional pain syndromes, without a previous diagnosis of FMS. Of note, patients with inflammatory conditions, such as rheumatoid arthritis (RA), and those with other known painful conditions, such as cancer, fractures, and neuropathic pain, were excluded from the study.

Phase 1 evaluated an extensive set of FMS symptoms as study variables. Evaluating physicians were chosen randomly from a list of 113 ACR members, and 5 known experts in the field were added. The study variables included painful body areas and somatic symptoms. Phase 2 was designed to develop a practical questionnaire shortened from the long list of phase 1 variables.

For comparison, patients were divided into 3 groups: “current FMS” (ACR classification positive, physician FMS diagnosis positive); “prior FMS” (ACR classification negative, physician diagnosis positive); and “controls” (ACR classification negative, physician diagnosis negative). Study variables were analyzed in short, intermediate, and complete lists to devise a suitable-length questionnaire with an acceptable level of misclassification rates.


ACR 2010 fibromyalgia diagnostic criteria

The misclassification rate for symptom variables when collected by a physician was 6% to 10%, compared with 13% with self-reported or patient-obtained data. It was decided that the ACR 2010 diagnostic criteria should be physician-assessed and not patient self-reported.

The model with an intermediate number of variables and categorical widespread pain index (WPI) value represented the best practical model; it had the lowest error rate, 7.3%. With the use of this model, a WPI value of 7 or higher best identified FMS cases and values of 6 or lower best identified noncases.

The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create a symptom severity (SS) scale value of 0 to 12. The SS scale and the WPI were then combined to form a new case definition of FMS: WPI of 7 or higher and SS of 5 or higher or WPI of 3 to 6 and SS of 9 or higher (

Using the 1990 ACR classification criteria as the gold standard, the new 2010 ACR diagnostic criteria made the correct diagnosis in 83% of cases. However, about 9% of controls satisfied the new criteria, compared with 2% satisfying the old classification criteria. Overall, the FMS rate among all of the study patients increased from 38% to 45%.

Conceptual Differences From the Old Classification Criteria

The new diagnostic criteria shifted the FMS definition from a “peripheral pain”–defined disease to a “systemic symptoms”–based disease. In the new criteria, the somatic symptoms of FMS are accorded appropriate importance by the provision of the SS scale, which also provides a measurement of disease severity. Thus, these criteria may be satisfied by a high level of symptoms even if the WPI is not high.

Advantages Over the Old Classification Criteria

The new diagnostic criteria are a simple tool for use in the primary care setting. The older classification criteria involved a tender point count performed by an expert physician in specialty clinics and has been useful in achieving patient homogeneity for clinical trials.

 However, they have not been embraced widely in primary care.

The new case definition of FMS correctly classifies about 83% of cases without a physical or a tender point examination. This rate almost equals the 84% rate achieved by a physician diagnosis. The previous classification criteria did not have a provision for assessing severity or monitoring patients with a previous diagnosis of FMS. The SS scale allows for assessment of severity in patients with current or previous FMS and monitoring the disease course over time.

Limitations of the New Diagnostic Criteria

The finding that as many as 25% of patients with physician-diagnosed FMS did not satisfy the 1990 ACR classification criteria was an important one. The new criteria do not solve this problem. Because inflammatory and other painful disorders were excluded, the new criteria cannot be applied to patients with RA, systemic lupus erythematosus, or other conditions.

The new criteria do not distinguish between primary and secondary FMS. The performance of these criteria in the primary care setting has not been validated by prospective studies. It could be argued that making a diagnosis of a condition without physical examination probably will miss important physical findings and other potential causes for patients’ symptoms. In addition, these criteria still rely on clinical grounds and do not incorporate any objective laboratory or imaging data in making the diagnosis, although currently no objective parameters are widely accepted for routine use in clinical practice.

2011 Modification of the ACR 2010 Diagnostic Criteria

To develop an FMS model for use in surveys and epidemiological studies, the same authors further modified the 2010 criteria to make it completely patient-driven, avoiding the need for physicians’ input.

 In essence, they eliminated the physician’s estimate of the extent of somatic symptoms (point B in 

), substituting it with the sum of 3 specific self-reported symptoms (

In addition, they created a 0 to 31 FMS symptom scale (FS) by adding the WPI to the modified SS scale, which measures what the authors call the overall “fibromyalgianess” of a patient. The FS scale was found to be the best univariate predictor of FMS. An FS score of 13 or higher best separated modified ACR 2010 criteria–positive and criteria–negative patients, classifying 93% correctly, with a sensitivity and specificity of more than 90% each.

Removing the physician from the diagnosis-making process and relying on patients to fill out questionnaires to self-diagnose a condition has its own problems. Therefore, these criteria warrant further epidemiological and clinical studies to assess their acceptance, reliability, and validity.

 Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment [published correction appears in 

 Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia: report of the Multicenter Criteria Committee. 

 Fitzcharles MA, Boulos P. Inaccuracy in the diagnosis of fibromyalgia syndrome: analysis of referrals. 

 Buskila D, Neumann L, Sibirski D, Shvartzman P. Awareness of diagnostic and clinical features of fibromyalgia among family physicians. 

 Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. 

 MacFarlane GJ, Croft PR, Schollum J, Silman AJ. Widespread pain: is an improved classification possible? 

 Wolfe F, Clauw DJ, Fitzcharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. 

Fibromyalgia syndrome has been fraught with ambiguity in diagnosis, uncertainty in understanding of the pathophysiology behind its myriad symptoms, and difficulties that physicians face in managing it competently.

The Journal of Musculoskeletal Medicine Vol 29 No 1

Lymphadenopathy and Constitutional Symptoms in a 49-Year-Old Man

Management of Plantar Fasciitis Evolving

Understanding Function in RA: An Update on “Treat to Target”

New and Modified Fibromyalgia Diagnostic Criteria