The ACR has published three documents intended to provide clarity and consensus on management of osteoarthritis, classification criteria for Sjögren’s syndrome, and classification criteria for polymyalgia rheumatica. The documents, which represent the most current clinical evidence, research, and expert panel input and review, can help inform clinical practice and provide clearer target populations for future research.
Rheumatologists involved in the development of these documents say that updated consensus was needed on each of the conditions. The previous ACR recommendations for management of hip and knee osteoarthritis (OA) were issued in 2000, and recommendations from other international groups have followed.1 Since that time, research has yielded new information about the safety and tolerability of treatments for OA, new therapies have become available, and the methodology for development of clinical practice guidelines has improved. Because the 2012 OA recommendations use a case-based approach built on common clinical scenarios, practitioners should recognize the patterns that they see in practice, according to Marc C. Hochberg, MD, MPH, head of the division of rheumatology and clinical immunology at the University of Maryland School of Medicine in Baltimore, and an author of the recommendations.
New classification criteria for Sjögren’s syndrome (SS) were needed, given the increasing availability of biologic agents to be tested as part of clinical trials for management of the disease, and the comorbidities associated with their use, according to Lindsey A. Criswell, MD, MPH, DSc, chief of the division of rheumatology at the University of California, San Francisco, and co-leader with Caroline Shiboski, DDS, MPH, PhD, of the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry that was used for development of the criteria. Although 11 classification criteria sets have been issued over the past several years by other organizations, the 2012 criteria are the first endorsed by the ACR. Most important for classification, the new criteria rely solely on objective tests rather than symptoms.
The way polymyalgia rheumatica (PMR) is diagnosed and how PMR is classified for clinical studies varies among practitioners because PMR’s symptoms can mimic other conditions, and it has no disease-specific inflammatory markers or biomarkers. The 2012 EULAR/ACR classification criteria for PMR help clarify the key features in a difficult-to-classify condition, says Eric L. Matteson, MD, chair of the division of rheumatology at the Mayo Clinic in Rochester, Minn., and an author of the criteria. The listed criteria are the features most characteristic of PMR that expert clinicians use to diagnose the disease, and they formed the basis for evaluation of the new disease classification criteria. Although these criteria can help clarify some diagnostic issues, they are primarily intended to aid development of therapeutic approaches and further research on the disease itself, Dr. Matteson says.
Management of Osteoarthritis
Unlike previous ACR recommendations for management of OA, the “ACR 2012 Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee” were developed using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) approach, a formal method for developing recommendations that is “more valid and internationally acceptable,” Dr. Hochberg says.2 “Rheumatologists should recognize that this was a very rigorous process and one that is evidence based.” GRADE is now the preferred process by many professional organizations, including the World Health Organization, the Cochrane Collaboration, and the Agency for Healthcare Research and Quality.
Another change from the previous ACR recommendations for OA management is that the 2012 document does not recommend a sequence of subsequent interventions if initial therapies for OA do not result in an adequate response. This change is due to a lack of high-quality studies that reliably examined the benefit and safety of treatment modalities that could support recommendations of a specific sequence of therapy.
According to Dr. Hochberg, nonpharmacologic and pharmacologic therapies were given “equal weighting” in panel deliberations and literature reviews for the 2012 recommendations. “The nondrug treatments were given a lot of attention because they are the cornerstone of the management approach to people with OA. We find [they are] often neglected in primary care because of the short amounts of time that providers have to interact with their patients,” he says.
Unlike the previous ACR recommendations, the 2012 document includes recommendations for management of symptomatic hand OA.
Dr. Hochberg highlighted some of the key points among the recommendations:
- Topical rather than oral nonsteroidal antiinflammatory drugs (NSAIDs) should be used whenever possible for people over age 75 years, a recommendation in accord with the American Geriatric Society.
- For hand OA, provision of assistive devices, use of thermal modalities and trapeziometacarpal joint splints, and use of oral and topical NSAIDs, tramadol, and topical capsaicin are conditionally recommended.
- Also for management of hand OA, it is conditionally recommended that intraarticular therapies and opioids not be used.
- Acetaminophen, recommended previously as initial therapy for knee and hip OA, is now only conditionally recommended among other pharmacologic agents, such as oral and topical NSAIDs, which can be used as initial therapy in patients with hip and knee OA.
- Aerobic, aquatic, resistance exercises, and weight loss are strongly recommended for knee and hip OA.
- For both knee and hip OA, nutraceuticals such as chondroitin sulfate, glucosamine, and topical capsaicin are conditionally recommended not to be used.
- Tai chi is conditionally recommended for knee OA, as is acupuncture in certain situations; no recommendation is given for tai chi for hip OA.
- Management is addressed for those patients who would normally be referred to orthopedic surgeons but who choose not to have a joint replacement or are not medically suitable for surgery.
Some of the recommendations may come as a surprise to rheumatologists, Dr. Hochberg predicts, including the recommendation related to topical therapy for knee OA for all age groups, and particularly for those over age 75. “I think most rheumatologists are not aware of it and have a feeling that it does not work as well as oral therapy,” he says, “However, the data from clinical trials indicate that it does work.”
Another surprise may be that intraarticular therapy and opioid analgesics are not recommended for hand OA. “We don’t have a good survey about how patients with hand OA are treated, so we really don’t know if those are common practices,” he says.
Most important for practitioners is the case-based approach that was used to develop the recommendations, an approach that should make their use easier in clinical practice. The case-based approach was accomplished by a diverse group of providers who worked on the recommendations, including primary care physicians, an orthopedic surgeon, podiatrists, arthritis-related health professionals, and rheumatologists. All members of the technical expert panel submitted patient scenarios based on the patients they typically see. These scenarios were amalgamated and then reviewed by the ACR Board of Directors “to make sure we were not missing anything,” Dr. Hochberg explains. Therefore, “the recommendations are clinically relevant and should cover the vast majority of OA patients.”
Dr. Hochberg anticipates that these recommendations will be used as quality indicators that could determine whether patients are receiving high-quality care. If this happens, “physicians who follow the strong recommendations and document that in their records—particularly regarding physical therapy referrals, nutrition counseling, assessment of pain severity, and provision of analgesic therapy—could eventually receive higher levels of reimbursement than those physicians who don’t document that care in their records.”
Criteria for Sjögren’s Syndrome
The driving force behind development of the “ACR Classification Criteria for Sjögren’s Syndrome” was the need for specificity rather than reliance on symptoms, such as dry eyes and dry mouth that can be very nonspecific and caused by many other conditions.3 With an increasing number of biologic agents being developed for autoimmune rheumatic diseases and being considered and tested in patients with SS, “disease-specific classification criteria were needed,” Dr. Criswell says. These specific and objective classification criteria can be used for future enrollment in clinical trials testing the new agents and other studies of this disease.
There have been 11 classification or diagnostic criteria sets for SS developed since the mid-1960s, and the latest was published by the American–European Consensus Group; none were endorsed by the ACR. According to Dr. Criswell, the new ACR-endorsed classification criteria represent a significant step forward because they were developed from the large SICCA registry, which includes a diverse, international population. The new criteria, unlike previous ones, do not include various alternative ways of meeting individual criteria.
Also, the criteria outlined in the document are simpler, Dr. Criswell says. “Anyone familiar with Sjögren’s syndrome will look at, basically, three points—eye involvement, oral involvement, and the autoantibodies representing the systemic involvement—and say that that makes a whole lot of sense for Sjögren’s syndrome as an autoimmune disease.”
The new classification criteria of SS require that a patient have at least two of the following objective features:
- Positive serum anti-SSA and/or anti-SSB or positive rheumatoid factor plus antinuclear antibodies ≥1:320;
- Ocular staining score ≥3; and
- Labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus score ≥1 foci/4 mm2.
Implications for Clinical Practice
Although the classification criteria for SS are straightforward and objective, using these criteria may be challenging, Dr. Criswell says. One of the challenges will be the need for earlier collaboration and interaction with other specialists, including ophthalmologists and oral medicine specialists, for classification. These specialists are also necessary for the ongoing management of SS patients. “While a rheumatologist might have felt comfortable doing a Schirmer’s test to measure dry eyes, a rheumatologist typically would not be using a slit lamp, which is required for ocular staining and assessment.” The need for this extra assessment “could be seen as a disadvantage, but we feel it is a tremendous service to the patient, given that ocular manifestations can have devastating complications,” she says.
Also, an oral medicine specialist will need to perform the labial salivary gland biopsy. Without that biopsy and assessment, an opportunity will be missed to document and quantify the autoinflammatory component of the disease and to begin treating the patient for the progressive effects of hyposalivation, Dr. Criswell says. A subset of patients with SS is at greater risk for developing lymphoma than patients with other autoimmune diseases. The biopsy can identify early lymphoma or a patient at high risk for the disease.
Some patients with SS do not complain of dry eyes or dry mouth, even though both symptoms have been considered hallmarks of the disease. Ocular staining or a biopsy of the salivary gland tissue can provide clear evidence of SS. “A syndrome of dry eyes and dry mouth can have many causes,” Dr. Criswell says. “We want these new criteria to identify those individuals who have an autoimmune basis for those symptoms. This arms clinicians and researchers with a new tool to identify and target individuals who have dry eye and dry mouth as part of an autoimmune disease.”
These criteria formally say that if you have rheumatoid serology, you are much less likely to have PMR. None of the other criteria out there for polymyalgia, diagnostic or otherwise, have addressed that. That is very important.
—Eric L. Matteson, MD
Classification Criteria for Polymyalgia Rheumatica
With no single test, no single symptom, and no known specific biomarkers, PMR has been difficult to diagnose and is often confused with other diseases. Those factors have also complicated research efforts. “It presents a problem if you try to formally study polymyalgia rheumatica because you need to be able to classify it and have confidence that the patient you have in your study actually has the disease,” Dr. Matteson says. The lack of standardized criteria has contributed to problems in assessing potentially effective therapies, he says.
The new “Provisional Classification Criteria for Polymyalgia Rheumatica” are addressing that problem.4 Not intended nor tested for diagnostic use, the criteria are intended, instead, to inform research efforts so that patients identified with these criteria are grouped together for the purpose of studying the disease course and treatments, Dr. Matteson says. “We hope in the future to [identify] a more specific biomarker or biomarkers so that we can say that if you have this biomarker or group of biomarkers and these symptoms, we are certain you have polymyalgia rheumatica and not some other disease that can be confused with it.”
Development of the PMR classification criteria was based on an international multicenter prospective study that examined consensus-based criteria proposed by a group of experts that included 111 rheumatologists and 53 nonrheumatologists in the United States and Western Europe. For the study, patients with new onset PMR were followed for a minimum of six months while receiving a standardized corticosteroid treatment regimen.
This group was compared with another group of patients who had new onset bilateral shoulder problems due to another condition. At the end of follow-up, the researchers determined which features were the most helpful in determining which patients had PMR.
The features identified for PMR classification were:
- Patient aged ≥50 years presenting with bilateral shoulder pain;
- Elevated C-reactive protein and/or erythrocyte sedimentation rate in the presence of morning stiffness >45 minutes;
- New hip pain in the absence of peripheral synovitis or positive rheumatoid arthritis serology; and
- Ultrasound score ≥5.
Noticeably absent from these criteria was response to low doses of corticosteroids, long believed to be a feature of PMR but found to have little validity in this study. “Many inflammatory rheumatic conditions such as rheumatoid arthritis are improved with corticosteroid therapy, so this response does not help in disease classification,” Dr. Matteson says. “An important aspect of dropping the response to corticosteroids is that it also facilitates enrollment of patients with PMR into studies evaluating the utility of various treatments compared with corticosteroids.
“There have been lots of criteria out there for polymyalgia rheumatica, and many of those criteria have been dropped because they were not found to be essential or helpful,” Dr. Matteson says. “These criteria formally say that if you have rheumatoid serology, you are much less likely to have PMR. None of the other criteria out there for polymyalgia, diagnostic or otherwise, have addressed that. That is very important.”
Another key feature of the new criteria is the role of ultrasound. “The main finding here is that ultrasound differentiated it from most other conditions that affect the shoulders that can be confused with polymyalgia, except rheumatoid arthritis. Ultrasound was not helpful for differentiating polymyalgia from rheumatoid arthritis because they have very similar or identical findings on ultrasound,” he says.
Dr. Matteson notes that researchers are still “on the search for better disease markers. We understand that, just as for other classification criteria, these criteria need to be validated further. We view this as a very dynamic area.”
For More Information
Researchers who would like more information about the SICCA registry can find that at http://sicca.ucsf.edu/index.html. To apply for access to the data and biospecimens available from the SICCA registry, visit http://sicca.ucsf.edu/specimen-data-dissemination-index.html.
Kathy Holliman is a medical journalist based in New Jersey.
- American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43:1905-1915.
- Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012;64:465-474.
- Shiboski SC, Shiboski CH, Criswell LA, et al. American College of Rheumatology classification criteria for Sjögren’s syndrome: A data-driven, expert consensus approach in the Sjögren’s international collaborative clinical alliance cohort. Arthritis Care Res (Hoboken). 2012;64:475-487.
- Dasgupta B, Cimmino MA, Kremers HM, et al. 2012 Provisional classification criteria for polymyalgia rheumatica: A European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheum. 2012;64:943-954.