2. | Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)

Appendix A. American College of Rheumatology Criteria for Diagnosis and Classification of Rheumatic Diseases

Manual of Rheumatology and Outpatient Orthopedic Disorders

Appendix A. American College of Rheumatology Criteria for Diagnosis and Classification of Rheumatic Diseases

Stephen A. Paget and Allan Gibofsky

Diagnostic criteria for rheumatoid arthritis (RA)
Proposed 1987 revised American Rheumatism Association criteria for rheumatoid arthritis
Proposed criteria for clinical remission in rheumatoid arthritis
Jones criteria (revised) for guidance in the diagnosis of rheumatic fever
Current proposed revision of criteria for juvenile rheumatoid arthritis
Revised (1982) criteria for the classification of systemic lupus erythematosus
Preliminary criteria for the classification of systemic sclerosis (scleroderma)

I. Diagnostic criteria for rheumatoid arthritis (RA) ^1,2

Classic rheumatoid arthritis. This diagnosis requires seven of the following criteria. In criteria 1 through 5, the joint signs or symptoms must be continuous for at least 6 weeks. (Any one of the features listed under section E will exclude a patient from this and all other categories.)
1. Morning stiffness.
2. Pain on motion or tenderness in at least one joint ( observed by a physician ).
3. Swelling (soft- tissue thickening or fluid, not bony overgrowth alone) of at least one joint (observed by a physician).
4. Swelling (observed by a physician) of at least one other joint (any interval of time between the two joint involvements when the patient is free of joint symptoms may not be longer than 3 months).
5. Symmetric joint swelling (observed by a physician) with simultaneous involvement of the same joint on both sides of the body (bilateral involvement of proximal interphalangeal, metacarpophalangeal, or metatarsophalangeal joints is acceptable without absolute symmetry). Terminal phalangeal joint involvement will not satisfy this criterion.
6. Subcutaneous nodules (observed by a physician) over bony prominences, on extensor surfaces, or in juxtaarticular regions .
7. Roentgenographic changes typical of RA (which must include at least bony decalcification localized to or most marked adjacent to the involved joints and not just degenerative changes). Degenerative changes do not exclude patients from any group classified as having RA.
8. Positive agglutination test result. Demonstration of rheumatoid factor (RF) by any method that in two laboratories has not yielded a positive result in more than 5% of normal controls, or positive streptococcal agglutination test result (the latter is now obsolete).
9. Poor mucin precipitate from synovial fluid (with shreds and cloudy solution).
10. Characteristic histologic changes in synovium with three or more of the following: marked villous hypertrophy; proliferation of superficial synovial cells, often with palisading; marked infiltration of chronic inflammatory cells (lymphocytes or plasma cells predominating) with tendency to form lymphoid nodules; deposition of compact fibrin, either on surface or interstitially; foci of necrosis.
11. Characteristic histologic changes in nodules. Granulomatous foci with central zones of cell necrosis surrounded by a palisade of proliferated macrophages, and peripheral fibrosis and chronic inflammatory cell infiltration, predominantly perivascular.
Definite rheumatoid arthritis. This diagnosis requires five of the above criteria. In criteria 1 through 5, the joint signs or symptoms must be continuous for at least 6 weeks.
Probable rheumatoid arthritis. This diagnosis requires three of the above criteria. In at least one of criteria 1 through 5, the joint signs or symptoms must be continuous for at least 6 weeks.
Possible rheumatoid arthritis. This diagnosis requires two of the following criteria, and the total duration of joint symptoms must be at least 3 weeks:
1. Morning stiffness.
2. Tenderness or pain on motion (observed by a physician) with a history of recurrence or persistence for 3 weeks.
3. History or observation of joint swelling.
4. Subcutaneous nodules (observed by a physician).
5. Elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).
6. Iritis [of dubious value as a criterion except in the case of juvenile rheumatoid arthritis (JRA)].
Exclusions
1. Typical rash of systemic lupus erythematosus (SLE) (with butterfly distribution, follicle plugging, and areas of atrophy).
2. High concentration of LE cells (four or more in two smears prepared from heparinized blood incubated not more than 2 hours) or other clear evidence of SLE.
3. Histologic evidence of periarteritis nodosa. Segmental necrosis of arteries associated with nodular leukocytic infiltration extending perivascularly and tending to include many eosinophils.
4. Weakness of neck, trunk, and pharyngeal muscles or persistent muscle swelling or dermatomyositis.
5. Definite scleroderma (not limited to the fingers). (The latter is an arguable point.)
6. A clinical picture characteristic of rheumatic fever with migratory joint involvement and evidence of endocarditis, especially if accompanied by subcutaneous nodules or erythema marginatum or chorea. (An elevated anti-streptolysin titer will not rule out the diagnosis of RA.)
7. A clinical picture characteristic of gouty arthritis. Acute attacks of swelling, redness, and pain in one or more joints, especially if relieved by colchicine.
8. Tophi.
9. A clinical picture characteristic of acute infectious arthritis of bacterial or viral origin. Acute focus of infection, or in close association with a disease of known infectious origin; chills; fever; acute joint involvement, usually migratory initially (especially organisms are present in the joint fluid or there is a response to antibiotic therapy ).
10. Tubercle bacilli in the joints or histologic evidence of joint tuberculosis.
11. A clinical picture characteristic of Reiter's syndrome. Urethritis and conjunctivitis associated with acute joint involvement, usually migratory initially.
12. A clinical picture characteristic of the shoulder-hand syndrome. Unilateral involvement of shoulder and hand, with diffuse swelling of the hand followed by atrophy and contractures.
13. A clinical picture characteristic of hypertrophic osteoarthropathy. Clubbing of fingers or hypertrophic periostitis along shafts of long bones, or both, especially if an intrapulmonary lesion (or other appropriate underlying disorder ) is present.
14. A clinical picture characteristic of neuroarthropathy. Condensation and destruction of bones of involved joints with associated neurologic findings.
15. Homogentisic acid in the urine, detectable grossly with alkalinization.
16. Histologic evidence of sarcoid or positive Kveim test result.
17. Multiple myeloma, evidenced by a marked increase in plasma cells in the bone marrow, or Bence-Jones protein in the urine.
18. Characteristic skin lesions of erythema nodosum.
19. Leukemia or lymphoma. Characteristic cells in peripheral blood, bone marrow, or tissues.
20. Agammaglobulinemia.

II. Proposed 1987 revised American Rheumatism Association criteria for rheumatoid arthritis. ³ Four or more criteria must be present to diagnose RA:

Morning stiffness for at least 1 hour and present for at least 6 weeks.
Swelling of three or more joints for at least 6 weeks.
Swelling of wrist, metacarpophalangeal, or proximal interphalangeal joints for 6 or more weeks.
Symmetric joint swelling.
Hand roentgenographic changes typical of RA that must include erosions or unequivocal bony decalcification.
Rheumatoid nodules.
Serum RF by a method yielding positive results in fewer than 5% of normal controls.

III. Proposed criteria for clinical remission in rheumatoid arthritis

Four or more of the following requirements must be fulfilled for at least 2 months consecutively:
1. Morning stiffness not exceeding 15 minutes in duration.
2. No fatigue.
3. No joint pain (by history).
4. No joint tenderness or pain on motion.
5. No soft-tissue swelling in joints or tendon sheaths.
6. ESR (Westergren method) below 30 mm/h for a female patient or 20 mm/h for a male patient.
These criteria are intended to describe either spontaneous remission or a state of drug-induced disease suppression, which stimulates spontaneous remission. To be considered for this designation, a patient must have met the American Rheumatism Association criteria for definite or classic RA at some time in the past.
No alternative explanation may be invoked to account for the failure to meet a particular requirement. For instance, in the presence of knee pain, which might be related to degenerative arthritis, a point may not be awarded for no joint pain.
Exclusions. Clinical manifestations of active vasculitis, pericarditis, pleuritis, or myositis, and unexplained recent weight loss or fever attributable to RA prohibit a designation of complete clinical remission.

IV. Jones criteria (revised) for guidance in the diagnosis of rheumatic fever ⁴

Major manifestations ⁵
1. Rheumatic carditis is almost always associated with a significant murmur. Consequently, the other manifestations listed below, when not associated with a significant murmur, should be labeled rheumatic carditis with caution.
  1. Murmurs
    1. In a patient without previous rheumatic fever or rheumatic heart disease, a significant apical systolic murmur, apical mid-diastolic murmur, or basal diastolic murmur.
    2. In a patient with previous rheumatic fever or rheumatic heart disease, a definite change in the character of any of these murmurs or the appearance of a new, significant murmur.
  2. Cardiomegaly. Unequivocal cardiac enlargement in a patient without a history of previous rheumatic fever, or an obvious increase in cardiac size in a patient with a past history of rheumatic heart disease.
  3. Pericarditis is manifested by a friction rub, pericardial effusion, or definite electrocardiographic evidence.
  4. Congestive heart failure in a child or young adult in the absence of other discernible causes.
2. Polyarthritis is almost always migratory and is manifested by swelling, heat, redness, and tenderness, or by pain and limitation of motion in two or more joints. (Arthralgia alone, without other evidence of joint involvement, may occur in rheumatic fever but is not considered a major manifestation.)
3. Chorea. Purposeless, involuntary, rapid movements often associated with muscle weakness are characteristic of chorea. These must be differentiated from tics, athetosis, and restlessness. Chorea is a delayed manifestation of rheumatic fever, and other rheumatic manifestations may or may not be present. In the latter case, one should make the diagnosis of rheumatic fever, chorea only.
4. Erythema marginatum. This evanescent, pink rash is characteristic of rheumatic fever. The erythematous areas often have pale centers and round or serpiginous margins. They vary greatly in size and occur mainly on the trunk and proximal part of the extremities, never on the face. The erythema is transient, migrates from place to place, and may be brought out by the application of heat. It is not pruritic and not indurated, and it blanches on pressure.
5. Subcutaneous nodules. These firm nodules are seen or felt over the extensor surface of certain joints, particularly elbows, knees, and wrists, in the occipital region, or over the spinous processes of the thoracic and lumbar vertebrae. The skin overlying them moves freely and is not inflamed.
Minor manifestations
1. Clinical. Other clinical features occur frequently in rheumatic fever. Because they also appear in many other diseases, their diagnostic value is minor. They are useful in supporting the diagnosis of rheumatic fever when this diagnosis rests mainly on a single major manifestation.
  1. A history of previous rheumatic fever or evidence of preexisting rheumatic heart disease increases the index of suspicion in the evaluation of any rheumatic complaint. The history must be well documented or the evidence of preexisting rheumatic heart disease clear.
  2. Arthralgia constitutes pain in one or more joints (not in the muscles and other periarticular tissues) without evidence of inflammation , tenderness to touch, or limitation of motion. The presence of arthralgia, in addition to polyarthritis, does not make the latter any more indicative of rheumatic fever and should not be used for diagnosis when polyarthritis is a major manifestation. In the case of monarthritis, however, arthralgia in other joints strengthens the diagnosis of rheumatic fever and can be considered a minor manifestation.
  3. Fever (rectal temperature >38C) is usually present early in the course of untreated rheumatic fever.
2. Laboratory findings
  1. Acute-phase reactions offer objective but nonspecific confirmation of the presence of an inflammatory process. The ESR and CRP tests are most commonly employed. Unless the patient has received corticosteroids or salicylates, the results of these tests are almost always abnormal in patients who present with polyarthritis or acute carditis, whereas they are often normal in patients presenting with chorea. The ESR may be markedly increased by anemia and may be decreased in congestive heart failure. The CRP test is a sensitive indicator of inflammation, and the result is negative in uncomplicated anemia. Heart failure of any cause is often accompanied by a positive CRP test result. Sera from normal persons do not contain this protein, but relatively minor inflammatory stimuli may result in a positive reaction. Leukocytosis, anemia, or other nonspecific responses to inflammation may also occur in acute rheumatic fever.
  2. Electrocardiographic changes, mainly prolongation of the PR interval, are frequent but may occur in other inflammatory processes. Furthermore, electrocardiographic changes, whether or not associated with clinical evidence of carditis, have no bearing on the ultimate development of rheumatic heart disease. Such changes by themselves , therefore, do not constitute adequate criteria for a diagnosis of carditis. The diagnosis of acute rheumatic fever should never be made solely on the basis of laboratory findings plus minor clinical manifestations. On the other hand, because laboratory indications of recent streptococcal infection and current inflammation occur so regularly with this disease, their unexplained absence should make the physician question the diagnosis of rheumatic fever.
Supporting evidence of streptococcal infection
1. Laboratory evidence of preceding streptococcal infection by specific antibody tests or by identification of the offending organism (positive throat culture) greatly strengthens the possibility of acute rheumatic fever. Clinical evidence of preceding streptococcal infection by a history of a recent attack of scarlet fever is the best clinical indication of antecedent streptococcal infection.
2. Recent scarlet fever.

V. Current proposed revision of criteria for juvenile rheumatoid arthritis ⁶

General. The JRA Criteria Committee has reviewed the initial criteria approved by the American Rheumatism Association in December 1971 and published in 1973. The Committee has determined that the criteria be revised at this time, that the term juvenile rheumatoid arthritis be retained, and that the disease should be classified into three subtypes based on onset (systemic, polyarticular, and pauciarticular). Confusion would result from attempts at this time to change the name to juvenile chronic polyarthritis and to create subclassifications. The term Still's disease, which pays legitimate homage to Dr. George Frederick Still, has nonetheless become confusing in that it denotes different clinical patterns in different parts of the world, and it should not be used. The purpose of a working classification is to allow clinicians everywhere to report experiences that can be readily categorized. A classification with appropriate subtypes allows uniform multicenter evaluation of patients with different manifestations. Clusters can then be identified with regard to prognosis or therapy. The following classification enumerates requirements for a diagnosis of JRA and three subtypes based on clinical onset.
General criteria for juvenile rheumatoid arthritis. Persistent arthritis of one or more joints for at least 6 weeks is sufficient for diagnosis if the conditions listed under exclusions have been eliminated. Arthritis is defined as swelling of a joint or limitation of motion with heat, pain, or tenderness. Pain or tenderness alone is not sufficient for the diagnosis of arthritis. Joints are counted individually with certain exceptions. The cervical spine is considered one joint. The carpal joints of each hand are counted as one joint, as are the tarsal joints on each foot . The metacarpophalangeal, metatarsophalangeal, and proximal and distal interphalangeal joints are counted individually.
Subtypes of juvenile rheumatoid arthritis according to onset. The onset subtype is determined by manifestations during the first 6 months of disease. Although manifestations more closely resembling those of another onset subtype may appear later, the subtype present during the initial 6 months remains the onset subtype.
1. Systemic-onset juvenile rheumatoid arthritis. This subtype is defined as JRA with persistent intermittent fever (daily intermittent temperature elevations to 103F or more) with or without rheumatoid rash or other organ involvement. Typical fever and rash are considered probable systemic-onset JRA if not associated with arthritis. Before a definite diagnosis can be made, arthritis as defined must be present.
2. Pauciarticular-onset juvenile rheumatoid arthritis. This subtype is defined as JRA with arthritis in four or fewer joints. Patients with systemic-onset JRA are excluded from this onset subtype.
3. Polyarticular-onset juvenile rheumatoid arthritis. This subtype is defined as JRA with arthritis in five or more joints. Patients with systemic-onset JRA are excluded from this subtype.
4. Other factors to be considered for purposes of continuing study. The following factors may be important for better understanding and future classification:
  1. Rheumatoid factors.
  2. Antinuclear antibodies (ANAs).
  3. Histocompatibility antigens.
  4. Sex.
  5. Age at onset.
  6. Iridocyclitis (chronic or acute).
  7. Sacroiliitis.
  8. Number of affected joints.
  9. Distribution of affected joints.
  10. Family history of arthritis and related rheumatic manifestations.
  11. Responses to drug therapy.
  12. Immunologic abnormalities.
Definitions of certain manifestations
1. Fever. Any type of fever may be seen in JRA; however, a persistent intermittent fever with diurnal variation from normal to 103F or more is suggestive of systemic-onset JRA if other diseases, such as infection, malignancy, inflammatory bowel disease, and SLE, are excluded.
2. Rheumatoid rash is an evanescent, pale, erythematous, usually circumscribed macular rash, with individual lesions varying in size from 2 to 10 mm. The larger lesions may have a pale center with peripheral pallor. The rash may become confluent and is found predominantly on the chest, axillae, thighs, and upper arms and less commonly on the face and distal extremities. It occurs most frequently in patients with systemic-onset disease, may occasionally precede arthritis, and is occasionally pruritic.
3. Iridocyclitis. An anterior nongranulomatous iridocyclitis is most common in patients with pauciarticular-onset JRA. One or both eyes may be involved. The onset of iridocyclitis is characteristically insidious, and initial physical findings may be difficult to detect. The earliest findings on slit-lamp examination are cells or increased protein in the anterior chamber . Sequelae include posterior synechiae, band keratopathy, cataracts, secondary glaucoma, and phthisis bulbi. Iridocyclitis should be considered a serious complication that may lead to blindness. Frequent ophthalmologic examinations should be performed to detect lesions in the earliest stages.
4. Cardiac involvement. Pericarditis is not common and can be asymptomatic. It is most frequently associated with systemic-onset JRA. Symptoms may include chest pain, dyspnea, and tachypnea. Signs include friction rub, tachycardia, and enlarged heart. Electrocardiography, echocardiography, and chest radiography may be helpful in diagnosis. Occasional patients may have myocarditis or valvular insufficiency.
5. Rheumatoid nodules occur in a small percentage of patients with JRA. They are usually subcutaneous, vary in size up to several centimeters, and can generally be found in or about tendons of the hands, below the elbow , and around the Achilles tendon. A lesion sometimes known as a pseudo-rheumatoid nodule has been reported in children to have a pathologic appearance indistinguishable from that of the adult type of rheumatoid nodules. In children, these benign nodules usually appear on the anterior tibial surface or occiput.
6. Stiffness exists in the joints and muscles when they lack flexibility and ease of movement and is frequently observed after inactivity. Stiffness is noted as a physical sign in young children but later also constitutes a symptom or complaint.
7. Tenosynovitis may involve the sheaths of the finger extensors or flexors of the wrist in addition to the posterior tibialis and peroneal tendons of the ankle. Arthritis of the adjacent joint is a frequent association.
8. Arthritis of the cervical spine. Pain and limitation of motion of the cervical spine are frequent in systemic- and polyarticular-onset JRA and less common in the pauciarticular-onset JRA subtype. Clinical findings and the radiographic appearance frequently do not correlate well. Motion is usually limited in extension and lateral flexion and rotation rather than in forward flexion. Radiographic changes consist primarily of narrowing of the apophyseal joints with subsequent fusion. The C2-3 apophyseal joint is most often involved, with the other cervical vertebrae less frequently affected. Abnormalities of the vertebral bodies are much less frequent. When seen, they consist of decreased growth of the bodies and their intervertebral disks. An uncommon but potentially severe complication is subluxation of C-1 on C-2.
9. Rheumatoid factors. Agglutination tests for RF are persistently positive in 5% to 20% of all patients with JRA. Positive test results are more frequently found in older children with polyarticular-onset disease. The presence of RF appears to correlate with a more chronic destructive arthritis.
10. Antinuclear antibodies. Results of fluorescent antibody tests for ANAs are positive in 10% to 40% of children with polyarticular- and pauciarticular-onset JRA; the frequency depends somewhat on the sensitivity of tests in individual laboratories. In the majority of children with the chronic iridocyclitis of JRA, results of tests for ANAs are positive. ANAs are less commonly found in children with systemic-onset JRA or with juvenile ankylosing spondylitis.
11. Growth disturbances in JRA patients are a consequence of the disease itself. Total growth can be severely reduced. Localized growth disturbances may also occur, such as epiphyseal overgrowth at the knee or ankle, or undergrowth of the mandible. Growth can resume with remission. Prolonged corticosteroid therapy can also suppress growth.
12. Anemia and leukocytosis occur frequently in systemic-onset JRA. Peripheral leukocyte counts may be greatly elevated, with a predominance of early forms (left shift); anemia may sometimes be profound. Less pronounced leukocytosis and anemia may also be seen during periods of active disease in children with polyarticular JRA.
13. Hepatosplenomegaly and lymphadenopathy. Marked hepatosplenomegaly and generalized lymphadenopathy may occur in children with active systemic-onset JRA. Mild abnormalities of liver enzymes may be associated with the disease or with therapy. Less pronounced degrees of organomegaly and lymphadenopathy also occur at times with other onset subtypes of JRA.
14. Amyloidosis as a complication of JRA is rarely reported in the United States. In some countries in Europe, the incidence is said to be 4% to 6%. Amyloidosis may be a contributing factor in up to 50% of deaths in JRA patients reported in European countries .
Exclusions
1. Other rheumatic diseases
  1. Rheumatic fever.
  2. SLE.
  3. Ankylosing spondylitis.
  4. Polymyositis and dermatomyositis.
  5. Vasculitis
    1. Anaphylactoid purpura (Henoch-Schnlein).
    2. Polyarteritis.
    3. Serum sickness and other allergic reactions.
    4. Mucocutaneous lymph node syndrome; infantile polyarteritis.
    5. Other.
  6. Scleroderma.
  7. Psoriatic arthritis.
  8. Reiter's syndrome.
  9. Sjgren's syndrome.
  10. Mixed connective tissue disease.
  11. Behet's syndrome.
2. Infectious arthritis
  1. Bacterial arthritis (including tuberculosis).
  2. Viral, fungal, and mycoplasmal arthritides.
  3. Nonbacterial arthritis associated with bacterial infections.
  4. Other.
3. Inflammatory bowel disease.
4. Neoplastic diseases, including leukemia.
5. Nonrheumatic conditions of bones and joints
  1. Osteochondritis.
  2. Toxic synovitis of the hip.
  3. Slipped capital femoral epiphysis.
  4. Trauma
    1. Battered child syndrome.
    2. Fractures.
    3. Joint, ligamentous, and muscular injuries.
    4. Congenital indifference to pain.
    5. Acute chondrolysis.
  5. Chondromalacia of the patella.
  6. Congenital anomalies and genetically determined abnormalities of the musculoskeletal system (including inborn errors of metabolism).
  7. Idiopathic tenosynovitis.
6. Hematologic diseases
  1. Sickle cell anemia.
  2. Hemophilia.
7. Psychogenic arthralgia.
8. Miscellaneous
  1. Immunologic abnormalities.
  2. Sarcoidosis.
  3. Hypertrophic osteoarthropathy.
  4. Villonodular synovitis.
  5. Chronic active hepatitis.
  6. Familial Mediterranean fever.

VI. Revised (1982) criteria for the classification of systemic lupus erythematosus. ⁷ The proposed classification is based on 11 criteria. For the purpose of identifying patients in clinical studies, a person is said to have SLE if any four or more of the 11 criteria are present, serially or simultaneously , during any interval of observation.

Malar rash. Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds .
Discoid rash. Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions.
Photosensitivity. Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation.
Oral ulcers. Oral or nasopharyngeal ulceration, usually painless, observed by a physician.
Arthritis. Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion.
Serositis
1. Pleuritis. Convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion.
2. Pericarditis. Documented by electrocardiogram or rub or evidence of pericardial effusion.
Renal disorder
1. Persistent proteinuria above 0.5 g/d or above 3+ if quantification not performed.
2. Cellular casts. May be red cell, hemoglobin, granular, tubular, or mixed.
Neurologic disorder
1. Seizures in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, or electrolyte imbalance).
2. Psychosis in the absence of offending drugs or known metabolic derangements (e.g., uremia ketoacidosis or electrolyte imbalance).
Hematologic disorder
1. Hemolytic anemia with reticulocytosis.
2. Leukopenia. Total below 4,000/mL on two or more occasions.
3. Lymphopenia. Below 1,500/mL on two or more occasions.
4. Thrombocytopenia. Below 100,000/mL in the absence of offending drugs.
Immunologic disorder
1. Positive LE cell preparation.
2. Anti-DNA. Antibody to native DNA in abnormal titer.
3. Anti-Sm. Presence of antibody to Smith nuclear antigen.
4. False-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test.
Antinuclear antibody. An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome.

VII. Preliminary criteria for the classification of systemic sclerosis (scleroderma). ⁸ Systemic sclerosis (progressive systemic sclerosis, systemic scleroderma) is a disorder of the connective tissues characterized by induration and thickening of the skin (scleroderma), by abnormalities involving both the microvasculature and larger vessels (e.g., Raynaud's phenomenon ), and by fibrotic degenerative changes in muscles, joints, and viscera, most notably the esophagus , intestinal tract , heart, lungs, and kidneys. The disease must be differentiated from a variety of other conditions associated with similar cutaneous changes (Table A-1). Advanced systemic sclerosis with diffuse scleroderma and characteristic involvement of internal organs is unmistakable. However, the disease also exists in a form in which only limited skin change is present, often confined to the fingers and face. This variant is now generally known as the CREST syndrome ( c alcinosis, R aynaud's phenomenon, e sophageal dysfunction, s clerodactyly, and t elangiectasia). Also included within the spectrum of systemic sclerosis are patients in whom scleroderma and other changes typical of progressive systemic sclerosis coexist with manifestations of one or more of the other connective tissue diseasesthe so-called overlap syndromes, such as mixed connective tissue disease.

Table A-1. Classification of scleroderma

Design of the American Rheumatism Association Scleroderma Criteria Cooperative Study. A multicenter study was designed to gather detailed data from patients with an early diagnosis of systemic sclerosis and comparison patients with certain selected rheumatic disorders. Physicians submitting cases from each of the participating centers were requested to group these into one of three categories: (a) definite, (b) probable or early stage, or (c) overlap syndrome. Comparison patients were entered from these centers with diagnoses of (a) SLE, (b) polymyositis-dermatomyositis, and (c) Raynaud's phenomenon, either primary or secondary (not associated with progressive systemic sclerosis or any of the comparison disorders). Patients with various forms of localized (focal) scleroderma were excluded from the study.
Results
1. Clinical features. Seven clinical variables were found to be significantly more frequent in the patients with systemic sclerosis than in comparison patients (Table A-2). Interestingly, these variables all related to sclerodermatous skin changes, except for Raynaud's phenomenon. Cutaneous scleroderma in any location was the most sensitive variable, but as many as 9% of the patients considered to have primary Raynaud's phenomenon by center physicians also showed this change (sclerodactyly in all instances). The presence of proximal scleroderma, a term indicating bilateral and symmetric sclerodermatous changes in any area proximal to the metacarpophalangeal or metatarsophalangeal joints, was the most discriminating variable for systemic sclerosis, having been found in 239 (91%) of the definite systemic sclerosis cases but in only one (0.2%) of the comparison patients, a woman thought to have SLE.
  
  Table A-2. Frequency of promising clinical variables originally considered for criteria analysis
2. Other findings. The frequency of digital tuft resorption and subcutaneous calcinosis, identified by clinical or roentgenographic examination (or both), was found to be several times higher among the systemic sclerosis patients than in the comparison patients. Lower esophageal hypomotility detected by radiographic or manometric study was also found chiefly in the systemic sclerosis group.
  Colonic sacculations were confined to patients with systemic sclerosis but occurred with a relatively low frequency (17% of the definite cases). Bilateral basilar pulmonary fibrosis (determined by roentgenogram) was found in approximately one-fourth of the definite and overlap patients with systemic sclerosis and in a smaller proportion of patients with the comparison disorders. The shin biopsy findings of dermal collagen thickening, condensation, or homogenization were the most sensitive of the laboratory features studied. These occurred in the highest frequency among the systemic sclerosis cases, but some of these changes were also found in 18% to 25% of the comparison patients studied.
3. Major criterion: proximal scleroderma. Because of its high specificity in separating systemic sclerosis from the comparison disorders, proximal scleroderma was selected as the single major criterion for systemic sclerosis. It was found in 91% of definite and 51% of probable cases of this disease and in 58% of the cases of systemic sclerosis-overlap syndromes, but in only one (0.2%) of 413 patients with comparison disorders (see Table A-2). No other variable provided such powerful discrimination.
4. Minor criteria. Multivariate analytic techniques were applied to the remaining definite systemic sclerosis and comparison patients without proximal scleroderma to select that combination of fewest items (minor criteria) that allowed the greatest discrimination. For simplicity, the probable and overlap systemic sclerosis patients were eliminated from these and subsequent analyses to derive criteria for an early diagnosis of definite disease. Many of the remaining clinically promising variables were redundant because they correlated with one another or were rather nonspecific for systemic sclerosis. Three additional variables in combination provided the most information and were selected as minor criteria: sclerodactyly, digital pitting scars of the fingertips or loss of distal finger pad substance, and bilateral basilar pulmonary fibrosis demonstrated by chest roentgenogram. An additional 17 (6%) patients with definite and four (11%) patients with probable systemic sclerosis satisfied at least two of these criteria, but only nine (2%) of the combined comparison patients did so (Table A-3).
  
  Table A-3. Number of patients who satisfied major or minor criteria for systemic sclerosis
5. Proposed classification criteria for definite systemic sclerosis. One major criterion or two or more minor criteria were found in 97% of the definite cases (97% sensitivity) but in only 2% of the comparison patients (98% specificity). This combination of variables constitutes the proposed preliminary classification criteria for systemic sclerosis.
  1. Proximal scleroderma is the single major criterion, with 91% sensitivity and greater than 99% specificity.
  2. Sclerodactyly, digital pitting scars of fingertips or loss of substance of the finger pad, and bilateral basilar pulmonary fibrosis contribute further as minor criteria, in cases in which proximal scleroderma is absent.
  3. One major or two or more minor criteria were found in 97% of patients with definite systemic sclerosis, but in only 2% of the comparison patients with SLE, polymyositis-dermatomyositis, or Raynaud's phenomenon. When the criteria were applied to patients grouped according to the original diagnoses of the participating centers (i.e., before any subcommittee recommended revisions), the results were essentially identical (96% sensitivity and 98% specificity). When these criteria were tested with data stored in ARAMIS from more than 1,300 systemic sclerosis and comparison patients, they yielded 92% sensitivity and 96% specificity.
Discussion: application of the classification criteria. The proposed classification criteria are not intended to apply to all forms of scleroderma, but only to systemic sclerosis.
1. Changes characteristic of scleroderma were reported in skin biopsy specimens of a high proportion of the patients with systemic sclerosis. These included atrophy of dermal appendages, flattening of rete pegs, and thickening, condensation, and homogenization of dermal collagen. Some of these changes were also found, however, in approximately one-fourth of patients with the comparison disorders. More subtle histologic evaluation, including grading of the abnormalities noted above and assessment of such features as the site of collagen deposition (localization and skin layer), small-vessel alterations, and collections of lymphocytes might provide better discrimination of the sclerodermatous change. However, these measures are not yet standardized.
2. When proximal scleroderma is absent, as was true in 9% of the definite cases of systemic sclerosis in this series, classification depends on a number of less discriminating minor criteria. However, critical judgment must be exercised in applying the minor criteria in view of the fact that they are detected more variably and can have other causes (e.g., comparison disorders, frostbite, trauma, or unrelated chronic lung disease).
3. Raynaud's phenomenon is important in the diagnosis of systemic sclerosis in the individual patient in view of its nearly uniform occurrence. However, this cold-reactive state is also found in 20% to 30% of the other connective tissue diseases studied and so is nonspecific. Similarly, typical gastrointestinal disturbances are frequent in systemic sclerosis but may also be found in related disorders.
4. The presence of serum anti-ribonucleoprotein (RNP) antibodies in very high titers was uncommon in patients with definite or probable systemic sclerosis but was found in 69% of patients with systemic sclerosis in overlap. The latter were chiefly patients with clinical findings typical of mixed connective tissue disease. Recent research has revealed certain serum antibodies that appear to be highly specific for systemic sclerosis (e.g., anti-Scl 70, anti-centromere), and continuing investigation is likely to uncover the existence of still more antigen-antibody systems closely associated with this and other connective tissue disorders.

VIII. Criteria for the classification of acute gouty arthritis ⁹

Presence of characteristic urate crystals in the joint fluid, or
Presence of a tophus proven to contain urate crystals by chemical means or polarized light microscopy, or
Presence of six of the following clinical, laboratory, and radiographic phenomena:
1. More than one attack of acute arthritis.
2. Development of maximal inflammation within 1 day.
3. Attack of monarticular arthritis.
4. Observation of joint redness.
5. Pain or swelling in first metatarsophalangeal joint.
6. Unilateral attack involving first metatarsophalangeal joint.
7. Unilateral attack involving tarsal joint.
8. Suspected tophus.
9. Hyperuricemia.
10. Asymmetric swelling within a joint (roentgenogram).
11. Subcortical cysts without erosions (roentgenogram).
12. Negative culture of joint fluid for microorganisms during attack of joint inflammation.

¹ It should be noted that these criteria were developed before the new classification of rheumatic diseases was adopted by the American Rheumatism Association in 1963, in which ankylosing spondylitis, psoriatic arthritis, and arthritis associated with ulcerative colitis and regional enteritis are listed as distinct from rheumatoid arthritis (Blumberg B, et al. ARA nomenclature and classification of arthritis and rheumatism. Arthritis Rheum 1964;7:93).

² Data from Ropes MW, et al. Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 1958;9:175.

³ Arnett FC, et al. The 1987 revised ARA criteria for rheumatoid arthritis. Arthritis Rheum 1987;30:S17.

⁴ Data from Stollerman GH, et al. Jones criteria (revised) for guidance in the diagnosis of rheumatic fever. JAMA 1992;268:2069.

⁵ The presence of two major criteria, or of one major and two minor criteria, indicates a high probability of the presence of rheumatic fever. Evidence of a preceding streptococcal infection greatly strengthens the possibility of acute rheumatic fever. Its absence should make the diagnosis doubtful (except in Sydenham's chorea or long-standing carditis).

⁶ Data from Brewer EJ Jr, et al. Current proposed revision of JRA criteria. Arthritis Rheum 1977;20:195.

⁷ Data from Tan EM, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271.

⁸ Data from preliminary criteria for the classification of systemic sclerosis (scleroderma). Bull Rheum Dis 1981;31:1.

⁹ Wallace SL, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895.

Books@Ovid
Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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