Robert S. Katz

The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity

To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms.

Fibromyalgia Criteria and Severity Scales for Clinical and Epidemiological Studies: A Modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia

Objective. To develop a fibromyalgia (FM) survey questionnaire for epidemiologic and clinical studies using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010). We also created a new FM symptom scale to further characterize FM severity. Methods. The ACR 2010 consists of 2 scales, the Widespread Pain Index (WPI) and the Symptom Severity (SS) scale. We modified these ACR 2010 criteria by eliminating the physician’s estimate of the extent of somatic symptoms and substituting the sum of 3 specific self-reported symptoms. We also created a 0–31 FM Symptom scale (FS) by adding the WPI to the modified SS scale. We administered the questionnaire to 729 patients previously diagnosed with FM, 845 with osteoarthritis (OA) or with other noninflammatory rheumatic conditions, 439 with systemic lupus erythematosus (SLE), and 5210 with rheumatoid arthritis (RA). Results. The modified ACR 2010 criteria were satisfied by 60% with a prior diagnosis of FM, 21.1% with RA, 16.8% with OA, and 36.7% with SLE. The criteria properly identified diagnostic groups based on FM severity variables. An FS score ≥ 13 best separated criteria+ and criteria− patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a specificity of 91.8% in the study population. Conclusion. A modification to the ACR 2010 criteria will allow their use in epidemiologic and clinical studies without the requirement for an examiner. The criteria are simple to use and administer, but they are not to be used for self-diagnosis. The FS may have wide utility beyond the bounds of FM, including substitution for widespread pain in epidemiological studies.

Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial†

OBJECTIVE To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. METHODS We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. RESULTS Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced > or =50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. CONCLUSION Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

Value of a Complete or Partial Remission in Severe Lupus Nephritis

BACKGROUND AND OBJECTIVES The value of a complete remission in severe lupus nephritis is well known but little is known about the impact of a partial remission in this patient population. The purpose of this study was to evaluate the long-term prognosis of achieving a complete or partial remission in a well-defined group of patients with severe lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this study, 86 patients with diffuse lupus glomerulonephritis were reviewed for assessment of the value of a partial remission (50% reduction in baseline proteinuria to < or =1.5 g/d and < or =25% increase in baseline creatinine) and complete remission (proteinuria < or =0.33 g/d and serum creatinine < or =1.4 mg/dl) on outcomes compared with patients who did not attain a remission. These well-characterized patients were entered into a prospective therapeutic trial conducted by the Collaborative Study Group and were followed for more than 10 yr. RESULTS All biopsies showed diffuse lupus nephritis. A complete remission was attained in 37 (43%) patients, a partial remission in 21 (24%) patients, and no remission in 28 (32%) patients. Baseline clinical and serologic features were similar among the groups, but patients with a complete remission had a lower serum creatinine and chronicity index compared with patients with partial or no remission. The patient survival at 10 yr was 95% for complete remission, 76% for partial remission, and 46% for no remission. The renal survival at 10 yr was 94% for complete remission, 45% for partial remission, and 19% for no remission, and the patient survival without end-stage renal disease at 10 yr was 92% for complete remission, 43% for partial remission, and 13% for no remission. CONCLUSION Even a partial remission in lupus nephritis is associated with a significantly better patient and renal survival compared with no remission.

The prevalence and clinical impact of reported cognitive difficulties (fibrofog) in patients with rheumatic disease with and without fibromyalgia.

Cognitive dysfunction in patients with rheumatic disease encompasses a range of impairment. Their prevalence, co-occurrence, and impact on symptom severity were assessed in 57 patients with fibromyalgia (FMS) and 57 patients with rheumatic disease without FMS. Information pertaining to memory decline, mental confusion, and speech difficulty was extracted from questions embedded in a health questionnaire and a blind retrospective chart review. Pain, morning stiffness, fatigue, and sleep difficulty were established on a 0- to 100-mm visual analog scale. Variables of mental confusion, fatigue, tension, depression, anger, and vigor were assessed using the Profile of Mood States. Compared with the non-FMS sample, patients with FMS complained more often of memory decline (70.2–24.6%), mental confusion (56.1–12.3%), and speech difficulty (40.4–3.5%). Memory decline and mental confusion were coupled more often in patients with FMS (50.9–8.8%). Patients with FMS with this combination of cognitive problems reported more pain (76.0–45.4%), stiffness (79.7–43.7%), fatigue (79.6–52.6%), and disturbed sleep (59.2–36.6%) compared with patients with FMS with memory problems alone. Patients with rheumatic disease substantially differ in cognitive vulnerability, with patients with FMS at considerably higher risk for cognitive difficulty. More importantly, the prevalence of a combined disturbance in memory and mental clarity is high and closely associated with the perception of increased illness severity and diminished mental health in FMS. That this linkage has the possibility of having a great deal to do with an important clinical variant of FMS underscores the need for greater clinical recognition of this underrecognized pattern and for further research. Patients with fibromyalgia frequently report memory and concentration problems, especially if asked about them. Clinicians could judge these complaints as similar to adult attention deficit syndrome and reassure the patient. Trying medication to improve attention and concentration is sensible but untested in fibromyalgia.

Chronic conditions and health problems in rheumatic diseases: comparisons with rheumatoid arthritis, noninflammatory rheumatic disorders, systemic lupus erythematosus, and fibromyalgia.

Objectives. To describe and compare the prevalence of lifetime and current self-reported comorbidity and associated quality of life in 4 rheumatic diseases, and to investigate comorbid conditions in light of the overlap between the index condition and comorbid conditions (CC), and in the context of symptom-type diagnoses. Methods. We studied comorbidity in 11,704 patients with fibromyalgia (FM), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and noninflammatory rheumatic disorders (NIRD). Patients completed semiannual self-reports relating to 22 present and past illnesses and completed the EuroQol (EQ-5D) utility index. Results. CC were most common in FM, followed by SLE. FM comorbidity was dominated by depression, mental illness, and symptom-type comorbidity (e.g., gastrointestinal and genitourinary disorders). In SLE, there were substantial increases in hypertension, depression, cataract, fractures, and cardiovascular and cerebrovascular, neurologic, lung, gall bladder and endocrine disorders compared with RA. Any current CC reduced the EQ-5D utility by 0.08 to 0.16 units. The lowest EQ-5D score was noted for current psychiatric illness (0.55) and current depression (0.60). Conclusion. Four patterns of comorbidity emerged: that associated with aging; that associated with aging but enhanced by the index condition, as in SLE and cardiovascular disease; comorbidity that is part of the symptoms complex of the index condition; and CC that represent lifetime traits or manifestations of the underlying illness. Depression was the most strongly associated correlate of EQ-5D quality of life, and current depression was present in about 15% of patients with RA or NIRD and 34% to 39% of those with SLE and FM.

The development of fibromyalgia--I: examination of rates and predictors in patients with rheumatoid arthritis (RA).

&NA; We determined rates and predictors of future development of fibromyalgia in patients with rheumatoid arthritis (RA). After excluding patients with fibromyalgia and those with high levels of fibromyalgia symptoms (fibromyalgianess score >10) at baseline, we studied fibromyalgia development in 9739 RA patients during 42,591 patient‐years of follow‐up. We defined fibromyalgia using a modification of the ACR 2010 fibromyalgia criteria. We used Cox regression to predict future fibromyalgia, and examined the accuracy of predictions using Harrell’s C concordance coefficient. At the last observation, 7.4% of patients satisfied criteria, although 19.8% satisfied criteria at some point during follow‐up, an incidence rate of 5.3 (95% CI 5.1, 5.6) per 100 patients years, and at rates that were similar in men (7.0%) and women (8.1%). Among those satisfying criteria, during 11,363 years of follow‐up from the time of first fibromyalgia diagnosis, half of follow‐up time was fibromyalgia+ and was associated with markedly abnormal RA variable and FM variable scores. Demographic factors were weak predictors of fibromyalgia (C = 0.604). Demographic plus RA variables (C = 0.720) and demographic plus fibromyalgia variables (C = 0.765), and all predictors (C = 0.782) increased accuracy. Clinically important hazard ratios were noted for cognition, depression, comorbidity, and high levels of RA and FM continuous variables Overall, study results indicate that multiple, inter‐correlated factors that include social disadvantage, psychological distress, comorbidity, RA severity, and fibromyalgia variables predict future development of fibromyalgia, but there is little evidence of the effect of underlying causes. After diagnosis, patients move in both directions across the diagnostic criteria cut points.

The Longitudinal Outcome of Fibromyalgia: A Study of 1555 Patients

Objective. To describe the diagnosis status and outcome of patients diagnosed with fibromyalgia (FM) by US rheumatologists. Methods. We assessed 1555 patients with FM with detailed outcome questionnaires during 11,006 semiannual observations for up to 11 years. At entry, all patients satisfied American College of Rheumatology preliminary 2010 FM criteria modified for survey research. We determined diagnosis status, rates of improvement, responder subgroups, and standardized mean differences (effect sizes) between start and study completion scores of global well-being, pain, sleep problems, and health related quality of life. (QOL) Results. The 5-year improvement rates were pain 0.4 (95% CI 0.2, 0.5), fatigue 0.4 (95% CI 0.2, 0.05), and global 0.0 (95% CI −0.1, 0.1). The standardized mean differences were patient global 0.03 (95% CI −0.02, 0.08), pain 0.22 (95% CI 0.16, 0.28), sleep problems 0.20 (95% CI 0.14, 0.25), physical component summary of the Short-form 36 (SF-36) 0.11 (95% CI −0.14, −0.07), and SF-36 mental component summary 0.03 (95% CI −0.07, 0.02). Patients switched between criteria-positive and criteria-negative states, with 716 patients (44.0%) failing to meet criteria at least once during 4228.5 patient-years (7448 observations). About 10% of patients had substantial improvement and about 15% had moderate improvement of pain. Overall, FM severity worsened in 35.9% and pain in 38.6%. Conclusion. Although we found no average clinically meaningful improvement in symptom severity overall, 25% had at least moderate improvement of pain over time. The result that emerged from this longitudinal study was one of generally continuing high levels of self-reported symptoms and distress for most patients, but a slight trend toward improvement.

EQ-5D and SF-36 Quality of Life Measures in Systemic Lupus Erythematosus: Comparisons with Rheumatoid Arthritis, Noninflammatory Rheumatic Disorders, and Fibromyalgia

Objective. The Medical Outcomes Study Short-form 36 (SF-36) provides numerical measurement of patient health, but does not include preferences for health states and cannot be used directly in cost-effectiveness analyses. By contrast the Euroqol EQ-5D can be used for cost-effectiveness analyses. The EQ-5D has rarely been used in systemic lupus erythematosus (SLE). We compared SF-36 and EQ-5D values across rheumatic diseases. Methods. We studied 1316 patients with SLE, 13,722 with rheumatoid arthritis (RA), 3623 with non-inflammatory rheumatic disorders (NIRD), and 2733 with fibromyalgia (FM). Results. The mean EQ-5D, physical (PCS) and mental (MCS) component summary scores were 0.72, 36.3, and 44.3, respectively, in SLE. There was essentially no difference among EQ-5D and PCS scores for patients with SLE, RA, or NIRD. MCS was lower in SLE compared with RA and NIRD (44.3, 49.1, 50.8, respectively). All scores were more abnormal in FM (0.61, 31.9, 41.9). Within SF-36 domains, physical function was better, but general health, vitality, social function, role-emotional, and mental health were more impaired in SLE compared with RA and NIRD. In SLE, quality of life (QOL) was predicted by damage, comorbidity, income, education, and age. Fifteen percent of patients with SLE were very satisfied with their health, and their QOL scores (0.84, 45.4, 50.1) were similar to those found in the US population for EQ-5D and MCS, but were slightly reduced for PCS. Conclusion. EQ-5D and PCS are at the same levels in SLE as in RA and NIRD, but are more abnormal in SLE in the MCS and mental health domains. EQ-5D values allow preference-based comparisons with other chronic conditions.

Fibromyalgia, Systemic Lupus Erythematosus (SLE), and Evaluation of SLE Activity

Objective To determine if fibromyalgia (FM) or fibromyalgia-ness (the tendency to respond to illness and psychosocial stress with fatigue, widespread pain, general increase in symptoms, and similar factors) is increased in patients with compared to those without systemic lupus erythematosus (SLE); to determine whether FM or fibromyalgia-ness biases the SLE Activity Questionnaire (SLAQ); and to determine if the SLAQ is overly sensitive to FM symptoms. Methods We developed a 16-item SLE Symptom Scale (SLESS) modeled on the SLAQ and used that scale to investigate the relation between SLE symptoms and fibromyalgia-ness in 23,321 patients with rheumatic disease. FM was diagnosed by survey FM criteria, and fibromyalgia-ness was measured using the Symptom Intensity (SI) Scale. As comparison groups, we combined patients with rheumatoid arthritis and noninflammatory rheumatic disorders into an “arthritis” group and also utilized a physician-diagnosed group of patients with FM. Results FM was identified in 22.1% of SLE and 17.0% of those with arthritis. The SI scale was minimally increased in SLE. The correlation between SLAQ and SLESS was 0.738. SLESS/SLAQ scale items (Raynaud’s phenomenon, rash, fever, easy bruising, hair loss) were significantly more associated with SLE than FM, while the reverse was true for headache, abdominal pain, paresthesias/stroke, fatigue, cognitive problems, and muscle pain or weakness. There was no evidence of disproportionate symptom-reporting associated with fibromyalgia-ness. Self-reported SLE was associated with an increased prevalence of FM that was unconfirmed by physicians, compared to SLE confirmed by physicians. Conclusion The prevalence of FM in SLE is minimally increased compared with its prevalence in patients with arthritis. Fibromyalgia-ness does not bias the SLESS and should not bias SLE assessments, including the SLAQ.