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PubMed1998

Distribution of HLA-DRB1 alleles of patients with polymyalgia rheumatica and giant cell arteritis in a Mediterranean population.

OBJECTIVE: To evaluate HLA-DRB1 associations in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) compared to rheumatoid arthritis (RA). METHODS: One hundred twenty-one patients were included and oligotyped: 79 with PMR alone and 42 with GCA (14 also had PMR). We also genotyped 1609 healthy controls and 433 patients with RA. Statistical analysis included Fisher's exact test and calculation of the odds ratio (95% CI). RESULTS: Compared to controls, the DRB1*04 phenotype was increased in PMR (39.2%; OR = 2.4, p = 0.0005) and GCA (45.2%; OR = 3.1, p = 0.0005). This association was weaker than in RA (p = 0.01). DRB1*07 was more frequent in GCA (31.0%) than in PMR (13.4%; p = 0.03), but the difference was not significant in comparison to controls. The distribution of DRB1*04 subtypes was similar in PMR and GCA, but different from RA and controls. However, the frequency of 0402 and 0403 subtypes could not be distinguished from that in patients with RA. Double occurrence of RA associated alleles was less frequent in PMR and GCA (9.9%; p = 0.005) than in patients with RA (20.8%). There was no significant relationship between markers of disease activity/severity and HLA-DRB1 genes in PMR or GCA. CONCLUSION: PMR and GCA were associated with HLA-DRB1*04, but more weakly than RA. Nevertheless, these data suggest that HLA-DRB1* genes are closely related to susceptibility in PMR, GCA, and RA and do not support the hypothesis of a different linkage to the 3rd hypervariable region of DRB1 alleles. By contrast with RA, HLA-DRB1* genes do not appear to be indicators of disease severity in PMR and GCA.

Aged↗
PubMed2005

Relapse in a population based cohort of patients with polymyalgia rheumatica.

OBJECTIVE: To determine the incidence and the clinical, laboratory, and treatment related predictors of relapse in polymyalgia rheumatica (PMR). METHODS: Using the population based resources of the Rochester Epidemiology Project, we assembled an incidence cohort of subjects with PMR first diagnosed between January 1, 1970, and December 31, 1999. For inclusion, subjects were required to fulfill 3 criteria: (1) age > or = 50 years; (2) bilateral aching and morning stiffness in neck, shoulders, or hip girdle regions; and (3) erythrocyte sedimentation rate (ESR) > or = 40 mm/h. In subjects who fulfilled the first 2 criteria but had a normal ESR, a rapid response to low dose corticosteroids (CS) served as the third criterion. Patients were followed until permanent remission, migration, or a maximum of 5 years after their incidence date. Relapse was defined as an exacerbation of PMR symptoms requiring an adjustment of CS dose (> or = 5 mg) occurring at least 30 days after the incidence date. Time to relapse was modeled using the Kaplan-Meier method. CS treatment patterns were modeled using linear and nonlinear models. Cox regression models were used to evaluate predictors of time to first and subsequent relapses. RESULTS: The study population included 364 patients with a mean age of 73.4 years and 244 (67%) were women. Among the 284 patients treated with CS, a higher initial CS dose and faster CS tapering rate were significant predictors of future relapses, after adjusting for age, sex, ESR, giant cell arteritis at PMR diagnosis, and the intensity of rheumatologist care. Every 5 mg/day increase in initial CS dose was associated with a 7% increase in the risk of relapse [hazard ratio (HR) 1.07, 95% CI 1.02, 1.13]. The hazard of having a relapse was 4-fold higher when the CS tapering rate was fast (HR 4.27, 95% CI 2.84, 6.44), and 2-fold higher when the CS tapering rate was medium (HR 2.19, 95% CI 1.54, 3.11) compared to slow tapering. CONCLUSION: Higher initial CS doses and faster tapering are significant predictors of future relapses. Our results suggest that efforts should be made to minimize initial CS dose and taper CS slowly in order to avoid disease relapses.

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PubMed1983

Polymyalgia rheumatica: a general practice experience.

In the eight years from April 1974 to April 1982, 10 diagnoses of polymyalgia rheumatica were made in an urban general practice. The natural history of the condition, diagnostic problems and occasional unpredictability of outcome are discussed. It is suggested that general practice research may provide answers to some unsolved questions.

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PubMed1984

Polymyalgia rheumatica--a clinical study with particular reference to arterial disease.

The clinical and laboratory findings in patients with polymyalgia rheumatica are described and reviewed against a background of 59 cases. An increased incidence of the disease in summer and winter was noted. The necessity for a sedimentation rate of 50 mm/1 hour as a diagnostic criteria is questioned and the difficulties in management are discussed. The value of examining the vascular tree is emphasized, since vascular bruits and tenderness may be found which disappear with treatment. Viral antibody studies produced negative results. However, an arterial basis for the disease is confirmed by lymphocyte transformation studies. An hypothesis is suggested that an autoallergic reaction to an antigen in the internal elastic lamina may explain the clinical, biochemical and histological abnormalities.

Diagnosis, Differential↗
PubMed1994

Polymyalgia rheumatica and thyroid papillary carcinoma.

This is a case report of a 64-year-old woman with polymyalgia rheumatica (PMR) and thyroid papillary carcinoma. Peripheral blood lymphocyte response to pokeweed mitogen, concanavalin A and phytohemagglutinin was increased compared to controls during aggravation of PMR. These responses were normalized to control values after low-dose corticosteroid therapy (prednisolone 10 mg; 7 days and 7.5 mg; 3 days) and PMR symptoms disappeared. The patient had undergone total neck thyroidectomy and metastatic neck lymph node dissection three and six years after the onset of PMR, respectively. Nine months after the removal of metastatic lymph nodes, she was free of symptoms of PMR and peripheral blood lymphocyte response to mitogens was within the control range. PMR appeared to be a component of the long-standing paraneoplastic syndrome, induced by the tumor which had impaired cell-mediated immunity.

Carcinoma, Papillary↗
PubMedDate not supplied

Immunogenetics of polymyalgia rheumatica.

The distribution of HLA-D region antigens was studied in 17 patients with well-documented polymyalgia rheumatica (PMR). HLA-D region antigens were defined by the oligonucleotide typing of polymerase chain reaction (PCR)-amplified genomic DNA. The results demonstrate that the prevalence of DR4 was significantly higher (p < 0.0002; RR = 8.10) in patients (70.6%) compared to normal controls (22.9%), and the frequency of DR1 and/or DR4 in patients (82.4%) was also higher (p < 0.0006; RR = 8.40) than that in normal healthy controls (35.7%). Of the subtypes of DR4,Dw13 was significantly higher (p < 0.002; RR = 9.30) in patients (29.4%) than in normal controls (4.3%). However, these data must still be confirmed by other investigators. The distribution of the remaining DR antigens and of the DQ and DP alleles in patients did not differ significantly from those in controls. The results suggest immunogenetic similarity between PMR and late onset rheumatoid arthritis in elderly populations.

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PubMed1991

Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy.

We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety-nine patients with PMR and/or GCA were identified over a 9-year period (1980-1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980-1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed.

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PubMed2002

[Follow-up studies in polymyalgia rheumatica and temporal arteritis].

OBJECTIVE: To analyze the clinical course and duration of therapy in 28 patients with polymyalgia rheumatica (PMR) and/or temporal arteritis (TA) for identifying factors that influence prolonged steroid use and relapses. METHODS: 28 cases of PMR and/or TA diagnosed from 1992 to 2001 were retrospectively studied in PUMC hospital. Patients were grouped according to the absence or presence of corticosteroid resistant and relapses. RESULTS: Of 28 patients, 22 had pure PMR, 3 had both PMR and TA and 3 had pure TA. 15 patients received corticosteroid therapy and 13 had both corticosteroid and immunosuppressor therapy. The median duration was (25.5 +/- 24.0) months. Increase of white blood cell level and higher baseline erythrocyte sedimentation rate (ESR) were significant risk factors associated with corticosteroid resistant (P < 0.01). Quicker reduction of corticosteroid dose was associated with relapse (P < 0.05). CONCLUSIONS: Patients with increase of white blood cell level and higher baseline erythrocyte sedimentation rate (ESR) are more likely to be resistant to corticosteroid therapy. Quicker reduction in corticosteroid is more likely to relapse. Immunosuppressor therapy should be added to patients who has corticosteroid resistant, and relapse or PMR associated with TA.

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PubMed1983

Decrease of the OKT8 positive T cell subset in polymyalgia rheumatica. Lack of correlation with disease activity.

Peripheral T cell populations were investigated in 35 patients suffering from polymyalgia rheumatica. The total number of T cells was low compared with those of a control group of similar age (P less than 10(-3). This decrease was demonstrated by using both classic E-rosette and monoclonal antibody techniques (OKT3, and OKT4 + OKT8) and was shown to be secondary to a selective T8 defect (P less than 10(-9). There was no correlation between the decrease in T8 (a cytotoxic suppressor T cell subset) and steroid therapy, disease activity, and temporal arteritis, nor between this decrease and the T gamma percentage and the presence of circulating immune complexes (CIC). The T gamma cell percentage was low in the patient group (P less than 10(-5) and correlated with the presence of detectable CIC (P less than 0.05). In contrast to the T8 and T gamma defects, concanavalin A-stimulated cells from 5 selected patients were found capable of suppressing in vitro anti-trinitrophenyl response. This suppression was found in both autologous and allogeneic experiments. From these data one can assume that an immune anomaly (T8 defect) could be the origin of CIC and the disease occurrence.

Aged↗
PubMed1998

Distal musculoskeletal manifestations in polymyalgia rheumatica: a prospective followup study.

OBJECTIVE: To determine the frequency and the characteristics of distal musculoskeletal manifestations in polymyalgia rheumatica (PMR). METHODS: Prospective followup study of 177 consecutive patients meeting clinical criteria for PMR, diagnosed over a 5-year period in 2 rheumatology secondary referral centers in Italy. RESULTS: Seventy-nine of the 177 patients (45%) had distal musculoskeletal manifestations. Peripheral arthritis occurred in 45 patients (25%), carpal tunnel syndrome in 24 (14%), distal extremity swelling with pitting edema in 21 (12%), and distal tenosynovitis in 5 (3%). These manifestations were usually associated with PMR proximal symptoms (69%); however, 31% of the episodes represented isolated relapse/recurrence at distal sites. Distal symptoms responded promptly to corticosteroids. No evidence of joint deformities, erosions, or development of rheumatoid arthritis was observed during the followup. The group of patients with peripheral arthritis included a higher proportion of females, had a longer duration of therapy, and had more relapses/ recurrences. Patients who had distal extremity swelling with pitting edema had a higher age at disease onset, a shorter duration of therapy, and lower initial and cumulative prednisone doses. CONCLUSION: Inflammatory involvement of distal articular and/or tenosynovial structures occurs in approximately half of the cases of PMR. Peripheral arthritis is associated with more severe disease, while distal extremity swelling with pitting edema appears to identify a more benign disease subset.

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PubMed2001

Survival in polymyalgia rheumatica and temporal arteritis: a study of 398 cases and matched population controls.

OBJECTIVE: To estimate survival in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS: The present study encompassed 338 incident cases who were diagnosed at the Department of Rheumatology during the period 1987-1997 and 60 cases diagnosed in the same period but admitted to hospital for reasons other than PMR or TA. The 398 patients were each assigned four age- and sex-matched controls from the same population and mortality ascertained. RESULTS: Among the 338 incident cases, there were 69 deaths compared with 360 deaths among their 1352 controls. The mortality was thus 28% lower in cases than in controls [relative risk (RR)=0.72, 95% confidence interval (CI) 0.55-0.95]. The 274 incident cases with pure PMR had increased survival compared with controls (RR=0.70, 95% CI 0.52-0.95), whilst among the 64 incident TA patients and their controls, no difference in mortality was found (RR=1.2, 95% CI 0.55-2.74). Patients diagnosed at other departments and their controls had the same mortality. In the incident cases, the mean initial dose of prednisolone, the mean maintenance dose of prednisolone, the mean initial erythrocyte sedimentation rate and C-reactive protein and frequency of peripheral arthritis did not differ between survivors and those dying during the observation period. CONCLUSION: The study showed increased survival in patients with PMR compared with controls, whilst mortality in TA equalled that of controls. There was no association between use of corticosteroids and level of disease activity and death. The increased survival in PMR might be explained by improved medical surveillance.

Female↗
PubMed1976

Liver involvement in polymyalgia rheumatica.

The incidence of abnormal results in liver function tests was determined in 37 of 51 patients with polymyalgia rheumatica (PMR) or temporal arteritis. Fine-needle biopsies fo the liver were performed on 6 of these patients and the bile canalicular network and liver cytology were studied in the aspirate by enzyme-cytochemical methods. Of the 37 patients in whom it was measured, 23 (62%) had elevated concentrations of serum alkaline phosphatases (AP), mainly of hepatic origin. The concentrations of other serum enzymes associated with hepatic function were normal in all 37 patients. BSP retention was studied in 13 patients and was abnormal in 6 (46%). Three of the 4 patients for whom smears were stained for AP activity had an increase in this activity in their bile canaliculi that corresponded to a rise in the serum concentration of AP. In one of these 3 patients, smears stained for naphthylamidase showed that bile canaliculi had a calibre wider than normal and had granular walls. A second biopsy performed 10 days showed a partial reversal of these changes. Mild fatty infiltration of the liver cells was seen in 2 patients; one patient whose serum concentration of AP was normal also had normal liver cells and bile canaliculi. The structural changes in the bile canaliculi detected in one patient may be evidence of a subclinical hepatic disease associated with PMR. The cholestatic hepatic dysfunction, common in PMR and manifested in over half of our patients by elevated serum AP levels, can easily be confirmed with special staining methods for visualizing the bile canaliculi in cytological liver specimens.

Adrenal Cortex Hormones↗
PubMed1998

Giant cell arteritis and polymyalgia rheumatica can be differentiated by distinct patterns of HLA class II association.

OBJECTIVE: To determine whether patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) exhibit identical HLA class II associations. METHODS: A case-control association study was performed on a population sample from Lugo, in Northwestern Spain. DNA samples were available for 128 patients and 145 ethnically matched controls. Within the patient group 26 exhibited both PMR and GCA, 75 PMR alone, and 27 GCA alone. HLA-DRB1, DQA1, and DQB1 phenotypes were defined by molecular based techniques. RESULTS: HLA-DRB 1*0401 was associated with GCA regardless of PMR status, although this only reached statistical significance in the total GCA group. This was also seen for DRB 1*0101, *0102, although the association was less strong. Patients with PMR without GCA were not associated with DRB1*0401 or *0101, *0102, but exhibited a significant association with DRB1*13, *14. Nonsignificant increases in DQA1 and DQB1 phenotype frequencies appeared to reflect known patterns of linkage disequilibrium with the HLA-DRB1 alleles associated with GCA and PMR groups. An association was observed between the presence of the RA DRB1 shared epitope (SE) and GCA but not with PMR in the absence of GCA. This association was primarily accounted for by the presence of a single copy of the SE, and homozygosity for the SE did not confer additional risk. A high frequency of SE-bearing DRB1 alleles was observed in patients with GCA with jaw claudication or visual manifestations, although the sample size of these subgroups was small. CONCLUSION: PMR and GCA in a Northwestern Spanish population have distinct HLA class II associations. HLA is unlikely to account for the observed high level of overlap in these patients, and other etiological factors may be involved.

Aged↗
PubMed2000

Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study.

OBJECTIVE: To determine the frequency and clinical features of patients with polymyalgia rheumatica (PMR) and normal erythrocyte sedimentation rate (ESR) at diagnosis or during relapse/recurrence. To evaluate the usefulness of C-reactive protein (CRP) and ESR in the assessment of PMR activity. METHODS: A prospective follow-up study on 177 consecutive patients meeting the criteria for PMR diagnosed over a 5-year period was conducted in two Italian secondary referral centers of rheumatology. At diagnosis and during follow-up, ESR (Westergren method) and CRP (nephelometry) were measured in all patients. Phenotypic analysis of lymphocyte subpopulations was performed on 78 PMR patients at diagnosis. A two-color technique using the association of specific monoclonal antibodies was applied. A control group consisting of 18 healthy adults older than 60 years was matched for age and sex with the PMR patients. RESULTS: Ten of 177 (6%) patients had normal ESR values at diagnosis (< or = 30 mm/h). Patients with normal ESR were predominantly men and had lower CRP levels; systemic signs and symptoms were more frequent in patients with higher ESR. The percentages of circulating CD8+ cells were similar in the two groups. CRP values at diagnosis were normal in only 2 of 177 (1%) patients. CRP values were elevated in 9 of 10 patients with normal ESR at diagnosis. Twenty-five episodes of relapse/recurrence with normal ESR occurred in 17 patients. CRP was high in 62% of these episodes. Results of univariate analysis indicated that the 10th percentile for ESR (40 mm/h) and the 70th percentile for CRP (7.8 mg/dL) values at diagnosis were the best cutoff points that discriminate between patients with and without relapse/recurrence. Cox proportional hazards modeling showed that ESR greater than 40 mm/h and CRP greater than 7.8 mg/dL at diagnosis were the two variables that independently increased the risk of relapse/recurrence. However, the relative risk related to ESR was twice than that related to CRP (4.9 vs 2.1). CONCLUSION: PMR with a normal ESR at diagnosis was infrequent in our study compared with previous studies. ESR was a superior predictor of relapse than CRP. However, CRP was a more sensitive indicator of current disease activity.

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PubMed1991

Prevalence of hypothyroidism in patients with polymyalgia rheumatica and giant cell arteritis.

The prevalence of thyroid disease and thyroid autoantibodies was evaluated in 367 patients with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA). Thirty-seven patients had antibodies to thyroid microsomes or thyroglobulin; 18 had hypothyroidism requiring thyroxine replacement therapy. The prevalence of hypothyroidism (4.9%) was significantly greater than that found in 84 control subjects.

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PubMed1983

Polymyalgia rheumatica: an arthroscopic study of the shoulder joint.

A careful selection of 19 patients fitting the classical description of polymyalgia rheumatica have been examined by arthroscopy and thoroughly screened and followed up to exclude rheumatoid arthritis and other disease processes. Synovitis of the shoulder joint has been observed through the arthroscope in 17 and synovitis of varying degrees noted histologically, 4 of whom were studied by immunofluorescence. Five patients had radioactive joint scans.

Aged↗
PubMed2002

Cortisol, dehydroepiandrosterone sulfate, and androstenedione levels in patients with polymyalgia rheumatica during twelve months of glucocorticoid therapy.

This paper aims to evaluate adrenal gland hormone levels in patients with polymyalgia rheumatica (PMR) during glucocorticoid (GC) therapy. A lower than expected basal production of cortisol was found in active and glucocorticoid-untreated PMR patients, particularly females. The abrupt onset of PMR with clinical features similar to those of the steroid-withdrawal syndrome or adrenal insufficiency, as well as the clinical response to GC therapy in elderly people already age-disposed to an inadequate adrenal and anti-inflammatory response, might represent the most significant pathophysiological basis of the disease.

Adrenal Cortex↗