Low serum levels of DHEAS in untreated polymyalgia rheumatica/giant cell arteritis

OBJECTIVE: To address a controversy regarding the existence of a relative adrenal hypofunction in patients with untreated polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) we evaluated baseline serum levels of ACTH, cortisol, and DHEAS in a cohort of patients with recent onset PMR/GCA not previously treated with glucocorticoids, in comparison with healthy controls. Possible correlations between baseline DHEAS levels and laboratory measures of disease activity were also explored. METHODS: Basal serum levels of these hormones were prospectively investigated in 25 patients with active untreated disease and compared with those of 25 age- and sex-matched control subjects. RESULTS: Of the 25 patients, 19 had isolated PMR and 6 had biopsy-proven GCA + PMR. Basal levels of cortisol and ACTH in PMR/GCA patients did not differ from control subjects; in relation to inflammatory status, lower than expected basal production of cortisol was observed in active untreated PMR/GCA. Baseline serum DHEAS levels were significantly lower in all patients compared with controls. In these patients, a significant correlation was found between baseline DHEAS values and laboratory measures of disease activity. The percentage of DHEAS reduction and the severity of inflammatory response were higher in women than in men. CONCLUSION: Patients with PMR/GCA with new-onset active disease before steroid treatment have inappropriately normal cortisol levels regarding the ongoing inflammation, and significantly lower levels of DHEAS compared to the age- and sex-matched healthy control subjects. These data support the existence of a relative adrenal hypofunction in PMR and GCA.     

The clinical and laboratory course of polymyalgia rheumatica/giant cell arteritis after the first two months of treatment.

OBJECTIVES--To examine the clinical course of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in a prospective study, after the initial two months. METHODS--Seventy four patients with PMR/GCA were followed for a median of 60 weeks. Detailed clinical and laboratory records were made on each visit. RESULTS--Twenty per cent of patients with PMR developed GCA and 24% of patients with GCA developed PMR from the onset of symptoms. After two months, most patients experienced at least one relapse. Relapses and persistence of abnormal symptoms and signs were most common in patients with both PMR and GCA and least common in those with GCA alone. Relapses were most common in the first year and 54% occurred in association with steroid reduction. Major complications were rare. Laboratory parameters and temporal artery histology were not helpful in predicting relapse. Only 24% of patients were able to stop steroid treatment after two years. CONCLUSIONS--Clinicians should consider more frequent review in patients at times of steroid reduction and especially within the first six months of treatment.     

Are polymyalgia rheumatica and giant cell arteritis the same disease?

OBJECTIVE: To summarize the evidence about the relationship between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: Review of relevant articles from the English-language literature. RESULTS: Epidemiologic studies suggest that PMR and GCA are closely related conditions affecting people over 50 years and frequently occurring in the same patient. PMR symptoms have been observed in 40 to 60 percent of GCA clinical series. Also, temporal artery biopsy may yield positive results for GCA in patients with isolated PMR. Conflicting HLA-DRB1 genotype results have been reported, and recent studies have shown that PMR and GCA have different expression of RANTES, TNFalpha microsatellite, and IL-6 promoter genetic polymorphisms. Search for a possible common infectious agent have yielded disappointing results. Although parvovirus B19 DNA is present in the artery wall of patients with GCA, this virus may be only an innocent bystander. Cytokine studies on a limited number of temporal artery biopsy specimens have shown that interferon-gamma is produced in GCA and not in PMR, suggesting that this cytokine may be crucial to the development of overt vasculitis. CONCLUSIONS: PMR and GCA frequently occur together but no definitive conclusions can be drawn about the nature of this association.     

Homocysteine levels in polymyalgia rheumatica and giant cell arteritis: influence of corticosteroid therapy

OBJECTIVES: It has been suggested that patients with giant cell arteritis (GCA) may share a common pathway with atherosclerosis. Furthermore, patients with GCA and polymyalgia rheumatica (PMR), in addition to advanced age, are treated for prolonged periods of time with corticosteroids, a factor that can also accelerate atherosclerosis. Hyperhomocysteinaemia is considered an independent risk factor for atherosclerosis, and might play a role in ischaemic manifestations that occur with a variable frequency during the course of GCA. The purposes of the present study were: (i). to analyse the plasma levels of homocysteine in patients with GCA and PMR, (ii). to determine the influence of corticosteroid therapy on the homocysteine levels and (iii). to analyse if the levels of homocysteine may predict the development of ischaemic complications in patients with GCA. METHODS: Plasma homocysteine concentration was measured in 56 patients with active PMR/GCA (17 GCA and 39 isolated PMR) before steroid treatment and 23 healthy age-matched volunteers were used as controls. The total plasma homocysteine level was quantified using a fluorescent polarization immunoassay. RESULTS: Homocysteine concentrations were higher in PMR and GCA patients than age-matched controls (P < 0.05). Patients with GCA had slightly higher levels of plasma homocysteine than those with isolated PMR (13.6+/-4.3 vs 12.7+/-3.1 micromol/l, P=0.6). In 30 of these patients (12 GCA and 18 PMR) a second measurement of homocysteine concentration was done when they were in clinical remission with steroid treatment. The post-treatment levels of homocysteine were significantly increased in GCA rather than in PMR patients. In 13 patients with homocysteine levels above the normal upper limit of our laboratory, therapy with folic acid and/or vitamin B12 was started. After 3 months of vitamin supplements, the homocysteine concentration significantly decreased from 19.2+/-3.1 to 13.6+/-3.2 micromol/l (P=0.001). Such decrease was less marked in the PMR than in GCA patients. Ten out of the 17 patients with GCA had ischaemic manifestations of the disease. The levels of homocysteine were slightly higher in GCA patients with ischaemia than in those without ischaemic manifestations, although the difference did not reach statistical significance (15+/-4.9 vs 11.6+/-1.9 micromol/l, P=0.46). CONCLUSIONS: Patients with active PMR and GCA had elevated plasma concentrations of homocysteine. Corticosteroid therapy significantly increased such levels, especially in GCA patients. Treatment with supplements of folic acid and/or vitamin B12 reduced the homocysteine concentrations. These data support the hypothesis that patients with GCA (and to a lesser extend PMR patients) may share a common pathway with atherosclerosis and suggest a new atherogenic mechanism of corticosteroids.     

Circulating CD8+ T cells in polymyalgia rheumatica and giant cell arteritis: a review

BACKGROUND AND OBJECTIVE: During the last few years, there have been several studies on T cell subsets in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), with conflicting results. Whereas some authors have found normal values of circulating CD8+ T cells, others have found a decreased number. Furthermore, in some studies, the level of CD8+ cells was found to be related to disease activity, and it has been proposed that a decrease of CD8+ T cells be used as a diagnostic criterion for PMR. The purpose of our study was to determine the value of assessing T cell subsets in PMR and GCA. METHODS: T lymphocyte subsets were determined by flow cytometry using a whole blood lysis technique in the following groups: 28 PMR and 6 GCA patients before corticosteroid treatment, 20 PMR and 12 GCA patients in clinical remission with steroid treatment, 55 PMR patients in remission without steroid treatment, 17 rheumatoid arthritis (RA) patients before treatment, and 18 age-matched controls with noninflammatory conditions. Total white cell, lymphocyte, and platelet counts, hemoglobin, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured by routine techniques. Comparisons were made by the Student's t-test and the Mann-Whitney test. A MEDLINE database search for studies published between 1983 and 1997 was performed. RESULTS: Compared with noninflammatory controls, CD8+ T cells were not reduced before steroid treatment in patients with active PMR/GCA in proportion (P =.7) or absolute numbers (P =.1). Patients with active disease had significantly lower hemoglobin levels and higher platelet counts, CRP, and ESR than noninflammatory controls (P <.05). When compared with active RA, CD8+ T cells were not reduced in patients with active PMR in proportion (P =.5) or absolute numbers (P =.2). Between these two groups, RA patients were significantly younger (P =.003) and had lower ESR values (P =.003). We did not find significant differences between patients with active PMR/GCA and those in remission with steroid therapy, except for the lower hemoglobin levels and higher platelet count, CRP, and ESR in the active disease group (P <.05). The same results were found when patients with active disease were compared with PMR in remission and no longer on steroid therapy, the only significant differences were those parameters reflecting the acute phase response (hemoglobin levels, platelet count, CRP and ESR). CONCLUSIONS: This study does not confirm the previous findings that the proportion or number of circulating CD8+ T cells are reduced in patients with active PMR/GCA. The utility of the determination of CD8+ T cells for diagnostic and prognostic purpose should be evaluated in a large multicenter study.     

Prognosis and management of polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is considered to be a benign disease by some, while others think it is a more serious illness which required similar treatment to giant cell arteritis (GCA). The progress of 85 patients with PMR who presented to a district general hospital has been studied in an attempt to study this relationship. Thirty-eight patients had PMR alone, and 14 developed PMR and GCA within 1 month. Five patients presented with GCA and then developed PMR, and 28 patients developed symptoms of GCA after presenting with PMR (PMR leads to GCA). Arteritis and complications developed up to 9 years after the onset of PMR (mean 1 year). Twenty-two patients (26%) developed some cerebral or visual complication. Fifteen of these patients were in the PMR leads to GCA group. All 6 patients with permanent loss of vision were in this group. Seven patients developed complications while on corticosteroids. 97% of patients required corticosteroids for at least 1 year; 32% of patients still required 10 mg of prednisone or more after 1 year. PMR is not a benign disease.     

Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

OBJECTIVE: To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical phenotypes of PMR/GCA. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 102 Danish patients with PMR (n = 37) or GCA (n = 65). Two hundred fifty and 193 healthy individuals served as controls for MBL and HLA genotyping, respectively. RESULTS: The prevalence of MBL variant alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin. CONCLUSION: We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR/GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease process.     

巨细胞动脉炎与风湿性多肌痛临床特征的对比分析

目的:通过比较风湿性多肌痛（PMR）和巨细胞动脉炎（GCA）的临床差异,总结GCA患者的临床特点。方法:收集皖南医学院附属弋矶山医院风湿免疫科2010年8月至2019年9月住院的12例巨细胞动脉炎患者临床资料,并选择同期住院的,与GCA组患者进行2∶1年龄、性别相匹配的PMR患者形成对照组,比较2组患者的临床表现、实验...     

Management of difficult polymyalgia rheumatica and giant cell arteritis: Updates for clinical practice

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) represent a family of systemic inflammatory diseases occurring in adults aged 50 years and above. Clinical presentation of PMR/GCA can be variable, making diagnosis at times challenging. There has been an increased appreciation of the role of various large-vessel imaging modalities to help confirm a diagnosis of GCA. Systemic corticosteroids (CS) remain the mainstay of treatment for both PMR and GCA, yet both relapses and CS-related side effects are common. Recent research has demonstrated efficacy of certain biologic agents in these diseases, with particular emphasis on the role of interleukin-6 (IL-6) blockade in GCA. This chapter discusses the latest updates on the diagnosis and treatment of PMR/GCA, with an emphasis on clinical care.     

MMP-3 can distinguish isolated PMR from PMR with GCA: A retrospective study regarding PMR and GCA in Japan

Objective. We sought to identify clinical features at diagnosis that can distinguish isolated polymyalgia rheumatica (PMR) without giant cell arteritis (GCA) from PMR with GCA, and clinical features at diagnosis of isolated PMR that can predict subsequent relapse and corticosteroid discontinuation.

Methods. A retrospective study of 115 patients with isolated PMR and 29 patients with GCA was performed. A comparison between isolated PMR patients, GCA patients (with or without PMR), and PMR with GCA patients was performed. Predictors of relapse and corticosteroid discontinuation were identified using a logistic regression in the patients with isolated PMR.

Results. Matrix metalloproteinase-3 (MMP-3) level was significantly different among the patient groups. MMP-3: 230.5 ± 201.5 ng/mL in isolated PMR, 80.5 ± 47.5 ng/mL in GCA (p < 0.01), and 96.8 ± 54.8 ng/mL in PMR with GCA (p = 0.03). In the patients with isolated PMR, female gender (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.16–6.41; p < 0.05) and creatinine (Cr) < 50 μmol/L (OR, 2.48; 95% CI, 1.02–5.99; p < 0.05) were significant prognostic factors that predicted relapse.

Conclusion. A low level of MMP-3 is an excellent positive predictor for PMR with GCA. Among patients with isolated PMR, female gender and Cr < 50 μmol/L were significant prognostic factors that predicted relapse.     

Polymyalgia rheumatica: a syndrome associated with HLA-DR4 antigen

HLA class II antigens were determined in 65 patients with biopsy-proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr less than 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P less than 0.005). HLA-DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P less than 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4-associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.     

Rheumatic polymyalgia

Polymyalgia rheumatica (PMR) is a common clinical syndrome that is characterized by pain and stiffness in neck, shoulder girdle and pelvic girdle. The aetiology is unknown. However, recent studies have documented an association with HLA antigens and infectious agents. It occurs mostly after the age of 50 years and is often accompanied by systemic features such as fever, asthenia, hyporexia and weight loss. An erythrocyte sedimentation rate (ESR) of at least 40 mm/hour has been considered diagnostic criterion. Nevertheless, a normal ESR accounted for up to 20% of cases of PMR. A dramatic and prompt response to corticosteroid treatment is characteristic. Giant cell arteritis/temporal arteritis (GCA) has been found in 0-80% of cases of PMR. Temporal biopsy could initially be deferred in patients with PMR younger than 70 years with no cranial symptoms, in which the risk of GCA is very low.     

Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms

OBJECTIVE: To determine whether giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are associated with different tumor necrosis factor (TNF) microsatellite polymorphisms. METHODS: Typing of TNF microsatellite polymorphisms was carried out by molecular-based techniques on DNA obtained from a population sample of residents from Lugo, northwestern Spain. A case-control approach was used to compare 136 patients with GCA and/or PMR with 147 ethnically matched controls. The association of disease with TNF microsatellite polymorphisms was investigated using chi-square tests and multivariate logistic regression analyses. RESULTS: Different TNF microsatellite associations were found with GCA and PMR. In patients with isolated GCA, the primary association was with TNFa2, which was independent of the GCA associations with HLA-DRB1*0401 and *0101. A negative association was found with TNFa10. In patients with isolated PMR, there was a positive association with TNFb3. This was found to be independent of the HLA-DRB1*13/*14 association in isolated PMR. TNFd4 was negatively associated with isolated PMR. Forward stepwise logistic regression analyses indicated that the strongest association with GCA was provided by the TNFa2 allele, although DRB1*0401 and *0101 were still associated. PMR was primarily associated with TNFb3. A direct comparison of TNF allele frequencies between isolated GCA and isolated PMR indicated that the main difference between these conditions occurred in the frequency of TNFa10. CONCLUSION: GCA and PMR in individuals from northwestern Spain are associated with different TNF microsatellite polymorphisms. The primary TNF associations (TNFa2 and TNFb3) appear to influence susceptibility to these conditions independent of any HLA-DRB1 association.     

Liver scan abnormalities in polymyalgia rheumatica/giant cell arteritis

Summary Liver involvement in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) before treatment and during follow-up of up to 3 1/2 years was assessed in 74 patients clinically, with liver function tests, isotope scans and blood flow studies. Twenty-seven patients had elevated alkaline phosphatase levels which fell to normal after 2.6 weeks treatment. Both PMR and GCA patients were affected, the latter more commonly. Isotope scans were abnormal in 7 of 29 patients and remained abnormal on follow-up. The arterial fraction of hepatic flow was significantly reduced in GCA patients in comparison with those having PMR only; values became normal after treatment. These abnormalities may be due to hepatic arteritis.     

Small-vessel vasculitis surrounding an uninflamed temporal artery: a new diagnostic criterion for polymyalgia rheumatica?

OBJECTIVE: To assess the prevalence and clinical significance of small-vessel vasculitis (SVV) surrounding an uninflamed temporal artery (TA) in patients diagnosed as having giant cell (temporal) arteritis (GCA) and/or polymyalgia rheumatica (PMR). METHODS: Patients with GCA and/or PMR (n = 490) were included in this multicenter prospective study. Slides of TA biopsy specimens were reviewed by 2 pathologists who were blinded with regard to clinical information. SVV was defined as aggregates of mononuclear inflammatory cells surrounding a capillary, distant from an uninflamed temporal artery. Clinical and biologic data of patients in the SVV group (n = 35) were compared with data of patients with biopsy-proven GCA (n = 280) and with negative TA biopsy findings (n = 175). RESULTS: SVV was diagnosed in 18 women and 17 men (mean +/- SD age 74.5 +/- 9.4 years). The group of patients with SVV had a higher proportion of men than in the entire GCA series, had systemic symptoms, headache, jaw claudication, and an abnormal temporal artery less frequently at clinical examination, but had symptoms of PMR more often than patients in the biopsy-proven GCA group (P = 2.6 x 10(-7), odds ratio 9.17 [95% confidence interval 3.44-24.4]). Levels of inflammation markers were significantly lower in the SVV group. Patients in the SVV group had fever less frequently than patients in the group with negative TA biopsy findings, but otherwise shared the same clinical (including PMR symptoms) and biologic features. Eighteen of the 94 patients with pure PMR (19%) had SVV. CONCLUSION: SVV is often neglected by pathologists, and appears to be strongly associated with PMR symptoms in patients with a clinical diagnosis of GCA and/or PMR. However, SVV as a new diagnostic criterion for PMR must be assessed in prospective studies.     

Circulating T cell subtypes in polymyalgia rheumatica and giant cell arteritis: variation in the percentage of CD8+ cells with prednisolone treatment.

OBJECTIVES--Some reports have described a decreased percentage of circulating CD8+ cells in patients with polymyalgia rheumatica and giant cell arteritis (PMR/GCA) before treatment and persisting for some months during treatment with corticosteroids. Other studies have found no such changes. There are overt methodological variations between these studies and there may also hidden differences, such as the timing of blood samples. The purpose of this study was to investigate T cell subtypes in patients with PMR/GCA while controlling for variables known to affect T cells. METHODS--Circulating T cell subsets were measured in 36 patients with PMR/GCA before and during treatment with prednisolone. Blood samples during treatment were taken before the daily dose of prednisolone. The whole blood lysis method was used followed by flow cytometry. RESULTS--Compared with controls, CD8+ cells were not reduced before treatment in patients with PMR/GCA (0.44 x 10(9)/l; 28% of lymphocytes). CD4+ cells were also normal (0.78 x 10(9)/l; 48% of lymphocytes). During treatment with prednisolone total T cells increased from 1.18 to 1.59 x 10(9)/l and CD4+ cells increased from 0.78 to 1.05 x 10(9)/l. The percentage of CD8+ cells decreased on treatment from 28 to 25%. CONCLUSIONS--This study does not confirm the finding of some groups that the percentage of circulating CD8+ cells is reduced in patients with PMR/GCA before treatment. It does show that the percentage of CD8+ cells decreases during treatment with corticosteroids. This needs to be considered when designing studies of lymphocyte subsets in diseases treated with corticosteroids.     

Polymyalgia rheumatica: a syndrome associated with hla–dr4 antigen

HLA class II antigens were determined in 65 patients with biopsy-proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr < 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P < 0.005). HLA–DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P < 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4-associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.     

Selective depletion and activation of CD8+ lymphocytes from peripheral blood of patients with polymyalgia rheumatica and giant cell arteritis.

A prospective study of 33 patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) was undertaken, firstly, to monitor sequentially peripheral blood CD8+ lymphocyte levels and, secondly, to assess the expression of activation markers on T lymphocyte subsets. The results indicated that there was a significant decrease in absolute numbers and relative percentages of CD8+ T lymphocytes, which returned to normal ranges after approximately 24 months' treatment, and that there was an increased percentage of CD8+ lymphocytes in PMR/GCA which express HLA class II antigens.