A longitudinal study of calprotectin in patients with polymyalgia rheumatica or temporal arteritis: relation to disease activity

OBJECTIVE: Calprotectin is a granulocyte and monocyte cytosolic protein that is released during activation of these cells. The plasma level of calprotectin is raised in various inflammatory conditions and correlates with disease activity in a wide range of rheumatic diseases. We wanted to investigate whether calprotectin may be useful as a measure of disease activity in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS: Forty-seven patients with PMR and/or TA were followed up to 3 years in a prospective longitudinal design. Plasma calprotectin was correlated with acute phase parameters, erythrocyte sedimentation rate (ESR), and peroral steroid usage before start of treatment and at four subsequent time intervals. RESULTS: Thirty-three patients had PMR, 10 had TA, and four had both diagnoses. Calprotectin was highly correlated with the acute phase parameters and ESR during the study period. Calprotectin was significantly decreased after start of treatment with oral prednisolone, and correlated with the daily dosage of prednisolone (r = 0.36, p < 0.01). CONCLUSION: Calprotectin plasma levels were significantly associated with acute phase parameters, ESR, and prednisolone usage in PMR and TA, indicating that calprotectin may be a good measure of disease activity in these conditions.     

Joint involvement in polymyalgia rheumatica/temporal arteritis

The coincidence of arthritis with polymyalgia rheumatica (PMR) or temporal arteritis (TA) is not well established. After reviewing the literature we found that 22% of patients suffering from PMR/TA present with additional signs of inflammatory joint involvement. Joints predominantly affected are the sternal junctions, knee and shoulder joints, and the wrists, involvement of the latter frequently resulting in carpal tunnel syndrome. With the exception of sternal junctions, bony erosions are rarely seen. In most cases, synovitis is mild, pauciarticular, asymmetrical, transient and not destructive. Little evidence for inflammatory involvement of spine or sacroiliac joints was found, thus, back pain in these patients should be considered as caused by osteoporosis of the spinal column, mostly due to prolonged corticosteroid treatment.     

Reduced helper (OKT4 +): suppressor (OKT8 +) T ratios in aplastic anaemia: relation to immunosuppressive therapy

T cell subset composition of peripheral blood and bone marrow from 22 patients with aplastic anaemia (AA) was studied by monoclonal antibodies (OKT3, OKT4 and OKT8). In the peripheral blood, OKT3 (pan-T), OKT4 (helper/inducer-T) and OKT8 (suppressor-T) cells varied widely in number. The ratios of OKT4:OKT8 exhibited the same tendency. However, a subgroup of AA with a reduced ratio of lower than 1.0 was present both in cases with or without prior prednisolone therapy. Of the eight patients treated with immunosuppressants, four with reduced ratios responded, whereas the other four with normal or higher ratios did not. The ratios of two of four responders gradually reached the normal level. These results suggest that the reduced OKT4:OKT8 ratio may be related to the cell-mediated immunosuppressive mechanism postulated as a cause of stem cell inhibition in a subgroup of AA, and indicate prospectively the effectiveness of immunosuppressive therapy.     

Musculoskeletal manifestations in polymyalgia rheumatica and temporal arteritis

OBJECTIVE: To evaluate the incidence and characteristics of musculoskeletal manifestations in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS: The records of 163 cases of PMR or TA diagnosed over a 15 year period in one area of Spain were reviewed for the presence and type of musculoskeletal manifestations. RESULTS: Of 163 patients, 90 had isolated PMR and 73 had TA. Eighteen of the 90 patients (20%) with isolated PMR developed distal peripheral arthritis either at diagnosis or during the course of the disease. When it occurred, synovitis was mild, monoarticular or pauci-articular, asymmetrical, transient, and not destructive. Other distal manifestations observed in these patients were carpal tunnel syndrome and distal extremity swelling with pitting oedema. In all cases these manifestations occurred in conjunction with active PMR. As expected, PMR was the most frequent musculoskeletal manifestation in patients with TA, occurring in 56% of cases. On the contrary, only 11% of patients with TA developed peripheral arthritis. An important finding was that peripheral arthritis in these patients appears to be linked only temporally to the presence of simultaneous PMR and is not observed in its absence. Distal extremity swelling or defined polyarthritis were not observed. CONCLUSION: The spectrum of distal musculoskeletal manifestations of PMR in our series is similar to that reported in other populations. By contrast, distal musculoskeletal symptoms are uncommon in TA. The almost complete absence of distal musculoskeletal manifestations in patients with pure TA suggests different mechanisms of disease in PMR and TA, supporting the view of two separate conditions or one common disease in which host susceptibility influences the clinical expression.     

Sex differences in temporal arteritis and polymyalgia rheumatica

OBJECTIVE: Sex-specific differences in treatment outcomes have been observed in polymyalgia rheumatica (PMR) and temporal arteritis (TA), with a significantly longer course of treatment in women than in men. We analyzed whether these sex differences are related to differences in disease presentation and severity of the inflammatory response. METHODS: The records of 163 cases of PMR and/or TA diagnosed over a 15 year period were reviewed. A comparative study of clinical and laboratory features between men and women was performed. RESULTS: Of 163 patients, 90 had isolated PMR and 73 had TA. Among patients with TA, 49 women and 24 men were identified, with a ratio of 2. While there were no differences in the frequency of classic disease manifestations, the presence of constitutional syndrome (malaise, anorexia, and weight loss) and fever were significantly more frequent in women than in men. Of note, evaluation of laboratory measures at time of diagnosis also revealed more marked laboratory abnormalities reflecting inflammation in the female group. Among patients with isolated PMR, 58 women and 32 men were identified, a ratio of 1.8. Comparing the clinical features at presentation, significant sex differences were also found, with a higher frequency of constitutional syndrome and lower values of hemoglobin in women. Moreover, women also had higher erythrocyte sedimentation rate values, and higher prevalence of fever and hepatic involvement, although the difference did not reach statistical significance. CONCLUSION: Modest differences were found in disease expression between women and men with TA and/or PMR. In both conditions, the inflammatory response seemed to be more severe in women. The strong inflammatory response in women could explain the longer duration of treatment reported in this subgroup of patients.     

Coexistence of temporal arteritis/polymyalgia rheumatica and rheumatoid arthritis

Summary A patient with biopsy proven temporal arteritis/polymyalgia rheumatica and erosive rheumatoid arthritis is presented. Only 15 such patients have previously been documented in the literature. The coexistence has been thought to be extremely infrequent, but could merely by chance appear in far more patients than previously reported.     

Coexistence of polymyalgia rheumatica/temporal arteritis and chronic polyarthritis

Prompted by one of our own case studies, which we report here, we reviewed the literature for coincidence of rheumatoid arteritis (RA) with polymyalgia rheumatica (PMR) and temporal arteritis (TA), respectively. The indicative feature of this uncommon condition was found in 13 cases, whereas in 70 other cases reported, the diagnosis of combined RA and PMR/TA was probable. Diagnostic criteria for determining combined RA and PMR/TA will be discussed, as well as the clinical important feature of senile RA.     

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.     

Subclavian and axillary involvement in temporal arteritis and polymyalgia rheumatica

PURPOSE: We describe 10 female patients with temporal arteritis (TA) and/or polymyalgia rheumatica (PMR) who presented with upper-extremity ischemia. PATIENTS, METHODS, AND RESULTS: Arm claudication or Raynaud's phenomenon was the initial manifestation of the disease in four cases, appeared with classical symptoms in one case, or occurred during decreasing corticosteroid therapy in five cases. Temporal artery biopsy was performed in nine patients and showed typical giant-cell granulomatous arteritis in seven cases. Angiograms in all cases showed multiple bilateral smooth stenoses, or obliterations of postvertebral subclavian and/or axillary arteries, or both. Symptoms always improved with corticosteroid treatment and none of the patients required reconstructive surgery, although angiography performed after stabilization did not show revascularization of occluded vessels. CONCLUSION: We conclude that large-artery involvement in TA and PMR affects most commonly the subclavian and axillary arteries, with a female predominance comparable to that in Takayasu's arteritis. Both these disorders should be considered in elderly women with occlusive disease of the upper extremities. Although response to steroid therapy was sufficient in our series to avoid surgery, we believe it is preferable to recognize large-artery involvement as early as possible and recommend performance of ultrasonic Doppler examination when any sign of oncoming ischemia or stenosis is observed.     

Fibrin(ogen)olysis in polymyalgia rheumatica and temporal arteritis: preliminary findings on association with disease activity.

Postulating an increased production of fibrin(ogen)olytic degradation products (FDP) and an abnormality of fibrinogen metabolism in polymyalgia rheumatica (PMR) and temporal arteritis (TA), we studied 16 PMR/TA patients and 10 control subjects using a sensitive radioimmunoassay for a specific type of FDP, namely, fibrin(ogen)-related D-antigen. Median serum D-antigen levels were increased five-fold in those 11 PMR/TA patients who were untreated compared with control subjects. In the five PMR/TA patients who were treated with prednisone the median D-antigen levels were not significantly different from those of the healthy controls. D-antigen concentration correlated significantly (r = 0.83) with ESR in the seven untreated PMR patients. In PMR patients prednisone therapy was followed by a reduction of serum D-antigen levels.     

Longterm therapy in polymyalgia rheumatica: effect of coexistent temporal arteritis.

OBJECTIVE: To analyze the clinical course and duration of therapy in a series of 104 patients with polymyalgia rheumatica (PMR), identifying factors that influence prolonged steroid use and relapses. METHODS: Retrospective study of 104 cases of PMR diagnosed from 1985 to 1995. Patients were followed from time of diagnosis until either their death or December 31, 1995. To assess the effects of the coexistence of temporal arteritis (TA) on outcome in PMR, patients were grouped according to the absence or presence of arteritis. Kaplan-Meier survival analysis was performed to evaluate the duration of therapy, the incidence of prolonged remissions and relapses, and the average time to relapse. The log-rank test was used to test for significant differences between groups. Multivariate Cox proportional hazards regression models were used to identify variables associated with the occurrence of these events. RESULTS: Of 104 patients, 69 had pure PMR and 35 had both PMR and TA. Although some patients had limited disease requiring limited corticosteroid (CS) therapy (usually about 2 years), a significant number of patients had sustained disease requiring longterm treatment. Patients with simultaneous arteritis tended to have a longer duration of therapy, but no increased risk of relapse. By multivariate analysis, increasing age at diagnosis, female sex, higher baseline erythrocyte sedimentation rate, and lower daily CS dose were significant risk factors associated with long duration of therapy. No clinical feature predicted patients who were more likely to relapse. CONCLUSION: Although there was great individual patient variation, we found that typically CS therapy lasted at least 2 years. Our findings allow the identification of patients who are particularly predisposed to need prolonged and higher dose cumulative steroid therapy and merit preventive strategies to decrease the incidence of steroid related adverse events.     

Hepatocellular disease in the giant-cell arteritis/polymyalgia rheumatica syndrome.

An elderly man developed temporal arteritis and polymyalgia rheumatica with coexisting biochemical abnormalities of liver function. Biopsy revealed hepatic changes which have not been previously reported. There was hepatocellular necrosis and inflammation together with a prominent hyperplasia of perisinusoidal lipocytes of Ito. Temporal artery biopsy confirmed the presence of granulomatous panarteritis. Corticosteroid therapy produced rapid resolution of symptoms and reversion of liver function tests to normal.     

Giant cell arteritis,temporal arteritis,and polymyalgia rheumatica in a danish county

The annual incidence of giant cell arteritis (the term used in this study to encompass the syndromes of temporal arteritis and polymyalgia rheumatica, occurring either together or alone) was prospectively determined in a Danish county that had a population of approximately 200,000. In a single year, 46 new cases of giant cell arteritis were diagnosed, a number which corresponds to an incidence in the overall population of 21.5/10⁵, and to an incidence of 76.6/10⁵ for individuals age 50 years or older. These rates are higher than those previously reported in retrospective studies. The 3-year followup of all patients showed no onset of other diseases that would require a revision of the original diagnosis. There was no deviation from the age- and sex-specific malignancy rate or the mortality rate in the overall population. Women had an incidence rate 4 to 5 times higher than that seen in men. Symptoms, for the most part, were the same as those found in other studies; however, vision loss was not observed during the followup period. Point prevalence at the start of the study was 37.8/10⁵, which is below the rates previously reported. This is probably because of failure on the part of participating physicians to record all cases.     

Monocyte chemoattractant protein 1 (MCP-1) in temporal arteritis and polymyalgia rheumatica

OBJECTIVE: To examine the localisation of monocyte chemoattractant protein 1 (MCP-1) in the inflamed vessel wall in temporal arteritis (TA) and to measure MCP-1 in plasma both in patients with TA and patients with polymyalgia rheumatica (PMR). METHODS: By immunohistochemical techniques MCP-1 was localised to the vessel wall in patients with TA. In TA, PMR, and healthy controls MCP-1 was quantified by enzyme linked immunosorbent assay (ELISA) in plasma. RESULTS: MCP-1 was localised to the majority of mononuclear cells, some smooth muscle cells, and giant cells in the arterial biopsy specimens from 12 patients with histologically verified TA. In all sections, including the vasa vasorum, the endothelium stained positive. In the intima 73% (range 57-91%), in the media 49% (range 32-67%), and in the adventitia 74% (range of 62-91%) of all cells stained positive. In plasma MCP-1 was significantly raised in untreated TA (n=33) and untreated PMR (n=27) compared with healthy controls (n=12). Untreated TA plasma levels of MCP-1 (mean 391 pg/ml (range 82-778 pg/ml)) were similar to untreated PMR plasma levels (mean 402 pg/ml (range 29-1153 pg/ml)), and no significant difference was found between the two groups of patients. In both patients with TA and patients with PMR no correlation was found between the plasma level of MCP-1 and the erythrocyte sedimentation rate, haemoglobin concentration, and CD4/CD8 ratio. CONCLUSIONS: These results show that MCP-1 plays a part in the disease processes of TA and PMR.     

Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis

Objective. To explore the role of proinflammatory cytokines in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically related syndromes characterized by an intense acute-phase reaction. In particular, to determine plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and to correlate changes in plasma IL-6 levels with clinical symptoms during corticosteroid therapy. Methods. IL-6 and TNFα concentrations were determined in plasma samples from patients with untreated PMR or GCA, and plasma IL-6 levels were monitored in patients receiving long-term therapy (14 months) with corticosteroids. To identify IL-6–producing cells, the polymerase chain reaction was used to detect IL-6 messenger RNA. In vitro production of IL-6 and IL-2 by peripheral blood mononuclear cells (PBMC) from treated and untreated patients was quantified using IL-6– and IL-2–specific bioassay systems. Results. IL-6 concentrations were increased in PMR and GCA patients, whereas TNFα concentrations were similar to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL-6 but did not correct the underlying mechanism inducing the increased IL-6 production. In individual patients, changes in plasma IL-6 levels and clinical manifestations during prolonged therapy were closely correlated. Short-term withdrawal of corticosteroids, even after several months of treatment, was followed by an immediate increase in plasma IL-6 concentrations. To identify the cellular source of plasma IL-6, PBMC from treated and untreated patients with PMR or GCA were analyzed for their ability to secrete IL-6 and the T cell–specific cytokine IL-2. Polyclonal T cell stimulation caused a rapid release of IL-6, which was shown to be derived exclusively from CD14+ cells. Conclusion. Increased production of IL-6, but not TNFα, is a characteristic finding in patients with PMR or GCA. Corticosteroids rapidly suppress IL-6 production but do not correct the underlying mechanism inducing the increased IL-6 production. The close correlation of plasma IL-6 concentrations with clinical symptoms suggests a direct contribution of this cytokine to the disease manifestations and presents the possibility that monitoring IL-6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients.