Lack of association between interleukin-6 promoter polymorphism at position -174 and Henoch-Schönlein pur pura.

OBJECTIVE: To assess whether polymorphism of the interleukin (IL)-6 gene at the position -174 was implicated in the incidence of Henoch-Schönlein pur-pura (HSP). A further objective was to determine if any relationship existed with severe systemic complications of HSP, in particular with severe renal and gastrointestinal involvement. METHODS: Unselected patients from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients included in the present study were required to have had at least 2 year's follow-up. Patients and controls were genotyped for a single biallelic (G/C) nucleotide polymorphism in the promoter region at the position -174 of the IL-6 gene by a polymerase reaction chain-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Forty-six Caucasian HSP patients and 124 healthy matched controls were studied. No allele or genotype differences between the whole group of HSP and controls were observed. This was also the case when HSP patients were stratified by the presence of gastrointestinal complications, nephritis, and permanent renal involvement (renal sequelae). CONCLUSION: The polymorphism in IL-6 gene promoter (-174 G/C) does not appear to be a genetic risk factor for HSP in Northwest Spain.

Short-term adalimumab therapy improves endo-thelial function in patients with rheumatoid arthritis refractory to infliximab.

OBJECTIVE: Endothelial dysfunction has been found in patients with rheumatoid arthritis (RA). In this study we aimed to assess whether adalimumab, a fully human monoclonal antibody directed against TNF-alpha, was able to improve endothelial function in RA patients with long-standing disease refractory to infliximab. METHODS: Eight RA patients (7 women; range: 24- 74 years) were studied. They had been treated with the chimeric monoclonal anti-TNF-alpha antibody-infliximab for at least 1 year and were switched to adalimumab therapy because of loss of efficacy following periodical treatment with infliximab. Endothelial dependent (EDV) and independent vasodilatation (EIV) were measured by brachial ultrasonography. Patients were assessed prior to (day 0) and at day 2, and weeks 2 and 12 after the onset of adalimumab therapy. RESULTS: Following adalimumab administration a rapid increase in the percentage (%) of EDV was found in all patients (mean +/- SD: 10.1 +/- 5.1% at day 2 compared to 5.8 +/- 4.1% at day 0). At weeks 2 and 12 the %EDV was also significantly increased compared to day 0. All patients showed decrease in the disease activity score 28 and C-reactive protein levels (P = 0.012). Moreover, at week 12 the atherogenic index was reduced in all patients (P = 0.012). CONCLUSION: Our study confirms that short-term adalimumab therapy yields an active and positive effect on endothelial function in long-standing RA patients with severe disease. This observation emphasizes the potential role of the TNF-alpha blockade in the mechanisms implicated in the development of atherogenesis in RA.

Microscopic polyangiitis following recurrent Staphylococcus aureus bacteremia and infectious endocarditis.

Secondary vasculitis resulting from unusual pathologic expressions of infections has been described and has important clinical significance. Infectious agents have also been implicated in the pathogenesis of different primary systemic necrotizing vasculitides. Infectious endocarditis is of particular importance in the differential diagnosis of a patient presenting with ANCA associated vasculitis. We report a well-documented case of a patient with recurrent Staphylococcus aureus bacteremia who developed bacterial endocarditis and also fulfilled the Chapel Hill Conference definitions for microscopic polyangiitis. To the best of our knowledge, it is the second case of bacterial endocarditis associated with both pANCA and anti-MPO specificity that fulfilled definitions for systemic necrotizing vasculitis. We emphasize the potential pathogenic role of infection as the trigger factor for the development of systemic vasculitis.

Lack of association between macrophage migration inhibitory factor gene (-173 G/C) polymorphism and cutaneous vasculitis.

OBJECTIVE: To assess whether polymorphism of the macrophage migration inhibitory factor (MIF) gene at position -173 was implicated in the incidence of Henoch-Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA). A further objective was to determine if any relationship existed with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction. METHODS: Unselected patients from Northwest Spain with primary cutaneous vasculitis classified as HSP or hypersensitivity vasculitis (HV) according to proposed criteria were studied. Patients with HV were included in this study if they fulfilled the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. Patients and controls were genotyped for a single nucleotide polymorphism (SNP) in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). RESULTS: Ninety-five Caucasian patients (57 classified as having HSP and 38 who fulfilled definitions for CLA) and 122 healthy controls were studied. No allele or genotype differences between the whole group of HSP or CLA patients and controls were observed. This was also the case when HSP patients were stratified by the presence of gastrointestinal complications, nephritis, and permanent renal involvement (renal sequelae). CONCLUSION: The polymorphism in MIF gene promoter (-173 G/C) does not appear to be genetic risk factors for cutaneous vasculitis in Northwest Spain.

Influence of anti-TNF-alpha infliximab therapy on adhesion molecules associated with atherogenesis in patients with rheumatoid arthritis.

OBJECTIVE: Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules were found significantly increased in RA patients with active disease. Since increased levels of some adhesion molecules were closely linked to the development of endothelial dysfunction and atherosclerosis and administration of anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of endothelial function in long-term infliximab treated RA patients, we assessed whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a rapid and favorable effect on serum levels of soluble adhesion molecules in RA patients periodically treated with this drug because of severe disease. METHODS: We recruited patients with RA refractory to conventional therapy seen over a period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical treatment with infliximab for at least 14 weeks. Blood samples for determination of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were taken immediately before and after infliximab infusion. RESULTS: Thirty-four RA patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the inclusion criteria. Following infliximab infusion a reduction of the overall mean values of the five adhesion molecules was observed. However, when a Wilcoxon signed-rank test was used, only significant differences for sICAM-3 and sP-selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26 (77%) and 28 (82%) of the 34 patients. CONCLUSION: Our study confirms a rapid and beneficial effect of infliximab infusion on expression of some adhesion molecules in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody because of severe disease.

Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis.

OBJECTIVE: Systemic inflammation, insulin resistance, and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA). Since insulin resistance can promote endothelial dysfunction and anti-TNF-alpha blockade yield a rapid improvement of endothelial function, we have sought to assess whether TNF-alpha blockade may also result in a reduction of insulin serum levels and improvement of insulin resistance in RA patients who require this therapy because of severe and refractory disease. METHODS: We recruited patients with RA seen over a period of 1 month at Hospital Xeral-Calde, Lugo, Spain, that were on treatment with anti-TNF-alpha monoclonal antibody-infliximab. Patients with diabetes mellitus or plasma glucose > 110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to and after infliximab infusion. RESULTS: Twenty-seven RA patients (21 women; mean age: 57.1 years; mean DAS28: 4.43) fulfilled the inclusion criteria. Dramatic reduction in the serum insulin levels and insulin/glucose index was observed following infliximab infusion. Also, a significant improvement of insulin resistance and insulin sensitivity was found. CONCLUSION: Our study confirms a rapid beneficial effect of infliximab on insulin resistance and insulin sensitivity in RA patients treated periodically with this drug. It may support the long-term use of drugs that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of atherosclerosis in patients with RA.

Systemic vasculitis in adults in northwestern Spain, 1988-1997. Clinical and epidemiologic aspects.

The vasculitides constitute a heterogeneous group of diseases characterized by blood vessel inflammation and necrosis with different but frequently overlapping clinical and pathologic manifestations. The incidence of these conditions is frequently controversial. To further investigate the incidence and clinical manifestations of vasculitides, we reviewed the spectrum of these diseases in an unselected population of adults (age > 20 years) from northwestern Spain during a 10-year period. From January 1988 through December 1997, 267 adults were diagnosed as having vasculitis. The overall average annual incidence rate of vasculitis in the region of Lugo, Spain, between 1988 and 1997 for the population older than 20 years was 141.54/million. Primary vasculitis (115.04/million for the population older than 20 years; 81.3%), especially giant cell arteritis (GCA) was the most common group. Small vessel primary vasculitis (hypersensitivity vasculitis and Henoch-Schönlein purpura) was the second most common group. Both GCA and small vessel primary vasculitis had a good outcome. However, although less common, patients with medium and small vessel primary vasculitis, in particular those with polyarteritis nodosa, had a high mortality related to the systemic manifestations of the disease or to the immunosuppressive therapy. Among the group of adults with secondary vasculitis (26.51/million; 18.7%), rheumatic diseases and specifically those occurring in the context of rheumatoid arthritis were the most common group. Patients with secondary vasculitis had clinical or laboratory data that may suggest the presence of an underlying disease. In summary, systemic vasculitides are somewhat more common than previously considered. As in other western countries, GCA constitutes the most common type of vasculitis in northwestern Spain. Better physician awareness may contribute to the progressive increase in the recognition of these conditions.

Rheumatic manifestations of infective endocarditis in non-addicts. A 12-year study.

Infective endocarditis (IE) is due to a microbial infection of the heart valves or of the endocardium in close proximity to either congenital or acquired cardiac defects. This infection is associated with a high risk of complications. Rheumatic manifestations are known to be frequent complications of IE. Controversy, however, frequently exists about the actual incidence of these complications. This may be due to the small number of series describing the frequency and type of rheumatic manifestations, the absence of uniform criteria used for the diagnosis of IE, and the fact that some studies on rheumatic manifestations in IE have been described from tertiary referral centers, which implicates associated problems of referral bias and uncertainty of denominator population. To investigate further the incidence, clinical spectrum, and outcome of patients with IE and rheumatic manifestations, we examined the features of patients diagnosed with clinically definite IE according to the Duke classification criteria at the single reference hospital for a defined population in northwestern Spain during a 12-year period. Between 1987 and 1998, 100 consecutive patients had 110 episodes of clinically definite IE. Rheumatic manifestations were observed in 46 of the 110 episodes (41.8%). As in other western countries, they occurred more commonly in men aged in their 50s. The most frequent valve involved was the aortic (43.5%) followed by the mitral valve (30.4%). Myalgia was a frequent symptom. Peripheral arthritis, generally as monoarthritis, was clinically evident in 15 cases (13.6%), and sacroiliitis in 1 patient. Low back pain was described in 14 cases (12.7%). Septic discitis was observed in 2 cases, and biopsy-proved cutaneous leukocytoclastic vasculitis was found in 4 cases. Other conditions such as trochanteric bursitis and polymyalgia were observed in 2 and 1 case, respectively. Apart from a significantly higher frequency of hematuria and a trend to lower serum complement levels in patients with rheumatic complications, no differences in clinical features, laboratory tests, or microbiologic blood culture results were found between cases with IE with or without rheumatic manifestations. Also, although patients with rheumatic manifestations had more embolic complications, the inhospital mortality rate in patients with rheumatic manifestations was not significantly different from that of the rest of the patients. The present study supports the claim that rheumatic complications are frequent in patients with clinically definite IE from southern Europe. The presence of musculoskeletal or vasculitic manifestations may be of some help, as warning signs, for the recognition of patients with severe disease who require rapid diagnosis and therapy.

Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients.

Giant cell (temporal) arteritis (GCA) is the most common systemic vasculitis in Western countries. It involves large and medium-sized vessels with predisposition to the cranial arteries in the elderly. Cranial ischemic complications, in particular permanent visual loss, constitute the most feared aspects of this vasculitis. Although the use of corticosteroids and a higher physician awareness may have contributed to a decrease in the frequency of severe ischemic complications, permanent visual loss is still present in 7%-14% of patients. To investigate further the incidence, trends, and clinical spectrum of visual manifestations in patients with GCA, we examined the features of patients with biopsy-proven GCA diagnosed at the single reference hospital for a defined population in northwestern Spain during an 18-year period. Predictive factors for the development of any visual manifestation, not only permanent visual loss, were also examined. Between 1981 and 1998, 161 patients were diagnosed with biopsy-proven GCA. Visual ischemic complications were observed in 42 (26.1%), and irreversible blindness, mainly due to anterior ischemic optic neuropathy and frequently preceded by amaurosis fugax, was found in 24 (14.9%). Despite a progressive increase in the number of new cases diagnosed, there was not a significant change in the proportion of patients with visual manifestations during the study period (p = 0.37). Patients with visual ischemic complications had lower clinical and laboratory biologic markers of inflammation. Indeed, during the last years of the study, anemia was associated with a very low risk of visual complications. Also, HLA-DRB1*04-positive patients had visual manifestations more commonly. Patients with other ischemic complications developed irreversible blindness more frequently. The best predictors of any visual complication were HLA-DRB1*04 phenotype (odds ratio [OR] 7.47) and the absence of anemia at the time of admission (OR for patients with anemia = 0.07). The best predictors of irreversible blindness (permanent visual loss) were amaurosis fugax (OR 12.63) and cerebrovascular accidents (OR 26.51). The present study supports the claim that ocular ischemic complications are still frequent in biopsy-proven GCA patients from southern Europe. The presence of other ischemic complications constitutes an alarm for the development of irreversible blindness. In contrast, a higher inflammatory response may be a protective factor against the development of cranial ischemic events.

Comparative clinical and epidemiological study of hypersensitivity vasculitis versus Henoch-Schönlein purpura in adults.

OBJECTIVES: To assess the incidence and clinical features of adults with hypersensitivity vasculitis (HV) and Henoch-SchOnlein purpura (HSP) in a well-defined population. METHODS: Retrospective study of an unselected population of adult patients (>20 years) with biopsy-proven cutaneous vasculitis diagnosed as having HV or HSP who presented at a primary hospital between 1988 and 1997. Patients with cutaneous vasculitis secondary to collagen vascular diseases, neoplasia, severe infections, and those with other well-defined clinical entities were excluded. Patients were classified as having either HV or HSP according to the criteria proposed by Michel et al (J Rheumatol 1992;19:721-28). RESULTS: Fifty-six adults (35 men/21 women), were classified as having HV and 27 adults as having HSP (19 men/8 women). The annual incidence rate for HV was 29.7/million and 14.3/million for HSP. At the onset of the disease, adults with HSP were younger than those with HV (46+/-18 years versus 59+/-18 years in HV; P = .005). Precipitating events were found in 50% of HV and in 30% of HSP patients. A history of drug therapy before the onset of vasculitis was found in 46% of HV and in 26% of HSP (P = .074). At disease onset, skin lesions were the most common manifestation in both groups. During the disease course, adults with HSP had joint manifestations more commonly (59% in HSP v25% in HV; P < .003) and more gastrointestinal (82% v 5% in HV; P < .001) and renal complications (48% v 5% in HV; P < .001). HSP subjects required more aggressive therapy consisting of steroids (P < .001) or cytotoxic agents (P < .001). After 37+/-28 (median, 31) months, complete recovery was observed in 98% of adults with HV. After 40+/-27 (median, 36) months, complete recovery was observed in only 67% of adults with HSP (P < .001). Renal insufficiency was observed in 8% of adults with HSP. CONCLUSIONS: In adults, HV and HSP as defined by these criteria, behave as two well-differentiated diseases. HV has a milder course and lack of severe complications, and HSP a higher risk of gastrointestinal and renal complications.

Biopsy-negative giant cell arteritis: clinical spectrum and predictive factors for positive temporal artery biopsy.

OBJECTIVES: To examine the frequency and features of patients with biopsy-negative giant cell arteritis (GCA), establish differences with biopsy-proven GCA, and identify the optimal set of predictors for a positive temporal artery biopsy (TAB) in patients with GCA. METHODS: Retrospective study of an unselected population of patients with GCA diagnosed at the reference hospital for a defined population between 1981 and 1998. Patients were classified into biopsy-proven GCA if a TAB was positive for GCA, or biopsy-negative GCA if they fulfilled the American College of Rheumatology 1990 criteria for the classification of GCA (Hunder GG, et al Arthritis Rheum 1990; 33:1122-8) despite having a negative TAB. RESULTS: One hundred ninety Caucasian patients were diagnosed with GCA. Twenty-nine of them (15.3%) had a negative TAB. In these biopsy-negative patients, headache and polymyalgia rheumatica were frequent presenting symptoms. In contrast, jaw claudication, abnormal temporal artery on physical examination, and constitutional syndrome (asthenia, anorexia, and weight loss of 4 kg or more) were less common. They also had lower biologic markers of inflammation. The best predictive model of biopsy-proven GCA included a history of constitutional syndrome (OR = 6.1), an abnormal temporal artery on physical examination (OR = 3.2), and the presence of visual complications (OR = 4.9). CONCLUSIONS: In GCA, a subset of patients have a high likelihood of having a negative TAB. This subset seems to have less severe ischemic complications than that of biopsy-proven GCA. In patients without visual manifestations, abnormal temporal artery on examination or constitutional syndrome the risk of having an abnormal TAB is low.

Epidemiology of the vasculitides.

In summary, systemic vasculitides constitute a heterogeneous group of overlapping diseases that are somewhat more common than previously considered. Although the causes of vasculitis are largely unknown, epidemiologic studies have implicated geographic, genetic, and environmental factors. Ethnicity, various genes such as those of the MHC, gender, and environmental factors seem to account for the different incidence rates of these syndromes. GCA is the most common vasculitis in elderly people from Western countries. Small-sized cutaneous vasculitides, particularly HSP in children and HV in adults, are also common diseases. Increased physician awareness and the routine use of ANCA tests may contribute to an increase in the recognition of conditions such as WG and MPA.

Bacterial infection presenting as cutaneous vasculitis in adults.

OBJECTIVE: To examine the frequency and clinical features of patients with bacterial infection presenting with biopsy-proven leukocytoclastic cutaneous vasculitis (CV) in a well-defined area of southern Europe (northwestern Spain). METHODS: A retrospective study of an unselected population of adult patients (age > 20 years) with biopsy-proven leukocytoclastic CV diagnosed at the Hospital Xeral-Calde (Lugo, Spain) was carried out from January 1988 through December 1997. Cutaneous vasculitis related to bacterial infection was considered if the vasculitis was confirmed by a skin biopsy showing leukocytoclastic vasculitis, if no drug intake was registered prior to the development of CV, and if bacteriologic evidence of infection was obtained. RESULTS: Four of 138 patients (2.9%) presenting with biopsy-proved CV were diagnosed with leukocytoclastic CV related to bacterial infection. Three patients (2 with bacterial endocarditis and 1 with meningococcemia) met the ACR criteria for the classification of hypersensitivity vasculitis. Another patient with bacterial endocarditis met the criteria for mixed cryoglobulinemia. All of them presented with palpable purpura, high or low grade fever, an elevated erythrocyte sedimentation rate and leukocytosis. CONCLUSION: Cutaneous vasculitis may be the presenting manifestation of bacterial infection. In this respect, rheumatologists should be aware of possible infectious causes of vasculitis, even though they are not common.

Polymyalgia manifestations in different conditions mimicking polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a generally benign syndrome involving the neck, shoulder, and hip girdles in the elderly. However, none of the clinical and laboratory findings are specific for this syndrome. Different diseases may present with features suggesting PMR. The consideration of other conditions which in some cases resemble PMR is very important, as their therapy and prognosis differ completely from that of PMR. Four patients presenting with typical PMR manifestations, who were finally diagnosed as having conditions very different from PMR, are described. The importance of the differential diagnosis in patients presenting with polymyalgia symptoms is underlined.

Predictors of cerebrovascular accidents in giant cell arteritis in a defined population.

OBJECTIVE: To examine the frequency and predictors of cerebrovascular accidents (CVA) in giant cell arteritis (GCA) patients from a defined population. METHODS: Retrospective study of biopsy-proven GCA patients diagnosed from 1981 through 2001 at the single hospital for the population of Lugo (Northwest Spain). RESULTS: Thirty (14.3%) of the 210 biopsy-proven GCA patients had CVA, 5 of them (16.7%) involving the vertebrobasilar territory. Five patients (4 of them involving the carotid territory) had CVA within the 2 years prior to the onset of GCA symptoms. Four patients had CVA within the first month after the diagnosis of the disease. Of these, 3 involved the vertebrobasilar territory. Another 5 patients suffered carotid stroke between the 4th and the 12th month after the disease diagnosis. The remaining 16 GCA patients had CVA (all but one involving the carotid territory) at least 1 year after the diagnosis of vasculitis. No differences in the clinical and laboratory features at the time of diagnosis between patients who had CVA and the rest of the biopsy-proven GCA patients were observed. However, hypertension and hyperlipidemia at the time of diagnosis of GCA were associated with the development of CVA (p < 0.05 for both). Also, anemia at the time of diagnosis (hemoglobin < 12 g/dL) [hazard ratio = 0.34 (95% CI 0.12 - 1.00; p = 0.05)] was negatively associated with CVA within the first 10 years after the diagnosis of the disease. Mortality in GCA patients with CVA was not significantly higher than that in patients without CVA (hazard ratio = 1.53; p = 0.14). CONCLUSION: The present study confirms that CVA may occur in GCA. Vertebrobasilar accidents are more common than carotid accidents at the time of diagnosis of the disease. Vascular risk factors should be carefully controlled in the follow-up of GCA patients.

Hypersensitivity vasculitis in adults: a benign disease usually limited to skin.

OBJECTIVES: To examine the clinical spectrum of hypersensitivity vasculitis (HV) in an unselected population of adults and establish differences between patients with HV limited to the skin and those with systemic involvement. METHODS: Retrospective study of adult patients (> 20 years) with biopsy-proven cutaneous leukocytoclastic vasculitis diagnosed as having HV, who were seen at the single hospital serving a well defined population between 1984 and 1998. Patients were classified as having HV according to the criteria of Michel et al. (9). To examine outcome and relapses of the disease only those patients with a follow-up of at least 1 year were included in this study. RESULTS: 64 patients with a mean follow-up of 4.9 +/- 3.5 (range: 1.1-13.6) years were studied. Ten (15.6%) had visceral involvement (3 gastrointestinal and 7 renal manifestations) during the course of the disease. The remaining patients had a leukocytoclastic vasculitis limited to the skin. When the study was concluded persistent hematuria and proteinuria was only observed in 1 patient and none developed renal insufficiency. Patients with a history of drug treatment and elevated ESR had more systemic complications but the difference was not statistically significant. The outcome was excellent in both patients with HV limited to the skin and in those with systemic complications during the course of the disease. CONCLUSIONS: In unselected adults HV is generally a benign disease confined exclusively to the skin. In those patients with systemic manifestations, visceral involvement is generally mild and transient.

RANTES gene polymorphism in polymyalgia rheumatica, giant cell arteritis and rheumatoid arthritis.

OBJECTIVE: To investigate whether a biallelic polymorphism (A or G) occurring within the promoter region of the RANTES gene (position-403) is associated with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and rheumatoid arthritis (RA). METHODS: A PCR-RFLP method was used to genotype cases and controls for this polymorphism. 3 groups of patients were examined; these comprised GCA patients who did not exhibit features of PMR (n = 30), PMR patients who did not exhibit features of GCA (n = 53) and RA patients (n = 99). All patients and controls (n = 65) originated from the area surrounding Lugo, Galicia, NW Spain. RESULTS: A significant increase in the frequency of allele A was found in PMR patients compared with normal controls. A marginal increase of this allele frequency was observed in RA but not in GCA patients. CONCLUSION: This is the first report of an association of a RANTES gene polymorphisms with PMR and RA. Our data suggest a possible role for of RANTES in the development of both PMR and RA.

Corticotropin releasing hormone promoter polymorphisms in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVE: Giant cell (temporal) arteritis (GCA) and polymyalgia rheumatica (PMR) are different but overlapping diseases of unknown etiology affecting the elderly. Corticotropin-releasing hormone (CRH) helps to regulate the immune response and maintain homeostasis during inflammatory stress. CRH promoter region polymorphisms in the 5'regulatory region of the CRH gene have been described. To investigate the possible implications of the CRH promoter polymorphisms in PMR and GCA susceptibility we have examined a series of patients with these conditions. METHODS: Sixty-two patients with biopsy-proven GCA, 86 patients with isolated PMR and 147 ethnically matched controls from the Lugo region of Northwest Spain were included in this study. Patients and controls were genotyped for CRH polymorphism in the 5' regulatory region of the gene at position 1273 (alleles A1 andA2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Allele frequencies and genotype distribution were evaluated by the chi-square test. RESULTS: When GCA and PMR patients were examined for alleles and genotypes for each CRH polymorphism no significant differences in frequency were found compared with controls. A higher CRH-A2 allele frequency was observed in GCA patients with visual complications (21.4%) compared with controls (9.2%) and GCA cases without eye involvement [6.3%; p= 0.017, Pcorr = 0.034, O.R: 4.1 (95% CI 1.2- 13.9)], although this was based on a small sample of patients with ischemic visual complications (n = 14) and should be interpreted with caution. No differences in CRH allele or genotype frequencies were observed in isolated PMR patients stratified by relapses and recurrence of disease symptoms. CONCLUSION: Polymorphisms in the CRH gene regulatory region do not appear to be associated with increased susceptibility to PMR or GCA. The CRH-A2 allele may encode risk for the development of visual complications in GCA, although further studies to confirm this will be required.