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POLYMYALGIA AND RHEUMATICA
ABSTRACTS

Polyarthralgia disclosing hyperthyroidism: Report of two cases
Molinier S.; Paris J.F.; Marlier S.; Galzin M.; Amah Y.; Carli P.
S. Molinier, Serv. Med. Int. Malad. Infect./Trop., HIA Laveran, F 13998 Marseille Armees France
Presse Medicale (France), 1998, 27/26 (1324-1326)

BACKGROUND: We report two cases of rheumatism associated with hyperthyroidism. In both cases, arthralgia totally regressed after thyroid treatment.

CASE REPORTS: Two 79-year-old and 59-year-old women developed manifestations of polymyalgia rheumatica and psoriasis arthritis respectively. Corticosteroid therapy was ineffective and followed by manifestations of hyperthyroidism. The first patient was treated with carbimazole and the second with thyroidectomy. Once the hyperthyroidism was controlled, both patients experienced a dramatically rapid cure of their arthralgias.

DISCUSSION: Scalpulo-humeral periarthritis is the main articular complication of hyperthyroidism. True manifestations of <<thyrotoxicosis rheumatism>> are unusual and may be linked with a direct toxicity of the thyroid hormones on joint cartilage or with an autoimmune manifestation of hyperthyroidism.

A 67-year-old woman with polymyalgia rheumatica and left hemispatial neglect
Mahfood J.P.; Gold M.; Gonzalvo A.; Valeriano-Marcet J.
Dr. M. Gold, Univ. of South Florida Coll. of Med., Department of Neurology, MDC, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612 United States
Journal of Neuroimaging (United States), 1998, 8/4 (222-227)

A 67-year-old woman with a diagnosis of polymyalgia rheumatica presented initially with periods of confusion and incontinence. ACT scan of the brain was normal and she was treated with tapering doses of corticosteroids and clinical improvement. After a brief period off steroids, the patient presented with a progressive dementia, left-sided clumsiness, gait disturbances and left hemispatial neglect. An MRI at this time demonstrated a large area of edema over the right parietal lobe and intense cortical enhancement. A chest CT demonstrated multiple nodules. Biopsies of the lung and brain failed to identify any infectious organisms or malignant tissue. The leptomeningeal biopsy revealed multiple granulomatous areas with central necrosis and hystiocytic cells consistent with idiopathic hypertrophic pachymeningitis.

Effects of glucocorticoids on bone mass in patients with polymyalgia rheumatica. A longitudinal study [4]
Mur E.; Watfah C.; Kinigadner U.; Fridrich L.; Riccabona G.; Moncayo R.
Dr. E. Mur, Department of Internal Medicine, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck Austria
Clinical and Experimental Rheumatology (Italy), 1998, 16/5 (623)

No abstract.

Polymyalgia rheumatica in biopsy proven giant cell arteritis does not constitute a different subset but differs from isolated polymyalgia rheumatica
Gonzalez-Gay M.A.; Garcia-Porrua C.; Vazquez-Caruncho M.
Dr. M.A. Gonzalez-Gay, Division of Rheumatology, Hospital Xeral-Calde, c/Dr. Ochoa s/n, 27004 Lugo Spain
Journal of Rheumatology (Canada), 1998, 25/9 (1750-1755)

Objective. To assess clinical and laboratory features that may be useful in differentiating isolated polymyalgia rheumatica (PMR) from PMR associated with biopsy proven giant cell arteritis (GCA); and in differentiating biopsy proven GCA associated with PMR from GCA without manifestations of PMR.

Methods. Clinical records of patients with PMR and biopsy proven GCA diagnosed at Hospital Xeral, Lugo, Spain from January 1987 through May 1997 were reviewed. Patients with a positive temporal artery biopsy were categorized into 2 different subgroups according to the presence or absence of associated PMR. The patients with biopsy proven GCA associated with PMR were compared with a group of patients with isolated PMR (not associated with GCA).

Results. From a total of 108 biopsy proven patients with GCA, 45 had associated PMR. Apart from a predominance of women and a longer delay to diagnosis, patients with PMR associated with GCA did not differ from the patients with GCA without PMR manifestations. In comparing patients with isolated PMR (n = 117) with patients with PMR associated with GCA, we observed that PMR associated with GCA was a more severe disease, with significant abnormality in most laboratory variables, including constitutional syndrome, higher elevation of erythrocyte sedimentation rate and platelet counts, and lower values of hemoglobin.

Conclusion. In both isolated PMR and PMR associated with GCA we observed a predominance of women. While there are no differences in the type of polymyalgia symptoms in patients with isolated PMR versus PMR associated with GCA, severe abnormalities associated with the inflammatory response in PMR may have prognostic value for more severe disease, which may be linked to the presence of GCA.

A case of anterior ischemic optic neuropathy associated with polymyalgia rheumatica
Hayama F.; Hasegawa S.; Takagi M.; Suzuki K.; Takada R.; Abe H.
Dr. F. Hayama, Dept of Ophthalmol, Niigata Univ School of Med, 1-754 Asahimachi-dori, Niigata 951-8510 Japan
Folia Ophthalmologica Japonica (Japan), 1998, 49/8 (720-725)

We treated a case of anterior ischemic optic neuropathy (AION) following polymyalgia rheumatica (PMR) that seemed to be associated with temporal arteritis (TA). A 70-year-old female developed AION in her right eye 9 years after the onset of PMR and 1 month after the onset of TA. She had also suffered for 4 years from maculopathy, of unknown etiology, in her left eye. Magnetic resonance (MR) angiography revealed stenosis of the right internal carotid artery at the point of branching of the ophthalmic artery. Visual function in both of this patient's eyes improved with topical steroid pulse therapy, although her visual field worsened when she interrupted topical steroid therapy for a course of systemic steroid therapy. Little is known about AION associated with PMR. However, this case suggests that cerebral angiography is essential to locating the source of AION associated with arteritis and that steroid therapy is strikingly effective and should be maintained for the long term to preserve visual function.

Polymyalgia rheumatica and giant cell arteritis
Evans J.M.; Hunder G.G.
Dr. J.M. Evans, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 United States
Clinics in Geriatric Medicine (United States), 1998, 14/3 (455-473)

Polymyalgia rheumatica and giant cell arteritis are related conditions that may represent a continuum of disease. These conditions are relatively common and appear to be mediated by an autoimmune cellular inflammatory response. A growing body of evidence suggests an infectious cause or causes precipitating this immune response in genetically susceptible individuals. Although previously thought to affect primarily branch vessels of the aortic arch, GCA is now thought of as a disease in which proximal aortic involvement is common. Despite the potential for serious, even fatal complications, overall prognosis for patients with GCA or PMR is excellent. Corticosteroids remain the standard treatment, although likely not curative. While the ESR continues to be a useful indicator of disease activity, other markers that may be more precise are currently being investigated in order to improve disease diagnosis and treatment.

Epidemiology and optimal management of polymyalgia rheumatica
Labbe P.; Hardouin P.
Dr. P. Labbe, Department of Rheumatology, Centre Hospitalier Specialise, Institut Calot, 62608 Berck sur Mer France
Drugs and Aging (New Zealand), 1998, 13/2 (109-118)

Polymyalgia rheumatica (PMR) is a disease of unknown aetiology that occurs in elderly patients, predominantly affecting the Caucasian population. The disease has a slightly higher prevalence in women than in men. There is ongoing discussion regarding the relationship between PMR and giant cell arteritis; an increasing number of studies indicate that they are closely related. PMR has also been linked with rheumatoid arthritis, myopathy and malignant disease. Oral corticosteroids remain the mainstay of drug therapy for PMR. These drugs usually induce prompt relief of symptoms, and some authors consider this dramatic response to be diagnostic for PMR. However, the ideal initial dosage, the duration of treatment and the optimal tapering schedule are much debated. Other drugs, such as methotrexate and azathioprine, have been suggested as corticosteroid sparing agents. Nonsteroidal anti-inflammatory drugs are generally considered to be unsuitable for the long term treatment of PMR.

Systemic corticosteroid therapy in rheumatology: Benefit-risk ratio
Gerster J.C.; So A.K.L.; Burckhardt P.
Dr. J.C. Gerster, Service de Rhumatologie, CHUV, 1011 Lausanne Switzerland
Schweizerische Rundschau fur Medizin/Praxis (Switzerland), 1998, 87/33 (1024-1027)

Apart from the therapy of autoimmune diseases, corticosteroids have an important position in the treatment of rheumatoid arthritis. Corticosteroids are used after the failure of non-steroidal antiinflammatory agents or of the basis therapies to control the illness. When the rheumatoid arthritis is accompanied by a systemic disease, they will be used earlier and in higher dosages. For polymyalgia rheumatica, independently of an association with temporal arteritis, corticosteroids are the therapy of choice. Risks of long- time corticosteroid therapy are a higher incidence of infection and bone demineralisation, especially in postmenopausal women. A careful prevention with Calcium and Vitamin D must be carried out systematically. The demineralisation can be limited by the use of Deflazacort, a corticosteroid, which decreases the loss of calcium.

Ophthalmoplegia in treated polymyalgia rheumatica and healed giant cell arteritis
Brilakis H.S.; Lee A.G.
Dr. A.G. Lee, Dept. Ophthalmol., Baylor Coll. Medicine, 6565 Fannin St, NC-205, Houston, TX 77030 United States
Strabismus (Netherlands), 1998, 6/2 (71-75)

Diplopia may be a sign of giant cell arteritis (GCA). Polymyalgia rheumatica (PMR) is a systemic rheumatic inflammatory disease characterized by shoulder and hip girdle pain, and PMR can be associated in some patients with GCA. The authors report diplopia in two patients with treated PMR and biopsy-proven GCA, and review the literature on diplopia in GCA.

Polymyalgia rheumatica in a patient with acute tubulointerstitial nephritis due to Sjogren's syndrome
Hisahara S.; Ohkoshi N.; Shoji S.; Muro K.; Yamaguchi N.; Kobayashi M.; Koyama A.
Dr. N. Ohkoshi, Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305 Japan
Journal of Internal Medicine (United Kingdom), 1998, 244/1 (83-86)

A 68-year-old Japanese woman with polymyalgia rheumatica associated with acute tubulointerstitial nephritis and subclinical Sjogren's syndrome is described. Gallium scintigraphy showed marked accumulation in both kidneys and the salivary glands. Renal biopsy revealed lymphocytic infiltration in the tubulointerstitium. She was treated with intravenous high-dose methylprednisolone followed by oral prednisolone. Her clinical symptoms improved. This is the first report of this particular association.

Distal musculoskeletal manifestations in polymyalgia rheumatica: A prospective followup study
Salvarani C.; Cantini F.; Macchioni P.; Olivieri I.; Niccoli L.; Padula A.; Boiardi L.
Dr. C. Salvarani, Servizio di Reumatologia, Arcispedale Santa Maria Nuova, V.le Umberto 1 N50, 42100 Reggio Emilia Italy
Arthritis and Rheumatism (United States), 1998, 41/7 (1221-1226)

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.

Anticardiolipin antibodies in giant cell arteritis and polymyalgia rheumatica: A study of 40 cases
Manna R.; Latteri M.; Cristiano G.; Todaro L.; Scuderi F.; Gasbarrini G.
R. Manna, Istituto Medicina Interna Geriatria, Policlinico A. Gemelli, L.go F. Vito 8, 00168 Roma Italy
British Journal of Rheumatology (United Kingdom), 1998, 37/2 (208-210)

The occurrence and clinical value of anticardiolipin antibodies (aCL) were studied in 33 patients with giant cell arteritis (GCA) and in seven patients with polymyalgia rheumatica (PMR), at onset and during follow-up. aCL were present in 19/40 (47.5%) GCA/PMR cases, most of them of the IgG isotype, whereas all controls (21 subjects) were aCL negative. The presence of aCL was not associated with inflammatory parameters or clinical signs of arteritis; however, they disappeared in a significant percentage (56%) of patients during steroid therapy. No correlation was found between ischaemic events and aCL, suggesting that they are not important for the development of vascular complications in GCA/PMR patients. Moreover, a retrospective evaluation of our data showed a correlation between aCL positivity and anaemia, whose significance remains to be elucidated.

An initially double-blind controlled 96 week trial of depot methylprednisolone against oral prednisolone in the treatment of polymyalgia rheumatica
Dasgupta B.; Dolan A.L.; Panayi G.S.; Fernandes L.
B. Dasgupta, Department of Rheumatology, Southend Health Care Trust, Prittlewell Chase, Westcliff-on-Sea, Essex SS0 0RY United Kingdom
British Journal of Rheumatology (United Kingdom), 1998, 37/2 (189-195)

The objective was to compare the effiacy and safety of intramuscular methylprednisolone acetate (i.m. MP) with oral prednisolone (OP) in the treatment of polymyalgia rheumatica (PMR), a common steroid-treated illness where prolonged therapy can lead to steroid side-effects. The cumulative dose with i.m. MP injections given every 3-4 weeks is considerably smaller than that with conventional OP, and may therefore be associated with fewer long-term side-effects. A hybrid design was used with an initial 12 week double-blind placebo-controlled phase followed by an open phase on active treatment up to 96 weeks. The study was multicentre hospital out-patient based and included 60 patients with untreated PMR. In the doubleblind phase, either 120 mg 3-weekly i.m. MP or gradually tapering daily OP (initial dose 15 mg) were administered. In the open phase, subjects continued their active treatment with gradual tapering of the steroid dosage. The remission rate at 12, 48 and 96 weeks, and other measures of disease activity, i.e. sedimentation rate, pain and morning stiffness, and percentage of adverse reactions and serious complications such as fractures, were the main outcome measures. Sixty patients entered (30 OP:30 i.m. MP) and 49 (25 OP:24 i.m. MP) completed the study. There were similar remission rates after the double-blind phase (60.6% OP and 66.6%, i.m. MP, respectively) and similar disease control in the succeeding open phase. With steroid tapering, the mean erythrocyte sedimentation rate for the entire cohort registered a significant increase in the absence of an increase in symptoms. At 96 weeks, the cumulative mean steroid dose in subjects treated with i.m. MP was equivalent to 56% that of subjects treated with OP. There were eight fractures with OP compared to one on i.m. MP. Mean weight gain was significantly greater with OP than i.m. MP (3.42 vs 0.82 kg, P < 0.005). Minor adverse reactions were similar in both groups apart from slightly increased bruising with i.m. MP. Only patients on OP reported moon face, hypertension, cataracts, back pain and depression, but the numbers were small. It is possible to achieve equivalent long-term disease control in PMR with i.m. MP compared to OP. I.m. MP was associated with far fewer fractures and lesser weight gain, presumably related to lower cumulative dose. These findings may have implications in the steroid treatment of PMR, and other rheumatic and nonrheumatic diseases.

The deleterious effects of low-dose corticosteroids on bone density in patients with polymyalgia rheumatica
Pearce G.; Ryan P.F.J.; Delmas P.D.; Tabensky D.A.; Seeman E.
E. Seeman, Department of Endocrinology, Austin Repatriation Medical Centre, Heidelberg 3084 Australia
British Journal of Rheumatology (United Kingdom), 1998, 37/3 (292-299)

The beneficial effects of corticosteroid therapy in the treatment of rheumatic diseases may be offset by the occurrence of corticosteroid-related osteoporosis. This problem may be overcome by using low-dose corticosteroids; however, the dose of corticosteroids that is both efficacious and skeletal sparing is uncertain. Therefore, the aim of this study was to determine whether low-dose prednisolone treatment results in bone loss and modifies bone turnover. Nineteen patients (12 female, seven male) suffering from polymyalgia rheumatica received 10 mg or less daily, given in reducing dosage, with a range of 2.5-10 mg and an average of 6.0 plus or minus 0.2 mg daily (plus or minus S.E.M.). Prior to the commencement of therapy and at regular intervals during treatment, bone mineral density (BMD) using dual X-ray absorptiometry and circulating biochemical and hormonal determinants of bone turnover were measured. The patients were followed for 14.4 plus or minus 1.6 months (range 6-27). They were compared to 19 age-matched controls. Despite a mean exposure dose of 6 mg/day and disease remission, BMD decreased in the patients at the lumbar spine (2.6 plus or minus 0.8%, P < 0.01), femoral neck (2.9 plus or minus 1.5%, P = 0.06), Ward's triangle (5.5 plus or minus 2.9%, P = 0.06) and the trochanter (4.3 plus or minus 1.9%, P < 0.05). Total body bone mass decreased by 50 plus or minus 19 g in the first 6 months (P < 0.02), and by 39 plus or minus 30 g in the remaining 8 months of follow-up [not significant (NS)]. In the first 6 months, BMD decreased at the lumbar spine (1.7 plus or minus 0.9%, P = 0.06). From 6 months to the end of follow-up, BMD decreased by 8.5 plus or minus 3.5% at Ward's triangle (P < 0.05) and by 4.8 plus or minus 2.5% at the femoral neck (P = 0.08). The fall in BMD correlated with the cumulative prednisolone dose at trabecular-rich regions (trunk r = -0.72, P < 0.001; ribs r = -0.53, P < 0.05). Bone resorption, assessed by urinary cross-laps, was 54.7% higher than controls before treatment was started (P < 0.05) and decreased by 23.5 plus or minus 7.1% in the first month of treatment when the mean prednisolone dose was 9.1 mg/day, range 5-10 (P < 0.0001). Serum osteocalcin was not suppressed by disease before treatment, decreased by 27.4 plus or minus 5.1% during the first month of treatment (P < 0.001), remained suppressed while the daily dose of prednisolone was > 5 mg/day, but returned to baseline below this dose. Serum parathyroid hormone was 19.3% lower in the patients than controls at baseline (NS), and increased by 46.1% (P < 0.05) but was no higher than controls at any time. Muscle strength increased by 20-60% (P < 0.05 to < 0.01). Prophylaxis should be considered in patients receiving less than or equal to 5 mg/day prednisolone daily as bone loss is 2- to 3-fold expected rates. Earlier trabecular bone loss may predispose to spine and rib fracture; later cortical bone loss may predispose to hip fractures. Doses of prednisolone of < 5 mg daily may be skeletal sparing, but may not be effcacious.

Cytokines and adhesion molecules in patients with polymyalgia rheumatica
Uddhammar A.; Sundqvist K.G.; Ellis B.; Rantapaa-Dahlqvist S.
A. Uddhammar, Department of Rheumatology, University Hospital Northern Sweden, S-901 85 Umea Sweden
British Journal of Rheumatology (United Kingdom), 1998, 37/7 (766-769)

Serum levels of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1ra), tumour necrosis factor alpha (TNF-alpha), IL-6, soluble IL-6 receptor (sIL-6R), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin were measured in 15 patients with newly diagnosed polymyalgia rheumatica (PMR) before and after 3 months of corticosteroid therapy. Both IL-6 and IL-1ra were significantly increased in untreated PMR and remained elevated compared with controls during therapy, although significantly only for sIL-1ra. sICAM-1 was raised in 12/15 (87%) patients at diagnosis and remained high in 10/14 (71%) patients; soluble E-selectin levels were initially raised in 6/15 (40%) patients and decreased with therapy in those with the highest levels. IL-6, IL-1ra and sICAM-1 are sensitive indicators of continuing immunological activation in PMR; the advantages of these markers in assessing the response to therapy should be investigated in a longitudinal study.

A 24-year-old man with symptoms and signs of polymyalgia rheumatica
Whittaker P.E.; Fitzsimons M.G.
Dr. P.E. Whittaker, MAMC (ATTN: MCHJ-FP), Tacoma, WA 98431 United States
Journal of Family Practice (United States), 1998, 47/1 (68-71)

Most physicians regard polymyalgia rheumatica (PMR) as a disease that affects only the elderly. This case report of a 24-year-old man with proximal limb girdle muscle pain, stiffness, tenderness, weakness, and an elevated erythrocyte sedimentation rate, who had a dramatic response to steroids, supports the premise that PMR may affect a wider range of our population. Increased physician awareness that this illness does occur in patients younger than 50 may prevent delays in diagnosis, and decrease the needless suffering and incapacitation of younger patients with this disorder.

Deltoid muscle in patients with polymyalgia rheumatica
Uddhammar A.; Dahlqvist S.R.; Hedberg B.; Thornell L.-E.
Dr. A. Uddhammar, Department of Rheumatology, Univ. Hospital of Northern Sweden, S-901 85 Umea Sweden
Journal of Rheumatology (Canada), 1998, 25/7 (1344-1351)

Objective. To investigate muscle tissue in patients with polymyalgia rheumatica (PMR). Methods. Deltoid muscle biopsies obtained from 10 female patients with PMR before corticosteroid therapy and from 5 healthy female controls of similar age were studied using light microscopy. Serial cryosections were stained for the activity of myofibrillar ATPases at various pH and for oxidative and glycolytic enzymes. Sections were also incubated with antibodies against different myosin heavy chain (MyHC) isoforms, and the laminin alpha1 chain, identifying capillaries and cell borders, and against ligands for selected adhesion molecules. Results. The muscle fibers in patients and controls were mainly of type I containing slow MyHC, or type II AB containing both fast A and fast B MyHC isoforms. The oxidative capacity of the muscle fibers was in general low. In the patients with PMR the numbers of capillaries per unit area of type I and type II fibers were higher than in controls (p = 0.05 and p < 0.5, respectively). No accumulation of inflammatory cells or increased expression of adhesion molecules in the muscle sections from patients with PMR was found. Conclusion. There is increased microvascularization of the deltoid muscle fibers in patients with PMR. Whether this is directly associated with the systemic inflammation and the musculoskeletal symptoms or is mainly due to muscle fiber atrophy could not be determined.

Polyarthritis associated with myelodysplastic syndromes: 5 cases
Bonnotte B.; Chauffert B.; Roubert X.; Milas L.; Caillot D.; Solary E.; Francois M.; Bernard L.
Prof. B. Lorcerie, Service de Medecine Interne, Hopital du Bocage, 2 Bd Marechal de Lattre de Tassigny, F-21034 Dijon Cedex France
European Journal of Internal Medicine (Italy), 1998, 9/1 (57-60)

We analyzed the clinical and biological characteristics of 5 patients who demonstrated polyarthritis associated with a myelodysplastic syndrome. Polyarthritis either preceded (3 cases) or appeared during the course (2 cases) of the hematological malignancy. Two patterns of rheumatic manifestations were observed: rheumatoid type arthritis and manifestations of polymyalgia rheumatica. X-ray demonstrated non erosive lesions. Biological evaluations showed a non specific inflammatory syndrome and rheumatoid factor was negative. In 3 patients prednisolone improved the symptomatology while chemotherapy cured the polyarthritis in the two remaining cases. These observations indicate that hematological diseases can be revealed by rheumatic manifestations and that both diseases have a parallel evolution.

Clinical outcome of 149 patients with polymyalgia rheumatica and giant cell arteritis
Bahlas S.; Ramos-Remus C.; Davis P.
Dr. P. Davis, 562 Heritage Medical Research Centre, University of Alberta, Edmonton, Alta. T6G 2S2 Canada
Journal of Rheumatology (Canada), 1998, 25/1 (99-104)

Objective. To assess the clinical outcome of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA).

Methods. All charts of consecutive patients with a diagnosis of PMR and/or GCA attending a tertiary referral center from June 1989 to February 1996 were reviewed following a predetermined protocol. Subsequently, the majority of patients (90%) were assessed clinically or by telephone interview. Registered variables included demographic data, disease characteristics, prednisone dosage and duration, comorbidities, and clinical outcomes.

Results. There were 149 patients (133 with PMR alone, 7 with GCA alone, 9 with both); 94 (63%) were females; the mean age was 68 plus or minus 9 years, and the mean disease duration from the first symptom to the rheumatology consultation was 13 plus or minus 12 weeks (1-99). Typical clinical features of PMR were present in patients with PMR. Synovitis was observed in 26 patients. The presenting symptoms for GCA were typical features in 13 patients and blindness in 3 (2%) patients. Mean follow-up was 3.7 plus or minus 2 years. Comorbid conditions were present in 71 patients: 12 patients had hypertension, 13 had fractures, 8 diabetes, 29 cataract, 8 major infection, and 37 had other complications. Cancer was diagnosed in 4 patients and 6 patients had died. Prednisone was prescribed in 148 patients (mean dose 23 plus or minus 14 mg) for a mean time of 28 plus or minus 29 mo. Nonsteroidal antiinflammatory drugs were prescribed in 51 (34%) patients and methotrexate in 2. Disease remission was achieved in 81 (54%) patients (72 remissions, 9 presumed remissions) in whom steroid therapy had been stopped. Another 54 (36%) patients were still taking prednisone at the time of the interview, all were in clinical remission. Seventeen patients developed rheumatoid arthritis subsequent to the diagnosis of PMR.

Conclusion. PMR and GCA should not necessarily be considered diseases with favorable outcome. In many of our patients, steroids were required for a prolonged period. Some patients developed significant complications attributable to steroid therapy. A significant number of patients progressed to rheumatoid arthritis.

Large vessel vasculitides
Cid M.C.; Font C.; Coll-Vinent B.; Grau J.M.
Dr. M.C. Cid, Department of Internal Medicine, Hospital Clinic, University of Barcelona, Barcelona Spain
Current Opinion in Rheumatology (United States), 1998, 10/1 (18-28)

During the past few years remarkable progress has been achieved in the understanding of the pathogenic mechanisms leading to vascular inflammation and injury in giant cell (temporal) arteritis. T lymphocytes are activated by specific recognition of a putative antigen residing in the arterial wall and, subsequently, activate macrophages that undergo a functional differentiation and contribute to vessel damage through various pathways. Vascular response to inflammation amplifies the inflammatory response through neovascularization and adhesion molecule expression. We are beginning to appreciate that products released by infiltrating inflammatory cells may play an important role in vessel occlusion and resulting ischemic complications. Concomitantly, synovitis underlying polymyalgia rheumatica musculoskeletal symptoms has been immunopathologically characterized and the nature of its relationship to giant cell arteritis is discussed. Although some components of the disease are highly corticosteroid responsive, other underlying pathogenic mechanisms may remain active. Long-term outcome is heterogeneous in patients with giant cell arteritis. Much less is known about the pathogenesis of Takayasu's arteritis. Recent work supports its association with HLA class I antigens, which may differ in different geographic areas or ethnic groups. Because Takayasu's disease expression may vary in different ethnic settings, this possibility has led to the proposal of new diagnostic criteria. Finally, the role of new imaging techniques in diagnosis and assessment of disease activity is discussed.

Diagnosis and management of polymyalgia rheumatica/giant cell arteritis
Salvarani C.; Macchioni L.; Olivieri I.; Cantini F.; Boiardi L.
Dr. C. Salvarani, Unita Reumatologica, Arcispedale S. Maria Nuova, Viale Umberto 1 50, 42100 Reggio Emilia Italy
BioDrugs (New Zealand), 1998, 9/1 (25-32)

There are no standardised diagnostic criteria for polymyalgia rheumatica. The combination of persistent pain (at least 1 month) with marked morning stiffness in at least 2 of the neck, shoulder or pelvic girdle is characteristic of polymyalgia rheumatica. The other criteria are age >50 years, erythrocyte sedimentation rate (ESR) >40 mm/hour, rapid response to corticosteroids and an absence of other diseases capable of causing the musculoskeletal symptoms. A normal ESR does not exclude a diagnosis of polymyalgia rheumatica. Diagnostic temporal artery biopsy is recommended in all patients suspected of having giant cell arteritis. The segment of temporal artery with abnormality on physical examination should be biopsied. The drugs of choice in the treatment of polymyalgia rheumatica/giant cell arteritis are corticosteroids. An initial prednisone dosage of 40 to 60 mg/day is adequate in almost all cases of giant cell arteritis. Higher dosages and/or intravenous pulse methylprednisolone can be tried on patients with partial response or with recent visual loss. Polymyalgia rheumatica in the absence of giant cell arteritis requires an initial dose of prednisone 10 to 20 mg/day. In some cases of mild polymyalgia rheumatica, a short course of nonsteroidal anti-inflammatory drugs may be tried. Long term corticosteroid therapy in polymyalgia rheumatica and giant cell arteritis is complicated by serious adverse effects in between 48 and 65% of patients. Vertebral fractures and infections are among the most dangerous and frequent complications. Although there are limited data on the use of cytotoxic or immunosuppressive drugs, such as methotrexate, azathioprine and cyclosporin, in these indications, they might be effective either in sparing corticosteroids or in treating patients who do not respond to treatment with corticosteroids.

Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica
Gabriel S.E.; Sunku J.; Salvarani C.; O'Fallon W.M.; Hunder G.G.
Dr. S.E. Gabriel, Dept. of Health Sciences Research, Mayo Clinic Rochester, 200 First Street, SW, Rochester, MN 55905 USA
Arthritis and Rheumatism (USA), 1997, 40/10 (1873-1878)

Objective. To evaluate the incidence and risks of adverse events associated with therapy (both corticosteroids (CS) and nonsteroidal antiinflammatory drugs (NSAIDs)) among a previously identified, population- based cohort of patients first diagnosed with polymyalgia rheumatica (PMR) between 1970 and 1991 who were followed up over the long term.

Methods. Information on demographics, PMR diagnosis, disease course, and drug therapy, in addition to data on adverse events commonly associated with CS and NSAID treatment, was obtained from the Rochester Epidemiology Project database. Cox proportional hazards and regression analysis models were used to evaluate the relationship between the occurrence of these events and therapy.

Results. Of the 232 patients (69 male, 163 female) included in the study, the mean age at PMR diagnosis was 72.9 years, the average followup was 8.0 years, and 30 patients were also diagnosed with giant cell (temporal) arteritis. Among the 175 patients (49 male, 126 female) treated with CS, the mean duration of CS therapy was 2.4 years, the average daily dose was 9.6 mg, and the mean cumulative dose was 8.4 gm. In total, 65% of the 124 patients treated with CS alone experienced at least 1 adverse event, compared with 67% of the 57 patients treated with NSAIDs alone and 80% of the 51 patients treated with CS and NSAIDs. The average time from initiation of therapy to the first adverse event was 1.6 years (n = 160). Proportional hazards modeling identified 3 variables that independently increased the risk of adverse events: age at PMR diagnosis, a cumulative dose of prednisone less than or equal to1,800 mg, and female sex. Person-year analysis revealed that the risks of diabetes mellitus, vertebral fractures, femoral neck fractures, and hip fractures were 2-5 times greater among PMR patients compared with age- and sex-matched individuals from the same population. Medical care or consultation by a rheumatologist was a highly significant predictor of a lower initial CS dose.

Conclusion. The use of CS and NSAIDs in the treatment of PMR is associated with important long- term morbidity.

The sequential analysis of T lymphocyte subsets and interleukin-6 in polymyalgia rheumatica patients as predictors of disease remission and steroid withdrawal
Corrigall V.M.; Dolan A.L.; Dasgupta B.; Panayi G.S.
V.M. Corrigall, Rheumatology Unit, Thomas Guy House, Guy's Hospital, London SE1 9RT United Kingdom
British Journal of Rheumatology (United Kingdom), 1997, 36/9 (976-980)

CD4 and CD8 T lymphocyte subsets, the late T cell activation marker, HLA-DR, and serum interleukin-6 (IL-6) levels of 57 polymyalgia rheumatica (PMR) patients were followed over 2 yr to investigate whether they could be used to predict the safe withdrawal of steroid therapy. Cell phenotypes were studied by flow cytometry and IL-6 levels by ELISA. %CD8 cells were reduced below the normal range in PMR patients prior to steroid therapy. In 56% of patients, the %CD8 T lymphocytes failed to return to normal levels when quiescent disease allowed cessation of steroid therapy. Activated CD8 T cells, as detected by HLA-DR positivity, were above the normal range at the initiation of therapy and showed a negative correlation with %CD8 T cells. The serum concentration of IL-6 fluctuated over 24 months, and the correlation between IL-6 and erythrocyte sedimentation rate (ESR) seen prior to treatment was not seen at later intervals. The %CD8 T cell and serum IL-6 levels are not a good indicator of disease activity in PMR and are, therefore, unable to predict the safe withdrawal of steroids.

Polymyalgia rheumatica - Therapy, course of disease, complications
Ehlert A.; Stoyanova-Scholz M.
Dr. A. Ehlert, Rheumatologische Klinik, Stadt. Kliniken, Zu den Rehwiesen 9, D-47055 Duisburg Germany
Geriatrie Forschung (Germany), 1997, 7/1 (13-18)

Polymyalgia rheumatica is a typical disease of the elderly. If vascular complications of giant cell arteritis have not developed before treatment starts, the prognosis is generally favourable. However, the course of the disease is often characterised by relapses requiring an increase in the corticosteroid dosage. This is associated with a higher rate of adverse reactions that modifies the otherwise favourable prognosis. We evaluated the course of the disease in 78 polymyalgia rheumatica patients who were observed for a mean of 28 plus or minus 20 months. Temporal arteritis was histologically confirmed in 20 out of 71 patients (28%). Of the 70 patients who were observed for more than six months, 18 (26%) suffered a relapse of corticosteroid dosages of 6.25 plus or minus 3.1 (0-12.5) mg. After 24 months 36% had been in remission without treatment for a period of 9.3 plus or minus 6.1 (3-18) months. Therapy-associated complications arose in 21 (34%) of 64 patients who were observed for more than nine months. The most common were steroid-induced diabetes mellitus or aggravation of a known diabetic metabolic condition (33%). The most severe adverse reaction osteoporotic vertebral fracture - was reported in 3 patients. Further complictions of therapy were various frequencies of arterial hypertension, cataract, glaucoma, subjectively disturbing weight gain and hypokalaemia. Overall, our data confirmed that the usually favourable course of polymyalgia rheumatica is modified by relapses and complications of therapy. Hence, we would tend to reduce steroids or use immunosuppressants at an early stage, especially in high risk cases such as patients with inadequately controllable diabetes mellitus or manifest osteoporosis.

Antibodies against Chlamydia pneumoniae, cytomegalovirus, enteroviruses and respiratory syncytial virus in patients with polymyalgia rheumatica
Uddhammar A.; Boman J.; Juto P.; Dahlqvist S.R.
Dr. A. Uddhammar, Department of Rheumatology, University Hospital, S-901 85 Umea Sweden
Clinical and Experimental Rheumatology (Italy), 1997, 15/3 (299-302)

Objectives: To investigate the association between the onset of polymyalgia rheumatica (PMR) and prior or persistent infection with Chlamydia pneumoniae or cytomegalovirus (CMV) (both known to infect the vessel wall) enteroviruses (EV) or respiratory syncytial virus (RSV).

Methods: Serum samples were collected from 48 patients with newly-diagnosed PMR and from 22 controls of the same age. The presence of IgG, IgA and IgM antibodies to C. pneumoniae, IgG and IgM antibodies to CMV and EV, and complement fixing antibodies to RSV were analysed.

Results: Clinical symptoms of infection preceding PMR symptoms were associated with the presence of synovitis at the first visit. There were no significant differences in the seroprevalence rates of antibodies to C. pneumoniae, CMV, EV or RSV between PMR patients and controls. IgM antibodies to EV were found in two patients and IgM antibodies to CMV in another two patients.

Conclusion: Serological evidence of an association between newly-diagnosed PMR and prior or chronic infection with C. pneumoniae was not found. IgM antibodies to EV in two patients, consistent with ongoing or recent infection, suggest that EV could represent one of perhaps several microbes which are able to trigger PMR.

False diagnosis: A common occurrence in autoimmune diseases
Seitz M.
Switzerland
Schweizerische Medizinische Wochenschrift (Switzerland), 1997, 127/9 (349-354)

False diagnosis of autoimmune diseases may have many different reasons. It may be caused by the relative rareness of these rather complicated diseases, by sometimes mono- or oligosymptomatic courses, and by the highly variable clinical presentations. In addition, many physicians lack experience in the treatment of these rheumatologic-immunological diseases. A first shot diagnosis, inadequate technique in obtaining a correct history or in performing a physical examination, as well as an incomplete evaluation of differential diagnosis, are possible causes of wrong diagnosis in the context of autoimmune diseases and may delay effective therapy. To illustrate these problems, three examples of patients with autoimmune diseases are discussed, namely a patient with polyarthritis and fever, a patient with polymyalgia rheumatica, and a patient with an ulcerative skin lesion. These examples serve to discuss the difficulty of correct diagnosis in complicated courses of autoimmune diseases, which are also relatively common in general practice.

Risk factors and predictive models of giant cell arteritis in polymyalgia rheumatica
Rodriguez-Valverde V.; Sarabia J.M.; Gonzalez-Gay M.A.; Figueroa M.; Armona J.; Blanco R.; Fernandez-Sueiro J.L.; Martinez-Taboada V.M.
Dr. V. Rodriguez-Valverde, Rheumatology Division, Hosp. Universitario 'M. Valdecilla', Av Valdecilla s/n, 39008 Santander Spain
American Journal of Medicine (USA), 1997, 102/4 (331-336)

OBJECTIVE: To identify in polymyalgia rheumatica the best set of predictors for a positive temporal artery biopsy and to define predictive models with either a high or low probability of giant cell arteritis (GCA).

PATIENTS AND METHODS: Retrospective study of 227 patients, 137 with polymyalgia rheumatica unassociated with arteritis (group A) and 90 with polymyalgia associated with biopsy-proven giant cell arteritis (group B or training set). Data on demographic features, clinical and laboratory abnormalities were collected. Risk factors for arteritis were estimated by nonlinear logistic regressions. Simple predictive models were constructed with those predictors more related to arteritis by multivariable analysis. These models were then tested in group B and in 89 cases of arteritis without polymyalgia rheumatica (group C or test set).

RESULTS: The best predictors of arteritis were a new headache odds ratio (OR) 13.6 (95% confidence interval (CI) 4.7 to 39.3); age at onset < 70 years OR 0.11 (CI 0.04 to 0.35); abnormal temporal arteries OR 4.2 (CI 1.3 to 13.7); raised liver enzymes OR 2.9 (CI 1.1 to 7.8), and jaw claudication OR 4.8 (CI 1.0 to 22.7). Amaurosis was only observed in patients with arteritis. Three subsets had a very high risk of arteritis: (1) Patients with recent headache, abnormal arteries, and less than or equal to70 years at disease onset: sensitivity 44%, positive predictive value (PPV) 93%, likelihood ratio (LR) 20.3; (2) patients with a new headache, jaw claudication, and abnormal arteries: sensitivity 34.4%, PPV 96.9%, LR 47.2; and (3) those, that in addition to the last 3 features, were less than or equal to70 years of age at disease onset: sensitivity 26.7%, PPV 100%. We could also identify a subset with a very low risk of arteritis constituted by patients < 70 years, without headache, and with clinically normal temporal arteries: sensitivity 1.1%, PPV 1.7%, LR 0.03. In group C or the test set, these four predictive models correctly identified 57.3%, 29.2%, 23.6, and 3.4% of patients, respectively.

CONCLUSIONS: In polymyalgia rheumatica it is feasible to identify subsets with a very high likelihood of GCA. Although in some of these subsets the diagnosis of arteritis is almost certain, we suggest that even then it should be confirmed by temporal artery biopsy. By contrast, in those patients with polymyalgia < 70 years and without cranial features of giant cell arteritis, the risk of vasculitis is so low that the biopsy could be initially avoided and the patient treated with low-dose corticosteroids.


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