Familial aggregation in giant cell arteritis and polymyalgia rheumatica: a comprehensive literature review including 4 new families.

OBJECTIVE: To review personal and published observations of giant cell (temporal) arteritis (GCA) or polymyal-gia rheumatica (PMR) with familial or conjugal aggregation and emphasise on epidemiological, clinical and genetic features of such cases. METHODS: We pooled data obtained from all cases of GCA or PMR with familial aggregation recruited in the department since 1976 and those from reports of familial or conjugal GCA or PMR published in the French-English literature since 1970. RESULTS: During the study period, we diagnosed 460 patients (128 with isolated PMR, 227 with isolated GCA, 105 with PMR/CGA). No conjugal couples were observed in the whole series. No familial cases were identified among PMR patients, whereas the prevalence of familial GCA was 1 in 83 (1 in 250 to 500 expected by chance), as we identified 4 patients (brother-brother, sister with history of affected sister, and daughter with priory affected mother). An additional pair of sisters with TA, recruited several months after diagnosis, is also presented. Pooling data from 85 patients (74 with GCA) including our patients, representing 32 families and 8 conjugal pairs, enabled us to draw the following observations: 1) partial or full agreement in the clinical picture (GCA, PMR, or GCA/PMR) was observed in 96% of the siblings pairs, suggesting a common pathogenic mechanism; 2) five kindred were described in whom at least three members were affected; 3) the lag between manifested diseases in familial or conjugal pairs averaged 5.7 years, with synchronous or close disease occurrence in only 26% of the pairs; 4) 18 of 32 assessed patients (56%) carried the DR4 antigen. CONCLUSION: Our survey on familial aggregation of GCA and PMR accumulated data pointing to a genetic predisposition. However, environmental contagious factors could have trigger synchronous disease onset in up to one-fourth of the cases.

Aortic angiosarcoma clinically mimicking polyarteritis nodosa.

We report two patients in whom angiosarcoma of the aorta (ASA) with distal emboli and skin metastases was initially clinically misdiagnosed as polyarteritis nodosa (PAN). Both presented with features highly suggestive of systemic necrotizing vasculitis, including constitutional symptoms, orchitis (in one), leg pain with sensory neuropathy, livedo, focal areas of skin necrosis, painful cutaneous nodules demonstrating vasculitis or inconspicuous changes on biopsy, raised acute phase reactants, and transient improvement with systemic corticosteroids. Repeated skin biopsies revealed an atypical endovascular cell proliferation with strong reactivity for factor VIII. Magnetic resonance angiography (MRA) demonstrated an intra-luminal aortic tumour at the infra-renal level. In retrospect, the (PAN)-like features appeared to involve exclusively the lower part of the body in these patients.

[Systemic lupus erythematosus and herpes virus infection: three new observations]. / Lupus érythémateux disséminé et herpes viridae: à propos de trois observations.

INTRODUCTION: Systemic lupus erythematosus is still of unknown origin. Viruses have long been postulated to play a role in its pathogenesis particularly cytomegalovirus and Epstein-Barr virus. EXEGESE: We describe three patients who presented acute onset of systémic lupus erythematosus concurrently with recent viral infection (two with cytomegalovirus and one with Epstein-Barr virus). CONCLUSION: The peculiar clinical events emphasize the difficulty of diagnosis at the onset of the disease and suggest possible role of these viruses in the pathogenesis of SLE.

[Non-simultaneous malignant lymphoma and antiphospholipid syndrome: 4 cases]. / Lymphomes malins et syndrome des antiphospholipides non simultanés: quatre observations.

OBJECTIVE: We report four cases of non-synchronous antiphospholipid syndrome (APS) and malignant lymphoma, which highlight the complex relationship that seems to exist between these illnesses. METHODS: In a retrospective study conducted in two departments (internal medicine and clinical hematology) of a university hospital, we collected all observations of patients with both APS and malignant lymphoma diagnosed throughout the past decade. RESULTS: An association of APS with malignant lymphoma was recorded in three female and one male patient, median age 42.5 years at the time of diagnosis of the first disease. In each case, the primary APS was diagnosed, with arterial thrombotic events in three cases and venous thrombotic events in one case. One patient had isolated IgG anticardiolipin antibody, whereas the others had a combination of IgG anticardiolipin antibody and lupus anticoagulant with or without IgG anti-beta 2 glycoprotein I antibody. One patient also had an acquired inhibitor to factor VIII:C and a chronic C virus hepatitis. The mean time apparently separating the two illnesses ranged from 18 months to 9 years, but in two cases the diagnosis of APS was delayed due to a progressive, atypical, neurological onset. In two instances, the APS took place at a distance from a cured malignant lymphoma (Hodgkin's disease and nodal large cell B-cell lymphoma), whilst in the others it preceded a B-cell lymphoma (nodal and cutaneous, small cells and primary hepatic, large cells). Treatment resulted in complete haematological response in both cases, with disappearance of anticardiolipin antibody and lupus anticoagulant in the latter following a double autologous peripheral blood stem cell transplantation. In addition, late carcinomas (breast, kidney, thyroid) were seen in two patients. CONCLUSIONS: Our data indicate that the diagnosis of a malignant lymphoma should be considered in patients with a primary APS and peripheral lymph node enlargement or unexplained constitutional symptoms. Conversely, a late onset of arterial or venous thrombotic diathesis after a malignant lymphoma may indicate not only late relapse of malignant lymphoma but also a subsequent APS.

Risk factors for visual loss in giant cell (temporal) arteritis: a prospective study of 174 patients.

OBJECTIVE: To determine the risk factors--especially the effects of thrombocytosis--for permanent visual loss in patients with temporal arteritis. METHODS: One hundred seventy-four patients with temporal arteritis (147 biopsy proven) were prospectively observed for the development of permanent visual loss. We used multivariate logistic regression analysis to determine which of 17 pretreatment characteristics were associated with visual loss. RESULTS: Visual ischemic manifestations occurred in 48 (28%) patients, including permanent visual loss in 23 (13%) patients. The independent predictors associated with an increased risk of permanent visual loss were a history of transient visual ischemic symptoms (odds ratio [OR] = 6.3; 95% confidence interval [CI]: 1.4 to 29; P = 0.02) and a higher platelet count (OR = 3.7 per SD; 95% CI: 1.8 to 7.9; P = 0.001). The presence of constitutional symptoms (OR = 0.14; 95% CI: 0.02 to 0.77, P = 0.01), polymyalgia rheumatica (OR = 0.04; 95% CI: 0.01 to 0.48, P = 0.02), and C-reactive protein level (OR = 0.35 per SD; 95% CI: 0.13 to 0.92, P = 0.03) were associated with a reduced risk. Upper limb artery involvement was excluded from the multivariate model, as no patients with that problem developed permanent visual loss. Of the 87 patients who presented with thrombocytosis (platelet count >400 x 10(9)/L), 32 (37%) developed ischemic visual symptoms, compared with 16 (18%) of those without thrombocytosis. CONCLUSIONS: An elevated platelet count is a risk factor for permanent visual loss in temporal arteritis. The finding of thrombocytosis in a patient with suspected temporal arteritis should emphasize the need for urgent treatment, with consideration of using inhibitors of platelet aggregation or anticoagulation therapy.

[Risk factors for irreversible cerebral ischemia complications from Horton's disease: prospective study of 178 patients]. / Facteurs prédictifs de complications céphaliques ischémiques irréversibles au cours de la maladie de Horton: étude prospective sur 178 patients.

PURPOSE: To search for risk factors of developing irreversible cranial ischemic complications (ICIC) in patients with giant cell arteritis (GCA) and to explore whether two subsets of patients (high risk and low risk of developing ICIC) can be defined. METHODS: One-hundred seventy-eight consecutive patients with temporal arteritis (149 biopsy-proven) were diagnosed and followed up in a department of Internal Medicine between 1976 and 1999. The patients were separated into two groups, according to the presence or absence of ICIC, with comparison of 17 clinical and biological parameters prospectively recorded for each patient using a pre-established comprehensive questionnaire. RESULTS: ICIC occurred in 25 patients (14%), with amaurosis in 22 cases. Suggestive symptoms and/or signs of temporal arteritis were present in 92% of the patients, lasting 50 days (median) before the onset of ICIC. Forty-three patients (24%) complained of transient visual ischemic symptoms (TVIS), which preceded acute blindness in 11 cases. A multivariate logistic regression, from which 28 cases with upper limb artery involvement were excluded for technical reasons (no CCII in any case, thus predicting perfectly the lack of ischemic risk, P = 0.02), indicated that the only independent variables associated with the ischemic risk were: a history of TVIS (P = 0.05), the lack of signs of polymyalgia rheumatica (PMR; P = 0.02), lower blood levels of fibrinogen (P = 0.024) and higher mean blood platelets levels (P = 0.006). However, these five variables predicted only 30% of the variability of the model. Sensitivity, specificity, positive and negative predictive values of the model reached respectively 36, 96, 64 and 88%. Overall, 86% of the cases were correctly classified with respect to the ischemic risk. CONCLUSION: The rate of ICIC should be reduced by an earlier recognition of the usual signs of temporal arteritis. Several independent risk factors of ICIC have been identified. However, the logistic model failed to predict accurately the ischemic risk in 14% of the cases, indicating that as yet unrecognised factors probably exist that play a role in the occurrence of ICIC. Nevertheless, regarding the strong association between platelet levels and ICIC, patients with thrombocytosis should receive initially both corticosteroids and antiplatelet agents.

Anticardiolipin antibody levels predict flares and relapses in patients with giant-cell (temporal) arteritis. A longitudinal study of 58 biopsy-proven cases.

OBJECTIVE: To evaluate the usefulness of anticardiolipin antibodies (aCL) in identifying flares and relapses in giant-cell arteritis. METHODS: We studied 58 consecutive patients with biopsy-proven temporal giant-cell arteritis. C-reactive protein and aCL serum levels were measured simultaneously at the time of diagnosis and at each out-patient visit until recovery. All observed episodes of a rise in C-reactive protein attributable to a precise cause, for which the simultaneous measurement of aCL was available, were analysed. RESULTS: The mean duration of clinical observation and serum aCL assessment was 34+/-18 and 24+/-11 months, respectively. Anticardiolipin antibody positivity (IgG or total antibodies > or =20 U) before treatment was found before treatment in 27 cases (46.6%) (mean 45.6+/-26 U/l, range 20-110 U). Levels of aCL decreased below 10 U with appropriate treatment in all patients except one, after a variable delay. No rise in aCL levels was recorded subsequently in any patient whose disease was controlled permanently. A significant rise in aCL was recorded in 20 of 27 (74%) of the flares or relapses of giant-cell arteritis, including seven of 12 flares in seven patients whose initial aCL level was <20 U vs none of the 28 inflammatory episodes unrelated to giant-cell arteritis (P<0.0000001). IgM aCL, infrequently found at diagnosis, was not associated with signs of disease activity. CONCLUSION: Serum aCL levels are useful in the detection of flares and relapses in giant-cell arteritis, with fairly good sensitivity (74%) and a specificity of 100%, and can be of value in distinguishing subclinical flares from infection.

[Horton's disease and hypereosinophilic syndrome: a non-fortuitous association]. / Maladie de Horton et syndrome hyperéosinophilique: une rencontre non fortuite.

Giant cell arteritis is a T-cell dependent auto-immune vasculitis that involves a T-helper l (Th1) cell response. We report the unusual case of a woman who developed successively a biopsy-proven temporal arteritis without tissue eosinophilia at age 65, an isolated blood eosinophilia at age 69 and an hypereosinophilic syndrome at age 71, while still taking corticosteroids at the dose of 3mg/day. Considering this temporal relationship, some characteristics of her hypereosinophilic syndrome pointing to a Th2-dependent disease (absence of definite signs of myeloproliferative syndrome, elevated IgE levels and quick normalisation of eosinophil counts under corticosteroid therapy) and the existence of an unexplained blood inflammatory response at the time of HES onset, we postulate that an unbalanced T helper response led in this exceptional case to both diseases.

Absence of anti-beta2 glycoprotein I antibodies in giant cell arteritis: a study of 45 biopsy-proven cases.

OBJECTIVE: To search for a relationship between serum anti-beta2 glycoprotein I (anti-beta2GPI) antibodies and the occurrence of ischaemic complications in giant cell arteritis (GCA), since the latter do not correlate with anti-cardiolipin antibodies (ACL), which are frequently observed in GCA. METHODS: IgG and IgM anti-beta2GPI antibodies and ACL were measured by enzyme-linked immunosorbent assays in sera, collected before treatment, from 45 unselected patients with biopsy-proven GCA, including 15 patients with ischaemic events. RESULTS: IgG and IgM anti-beta2GPI antibodies were not detected in any of the patients, contrasting with the presence of ACL in 51%, of them, without correlation with ischaemia. CONCLUSION: Anti-beta2GPI antibodies are not detectable in GCA, contrasting with the occurrence of ACL, and ischaemic complications are apparently unrelated to the most frequent anti-phospholipid antibodies.

Thymoma-associated pancytopenia: effectiveness of cyclosporine A.

Aplastic anemia is a rare complication of thymoma and is properly documented in only few cases. Here, we report the case of a previously healthy, 65-year-old patient who was found simultaneously to have a spindle-cell thymoma and severe hypoplastic anemia with a mild infiltration of the bone marrow by CD4+ and CD8+ T lymphocytes, CD16+ natural killer cells, and a decrease in blood CD4/CD8 ratio. Cultures of marrow erythroid progenitors demonstrated serum inhibitor. While steroids, cyclophosphamide and antilymphocyte globulin failed to improve hematopoiesis, cyclosporine A (Cy-A) led to a partial, stable remission that was sustained for 4 years. Since Cy-A has been associated with good responses in three cases of thymoma-associated red cell aplasia, we recommend its use in cases of thymoma-associated cytopenias refractory to steroids and cyclophosphamide.

Breast cancer with systemic manifestations mimicking Still's disease.

We describe a case whose clinical features strongly suggested Still's disease, which led to the discovery of breast cancer. Our patient's symptoms consisting of fever, joint inflammation, pleuritis, and pericarditis, were initially resistant to high doses of steroids, and disappeared only after the cancer was removed, despite rapid tapering and cessation of steroid therapy. A paraneoplastic phenomenon seems probable.

[Periarteritis nodosa and parvovirus B19 infection]. / Périartérite noueuse et infection par le parvovirus B19.

The authors report a case of polyarteritis nodosa which coincide with serological conversion to parvovirus B19. After review of the literature, they recall the role of this virus in human pathology and also the role of different infectious agents in the PAN pathogenesis.