Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Recurrent (or episodic) fever of unknown origin (FUO) as a variant subgroup of classical FUO: A French multicentre retrospective study of 170 patients.

BACKGROUND: Recurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking. METHODS: We performed a retrospective multicentre study of patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality. RESULTS: Of 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death. CONCLUSION: This study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent.

Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

DBH deficiency in an elderly patient: efficacy and safety of chronic droxidopa.

We describe the effects of chronic droxidopa in a patient with Dopamine beta-hydroxylase deficiency diagnosed at the age of 73. Investigations were performed to assess sympathetic activity (MIBG scintigraphy, catecholamines) and cardiovascular droxidopa safety.

[The current place of non-invasive large-vessel imaging in the diagnosis and follow-up of giant cell arteritis]. / Place actuelle de l'imagerie non invasive des artères de gros calibre dans l'artérite à cellules géantes: du diagnostic au suivi.

Large vessel involvement in giant cell arteritis has long been described, although its right frequency and potential prognostic value have only been highlighted for two decades. Large vessel involvement not only is associated with a high incidence of late aortic aneurysms, but also might cause greater resistance to glucocorticoids and longer treatment duration, as well as worse late cardiovascular outcomes. These data were brought to our attention, thanks to substantial progress recently made in large vessel imaging. This relies on four single, often complementary, approaches of varying availability: colour Doppler ultrasound, contrast-enhanced computed tomography with angiography and, magnetic resonance imaging, which all demonstrate homogeneous circumferential wall thickening and describe structural changes; 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT), which depicts wall inflammation and assesses many vascular territories in the same examination. In addition, integrated head-and-neck PET/CT can accurately and reliably diagnose cranial arteritis. All four procedures exhibit high diagnostic performance for a large vessel arteritis diagnosis so that the choice is left to the physician, depending on local practices and accessibility; the most important is to carry out the chosen modality without delay to avoid false or equivocal results, due to early vascular oedema changes as a result of high dose glucocorticoid treatment. Yet, ultrasound study of the superficial cranial and subclavian/axillary arteries remains a first line assessment aimed at strengthening and expediting the clinical diagnosis as well as raising suspicion of large-vessel involvement. In treated patients, vascular imaging results are poorly correlated with clinical-biological controlled disease so that it is strongly recommended not to renew imaging studies unless a large vessel relapse or complication is suspected. On the other hand, a structural monitoring of aorta following giant cell arteritis is mandatory, but uncertainties remain regarding the best procedural approach, timing of first control and spacing between controls. Individuals at greater risk of developing aortic complication, e.g. those with classic risk factors for aneurysm and/or visualised aortitis, should be monitored more closely.

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.

[Hemorrhagic syndrome due to a heparin-like anticoagulant in a patient with systemic lupus erythematosus]. / Syndrome hémorragique dû à un anticoagulant héparine-like chez un patient lupique.

INTRODUCTION: In systemic lupus erythematosus, hemostasis disorders are mainly thrombotic, but more rarely hemorrhagic. CASE REPORT: A 25-year-old man presented with a macrophagic activation syndrome revealing a systemic lupus erythematosus, secondarily complicated by a hemorrhagic syndrome ; biological investigations revealed an increase thrombin time and an activated partial thromboplastin time, normalized by protamin neutralization in vitro, thus confirming the presence of a heparin-like anticoagulant. The hemostasis balance normalized after the specific treatment of lupus. CONCLUSION: This rare anomaly of hemostasis balance has been described in blood cancers and solid cancers. This is the first description of a case associated with an autoimmune connective tissue disorder such as lupus. After one year of follow-up, no diagnosis of blood or solid cancer was made.

Concomitant association of giant cell arteritis and malignancy: a multicenter retrospective case-control study.

INTRODUCTION: Some studies suggest that there is an increased risk of malignancies in giant cell arteritis (GCA). We aimed to describe the clinical characteristics and outcomes of GCA patients with concomitant malignancy and compare them to a GCA control group. METHOD: Patients with a diagnosis of GCA and malignancy and with a maximal delay of 12 months between both diagnoses were retrospectively included in this study and compared to a control group of age-matched (3:1) patients from a multicenter cohort of GCA patients. RESULTS: Forty-nine observations were collected (median age 76 years). Malignancies comprised 33 (67%) solid neoplasms and 16 (33%) clonal hematologic disorders. No over-representation of a particular type of malignancy was observed. Diagnosis of GCA and malignancy was synchronous in 7 (14%) patients, while malignancy succeeded GCA in 29 (59%) patients. Malignancy was fortuitously diagnosed based on abnormalities observed in laboratory tests in 26 patients, based on imaging in 14 patients, and based on symptoms or clinical examination in the nine remaining patients. Two patients had a concomitant relapse of both conditions. When compared to the control group, patients with concomitant GCA and malignancy were more frequently male (p < 0.001), with an altered general state (p < 0.001), and polymyalgia rheumatica (p < 0.01). CONCLUSIONS: This study does not indicate an over-representation of any particular type of malignancy in GCA patients. Initial follow-up dictated by vasculitis may have led to an early identification of malignancy. Nevertheless, GCA male patients with an altered general state and polymyalgia rheumatica might more frequently show concomitant malignancies.

Evaluation of at-home phlebotomy for iron overload: feasibility and satisfaction of patients and healthcare workers.

OBJECTIVE: This study aimed to evaluate at-home phlebotomy and the satisfaction of iron-overload patients and healthcare workers with the procedure. METHODS: Forty-two patients underwent at-home phlebotomy between 2003 and 2006. The phlebotomy was performed by the patient's nurse, who was trained by the private healthcare firm that also took charge of the disposal of the blood products. Data concerning these phlebotomies were collected via telephone interviews with all 42 patients, as well as 35 nurses and 40 primary-care physicians. The Limousin Regional Health Observatory processed the data collection. RESULTS: Ninety percent (38/42) of the patients, 80% (28/35) of the nurses and 67% (27/40) of the primary-care physicians responded. For 80% of the patients, phlebotomy volume and frequency were as prescribed. Patients chose home phlebotomy for personal reasons, or because of the limited availability of French Blood Establishment facilities (68%), or in response to being offered it by their hospital physician (32%). For 81.6% of the patients, at-home phlebotomy was more satisfactory than phlebotomy in hospital or at the French Blood Establishment and, for 84%, the constraints required were fully acceptable. The nurses considered that these homecare procedures were within their area of responsibility (100%), but felt that the remuneration was insufficient (65%). Ninety-six percent of the primary-care physicians said they were correctly informed, but only 40% felt that they were truly committed to the procedure. CONCLUSION: At-home phlebotomy is feasible, less costly than institutional phlebotomy and improves patient comfort.

[Gastroparesis may be the cause of unexplained dyspepsia in patients with primary Sjögren syndrome]. / La gastroparésie peut être à l'origine de symptômes digestifs hauts inexpliqués chez les patients souffrant d'un syndrome de Goujerot-Sjögren.

INTRODUCTION: Upper digestive symptoms may be present in up to 50% of patients with primary Sjögren syndrome (pSS). We report a retrospective cohort of gastroparesis in a population of pSS presenting unexplained dyspepsia. Delayed gastric emptying was defined by a gastric emptying time above 113min or by a retention percentage at 4h more than 10% on scintigraphy. RESULTS: Eleven patients with primary Sjögren syndrome and gastroparesis were included in a retrospective study. Every patients were women of age 48±18y. The average time of gastric emptying was 725,18±704,45min. 64% of patients had abdominal pain or gastric heaviness. A central or peripheral neurologic involvement was described in respectively 9 and 27% of cases. The diagnostic delay of gastroparesis was higher than 24 months. CONCLUSION: In primary Sjögren syndrome, gastroparesis should be suspected in case of unexplained dyspepsia, and a scintigraphy performed to prove the diagnosis. A neurologic involvement could explain gastroparesis, but prospective studies are needed for a better understanding of this disorder.

[Multinodular goitre with widespread vasculitis of thyroid arteries revealing temporal giant cell arteritis]. / Goitre multinodulaire et artérite à cellules géantes intrathyroïdienne diffuse révélatrice d'une maladie de Horton.

We describe a 62-year-old woman with slowly growing usual nodular goitre in whom diffuse giant cell arteritis (GCA) of the thyroid arteries was found upon thyroidectomy, revealing otherwise unsuspected biopsy-proven temporal arteritis. To our knowledge, this association had been previously reported in only three instances. In each case, GCA of the thyroid arteries appeared clinically silent, did not produce significant glandular dysfunction, and was uncovered thanks to a planned thyroidectomy for nodular goitre. These observations highlight that thyroid artery involvement by GCA, even widespread, as in our patient, may be overlooked clinically and may produce little or no thyroid dysfunction.

Head-and-neck swelling: an under-recognized feature of giant cell arteritis. A report of 37 patients.

OBJECTIVE: To describe the frequency of occurrence and characteristics of head-and-neck swelling (HNS) in temporal (giant cell) arteritis (TA). METHODS: We analyzed the charts of patients with HNS retrieved from a single department series of 260 consecutive patients with TA and reviewed the published French-English literature. Patients with a swelling limited to the temporal fossa were excluded. RESULTS: A history of HNS was elicited in 17 patients in our series (i.e. 6.5%) and in 20 previously published patients. The swelling was an inaugural feature in most cases and was often transient. Ear-nose-and-throat (ENT )symptoms were observed in 80% of the cases, including jaw claudication or pain upon opening mouth in 22, causing trismus in 10. Two patients had permanent visual impairment and 1 had sudden hearing loss. The temporal artery biopsy yielded giant cell arteritis (GCA) in all the patients but 2. The HNS was often painful and mainly involved mainly the orbital region and face, particularly the lower part of the cheeks and maxillae, less often the neck and, rarely, the forehead and tongue. Concurrent localized limb swellings were also observed in 3 patients. The HNS disappeared in all the patients, either spontaneously or under steroid treatment, and recurred only in 6 patients. CONCLUSION: HNS is not exceptional in untreated TA and is strongly associated with ENT symptoms and a positive TAB, but not with visual loss or stroke. Such characteristics imply in these cases a prominent, widespread involvement of the external carotid artery system by giant cell arteritis.

[Topical tacrolimus and resistant skin lesions of dermatomyositis]. / Tacrolimus topique et atteintes cutanées résistantes de la dermatomyosite.

INTRODUCTION: Dermatomyositis is an inflammatory myopathy associated with an increased risk of mortality due to visceral involvement. Cutaneous involvement has no vital impact but considerably affects the quality of life of the patients and can resist to classical therapies. More treatment options are needed. We report here the case of three patients presenting resistant cutaneous lesions of dermatomyositis successfully treated with topical tacrolimus. OBSERVATIONS: A dramatic cure of the lesions of the face and the hands and a moderate response of other areas were observed without adverse effects. CONCLUSION: Tacrolimus is an immunosuppressive agent and topical tacrolimus is used for the treatment of atopic dermatitis and has been occasionally used to treat skin involvement of some systemic inflammatory diseases. Topical tacrolimus seems to be a good therapeutic alternative for resistant skin lesions of dermatomyositis. It could also be proposed as a first intention therapy because of its good tolerance.

[Adverse drug related events in a postemergency unit: prospective cohort study with 6 months follow up]. / Iatrogénie chez le sujet âgé de plus de 75 ans dans un service de posturgences. Etude prospective de cohorte avec suivi à six mois.

PURPOSE: To analyse iatrogenic events in elderly people and determine the part of unplanned admission in postemergency units directly related to thus iatrogenic events. METHODS: The authors conducted a prospective chart review on treatments and potentials adverse drug-related events of all elderly consecutively hospitalized between January and Marsh 2003 in a postemergency department. A 6 months prospective evaluation after discharge was made for all elderly with adverse drug-related event. RESULTS: One hundred (and) eighty-six elderly (mean age 83+/-5.7 years) were prospectively included. Eighty-one per cent are ambulatory with a self-medication administration in spite of a real disability (activity of daily-living: 4.5+/-1.8). The number of medications consumed ranged from 0 to 15 and averaged 6, with to different source of prescriptions in 34% of the cases. The treatment was recently modified in 41 cases (22%). Adverse drug related events accounted in 55 cases (29%) and hospitalization was directly related to iatrogenic event in 32 cases (17%). Adverse drug related events could be avoided in half cases. There was no death directly related with adverse drug reactions. Follow up after discharge was obtained in 47 cases and pointed out elderly disability: 34 were again hospitalized, 14 admitted in nursing home facilities and 12 died. Treatment was equivalent to our prescription only in 35% of the cases; on the other hand, we found only four elderly with medication directly related to previous adverse event. DISCUSSION: Theses results pointed out once again polymedication observed in frail elderly people leading to extreme difficulty to prescription due to polypathology. Prescription renewal could be related to adverse drug related events and precipitated elderly people in disability leading to institutionalization.

Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA).

PURPOSE: Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. METHODS: Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d'étude français des artérites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed. RESULTS: The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence. CONCLUSIONS: The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.

Serum levels of a negative regulator of cell proliferation (AcSDKP) are increased in certain human haemopathies.

One of the first known effects of the endogenous peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) is to inhibit entry into DNA synthesis of pluripotent haematopoietic stem cells (CFU-S) in mice. A specific anti-AcSDKP polyclonal antibody allows the level of the tetrapeptide by to be determined by enzyme immunoassay with good sensitivity and specificity. We present results demonstrating the presence of AcSDKP in humans: serum levels of 34 healthy controls were found to be between 0.7 and 2.5 pm/ml, regardless of age and sex. High levels were found in 44% of asymptomatic controls but only in 8% of AIDS patients out of a total of 37 patients with HIV. Subsequently, studies of serum levels were performed before treatment in 121 subjects with disorders of the nonlymphoid and the lymphoid lineages. Our results did not demonstrate any decrease in serum levels, however a moderate or marked increase was noted in one-third of the subjects, which was greater in disorders of the non-lymphoid lineages (48% of 72 patients) than the lymphoid lineage (21% of 50 patients). The most significant differences were observed between controls versus patients with myeloproliferative disorders (MPD, 24 patients: p < 0.001), controls versus patients with acute myelogenous leukaemia (AML, 15 patients: p < 0.02), as well as patients with AML versus patients with primary myelodysplastic syndromes (PMDS, 10 patients: p < 0.05). The pathophysiology of these abnormalities is discussed.

[Horton's disease revealed by brachial C5 plexopathy]. / Maladie de Horton et plexite brachiale C5-C6: une observation avec revue de la littérature.

BACKGROUND: Shoulder palsy due to brachial plexopathy (or lower cervical radiculopathy) is a rare occurrence in patients with giant cell temporal arteritis (TA). We report a patient with C5 plexopathy revealing TA, with review of the literature. EXEGESIS: A 67-year-old woman presented with a complex neurological syndrome of rapid onset, including a left trigeminal neuralgia, painless masticatory palsy, impaired swallowing, and severe palsy of the left shoulder, corresponding to a C5 plexitis. Giant cell arteritis was suspected on clinical and laboratory grounds and was documented on temporal artery biopsy. Treatment with pulse methylprednisolone (100 mg every 8 hours for three days), followed by prednisone (1 mg/kg daily), resulted in progressive improvement of the neurological deficits, full shoulder strength being recovered within 6 months. An extensive world literature allowed us to review 23 other cases of TA complicated by either lower cervical radiculopathy or C5 brachial plexopathy. These peripheral neuropathic manifestations occurred sometimes bilaterally and were isolated or, less often, part of a mononeuritis multiplex. Involved patients were relatively young (mean age 67 years) and 54% were men. The pathophysiology of TA-associated C5 radiculopathy or brachial plexitis is still poorly understood. Fortunately, functional prognosis was consistently good with corticosteroid treatment. CONCLUSION: Giant cell arteritis should always be considered in elderly or middle-aged patients presenting with C5 radiculopathy or plexopathy and elevated inflammatory markers.

[Evolution of Sjögren syndrome associated with hepatitis C virus when chronic hepatitis C is treated by interferon or the association of interferon and ribavirin]. / Evolution des syndromes de Gougerot-Sjögren associés au virus de l'hépatite C sous interféron et l'association interféron-ribavirine.

UNLABELLED: Hepatitis C virus is one of the most likely candidates as a potential pathogenic agent causing Sjogren's syndrome (SS) in a subset of patients. Nobody has until now described the evolution of SS associated with HCV when chronic hepatitis C is treated with antiviral therapy, interferon being an auto-immunity inductor. This is the purpose of our study. METHODS: Prospective study of 12 patients with a HCV-associated SS defined as certain according to the first european criteria and treated with interferon or interferon/ribavirin for their chronic hepatitis C. RESULTS: More than fifty percent of these patients developed a severe immunological complication especially when they were treated with interferon alone. Ribavirin may have had a protective role on interferon-mediated immunological complications. These complications went on after cessation of therapy. Sicca syndrome was improved only in the patients treated with the association (in 50% of the cases), but these patients also had a sustained virological response. It is difficult to tell if this improvement was due to the hepatitis C virus eradication or ribavirin treatment. CONCLUSION: Hepatitis C virus is implicated in the development of SS in a specific subset of patients for which we can propose the term SS "secondary to HCV" and this disease is not utterly benign especially after the introduction of interferon therapy. Ribavirin when associated with interferon gives a significative sustained virological response and could lower the incidence of immunological interferon-mediated complications with a favorable outcome of sicca syndrome.

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.

Acquired hemophilia due to factor VIII inhibitors in 34 patients.

BACKGROUND: Acquired hemophilia is a rare disease caused by the development of auto-antibodies against factor VIII. SUBJECTS AND METHODS: We studied the characteristics and outcomes of 34 patients (19 women and 15 men) with acquired hemophilia from 1980 to 1997. RESULTS: The mean age of the patients was 61 years (range, 22-93 years). An underlying disease was observed in 18 (53%) patients: 5 patients had cancer, 4 an autoimmune disorder, 2 a dermatologic disorder, 3 asthma, 3 were postpartum, and 1 had an adverse reaction to ampicillin. Factor VIII level was <5% in 30 (90%) patients; factor VIII antibodies were elevated (>10 Bethesda units) in 23 (69%) patients. Bleeding requiring transfusions was reported in 25 (75%) patients. Human factor VIII was given to 14 patients and porcine factor VIII to 5. Six patients received prothrombin complex concentrates and one desmopressin. Several immunosuppressive treatments were used, mainly corticosteroids, cyclophosphamide, and intravenous immunoglobulin. Bleeding stopped in all but one patient within 2 weeks. Most patients achieved complete remission, although two relapses were observed subsequently. CONCLUSION: This large study helps to clarify the presentation and clinical course of acquired hemophilia. Prospective studies are needed to determine the efficacy of treatment.