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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').To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.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.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.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.

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.

In systemic lupus erythematosus, hemostasis disorders are mainly thrombotic, but more rarely hemorrhagic.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.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.

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.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.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.

Permanent visual loss (PVL) is the most dreaded complication of giant cell arteritis (GCA). It results from anterior ischemic optic neuropathy or, less commonly, retinal artery occlusion. This complication still occurs in 14 to 20% of patients and is typically devastating and permanent, although it is highly preventable by an early diagnosis of giant cell arteritis and appropriate glucocorticoid treatment. Transient ischemic symptoms such as amaurosis fugax, episodes of blurred vision or diplopia may occur, either heralding visual loss or remaining isolated. In studies, the main predictors of PVL are jaw claudication, amaurosis fugax, lack of systemic "B" symptoms, a modestly increased ESR and a higher haemoglobin level. The evaluation of a GCA patient with PVL includes emergency fundoscopy completed by fluorescein angiography, immediate erythrocyte sedimentation rate, C-reactive protein, and complete blood count. Treatment is extremely urgent mainly because, if left untreated, GCA is associated with visual loss in the fellow eye within days in up to 50% of individuals. Treatment may begin with high-dose intravenous methylprednisolone, followed by oral prednisone administered at 1 mg/kg per day. Daily adjunctive aspirin orally may be added since it has been shown, in retrospective studies, to protect against stroke and visual loss. Although treatment duration of complicated GCA is not codified, an initial PVL deserves close monitoring of patient's systemic symptoms, ESR and CRP to avoid relapses due to a significant risk of late recurrence of visual loss during steroid tapering.

Resume Objectif Diverses pathologies ont ete decrites en association avec la maladie de Horton (MH), le plus souvent de maniere anecdotique, hormis l’atherome. Methode Dans une etude retrospective, nous rapportons une experience personnelle des associations pathologiques de 250 MH diagnostiquees et suivies dans le service entre 1976 et 2003. Resultats Une pathologie associee a ete observee chez 43 malades, soit 17 % des cas : affection maligne (23 malades : 17 cancers et 6 hemopathies), syndrome de Gougerot-Sjogren primitif (6 cas), endocrinopathie autre qu’une thyroidite d’Hashimoto (7 cas : 3 hyperparathyroidies [HPP], 3 hyperthyroidies, 1 association HPP + hyperthyroidie), polyneuropathie (3 cas), thrombocytemie essentielle (2 cas), presence d’anticorps anti cytoplasme des polynucleaires (ANCA) de type anti-myeloperoxydase (2 cas), associations diverses (1 cas respectivement de syndrome RS3PE, de syndrome nephrotique, de myasthenie, de sarcoidose, de macro-creatine kinase de type 2). Il existait plus d’une association pathologique chez 5 malades. L’association etait temporellement etroite dans 77 % des cas. Ni vascularite systemique necrosante, ni polyarthrite rhumatoide n’ont ete observees. Conclusion Dans notre experience, il existait une association frequente, peut-etre non fortuite, entre MH et neoplasie. Les associations auto-immunes etaient rares, mais la prevalence du syndrome de Gougerot-Sjogren pourrait etre sous-estimee. L’hyperthyroidie et l’HPP, non exceptionnelles, doivent etre reconnues pour eviter une catastrophe osseuse sous corticoides.

International audience; 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.

Giant cell arteritis is a large-vessel vasculitis affecting all three layers of the arterial wall. Histopathology of this vasculitis consists of an inflammatory infiltrate with CD4(+) T cells, macrophages, multinucleated giant cells, forming granulomas in the media. This infiltrate is associated with a destruction of the arterial wall, a fragmentation of the internal elastic lamina and a vascular remodeling leading to intimal hyperplasia. Recent studies have clarified the role of Th17 cells in the initial phase of the disease, pro-inflammatory cytokines and vascular smooth muscle cells in vascular remodeling. This review aims to update data on giant cell arteritis pathogenesis and to propose clues of investigation for a better understanding of this condition.

Permanent visual loss (PVL) is the most dreaded complication of giant cell arteritis (GCA). It results from anterior ischemic optic neuropathy or, less commonly, retinal artery occlusion. This complication still occurs in 14 to 20% of patients and is typically devastating and permanent, although it is highly preventable by an early diagnosis of giant cell arteritis and appropriate glucocorticoid treatment. Transient ischemic symptoms such as amaurosis fugax, episodes of blurred vision or diplopia may occur, either heralding visual loss or remaining isolated. In studies, the main predictors of PVL are jaw claudication, amaurosis fugax, lack of systemic "B" symptoms, a modestly increased ESR and a higher haemoglobin level. The evaluation of a GCA patient with PVL includes emergency fundoscopy completed by fluorescein angiography, immediate erythrocyte sedimentation rate, C-reactive protein, and complete blood count. Treatment is extremely urgent mainly because, if left untreated, GCA is associated with visual loss in the fellow eye within days in up to 50% of individuals. Treatment may begin with high-dose intravenous methylprednisolone, followed by oral prednisone administered at 1 mg/kg per day. Daily adjunctive aspirin orally may be added since it has been shown, in retrospective studies, to protect against stroke and visual loss. Although treatment duration of complicated GCA is not codified, an initial PVL deserves close monitoring of patient's systemic symptoms, ESR and CRP to avoid relapses due to a significant risk of late recurrence of visual loss during steroid tapering.

A malignancy must be carefully excluded before ruling in the diagnosis of adult onset Still's disease (AOSD). However, an occult or poorly symptomatic malignancy can easily be overlooked.We report a 50-year-old female patient who presented with features of adult onset Still's disease (AOSD), in fact heralding a malignant melanoma with fatal outcome since discovered lately, at a metastatic stage. In retrospect, the only significant atypical feature was cholestatic hepatitis, which soon disappeared upon institution of glucocorticoid treatment. The literature review identified 27 additional cases of AOSD-like disease associated with malignancy published since 1980 including solid cancer in 61% of the cases (especially breast and lung) and haematological malignancies in 39% of the cases (especially malignant lymphoma). The interval between OASD-like symptoms and malignancy averaged 8 months, and AOSD most often preceding malignancy. Although idiopathic AOSD and neoplastic AOSD-like disease are often indistinguishable initially, some features could point toward the latter: an onset of AOSD after the age of 40 years, the presence of atypical clinical, biological, or immunological features in less than one third of the cases, and a poor response to NAIDS or systemic glucocorticoids in 61% of the cases.Making the differential diagnosis of malignancy-associated AOSD in a timely fashion remains a primary goal, even in the most typical cases and those showing good initial therapeutic response.

Ascaris lumbricoides, a large round nematode, which causes human ascariasis, is the most prevalent helminth in the world. Ascariasis is usually asymptomatic but can cause serious complications, with a mortality rate of 5%. We report a 55-year-old woman from Comoros who presented with ascariasis complicated by occult cholangitis, severe acute pancreatitis, and transient complete heart-block. Cardiac damage due to migrating ascaris larvae was the likely explanation of the transient heart-block in this patient, although such a complication had never been described previously.

[18F]fluorodeoxyglucose positron emission tomography (PET) is a noninvasive metabolic imaging modality that is well-suited to the assessment of activity and extent of large vessel vasculitis. PET imaging has demonstrated its usefulness in diagnosing giant cell arteritis (notably in its silent form), Takayasu's arteritis, and unclassified aortitis. PET imaging could be more effective than magnetic resonance imaging in detecting the earliest stages of vascular wall inflammation. The visual grading of vascular [18F]FDG uptake makes it possible to discriminate arteritis from active atherosclerosis, providing therefore high specificity. High sensitivity can also be achieved provided scanning is performed during active inflammatory phase, preferably before starting corticosteroid treatment. Prospective studies are needed to determine the exact value of PET imaging in assessing other vasculitis subsets, infectious aortitis, and large vessel vasculitis outcome and response to immunosuppressive treatment.

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.

Introduction/Objectif Evaluer l’association entre les hemopathies et la maladie de Horton (MH) ou la pseudopolyarthrite rhizomelique isolee (PPR). Patients et methodes Nous avons recueilli de maniere retrospective les donnees epidemiologiques, cliniques et evolutives de tous les patients recrutes dans le service de medecine interne d’un hopital universitaire francais depuis 1982, chez qui ont ete portes les diagnostics de MH ou de PPR et d’hemopathie (leucemie aigue, syndrome myelodysplasique (SMD), syndrome myeloproliferatif (SMP), lymphome, myelome). Les deux affections ont ete classees concomitantes lorsque diagnostiquees avec moins d’1 an d’ecart. Resultats Trente-quatre patients (âge 73,1 ± 8,2 ans, 23 femmes) sont identifies, parmi lesquels 23 proviennent d’une cohorte prospective de MH (1). Vingt-huit patients ont une MH (biopsie positive : 64 % des cas, ischemie visuelle permanente : 3 cas, PPR associee : 18 cas) ; 6 patients ont une PPR isolee. La prevalence d’une hemopahie dans la cohorte de MH est de 5,6 % (23/415 cas) ; elle est inconnue au sein des PPR isolees. Les diagnostics hematologiques sont : 19 SMD (6 leucemies myelo-monocytaires chroniques (LMMC), 5 cytopenies refractaires, 3 anemies refractaires avec myeloblastose partielle, 2 anemies sideroblastiques, 2 cytopenies refractaires multi lignees, 1 syndrome 5q-) ; 3 leucemies aigues myeloblastiques, 1 leucemie myeloide chronique, 3 thrombocytemies essentielles, 4 leucemies lymphoides chroniques B (stade A), 3 lymphomes B et 1 myelome IgG. Le delai moyen entre MH ou PPR et hemopathie est de 41 mois (26 mois pour le sous-groupe des SMD, ecarts 0–144 mois, mediane 15 mois). Les diagnostics sont concomitants chez 14 patients (12 MH, 9 SMD). Un 15 e patient a rechute tardivement d’une MH sous forme d’une PPR, avec decouverte simultanee d’un SMD. Un chevauchement temporel entre MH ou PPR et hemopathie est observe chez 24 patients, surtout en cas de MDS (84 % des cas). Avec un recul moyen de 69 mois, 14/31 patients evaluables ont gueri de leur MH ou PPR, dans un delai moyen de 25,7 ± 17,3 mois ; 9 ont une maladie inflammatoire de controle difficile (dose de prednisone > 10 mg/j a un an, ou > 5 mg/j apres plusieurs annees) ; 11 sont decedes, dont 7 de leur hemopathie. Aucun deces n’etait imputable a la corticotherapie. Conclusion Une association non fortuite, de nature indeterminee, pourrait exister entre la MH ou la PPR et certaines hemopathies, particulierement les SMD. La PPR est une manifestation predominante (71 % des cas) et l’exces observe de MH est lie a des biais de recrutement et d’inclusion. L’association a une hemopathie lymphoide est plus probablement fortuite. Les MH/PPR associees a une hemopathie repondent le plus souvent bien a la corticotherapie.

To describe the frequency of occurrence and characteristics of head-and-neck swelling (HNS) in temporal (giant cell) arteritis (TA).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.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.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.

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.A dramatic cure of the lesions of the face and the hands and a moderate response of other areas were observed without adverse effects.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.

To analyse iatrogenic events in elderly people and determine the part of unplanned admission in postemergency units directly related to thus iatrogenic events.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.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.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.

Miscellaneous disorders have been described in association with temporal (giant cell) arteritis (TA), most often anecdotally, except with arteriosclerosis.In a retrospective study, we reported our personal experience of disease associations in a series of 250 patients diagnosed with TA and followed-up in the department between 1976 and 2003.Disease associations were found in 43 patients, i.e. 17% of cases: concurrent malignancy (23 patients: 17 cancers and 6 blood diseases), primary Gougerot-Sjögren's syndrome (6 cases), endocrine disease other than Hashimoto's thyroiditis (7 cases: 3 hyperparathyroidism [HPP], 3 hyperthyroidism, 1 association HPP + hyperthyroidism), polyneuropathy (3 cases), essential thrombocythaemia (2 cases), anti-neutrophilic cytoplasmic (anti-myeloperoxidase) antibodies (2 cases), and miscellaneous associations (1 case of RS3PE syndrome, nephrotic syndrome, myasthenia, sarcoidosis, and macro-creatine kinase type 2). More than one disease associated was present 5 patients. In 77% of the patients, there was a strong temporal association between TA and the alternate illness. No systemic necrotizing vasculitis or rheumatoid arthritis was observed in any patient.In our experience, there was a frequent, non-fortuitous, association between TA and malignancy. Auto-immune conditions were rare, but the prevalence of Gougerot-Sjögren's syndrome might have been underestimated. Hyperthyroidism and HPP are not exceptional and must be recognised in order to avoid severe bone loss induced by corticosteroids.

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.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.Giant cell arteritis should always be considered in elderly or middle-aged patients presenting with C5 radiculopathy or plexopathy and elevated inflammatory markers.

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.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.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.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.

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.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).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.

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.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.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.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.

To define pathogenesis, incidence, clinical presentation and prognosis of leukemic transformation (LT) in patients with essential thrombocytemia (ET); to compare the incidence of LT in previously treated versus untreated patients; to search for risk factors of LT, with special reference to the iatrogenic risk of myelosuppressive drugs.Most significant French and English-language papers published between 1981 and 1997 dealing with either ET, LT, clonality, cytogenetics, alkylating agents or hydroxyurea were reviewed. Patient characteristics, clinical presentation, bone marrow and cytogenetic findings, and survival data were extracted from each case report and review, and possible risk factors were analyzed.Despite the existence of clonal hematopoiesis in up to 60-80% of patients with ET, suggesting an intrinsic potential for subsequent leukemia, spontaneous LT is poorly documented and the common presumption that TL occurs in excess in treated patients with ET is still questionable. The incidence of LT, probably underestimated in the past, varies from 0.7% to 5.3% in retrospective series, and from 8% to 12% in prospective studies. Recurrent cytogenetic abnormalities are significantly more frequent and complex in marrow karyotypes performed at the time of blastic crisis, as compared with those performed at diagnosis. A review of 62 reports of LT highlights some important characteristics: a) LT can occur anytime during the chronic phase of ET, especially within the first eight years, b) all subtypes of leukemia are described, notably unclassifiable cases and megakary oblastic acute leukemias, c) bone marrow fibrosis is frequent, as is a progressive onset of a myelodysplastic syndrome preceeding the blastic crisis, d) the prognosis of LT is very poor, two-third of all patients die within 6 months. Apart from the onset of a myelodysplastic syndrome, which carries a poor outcome, there is no well-established risk factor of LT. The leukemogenic risk of myelosuppressive therapies, clearly demonstrated for years in polycythemia vera, cannot be directly ascertained in patients with ET, but is suggested by various indirect observations. This putative risk of inducing secondary leukemia affects not only alkylating agents but also hydroxyurea.LT is a highly serious and largely unpredictable complication of ET. The current debate on the specific risk of myelosuppressive treatments deserves large-scale prospective randomized studies. Until this crucial point is elucidated, any cytotoxic therapy should be reserved to elderly and/or symptomatic patients and to those having other vascular risk factors.

The sensation of dry mouth is a common problem, often neglected. The decrease of salivary flow causes chronic oral discomfort and functional problems and predisposes to rampant dental caries and oral candidiasis. Various methods are described to evaluate salivary gland hypofunction but no single test has sufficiently high specificity and sensitivity. Categorised questionnaires and unstimulated whole saliva flow are valuable. The causes of xerostomia are numerous, of which the principal are, drug or radiation induced xerostomia and primary an secondary Sjögren's syndrome. Treatment calls for good hydration, optimal oral hygiene and prophylaxis of candidosis. All unnecessary medications must be avoided. Oral pilocarpine is the only drug which had demonstrated beneficial effects if no contraindications exist.

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.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.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.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.

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.

Alpha, beta or gamma interferon (INF) are cytokines produced by cells in response to antigenic stimulation. They are used to treat various hepatic, hematological, oncological and neurological diseases. Cutaneous reactions (rash, alopecia, labial herpes, erythema, or induration at the site of injection, and more rarely cutaneous necrosis) represent 5 to 12% of side-effects observed in patients receiving INF. The authors report six cases of local cutaneous reactions to alpha INF, five of which corresponded to cutaneous necrosis. This makes them question the relevance of INF reintroduction.The study included 5 male and 1 female patients (mean age: 59.1 years; range: 42 to 74 years old). Three patients had chronic hepatitis C, while three others presented a blood disease.Cutaneous necrosis occurred after 1 to 10 months of treatment. The mean time to healing was 16.2 weeks. Reintroduction of the drug including injection in other sites did not lead to recurrence of necrosis in five out of the six cases.INF-induced cutaneous necrosis does not depend on the type of INF, the site of injection, the dose and may occur 2 months to 9 years after treatment implementation. The exact mechanisms involved in cutaneous necrosis remain unknown. Morbidity is due to a very long time to healing (4 to 6 months). Futhermore, healing sometimes requires prior surgery. Physicians should be aware of the potential occurrence of erythema in patients treated by INF, as it is the first sign of necrosis. The site of injection should then be modified. In case of necrosis, risk factors for thrombophilia, factors reducing microcirculation (DHE, beta-blockers, cigarette smoking) should be investigated. INF injections should be cautiously reintroduced in other sites with the help of a nurse in case of self-injections prior to the occurrence of necrosis. Regarding self-injections patients' training should be emphasized.

To describe the clinical, biologic, and histologic features of temporal artery biopsy (TAB)-localized systemic necrotizing vasculitides (SNV), and to assess their frequency among elderly patients undergoing TAB for suspected giant cell (temporal) arteritis (GCA).The frequency of a TAB localization of SNV was prospectively assessed in a multicenter study of elderly patients undergoing TAB for suspected GCA. All patients with SNV fulfilling the American College of Rheumatology criteria for a specific vasculitic syndrome and with evidence of vasculitis on TAB were included in a retrospective, descriptive study.SNV was diagnosed based on the TAB in 1.4% of the patients with suspected GCA and in 4.5% of the positive (inflamed) TAB specimens. We retrospectively selected 27 patients (18 female, 9 male; mean +/- SD age 62+/-15 years, range 22-79 years) with SNV and TAB-localized vasculitis. Only 2 of these patients were known to have SNV before TAB localization. Twenty-two patients (81%) had cephalic symptoms, including jaw claudication in 33%, clinically abnormal temporal arteries in 33%, and neuro-ophthalmologic symptoms in 11%. All patients had systemic symptoms suggestive of SNV and histologically proven NV in the TAB specimens (70%) or elsewhere in other biopsy sites (74%). Abnormal biologic results suggestive of SNV were present in 17 patients (63%). For 4 patients, the TAB-documented involvement led to initial misdiagnoses of GCA, and systemic manifestations that developed under steroid therapy revealed the correct diagnosis. The final diagnoses of the patients were polyarteritis nodosa (PAN) (n = 11), Churg-Strauss syndrome (n = 6), micropoly-angiitis (n = 3), Wegener's granulomatosis (n = 3), hepatitis B virus-related PAN (n = 2), hepatitis C virus-related cryoglobulinemic vasculitis (n = 1), and rheumatoid vasculitis (n = 1).TAB-localized SNV presents a major diagnostic dilemma because it can mimic GCA. Careful analysis of clinical, biologic, and histologic data should lead to the correct diagnosis and help guide the clinician's choice of appropriate therapy.

Ocular manifestations of giant cell arteritis, of which permanent amaurosis overshadows all others, occur still frequently. They are usually preceeded by the classical signs of temporal arteritis, which should allow an earlier diagnosis and prompt corticosteroid treatment. Indeed, corticosteroids have proved very effective in preventing ocular complications. Once permanent amauposis is present, the treatment is still urgent, in order to avoid the involvement of the other eye and to restore some vision of the affected eye. However, once the eye is damaged, there is little hope that corticosteroid treatment will improve the vision, depending essentially upon which delay it has been started. These fearsome ocular complications argue for a better knowledge of the suggestive signs of temporal arteritis and highlight the urgency of corticosteroid treatment.