Pregnancy and primary Sjögren's syndrome: management and outcomes in a multicentre retrospective study of 54 pregnancies.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most common autoimmune diseases, mainly affecting women during the fourth decade of life. During pregnancy, the presence of anti-Ro/SSa and anti-La/SSb antibodies increases the risk of congenital heart block (CHB). Foetal and pregnancy outcomes in pregnant women with pSS compared with the general population are difficult to evaluate because of confounding factors including age and body mass index (BMI). METHOD: The aim of this case-control study was to analyse the impact of pSS in pregnant women on foetal and pregnancy outcomes. RESULTS: We enrolled 19 women with pSS (54 pregnancies) matched by age and BMI to 216 controls. Patients with pSS delivered significantly earlier (38 weeks + 3 days vs. 39 weeks + 2 days) and experienced more spontaneous abortions [< 22 weeks of gestation (WG)] than the controls [n = 16/54 (30.0%) vs. n = 1/216 (0.4%); p < 0.00001]. Preterm delivery (≤ 37+6 WG) was significantly higher in the pSS group than in the control group (29% vs. 12%, p = 0.04). pSS activity significantly affected the birthweight percentile, which was lower in pregnancies occurring after the diagnosis of pSS than in those occurring before (32.43 ± 21.57 vs. 60.46 ± 27.37; p = 0.008). No case of CHB was observed. CONCLUSIONS: pSS is responsible for an increased risk of spontaneous abortion. The duration of pregnancy is lower in patients with than without pSS, with more premature deliveries. Pregnancies that occur after the onset of the disease result in lower birthweight percentile children than when pSS is not clinically overt.

Increased risk of vascular complications in Takayasu's arteritis patients with positive lupus anticoagulant.

OBJECTIVES: Previous studies have shown antiphospholipid antibodies (aPL) to be prevalent in primary systemic vasculitides; however, the possible clinical impact of aPL positivity in such patients has not been explored in depth. The aims of this study were to determine the prevalence of aPL in patients with Takayasu's arteritis (TA) and to ascertain whether aPL positivity was predictive of a worse clinical outcome in TA. METHOD: Clinical data were collected retrospectively on 22 TA patients over an 11-year period. Data collected included the presence of lupus anticoagulant (LA) and immunoglobulin (Ig)G and IgM anticardiolipin antibody (aCL) titres. Adverse clinical outcomes included cerebrovascular accident (CVA), transient ischaemic attack (TIA), loss of vision, vascular lesions (carotid, femoral, renal, coronary, or other vessels) requiring stenting, angioplasty, or other surgical intervention, aortic valve replacement, end-stage renal failure or death. RESULTS: Persistently positive aPL or a concurrent diagnosis of antiphospholipid syndrome (APS) was found in 45% (n = 10) of TA patients while 55% (n = 12) had TA alone. LA was present in a significant proportion of TA patients with aPL (p = 0.002). Vascular complications occurred in 70% (n = 7) of TA patients with aPL and in 25% (n = 3) of TA patients without aPL (p = 0.035). LA was associated with a higher prevalence of vascular complications. CONCLUSIONS: Persistently positive aPL are present in a significant proportion of TA patients. This study shows that vascular complications and need for intervention are more prevalent in TA patients with aPL, particularly those with LA. Prospective studies are needed to determine the long term prognosis in such patients.

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.

Progressive multifocal encephalopathy after cyclophosphamide in granulomatosis with polyangiitis (Wegener) patients: case report and review of literature.

Progressive multifocal encephalopathy (PML) is a rare demyelinating disorder targeting the central nervous system and resulting from JC virus reactivation. PML occurs in patients immunocompromised because of haematological malignancies, HIV infection or treatment with cytotoxic drugs. Herein, we describe PML occurring in 2 granulomatosis with polyangiitis (Wegener) patients treated with steroids and cyclophosphamide. The outcome was progressively favourable after immunosuppressant discontinuation for 1 patient and fatal for the other. Four previously reported GPA patients developed PML in the course of their disease. One of them improved gradually after immunosuppressant withdrawal. PML should be strongly suspected whenever unusual central neurological manifestations appear in this context. No effective treatment is available, but immunosuppressants should be discontinued if possible.

French National Diagnostic and Care Protocol for antiphospholipid syndrome in adults and children.

Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as "catastrophic antiphospholipid syndrome" (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.

Obstetric medicine care in South Europe.

Obstetric medicine is an emerging area of interest within Internal Medicine in Europe. Despite that, "OM" is still an unpopular concept and an unrecognised subspecialty in South Europe. A considerable number of internists and medical specialists deal with maternal medical problems in association with obstetricians and other specialists on a daily basis. Due to their interest and mostly part-time dedication to maternal care, a growing mass of physicians are getting specific training in the field either locally or, less frequently, abroad, and are also building specific clinics, inpatient care services and other new bonds with obstetricians in numerous tertiary care centres. In this article, we aim to describe the state of the growing field of obstetric medicine in Portugal, Italy, France and Spain, the particular clinical, educational and academic efforts and steps that have recently been developed by internists in each country, as well as planned initiatives for the future.

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.

[Isolated hemorrhagic pleurisy due to Panton-Valentine leukocidin-positive Staphylococcus aureus]. / Pleurésie hémorragique isolée à Staphylococcus aureus à leucocidine de Panton-Valentine.

Panton-Valentine leucocidin is a major virulence factor produced by some strains of Staphylococcus aureus (SA-PVL). The best-described invasive infection is a necrotizing haemorrhagic pneumonia. Pleural effusion is not uncommon but is always associated with a parenchymal lesion. Here, we report a case of haemorrhagic pleurisy attributable to isolated SA-PVL.

[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.

[Molecular strain typing contribution to epidemiology of tuberculosis in Limousin (1998 to 2006)]. / Intérêt du typage moléculaire pour l'épidémiologie de la tuberculose en Limousin (1998-2006).

OBJECTIVES: We conducted a molecular epidemiology of Mycobacterium tuberculosis in Limousin, a French area with a low incidence of tuberculosis (4.8/100,000 inhabitants in 2005) to define the molecular diversity and the pattern of transmission. DESIGN: Two hundred and fifty-nine strains were isolated (each strain corresponds to one patient) from 1998 to 2006. Both spoligotyping and MIRU15 were chosen for our study because of their discriminatory power. RESULTS: Only 165 medical records were available: 99M/66F, mean age 56.4 years (14-94), 32.7% foreign-born patients, 16.9% homeless or living in shelters, 21.8% of immunocompromised patients (three HIV positive), 14.5% of alcohol addicts. Pulmonary manifestations were predominant (81.8%) with 45.1% of positive smears. Two strains among the 259 presented a multidrug resistance. Spoligotyping identified 136/259 spoligotypes (110 unique, 26 clusters composed of two to 36 isolates); within these 26 clusters, ST53 (n=36) and ST50 (n=19) were the most frequent. Three major families were observed as follow: T1 (30%), Haarlem (30%) and LAM (20%). MIRU15 identified 28/36 isolates in the ST53 group and 14/19 in the ST50 group. Eleven clusters (32 strains) with identical ST-MIRU15 were obtained with a proved case of recent transmission. Alcohol dependence, immunosuppression and pulmonary infections seem to be involved in transmission factors. CONCLUSION: M. tuberculosis strains isolated in Limousin are characterized by their high genetic diversity. The rate of recent transmission (8.1%) is low and therefore a reactivation process is predominant in this area.

[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.

[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.

[Post-menopausal endometrial tuberculosis]. / Tuberculose utérine post-ménopausique.

A 69-year-old menopaused woman, presented a 2-month history of metrorrhagia. We suspected a malignant disease, but, the histopathologic examination of biopsies, found an endometrial inflammation without malignant cells. Culture for mycobacteria showed a Mycobacterium tuberculosis. A course of four-drug antituberculous therapy was started and the patient recovered. Tuberculosis remains a common disease, but genital infection is infrequent. Usually, it concerns young infertile women from non-industrial countries. More attention should be paid to this disease. Women, irrespective of their age, should be investigated for silent or subclinical genital symptoms, with mycobacterial examination.

[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.

[Salmonella of Indian origin: pseudo-susceptibility to fluoroquinolones]. / Salmonelle d'origine indienne: attention à la fausse sensibilité aux fluoroquinolones.

We report the case of a patient presenting with typhoid fever after returning from a stay in India. This infection was not cured with a course of ciprofloxacin, due to a reduced susceptibility of the bacteria to the drug. This decreased susceptibility to fluoroquinolones was not detected by the antibiogram, but the MIC for nalidixic acid was greater than 32 mg/l. This case suggests using a third generation cephalosporin instead of a quinolone, for people coming from a high-risk zone. It also suggests that the MIC for nalidixic acid and for norfloxacin can be used as the first clue for a reduced susceptibility to fluoroquinolones.

[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.

[Disease associations in 250 patients with temporal (giant cell) arteritis]. / Maladie de Horton: associations morbides chez 250 malades.

INTRODUCTION: Miscellaneous disorders have been described in association with temporal (giant cell) arteritis (TA), most often anecdotally, except with arteriosclerosis. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

[Non-cirrhotic ascites: pathophysiology, diagnosis and etiology]. / L'ascite non liée à la cirrhose : physiopathologie, diagnostic et étiologies.

Ascites, in 20% of cases, is not linked to liver cirrhosis. The pathophysiology is most often different. The understanding of these pathophysiological mechanisms can lead to etiologic diagnosis. The diagnostic approach is mainly based on the biological study of ascites, especially protein concentration and albumin gradient between serum and ascites. In Western countries, tumors and heart diseases are the predominant causes, while developing countries are mainly concerned by infectious diseases, among which tuberculosis is the leading cause. Other uncommon causes must be recognized, as ascites may be the presenting feature of the disease. Their knowledge will facilitate the therapeutic approach.

[Small fibre neuropathy in primary Sjögren syndrome]. / Neuropathie des petites fibres au cours du syndrome de Sjögren primitif.

PURPOSE: About forty percent of the patients with primary Sjögren's syndrome (pSS) experience chronic neuropathic pain with normal electrodiagnostic studies. Two previous studies suggest that chronic neuropathic pain in pSS is due to small fiber neuropathy (SFN). Quantification of epidermal nerve fiber density after skin biopsy has been validated to diagnose small fiber neuropathy. METHODS: Skin biopsy was performed in 14 consecutive pSS patients (satisfying the american-european classification criteria) with chronic neuropathic pain and normal electrodiagnostic studies suggesting SFN. RESULTS: Fourteen female pSS patients exhibited chronic neuropathic pain [burning sensation (n=14), prickling (n=4), dysesthesia (n=8)] with paroxystic exacerbations (n=10) and allodynia (n=13), for a mean period of 18.4±12.4 months. Neuropathic pain involved mostly hands and feet (n=13), with a distal (n=9) and leg (n=4) predominant distribution. Neurological examination disclosed normal deep tendon responses and absence of motor weakness (n=14). Small fiber neuropathy was confirmed by skin biopsy in 13 cases. Epidermal nerve fiber density was decreased in distal [(n=12), mean 3.5±1.7 fibers/mm (N>6.9)] and proximal site of biopsy [(n=9), mean 7.04±2.63 fibers/mm (N>9.3)]. CONCLUSION: Small fiber neuropathy is commonly responsible of chronic neuropathic pain in pSS. Prevalence, physiopathology and neurological evolution of such neuropathies still remain unknown.