Atteintes cardiaques dans les connectivites: l'exemple du lupus érythémateux systémique [Cardiac involvement in connective tissue disease: the example of systemic lupus erythematosus]

When we think of cardiac affection in the context of systemic lupus erythematosus (SLE), we usually refer to pericarditis first. As frequent as this affection is, it is actually not the only cardio-vascular problem that occurs with this systemic inflammatory disease. Are the cardiac events--ranging from multiple heart valve involvements to increased cardiovascular risks--clinically significant? And are they involving a specific follow-up, treatment or support? We are therefore trying to evaluate these questions in order to give some recommendations to any practitioners following up a lupus patient, or a patient suffering from any other inflammatory systemic disease.

Treatment of extraintestinal manifestations in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a systemic disease associated with a large number of extraintestinal manifestations (EIM). EIM are present in 15-20% of patients with ulcerative colitis and in 20-40% of patients with Crohn's disease. The management of EIM is best provided by a multidisciplinary team, which includes specialists in the affected organ systems with training in the treatment of IBD. Therapeutic strategy is often empirical. This is explained by the paucity of randomized-controlled studies for the specific treatment of EIM in IBD and by the fact that treatment models are based on extrapolation from patients with similar conditions but without IBD. For most EIM, the mainstay of therapy is the treatment of the underlying active IBD. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis and primary sclerosing cholangitis run a clinical course independent of IBD activity and need specific therapy (e.g. TNF antagonists in ankylosing spondylitis and skin manifestations). This review summarizes the conventional and novel (e.g. anti-TNF) treatment modalities, and the therapeutic implications for the management of extraintestinal symptoms in IBD, in order to assist clinicians in optimizing treatment strategies for IBD patients with EIM.

Vascularite rhumatoïde et autres complications systémiques: aspects diagnostique et thérapeutique [Diagnosis and treatment of rheumatoid vasculitis and other systemic complications of rheumatoid arthritis]

Rheumatoid arthritis is a systemic disease that can potentially affect any organ. If the articular manifestations are central to the disease; skin, ophthalmic, neurological, cardiac, pulmonary as well as renal manifestations are well recognized, the latter particularly in the context of a secondary amyloidosis. Although incidence of extraarticular manifestations appears to decrease, likely a result from our more aggressive and early management of rheumatoid arthritis, their consequences remain severe in terms of morbidity and mortality, and their treatments complicated. The new biological therapies seem to be a promising alternative to current therapies, such as cyclophosphamide and high dose prednisone, even if evidences are still limited.

Complications et atteintes systémiques de la polyarthrite rhumatoïde [Complications and systemic manifestations of rheumatoid arthritis].

Rheumatoid arthritis (RA), in addition to the traditional joint damage can affect all organs as a systemic disease. Extra-articular manifestations of RA are highly variable ranging from rheumatoid nodules (most common) to rheumatoid vasculitis presenting a significant morbidity and mortality (49% at 5 years). With the new algorithms of treatment (earlier) and the use of biologics, the incidence of severe extra-articular manifestations decreases. Regarding the treatment of rheumatoid vasculitis, rituximab looks promising. RA also increases cardiovascular risk and the risk of osteoporosis. It is therefore important to identify these risks and, if appropriate, treat them. Collaboration with the general practitioner is essential in this situation.

Extra-osseous involvement of Langerhans' cell histiocytosis in children.

The predominant clinical and radiological features of Langerhans' cell histiocytosis (LCH) in children are due to osseous involvement. Extra-osseous disease is far less common, occurring in association with bone disease or in isolation; nearly all anatomical sites may be affected and in very various combinations. The following article is based on a multicentre review of 31 children with extra-osseous LCH. The objective is to summarise the diverse possibilities of organ involvement. The radiological manifestations using different imaging modalities are rarely pathognomonic on their own. Nevertheless, familiarity with the imaging findings, especially in children with systemic disease, may be essential for early diagnosis.

Des céphalées, cinq avis spécialisés: les pièges diagnostiques pour la maladie de Horton [Headaches, five expert opinions: the pitfalls involved in the diagnosis of giant cell arteritis].

Giant cell arteritis (GCA) (or Horton's disease) is a systemic disease affecting the vessels of medium and large sizes. The incidence increases with age (the disease develops rarely before age 50) and the etiology remains unknown. Clinical manifestations may vary (including asthenia, temporal headache, visual disturbances, etc.) and GCA can potentially lead to dramatic consequences (permanent loss of vision). Although some anomalies in the investigations may help in the diagnosis of GCA, research and confirmation of the diagnosis of GCA may be difficult, especially when the symptoms presented by patients are spread out in time and appear to be nonspecific at first.

Surgical procedure in immunoglobulin G4-related ascending aortitis?

Immunoglobulin G4 (IgG4)-related fibroinflammatory systemic disease accounts for 7% of all noninfectious aneurysms of the thoracic aorta. A patient was admitted with a symptomatic ascending aortic aneurysm and thickened aortic wall (outer/inner diameter 55/45 mm), which was replaced. Probes revealed IgG4-related aortitis associated with a primary tuberculosis infection. Corticosteroid and antituberculosis therapies were used, and the patient's clinical evolution was favorable. The optimal treatment strategy of IgG4-related aortitis, a new entity, remains vague. Inner aortic diameter alone does not justify aortic replacement, but wall thickening may mimic intramural hematoma. In this particular case of IgG4-related aortitis, immunosuppressive treatment alone, as an alternative to a surgical procedure, may be debatable.

Clinical characteristics and outcome of isolated extracerebral relapses of primary central nervous system lymphoma: a case series.

There is very limited data on isolated systemic relapses of primary central nervous system lymphomas (PCNSL). We retrospectively reviewed the clinical characteristics and outcome of 10 patients with isolated systemic disease among 209 patients with PCNSL mainly treated with methotrexate-based chemotherapy (CT) with or without radiation therapy (RT). Isolated systemic relapse remained rare (4.8%, 10/209 patients). Median time from initial diagnosis to relapse was 33 months (range, 3-94). Sites of relapse were mostly extranodal. Three patients presented with early extra-cerebral (EC) relapse 3, 5 and 8 months from the beginning of initial treatment, respectively, and 7 patients had later relapses (range, 17-94 months). Treatment at relapse included surgery alone, RT alone, CT with or without radiotherapy, or CT with autologous stem cell transplantation (ASCT). Median overall survival (OS) after relapse was 15.5 months (range, 5.8-24.5) compared to 4.6 months (range, 3.6-6.5) for patients with central nervous system (CNS) relapse (p = 0.35). In conclusion, isolated systemic relapses exist but are infrequent. Early EC relapse suggests the presence of systemic disease undetectable by conventional evaluation at initial diagnosis. Patient follow-up must be prolonged because systemic relapse can occur as late as 10 years after initial diagnosis. Whether EC relapses of PCNSL have a better prognosis than CNS relapses needs to be assessed in a larger cohort. Copyright © 2010 John Wiley & Sons, Ltd.

Clinical outcome after a reactive hypothermic EEG following cardiac arrest.

BACKGROUND: Reactive electroencephalography (EEG) background during therapeutic hypothermia (TH) is related to favorable prognosis after cardiac arrest (CA), but its predictive value is not 100 %. The aim of this study was to investigate outcome predictors after a first reactive EEG recorded during TH after CA. METHODS: We studied a cohort of consecutive comatose adults admitted between February 2008 and November 2012, after successful resuscitation from CA, selecting patients with reactive EEG during TH. Outcome was assessed at three months, and categorized as survivors and non-survivors (no patient was in vegetative state). Demographics, clinical variables, EEG features, serum neuron-specific enolase (NSE) and procalcitonin, were compared using uni- and multivariable analyses. RESULTS: A total of 290 patients were treated with TH after cardiac arrest; 146 had an EEG during TH, which proved reactive in 90 of them; 77 (86 %) survived and 13 (14 %) died (without recovery from coma). The group of non-survivors had a higher occurrence of discontinuous EEG (p = 0.006; multivariate analysis p = 0.026), and a higher serum NSE peak (p = 0.021; multivariate analysis p = 0.014); conversely, demographics, and other clinical variables including serum procalcitonin did not differ. CONCLUSIONS: A discontinuous EEG and high serum NSE are associated with mortality after CA in patients with poor outcome despite a reactive hypothermic EEG. This suggests more severe cerebral damage, but not to higher extent of systemic disease.

Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells.

Mutant mice where tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (Lat(Y136F) mice) develop a fast-onset lymphoproliferative disorder involving polyclonal CD4 T cells that produce massive amounts of Th2 cytokines and trigger severe inflammation and autoantibodies. We analyzed whether the Lat(Y136F) pathology constitutes a bona fide autoimmune disorder dependent on TCR specificity. Using adoptive transfer experiments, we demonstrated that the expansion and uncontrolled Th2-effector function of Lat(Y136F) CD4 cells are not triggered by an MHC class II-driven, autoreactive process. Using Foxp3EGFP reporter mice, we further showed that nonfunctional Foxp3(+) regulatory T cells are present in Lat(Y136F) mice and that pathogenic Lat(Y136F) CD4 T cells were capable of escaping the control of infused wild-type Foxp3(+) regulatory T cells. These results argue against a scenario where the Lat(Y136F) pathology is primarily due to a lack of functional Foxp3(+) regulatory T cells and suggest that a defect intrinsic to Lat(Y136F) CD4 T cells leads to a state of TCR-independent hyperactivity. This abnormal status confers Lat(Y136F) CD4 T cells with the ability to trigger the production of Abs and of autoantibodies in a TCR-independent, quasi-mitogenic fashion. Therefore, despite the presence of autoantibodies causative of severe systemic disease, the pathological conditions observed in Lat(Y136F) mice unfold in an Ag-independent manner and thus do not qualify as a genuine autoimmune disorder.

Riesenzellarteriitis : Ätiologische Erkenntnisse und diagnostische Herausforderung für den Pathologen [Giant cell arteritis : Etiological knowledge and diagnostic challenge for pathologists].

Giant cell arteritis is a potentially systemic disease of medium-sized and large caliber arteries, showing a preferential manifestation in the extracranial branches of the carotid artery. The diagnosis is oriented to clinical and histomorphological criteria which will be critically reviewed. Particular emphasis is placed on the differentiation from normal aging processes and from healing stages under steroid therapy. In addition, the advances in our understanding of the disease pathomechanism during the last 10 years will be briefly presented as the basis for the hitherto empiric steroid treatment.

Scleritis after proton therapy in uveal melanoma [Skleritis nach Protonentherapie bei Aderhautmelanom]

BACKGROUND: Sclera is a very radioresistant tissue and scleritis after proton therapy has not been described so far. HISTORY AND SIGNS: Four female patients, aged between 31 and 74 years, were treated with proton therapy for uveal melanoma (height range: 2.2 - 3.5 mm), located in the macula, the superior equator and 2 in the ciliary body. All patients had a history of a previous or active inflammatory disease and developed scleritis after radiotherapy. THERAPY AND OUTCOME: Two patients had infectious scleritis and were treated with adequate antibiotic therapy. After systemic corticotherapy, 3 patients recovered completely; the remaining patient was managed with additional immunosuppressive treatment as well as a conjunctival and scleral graft, but has not become pain free yet. CONCLUSION: Scleritis is a possible complication after proton therapy, probably on an ischemic basis, where there is a predisposing factor such as inflammatory systemic disease.

Bilateral periorbital ecchymoses. An often missed sign of amyloid purpura.

Immunoglobulin light chain (AL) amyloidosis is a systemic disease caused by a plasma cell clone synthesizing an unstable light chain, which forms amyloid fibrils. Deposition of amyloid fibrils affects primarily kidney, heart, nervous system, spleen, liver, gastrointestinal tract and the skin. Skin bleeding in these patients is called amyloid purpura. Classically, it occurs spontaneously and bilaterally in the periorbital region. Vessel wall fragility and damage by amyloid are the principal causes of periorbital and gastrointestinal bleeding. Additionally, coagulation factor inhibitory circulating paraprotein, hyperfibrinolysis, platelet dysfunction or isolated acquired factor X deficiency may contribute to even more severe, diffuse bleedings. Early diagnosis remains essential for improving prognosis of patients with AL amyloidosis. Although pictures of amyloid purpura have been often reported in the literature, the clinical diagnosis may be delayed. We report a case of cutaneous manifestation of AL amyloidosis diagnosed not until one year after the appearance of the first symptoms. Diagnostic work-up revealed that the patient suffered from multiple myeloma with secondary AL amyloidosis. Atraumatic ecchymoses at the face, particularly the eyelids as well as in the neck should raise the suspicion of AL amyloidosis.

Prevalence of vascular disease in systemic lupus erythematosus compared with type-1 diabetes mellitus: A cross-sectional study of two cohorts.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with considerable cardiovascular morbidity that has not yet been directly compared with other diseases with known cardiovascular risk. METHODS: Two hundred and forty-one patients of the multicentre Swiss SLE cohort study (SSCS) were cross-sectionally assessed for coronary heart disease (CHD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). SLE patients were compared with a cohort of 193 patients with type-1 diabetes mellitus being followed at the University Hospital Basel. A subgroup analysis of 50 age- and sex-matched patients from the University Hospital Basel was performed. RESULTS: Of patients within the SSCS 13.3% had one or more vascular events: 8.3% CHD, 5% CVD and 1.2% PAD. In type-1 diabetes mellitus patients, 15% had vascular events: 9.3% CHD, 3.1% CVD and 5.6% PAD. In the matched subgroup, 26% of SLE patients had vascular events (14% CHD) compared with 12% in type-1 DM patients (2% CHD). Cardiovascular risk factors were similar in both groups. Vascular events in SLE patients were associated with age, longer disease duration, dyslipidaemia, and hypertension. CONCLUSION: Cardiovascular morbidity in SLE is at least as frequent as in age- and sex-matched type-1 diabetes mellitus patients. Therefore, aggressive screening and management of cardiovascular risk factors should be performed.