[Rheumatological emergency on the edge of intensive care medicine]. / Rheumatologische Notfälle an der Grenze zur Intensivmedizin.

In rheumatological practice situations repeatedly occur where critical problems which need to be quickly addressed in order to prevent permanent damage to the patient. The focus of this article is on rapidly progressive inflammatory diseases, severe side effects of many medications and complications of infections during immunosuppressive treatment.

S3-Leitlinie zur Therapie der Psoriasis vulgaris Update - Kurzfassung Teil 2 - Besondere Patientengruppen und spezielle Behandlungssituationen.

Die deutsche Psoriasis-Leitlinie zur Behandlung der Psoriasis vulgaris wurde unter Verwendung der GRADE-Methodik aktualisiert. Die Leitlinie wurde aufbauend auf einer systematischen Literaturrecherche (letzte Update-Recherche am 01.12.2016) entwickelt und in einem formalen Konsensus- und Freigabeverfahren verabschiedet. Der zweite Teil dieser Kurzfassung stellt die Empfehlungen zum Tuberkulose-Screening vor und unter Therapie, zur Therapieauswahl bei Kinderwunsch, Schwangerschaft und Stillzeit, vorliegender Gelenkbeteiligung sowie zum Umgang mit Impfungen dar. Zudem werden die Empfehlungen zur Therapieauswahl bei Komorbidität mit Hepatitis und Leberfunktionseinschränkungen, HIV, Tumorerkrankungen, Erkrankungen aus dem neurologischen und psychiatrischen Formenkreis, koronarer Herzkrankheit und Herzinsuffizienz, Diabetes mellitus, Niereninsuffizienz sowie chronisch entzündlicher Darmerkrankung dargestellt.

S3 Guideline for the treatment of psoriasis vulgaris, update - Short version part 2 - Special patient populations and treatment situations.

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The second part of this short version of the guideline covers the following special patient populations and treatment situations: tuberculosis screening before and during psoriasis treatment, choice of psoriasis treatment for individuals wishing to have children, as well as during pregnancy and breast-feeding, and patients with joint involvement and vaccinations. In addition, recommendations on the choice of treatment are presented for patients with the following comorbidities: hepatitis and other hepatic impairment, HIV, malignancies, neurological and psychiatric disorders, ischemic heart disease and congestive heart failure, diabetes mellitus, renal impairment and inflammatory bowel disease.

S3 Guideline for the treatment of psoriasis vulgaris, update - Short version part 1 - Systemic treatment.

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The first section of this short version of the guideline covers systemic treatment options considered relevant by the expert panel and approved in Germany at the time of the consensus conference (acitretin, adalimumab, apremilast, cyclosporine, etanercept, fumaric acid esters, infliximab, methotrexate, secukinumab and ustekinumab). Detailed information is provided on the management and monitoring of the included treatment options.

Sensitivity of the GEPARD Patient Questionnaire to Identify Psoriatic Arthritis in Patients with Psoriasis in Daily Practice: The GEPARD-Life Study.

Early detection of psoriatic arthritis (PsA) remains a challenge in clinical practice. Tools such as the German Psoriasis Arthritis Diagnostic (GEPARD) questionnaire have been developed for this purpose. The aim of this study was to determine the performance of the GEPARD questionnaire in the detection of PsA in psoriasis patients following rheumatology evaluation in daily clinical practice in Germany. This was a multicenter study involving 59 dermatology units (university/general hospital/office based), and the GEPARD questionnaire was distributed to psoriasis patients. Patients who had a sum score of ≥4 positive answers were referred to a rheumatologist for evaluation of PsA. We recruited 1,512 patients, of whom approximately 50% were referred. One third of the referred patients were classified as having PsA after rheumatological assessment. Rates of PsA in university/general hospital settings were higher than those observed in a doctor's office-based setting (43.7 vs. 25.8%). The GEPARD questionnaire demonstrated easy screening of psoriasis patients for PsA.

The cartilage protein melanoma inhibitory activity contributes to inflammatory arthritis.

OBJECTIVE: Melanoma inhibitory activity (MIA) is a small chondrocyte-specific protein with unknown function. MIA knockout mice (MIA(-/-)) have a normal phenotype with minor microarchitectural alterations of cartilage. Our previous study demonstrated that immunodominant epitopes of MIA are actively presented in an HLA-DR4-restricted manner in the inflamed RA joint. The objective of this study was to investigate the potential role of MIA as an autoantigen. METHODS: Collagen-induced arthritis (CIA) and anti-collagen antibody-induced arthritis (CAIA) were induced in MIA(-/-) mice. Anti-type II collagen (anti-CII) antibodies were measured by ELISA. T cell proliferation and cytokine production were assessed by flow cytometry. RESULTS: MIA(-/-) mice had a markedly reduced incidence and severity of CIA and CAIA compared with wild-type (WT) mice. Attenuation of disease was not related to defective binding of anti-CII antibodies to cartilage in the absence of MIA. However, MIA(-/-) mice had significantly reduced anti-CII IgG1 and IgG2a antibody levels accompanied by an increase in FoxP3-expressing CD25(+)CD4(+) regulatory T cells. This was paralleled by a significant reduction in CII-specific IFN-γ production by T cells in MIA(-/-) but not WT animals, suggesting a qualitative impact of MIA on the collagen-induced Th1 response. Furthermore, Ag-specific proliferation of T cells after restimulation with MIA in WT but not MIA(-/-) mice indicated the existence of MIA-specific T cells in the context of CIA. CONCLUSION: These data support a role for MIA as an autoantigen during arthritis development. Whether MIA can influence the balance of pathogenic vs regulatory responses in human RA remains to be investigated.

First appearance and location of catecholaminergic cells during experimental arthritis and elimination by chemical sympathectomy.

OBJECTIVE: The sympathetic nervous system is proinflammatory in early collagen-induced arthritis (CIA) and antiinflammatory in late disease. In late arthritis, sympathetic innervation of synovial and lymphoid tissue is markedly reduced. Thus, its suggested antiinflammatory role is difficult to explain. We hypothesized that newly discovered catecholamine-producing (catecholaminergic) cells are targets of chemical sympathectomy. However, in CIA, the time point of appearance, the location, and the possible chemical elimination of catecholaminergic cells have not been studied. The purpose of this study was to investigate the emergence and location of catecholamine-producing and -storing cells in different organs and joints of mice after induction of CIA and to determine whether catecholamine-producing cells can be depleted by 6-hydroxydopamine (6-OHDA) during the early and late phases of CIA in vivo. METHODS: The presence of cells positive for tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT-2) was evaluated immunohistologically in the lymph nodes, thymus, bone marrow, spleen, and joints of control and arthritic mice. Density was evaluated at different time points after early and late chemical sympathectomy. (131)I-metaiodobenzylguanidine ((131)I-MIBG) scintigraphy demonstrated functional activity of these cells in joint inflammation. RESULTS: The density of TH+ and VMAT-2+ cells was highest after arthritis onset (from day 28 onward) and was observed to occur in the following sequence: lymph nodes, thymus, joints, bone marrow, and spleen. Even before arthritis onset (days 5-21), these cells were already more numerous, particularly in the draining lymph nodes, thymus, and joints. (131)I-MIBG scintigraphy demonstrated catecholamine-storing cells in inflammatory hot spots in the paw. Chemical sympathectomy strongly reduced the density of catecholaminergic cells in vitro and in vivo. CONCLUSION: After disease onset, catecholaminergic cells are particularly present in primary and secondary lymphoid organs and joints. Since catecholaminergic cells have been reported to have antiinflammatory properties in arthritis, the proinflammatory role played by chemical sympathectomy in late arthritis, as we previously determined, is probably dependent on catecholaminergic cell elimination.

Volcano-like intermittent bleeding activity for seven years from an arterio-enteric fistula on a kidney graft site after pancreas-kidney transplantation: a case report.

INTRODUCTION: We report the first case of a patient who underwent simultaneous kidney and pancreas transplantation and who then suffered from repeated episodes of severe gastrointestinal bleeding over a period of seven years. Locating the site of gastrointestinal bleeding is a challenging task. This case illustrates that detection of an arterio-enteric fistula can be very difficult, especially in technically-challenging situations such as cases of severe intra-abdominal adhesions. It is important to consider the possibility of arterio-enteric fistulas in cases of intermittent bleeding episodes, especially in transplant patients. CASE PRESENTATION: A 40-year-old Caucasian man received a combined pancreas-kidney transplantation as a result of complications from diabetes mellitus type I. Thereafter, he suffered from intermittent clinically-relevant episodes of gastrointestinal bleeding. Repeat endoscopic, surgical, scintigraphic, and angiographic investigations during his episodes of acute bleeding could not locate the bleeding site. He finally died in hemorrhagic shock due to arterio-enteric bleeding at the kidney graft site, which was diagnosed post-mortem. CONCLUSIONS: In accordance with the literature, we suggest considering the removal of any rejected transplant organs in situations where arterio-enteric fistulas seem likely but cannot be excluded by repeat conventional or computed tomography-angiographic methods. Arterio-enteric fistulas may intermittently bleed over many years.

Perioperative management of immunosuppression in rheumatic diseases--what to do?

To stop or not to stop immunosuppressive therapy in the perioperative setting puts the clinician to a challenge. The risk of potential wound infection with possible septic or even lethal consequences needs to be weighted against exacerbation of the rheumatic disease. However, exacerbation of autoimmune inflammatory activity needs to be treated with increasing immunosuppressive medication, thus leading to enhanced risk of local and systemic infection as well. Unfortunately, up to now there is no data from randomized, double-blind controlled clinical trials available on how to steer immunosuppressive therapy in the perioperative setting, making evidence-based recommendations difficult. Neither is there good evidence, if the risk of infectious complications under immunosuppressive therapy differs according to the type and localization of surgery performed. Finally, immunosuppressive co-medication, like glucocorticoid dosage, is not adequately addressed in the available studies, making interpretation of these studies even more problematic. Therefore, a decision has to be made on an individual basis. We discuss the available data on DMARD and biologics therapy in the perioperative setting and describe our own perioperative management with different DMARDs and biologics.

An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells.

OBJECTIVE: Activation of the sympathetic nervous system (SNS) ameliorates collagen-induced arthritis (CIA) in the late phase of the disease but aggravates it in the presymptomatic phase. The aim of the present study was to determine whether CD4+CD25+ T cells are influenced by the SNS of mice and play a disease-modifying role in the early symptomatic phase of the disease. METHODS: We tested the effects of the SNS on arthritis by transferring CD4+CD25+ T cells from sympathectomized mice immunized with type II collagen and from immunized, SNS-intact animals (controls). We further characterized transferred cells by studying forkhead box P3 (FoxP3) expression, cell proliferation, and cytokine secretion. RESULTS: Using anti-dopamine-beta-hydroxylase antibodies for systemic sympathectomy, we noticed a time-dependent disease amelioration (strongest when sympathectomy was performed 7 days before immunization, with no effect 30 days after immunization). When CD4+CD25+ T cells from immunized and sympathectomized animals were transferred into mice with CIA (on day 32), disease severity was reduced compared with that in controls. However, the number of CD4+CD25+FoxP3+ cells and the FoxP3 expression level in CD4+CD25+ cells were not changed by sympathectomy. In a mixed assay of donor CD4+CD25- and CD4+CD25+ cells, proliferation was reduced when cells from sympathectomized animals were studied. In the same assay, secretion of tumor necrosis factor, interleukin-17 (IL-17), IL-10, and IL-4 (not interferon-gamma) was markedly reduced when cells were taken from sympathectomized animals. Culture of CD4+CD25+ cells with norepinephrine (10(-5)M) for 24 hours before transfer worsened the arthritis. CONCLUSION: The SNS increases disease severity in the early phase of symptomatic CIA by stimulating several proinflammatory aspects of CD4+CD25+ T cells.

Direct application of plasmid DNA containing type I interferon transgenes to vaginal mucosa inhibits HSV-2 mediated mortality.

The application of naked DNA containing type I interferon (IFN) transgenes is a promising potential therapeutic approach for controlling chronic viral infections. Herein, we detail the application of this approach that has been extensively used to restrain ocular HSV-1 infection, for antagonizing vaginal HSV-2 infection. We show that application of IFN-alpha1, -alpha5, and -beta transgenes to vaginal mouse lumen 24 hours prior to HSV-2 infection reduces HSV-2 mediated mortality by 2.5 to 3-fold. However, other type I IFN transgenes (IFN- alpha4, -alpha5, -alpha6, and -alpha9) are non effectual against HSV-2. We further show that the efficacy of IFN-alpha1 transgene treatment is independent of CD4+ T lymphocytes. However, in mice depleted of CD8+ T lymphocytes, the ability of IFN-alpha1 transgene treatment to antagonize HSV-2 was lost.

Leptin is a link between adipose tissue and inflammation.

Leptin is a hormone of the pluripotent white adipose tissue and confers a multitude of regulatory functions within the organism. It controls the energy storage, lipoprotein metabolism, acute phase reactants, sex hormones and glucocorticoid metabolism, and immune function. In this review, we describe these multiple functions of leptin, the regulation of leptin expression, and how leptin can modulate the immune system via direct and indirect mechanisms. We show how leptin can be a link between the adipose tissue and inflammation.