Complications of systemic juvenile idiopathic arthritis: risk factors and management recommendations.

Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. Systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that SJIA is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of SJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation, continue to be a major issue in SJIA patients' care. Translational research leading to a profound understanding of the cytokine crosstalk in SJIA and the identification of risk factors for SJIA complications will help to improve long-term outcome.

Rhumatologie. Rhumatisme psoriasique [Update in psoriatic arthritis treatment].

Psoriatic arthritis is a chronic inflammatory disease. It affects up to 40% of patients suffe- ring from skin psoriasis. Joint involvement is relatively heterogeneous. Some clinical manifestations are similar to those of rheumatoid arthritis, others are close to spondylarthritis manifestations and are therefore considered as part of this entity. Treatment depends on initial presentation (peripheral or axial) but often begins with non-steroidal anti-inflammatory drugs and methotrexate, followed by anti-TNFalpha if needed. New therapeutic op- tions are available or under evaluation, parti- cularly targeting cytokines involved in psoriatic arthritis (IL-12/IL-23 and IL-17).

Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

A prospective evaluation of ultrasound as a diagnostic tool in acute microcrystalline arthritis.

INTRODUCTION: The performance of ultrasound (US) in the diagnosis of acute gouty (MSU) arthritis and calcium pyrophosphate (CPP) arthritis is not yet well defined. Most studies evaluated US as the basis for diagnosing crystal arthritis in already diagnosed cases of gout and few prospective studies have been performed. METHODS: One hundred nine consecutive patients who presented an acute arthritis of suspected microcrystalline arthritis were prospectively included. All underwent an US of the symptomatic joints(s) and of knees, ankles and 1(st) metatarsopalangeal (MTP) joints by a rheumatologist "blinded" to the clinical history. 92 also had standard X-rays. Crystal identification was the gold standard. RESULTS: Fifty-one patients had MSU, 28 CPP and 9 had both crystals by microscopic analysis. No crystals were detected in 21. One had septic arthritis. Based on US signs in the symptomatic joint, the sensitivity of US for both gout and CPP was low (60 % for both). In gout, the presence of US signs in the symptomatic joint was highly predictive of the diagnosis (PPV = 92 %). When US diagnosis was based on an examination of multiple joints, the sensitivity for both gout and CPP rose significantly but the specificity and the PPV decreased. In the absence of US signs in all the joints studied, CPP arthritis was unlikely (NPV = 87 %) particularly in patients with no previous crisis (NPV = 94 %). X-ray of the symptomatic joints was confirmed to be not useful in diagnosing gout and was equally sensitive or specific as US in CPP arthritis. CONCLUSIONS: Arthrocenthesis remains the key investigation for the diagnosis of microcrystalline acute arthritis. Although US can help in the diagnostic process, its diagnostic performance is only moderate. US should not be limited to the symptomatic joint. Examination of multiple joints gives a better diagnostic sensitivity but lower specificity.

Infectiologie et postulats de Koch: tourner la page [Infectious diseases and Koch's postulates: turning the page].

The thoracolumbar junctional region (T10-L1) of the spine is a transitional zone, where more than half of the thoracic and lumbar fractures occur. In this presentation the origin of the pathoanatomical changes in the thoracolumbar junctional region of the spine is discussed in view of the previous studies. These studies refer to a torsional force contributing to the formation of the degenerative changes, especially in the facet joints. Degenerative changes anteriorly and posteriorly do not concur in the thoracolumbar junctional region. Only a weak concurrence is found between disc degeneration and spondylosis, which refer to differences in their pathomechanisms. A strong concurrence between the degenerative changes at different levels, especially anteriorly, reflects factors causing overall degeneration in the thoracolumbar junctional region.

Signs of a vector's adaptive choice: on the evasion of infectious hosts and parasite-induced mortality

Laboratory and field experiments have demonstrated in many cases that malaria vectors do not feed randomly, but show important preferences either for infected or non-infected hosts. These preferences are likely in part shaped by the costs imposed by the parasites on both their vertebrate and dipteran hosts. However, the effect of changes in vector behaviour on actual parasite transmission remains a debated issue. We used the natural associations between a malaria-like parasite Polychromophilus murinus, the bat fly Nycteribia kolenatii and a vertebrate host the Daubenton's bat Myotis daubentonii to test the vector's feeding preference based on the host's infection status using two different approaches: 1) controlled behavioural assays in the laboratory where bat flies could choose between a pair of hosts; 2) natural bat fly abundance data from wild-caught bats, serving as an approximation of realised feeding preference of the bat flies. Hosts with the fewest infectious stages of the parasite were most attractive to the bat flies that did switch in the behavioural assay. In line with the hypothesis of costs imposed by parasites on their vectors, bat flies carrying parasites had higher mortality. However, in wild populations, bat flies were found feeding more based on the bat's body condition, rather than its infection level. Though the absolute frequency of host switches performed by the bat flies during the assays was low, in the context of potential parasite transmission they were extremely high. The decreased survival of infected bat flies suggests that the preference for less infected hosts is an adaptive trait. Nonetheless, other ecological processes ultimately determine the vector's biting rate and thus transmission. Inherent vector preferences therefore play only a marginal role in parasite transmission in the field. The ecological processes rather than preferences per se need to be identified for successful epidemiological predictions.

The difference of disease perception by juvenile idiopathic arthritis patients and their parents : analysis of the JAMAR questionnaire.

BACKGROUND: The JAMAR (Juvenile Arthritis Multidimensional Assessment Report) has been developed to evaluate the perception of the patient and his parents on different items: well-being, pain, functional status, quality of life, disease activity, disease course, side effects of medication, therapeutic compliance and satisfaction with illness outcome. Our aim was to compare disease's perception by JIA patients and their parents. METHODS: We included into the study 100 consecutive patients over 7 years of age. We asked both parent and child to complete the JAMAR questionnaire. For each patient we recorded demographic and disease related data. We examined the level of disagreement between children and parents for the quantitative items of the JAMAR: VAS Pain, VAS Disease Activity, VAS Well Being, Juvenile Arthritis Functional Score, HRQoL. Then we looked for a relation between discordance-rate and demographic and clinical variables. RESULTS: Children and parents' median scores for all five items were similar. Individual dyads agreement was low, with a large amount of pairs (80) discordant for at least one item. We found higher MD VAS and JADAS in more discordant dyads, suggesting that when the disease is more active discordance between child and parent increase. CONCLUSION: The JAMAR questionnaire is an important tool that helps clinicians to detect divergent child and parent's disease perceptions. It is essential that both patients and parents fill the JAMAR questionnaire for a complete clinical and psychosocial evaluation.

Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

Introduction: Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA. Methods: Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value. Results: With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity. Conclusions: CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.

Consultations infectiologiques ambutatoires non VIH: analyse d'un centre universitaire sur cinq ans [Non-HIV infectious disease outpatient consultations: a 5-year study in a Swiss University Hospital].

Few studies have examined the workload or clinical spectrum of non-HIV infectious diseases outpatient consultations (IDOC). This retrospective study aims to describe IDOC referrals over the past 5 years. In total, 483 patients were referred (with an increase of 63% between 2009 and 2013). Most referrals were received from primary care clinicians (45%). Median patient age was 47 years, 57% of patients were men and 17% were immunosuppressed. Of the diagnoses retained, 74% were infectious, 20% were non-infectious and 6% were of unknown aetiology. Two community outbreaks were identified (tattoo-related mycobacterial infection and Q fever). In conclusion, the infectious diseases outpatient clinic, which has expanded progressively in the past 5 years, provides a specialised service for primary health clinicians and for public health.

Pulmonary tuberculosis in a patient with rheumatoid arthritis undergoig immunosuppressive treatment: case report

Rheumatoid arthritis is a disease which characteristically affects the joints. Because it is an autoimmune disease, immunosuppressive drugs are widely used in its treatment. The present case report illustrates the association of immunosuppressive treatment with the development of opportunistic infections in a 64-year-old patient.

Two-photon excitation fluorometry in detection of infectious diseases

Because of the heavily overlapping symptoms, pathogen-specific diagnosis and treatment of infectious diseases is difficult based on clinical symptoms alone. Therefore, patients are often treated empirically. More efficient treatment and management of infectious diseases would require rapid point-of-care compatible in vitro diagnostic methods. However, current point-of-care methods are unsatisfactory in performance and in cost structure. The lack of pointof- care methods results in unnecessary use of antibiotics, suboptimal use of virus-specific drugs, and compromised patient care. In this thesis, the applicability of a two-photon excitation fluorometry is evaluated as a tool for rapid detection of infectious diseases. New separation-free immunoassay methodologies were developed and validated for the following application areas: general inflammation markers, pathogen-specific antibodies, pathogen-specific antigens, and antimicrobial susceptibility testing. In addition, dry-reagent methodology and nanoparticulate tracers are introduced in context to the technique. The results show that the new assay technique is a versatile tool for rapid detection of infectious diseases in many different application areas. One particularly attractive area is rapid multianalyte testing of respiratory infections, where the technique was shown to allow simple assay protocols and comparable performance to the state-of-the-art laboratory methods. If implemented in clinical diagnostic use, the new methods could improve diagnostic testing routines, especially in rapid testing of respiratory tract infections.

Borrelia burgdorferi evades the effects of ceftriaxone treatment in a mouse model of Lyme borreliosis

Borrelia burgdorferi infektoitujen hiirten antibioottihoidon jälkeinen oireilu Lymen borrelioosi on puutiaisten välittämä monimuotoinen infektiotauti, jonka tunnetuin oire on ns. vaeltava ihottuma eli erythema migrans. Muita tavallisia ilmentymiä ovat erityisesti nivel- ja hermosto-oireet sekä harvemmin sydän- ja silmäoireet. Suurin osa potilaista paranee täysin terveeksi antibioottihoidon avulla, mutta jopa 10 % borrelioosiin sairastuneista oireilee suositusten mukaisesta hoidosta huolimatta. Pitkittyneen oireilun on ajateltu johtuvan mm. infektion laukaisemasta autoimmuunitaudista tai kroonisesta infektiosta, mutta teorioiden tueksi ei ole kyetty esittämään kiistattomia todisteita. Onkin todennäköistä, että antibioottihoidon jälkeisen oireilun takana on useampia mekanismeja eikä yksi teoria selitä kaikkien potilaiden oireilua. Tässä väitöskirjatyössä on tutkittu hoidonjälkeistä borrelioosia hiirimallin avulla. Varhaisvaiheessa (2 viikkoa infektoinnin jälkeen) annettu antibiootti vähensi hiirten nivelturvotusta ja esti B. burgdorferi – bakteerin kasvun kudoksista otetuista näytteissä. Hoidettu¬jen hiirten B. burgdorferi -spesifiset IgG-luokan vasta-aineet pysyivät kuitenkin koholla ja osasta kudosnäytteistä löytyi B. burgdorferi:n DNA:ta PCR-tutkimuksen avulla. Mikäli hiiret hoidettiin myöhäisessä vaiheessa (yli 18 viikkoa infektoinnista) tulokset olivat muuten samanlaiset, mutta keftriaksoni ei vaikuttanut nivelturvotukseen. Näin hiirissä oli aikaansaatu tilanne, joka on hyvin samankaltainen ihmisen hoitoresistentin borrelia-artriitin kanssa: oireet jatkuvat, mutta taudinaiheuttajaa ei saada esiin. Inflammaatiota vaimentavaa anti-TNF-alphaa on käytetty nivelreuman hoidossa menestyksekkäästi huonosti muuhun hoitoon reagoivilla potilailla ja siitä syystä sen ajateltiin voivan vaikuttaa suotuisasti myös B. burgdorferi -infektoitujen hiirten hoidonjälkeiseen nivelturvotukseen. Sillä ei kuitenkaan ollut vaikutusta nivelturvotukseen, mutta yllättäen hoidon jälkeen osa hiirten kudosnäytteistä osoittautui viljelypositiivisiksi. On siis ilmeistä, että hiirimallissamme osa B. burgdorferi spirokeetoista pystyy välttämään keftriaksonihoidon vaikutuksen joko hakeutumalla elimistössä kudokseen, jossa antibiootin pitoisuus ei nouse riittävän korkeaksi, tai ne kykenevät muuntautumaan metabolisesti inaktiiviin tilaan eikä mikrobilääke yhdessä immuunipuolustuksen kanssa onnistu tappamaan niitä. Jatkotutkimuksissa selvitimme B. burgdorferi - spirokeetan mahdollista piilopaikkaa tutkimalla antibioottihoidon jälkeen useita eri kudoksia PCR-menetelmällä. Tulosten perusteella spirokeetta näyttää suosivan nivelkudosta tai soluja, joita esiintyy nivelessä runsaasti. On kuitenkin edelleen epäselvää, missä muodossa B. burgdorferi –spirokeetat säilyvät kudoksessa antibioottihoidon jälkeen.