Objective. Gradual local heating of the skin induces a largely nitric oxide(NO)-mediated vasodilatation. However, use of this assessment of microvascular health is limited because little is known about its reproducibility.Methods. Healthy volunteers (n=9) reported twice to the laboratory. Cutaneous vascular conductance (CVC), derived from laser Doppler flux and mean arterial pressure, was examined in response to a standardised local heating protocol (0.5ºC per 150s from 33-42ºC, followed by 20-minutes at 44ºC). Skin responses were examined at two locations on the forearm (betweensite). Heating was repeated after a break of 24-72 hours (between-day). Reproducibility of skinresponses at 33-42ºC is presented for absolute CVC and relative CVC-responses corrected for maximal CVC at 44ºC (%CVCmax).Results. Between-day reproducibility of baseline CVC and %CVCmax for both sites was relatively poor (22-30%). At 42ºC, CVC and %CVCmax responses showed less variation (9-19%), whilst absolute CVC-responses at 44ºC were 14-17%. Between-day variation for %CVCmax increased when using data from site 1 on day 1, but site 2 on the subsequent day (25%).Conclusion. Day-to-day reproducibility of baseline laser Doppler-derived skin perfusion responses is poor, but acceptable when absolute and relative skin perfusion to a local gradual heating protocol is utilised and site-to-site variation is minimised.

The ‘MHC-I (major histocompatibility complex class I)-opathy’ concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet’s disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

BackgroundDue to a small number of clinical studies, treatment of Behçet's syndrome (BS) mainly depends on the type and severity of symptoms and may vary substantially. In 2008, EULAR recommendations were published, aiming for an evidence-based approach for the management of BS [1].ObjectivesTo assess guideline adherence in treatment of BS in two different geographic areas.MethodsWe extracted guideline statements from the 2008 EULAR recommendations [1]. Adherence to these statements in both New York (USA) and Amsterdam (The Netherlands) was evaluated retrospectively by reviewing records from patients fulfilling the ISG criteria. We analyzed data per statement and event, and divided the data according to the year in which an event occurred. We compared events prior to 2009 to those in 2009 or later (after publication of the EULAR recommendations).Results474 patients were evaluated, 24 of whom were from Amsterdam (Table 1).Adherence in posterior uveitis was relatively low in clinical practice. However, secondary analysis of the patients in the second time frame showed that 66% of cases with partial- and 77% with non-adherence were on cyclosporine or a biologic DMARD.Colchicine in treatment of arthritis was hardly ever used as monotherapy (3 cases <2009, 9 cases ≥2009). Other drugs used included prednisone (n=197), Plaquenil (n=63), methotrexate (n=67), azathioprine (n=133) and anti-TNF agents (n=124).Table 1.Guideline adherence in treatment of BSEvent (n events in n of patients)Adherence% <2009% ≥2009EULAR recommendation(n events)(n events)Posterior uveitis (76 in 59 pts)Yes21% (3)31% (19)Systemic corticosteroids + AZAPartial36% (5)48% (30)No43% (6)21% (13)Severe ocular disease (11 in 11 pts)Yes25% (1)57% (4)Add Cyclosporin or IFX; or treat with IFNPartial50% (2)29% (2)No25% (1)14% (1)Arthritis (347 in 192 pts)Yes29% (24)29% (76)ColchicineNo71% (58)71% (189)Neurological disease (47 in 35 pts)Yes100% (18)100% (29)No cyclosporine, unless ocular inflammation1 pt with eye disease on cyclosporine ConclusionsAdherence to the guidelines varies substantially across type of events. Adherence in treatment of posterior uveitis was low and a variety of other drugs were used in its treatment, which are also considered DMARDs for this condition. The extensive use of anti-TNF agents might indicate a shift towards more aggressive treatment and acceptance of TNF inhibitors for the treatment of other rheumatic and inflammatory eye conditions in the countries studied.In patients with neuro-Behçet, adherence to the recommendation is quite good in clinical practice.In the majority of patients with arthritis, colchicine is either used in combination with other (biological) DMARDs or not at all. This might indicate that colchicine alone is not sufficient as treatment of arthritis in BS or that arthritis is often combined with other manifestations implying a need for more combination treatment.Our results suggest that a revision of the current guidelines may be due, given widespread use of other immunosuppressive medications and newly avai...

Objective To investigate the differential diagnostic spectrum in patients with suspected Behçet’s syndrome (BS) in low prevalence regions. In addition, the number of patients fulfilling the ICBD criteria despite not having BS was evaluated. Methods This retrospective analysis was performed in two referral centers for BS. Patients with confirmed BS (clinical diagnosis with fulfilment of ISG criteria or a score of ≥ 5 points in the ICBD criteria) were excluded. The remaining patients were divided into eleven differential diagnosis categories. If no definitive alternative diagnosis could be established, patients were termed ‘probable BS’ in case of (1) relapsing orogenital aphthosis in the absence of other causes and either HLA-B51 positivity, origin from an endemic area or presence of an additional typical BS symptom that is not part of the classification criteria or (2) with 3–4 points scored in the ICBD criteria. Results In total 202 patients were included and categorized as follows: 58 patients (28.7%) as ‘probable BS’, 57 (28.2%) skin disease, 26 (12.9%) chronic pain syndrome, 14 (6.9%) eye disease, 11 (5.4%) spondyloarthropathy, 9 (4.5%) gastrointestinal disease, 7 (3.5%) neurological disease, 4 (2%) arthritis, 3 (1.5%) auto-inflammation, 3 (1.5%) connective tissue disease, 10 (5.0%) miscellaneous disease. HLA-B51 was positive in 55/132 (41.6%); 75/202 (37.1%) of the patients fulfilled the ICBD criteria. Conclusion In a low disease prevalence setting the straightforward application of the ICBD criteria may lead to overdiagnosis of BS. The differential diagnosis of BS is enormously broad. Clinicians should be aware that HLA-B51 positivity is still not considered as a diagnostic feature in BS.

Objective. Behçet's syndrome (BS) is a systemic vasculitis with heterogeneous clinical presentation and a relapsing disease course. The International Study Group (ISG) criteria are most often used for classification. A significant proportion of patients is classified as probable BS because they do not fulfil the criteria at initial presentation. The aim of this study is to explore clinical BS symptoms present at initial patient visit predictive of ISG criteria diagnosis during follow-up. Methods. Patients classified as probable BS at initial visit were included. Follow-up ISG status (defined as meeting criteria ISG+ vs. not meeting criteria ISG-) was abstracted from last visit. Univariable logistic regression was used to screen initial visit clinical features and symptoms with follow-up ISG status. All variables that passed screening at p<0.10 were included in the final multivariable model, which was then used to create a probability risk score. Results. 189 patients were included (169 from New York and 20 from Amsterdam). 71 (37.6%) patients were classified as ISG+ during follow-up. In the final model, presence of morning stiffness, genital ulcers, skin lesions, and eye disease were associated with increased odds of ISG+, adjusting for age, symptom duration and family history. This was used to create a probability risk score. Conclusion. Over a third of patients with suspected or probable BS developed new manifestations over time that led to classification as ISG+ BS. The presence of morning stiffness, genital ulcers, skin lesions and eye disease at initial visit were independently associated with significantly higher odds for developing ISG+ Behçet's during follow-up.