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This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis. In six dermatomyositis cases, we found five solid forms of cancer and one Hodgkin's lymphoma in long-term remission. Among patients with cancer-associated dermatomyositis, three were positive for anti-TIF1γ/α, two for anti-Mi-2, and one for anti-MJ/NXP-2. The strongest positivity of anti-TIF1γ was seen in two active forms of cancer, and this antibody was either negative or positive at low titers in the absence of cancer or in the 7-year remission Hodgkin's lymphoma. Four out of twenty (20 %) patients with polymyositis had solid cancer, but no specific association with autoantibodies was identified; further, none of the four cases of antisynthetase syndrome had a history of cancer. No serum myositis-associated autoantibody was observed in control sera, resulting in positive predictive value 75 %, negative predictive value 78.5 %, sensitivity 50 %, specificity 92 %, and area under the ROC curve 0.7083 for the risk of paraneoplastic DM in anti-TIF1γ/α (+) patients. Myositis-specific autoantibodies can be identified thanks to the use of immunoprecipitation, and their association with cancer is particularly clear for anti-TIF1γ/α in dermatomyositis. This association should be evaluated in a prospective study by immunoprecipitation in clinical practice.

Summary The aim of this study is to investigate the effect of the native, citrullinated or carbamylated type II human collagen T cell- and B cell-epitopes on the adaptive immune response in rheumatoid arthritis (RA). Peripheral blood T and B cells obtained from a human leucocyte D4-related (antigen DR4− HLA-DR4)+ woman with early RA, her healthy monozygotic twin and an unrelated HLA-DR3+ woman with early RA were analysed for activation (CD154/CD69), apoptosis (annexin/7-aminoactinomycin), cytokine production [interferon (IFN)γ/interleukin (IL)−17/IL-4/IL-10/IL-6] and functional phenotype (CD45Ra/CCR7) after stimulation with the collagen native T cell epitope (T261-273), the K264 carbamylated T cell epitope (carT261–273), the native B cell epitope (B359–369) or the R360 citrullinated B cell epitope (citB359–369), and the combinations of these. The T cell memory compartment was activated by T cell epitopes in both discordant DR4+ twins, but not in the DR3+ RA. The collagen-specific activation of CD4+ T cells was induced with both the native and carbamylated T cell epitopes only in the RA twin. Both T cell epitopes also induced IL-17 production in the RA twin, but a greater IL-4 and IL-10 response in the healthy twin. The citrullinated B cell epitope, particularly when combined with the carbamylated T cell epitope, induced B cell activation and an increased IL-6/IL-10 ratio in the RA twin compared to a greater IL-10 production in the healthy twin. Our data suggest that circulating collagen-specific T and B cells are found in HLA-DR4+ subjects, but only RA activated cells express co-stimulatory molecules and produce proinflammatory cytokines. Carbamylation and citrullination further modulate the activation and cytokine polarization of T and B cells.

At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Stockholm, Sweden, rheumatology and dermatology trainees engaged in psoriasis or psoriatic arthritis research presented their work to meeting attendees in a trainees symposium. This report briefly reviews 6 oral presentations and 20 posters presented at the meeting.

Tattoos are defined as the introduction of exogenous pigments into the dermis in order to produce a permanent design. This process may occur unintentional or may be deliberately administered for cosmetic or medical reasons. Tattoos have been around for over 5000 years and over time have evolved to represent a common cosmetic practice worldwide. Currently, adverse reactions are relatively rare and generally unpredictable and predominantly include immune-mediated reactions and skin infections. Along with better healthcare standards and more stringent public health mandates such as the provision of disposable needles, major infectious complications related to hepatitis and human retroviral infections have decreased significantly. When they do occur, skin infections are most frequently associated with Staphylococcus aureus or Streptococcus pyogenes. The aim of this study is to review the types and rates of medical complications of permanent tattoos. PubMed search and search dates were open ended. Acute local inflammation is the most common complication, but infections, allergic contact dermatitis, and other inflammatory or immune responses that are not well-characterized may occur. As many patients with immune reactions to tattoos do not react on skin or patch testing, it is postulated that the antigens contained in dyes or pigments are such small molecules that they need to be haptenized in order to become immunogenic. Red ink is associated more frequently with long-term reactions, including granulomatous and pseudolymphomatous phenomena or morphea-like lesions and vasculitis. Exacerbation of preexisting psoriasis, atopic dermatitis, and pyoderma gangrenosum may occur after tattooing. There is no well-defined association between cancer and tattoos. The treatment of tattoo-related complications may include local destructive measures (cryotherapy, electro-surgery, dermabrasion, chemical destruction, ablative laser destruction), surgical excision, and thermolysis of the pigment using Q-switched laser therapy.

Purpose Nailfold videocapillaroscopy (NVC) identifies the microvascular hallmarks of systemic sclerosis (SSc) and vascular endothelial growth factor (VEGF) and may play a pivotal role in the associated vasculopathy. The aim of the present study was to compare NVC alterations with clinical subsets, internal organ involvement, and serum VEGF levels in a cohort of selected SSc cases. Methods We studied 44 patients with SSc who were evaluated within 3 months from enrollment by NVC, skin score, severity index, pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography, pulmonary high-resolution computed tomography (HRCT), gastroesophageal (GE) endoscopy or manometry or X-ray, and serum autoantibodies. Serum VEGF-A levels were determined by ELISA in 72 SSc patients and 31 healthy controls. Results Giant capillaries were inversely correlated with age (p = 0.034, r = −0.34) and to the extent of reticular pattern at HRCT (p = 0.04, r = −0.5). Avascular areas were directly correlated with capillaroscopy skin ulcer risk index (CSURI) (p = 0.006, r = +0.4) and severity index (p = 0.004, r = +0.5). The mean capillary density was directly correlated to the ulcer number (p = 0.02, r = +0.4) and to DLCO/alveolar volume (p = 0.02, r = +0.4) and inversely correlated with severity index (p = 0.01, r = −0.4) and skin score (p = 0.02, r = −0.4). Serum VEGF levels were higher in the SSc population vs controls (p = 0.03) and inversely correlated with DLCO (p = 0.01, r =−0.4) and directly with ground-glass and reticular pattern at HRCT (p = 0.04, r = +0.4 for both). Conclusions Our data suggest the importance of NVC not only for the diagnosis, but also for the global evaluation of SSc patients. Of note, serum VEGF levels may act as a biomarker of interstitial lung involvement.

Psoriatic arthritis (PsA) is characterized by chronic inflammation of peripheral joints and axial skeleton, associated with a strong genetic background. Clinics include enthesitis or dactylitis and extra-articular involvement as uveitis or inflammatory bowel disease, while treatment options range from nonsteroidal anti-inflammatory drugs (NSAIDs) to biologics, targeting TNF α or Th17. No serum autoantibody is associated with PsA, while other biomarkers have been proposed for early diagnosis or to predict treatment response. To better discuss this area of growing interest we performed a systematic review of the literature on biomarkers in PsA. Our research retrieved 408 papers, and 38 were included in the analysis. Based on the available literature, we draw some recommendations for the use of biomarkers in the management of patients with PsA.

Autoimmune diseases are comprehensive models of complex conditions in which an individual’s genetic susceptibility is necessary but not sufficient to explain disease onset, perpetuation, and severity. This is well represented by the variable but invariably incomplete concordance rates for all autoimmune diseases in monozygotic twins. In the broad group of autoimmune diseases, heritability ranges between 0.008 and 1 with median values of approximately 0.60. A complementary term coined “environmentability” may well represent the environmental influence on the individual phenotype and can include dietary habits, chemicals, or hygienic conditions via several molecular and epigenetic mechanisms. Numerous environmental factors have been proposed for systemic and organ-specific autoimmune diseases. The National Institute of Environmental Health Sciences (NIEHS) convened an expert panel workshop to review the body of literature examining the role of the environment in the development of autoimmune disease and to identify conclusions, certainties, and critical knowledge gaps in this area. The results of the workshop and the literature illustrate that several kinds of epidemiological, mechanistic, and model evidence support specific chemical and physical factors as well as infectious agents.

Spondyloarthritidies represent a group of conditions affecting the axial and peripheral muscoloskeletal apparatus and are often associated with psoriasis, infections, and inflammatory bowel diseases. Other diseases included in this category are psoriatic arthritis, ankylosing spondylitis, and enteropathic arthritis. Reactive arthritis is an elusive spondyloarthritis, commonly occurring 1 to 3 weeks after a digestive or a genitourinary tract infection, in which microorganisms do not infect the joint directly. Reactive arthritis is classically characterized by large-joint arthritis, urethritis in men and cervicitis in women, and eye inflammation (usually conjunctivitis or uveitis) but encompasses numerous other symptoms and signs, including manifestations of dermatologic interest such as keratoderma blenorrhagicum and circinate balanitis. The diagnosis of reactive arthritis is clinical, and the infectious agent cannot always be identified due to disease latency after the infection. Most cases are self-limiting, but reactive arthritis may become chronic in 30% of cases. Treatment options include anti-inflammatory drugs, steroids, and sulfasalazine; biologic agents, such as tumor necrosis factor α (TNF-α) blockers, have been recently used, but there are only a few randomized clinical trials on the treatment of reactive arthritis. The effectiveness of antimicrobials needs further evaluation.

Eye involvement represents a common finding in patients with systemic autoimmune diseases, particularly rheumatoid arthritis, Sjogren syndrome, seronegative spondyloarthropathy, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The eye is a privileged immune site but commensal bacteria are found on the ocular surface. The eye injury may be inflammatory, vascular or infectious, as well as iatrogenic, as in the case of hydroxychloroquine, chloroquine, corticosteroids, and bisphosphonates. Manifestations may affect different components of the eye, with episcleritis involving the episclera, a thin layer of tissue covering the sclera; scleritis being an inflammation of the sclera potentially leading to blindness; keratitis, referring to corneal inflammation frequently associated with scleritis; and uveitis as the inflammation of the uvea, including the iris, ciliary body, and choroid, subdivided into anterior, posterior, or panuveitis. As blindness may result from the eye involvement, clinicians should be aware of the possible manifestations and their management also independent of the ophthalmologist opinion as the therapeutic approach generally points to the underlying diseases. In some cases, the eye involvement may have a diagnostic implication, as for episcleritis in rheumatoid arthritis, or acute anterior uveitis in seronegative spondyloarthritis. Nonetheless, some conditions lack specificity, as in the case of dry eye which affects nearly 30 % of the general population. The aim of this review is to elucidate to non-ophthalmologists the major ocular complications of rheumatic diseases and their specific management and treatment options.

Gastrointestinal symptoms are common complaints during pregnancy and are generally of mild intensity. Nausea and vomiting and related repulsion toward foods in the first trimester of pregnancy might represent also an intricate evolutionary protective mechanism, an adaptation to protect the embryo from phytotoxins and other environmental hazards. Indeed, 20–30 % of the adult population in the USA and Europe suffer from adverse reactions to food, and only in one out of ten cases these reactions are caused by IgE-mediated allergic mechanisms; all other forms are broadly considered food antigen hypersensitivity. The percentage of women who experience heartburn symptoms, at any time during pregnancy, range from 30 to 80 %, being highest in the third trimester. These symptoms should encourage changes as regards composition of meals (check for food hypersensitivity), time from meal to bedtime, moderate exercise after eating, supported by short therapies with alginate-based formulations. Constipation in pregnant women is the most underreported disturbance during the second and third trimester commonly interpreted as a simple progesterone-related symptom. Indeed, fiber intake is usually well below the standard recommendations in the daily health plate and thus is frequently forgotten by healthcare providers. The lack of prebiotics and hydrophilic fibers is frequently associated with subclinical inflammatory bowel disease thus translating a latent dysfunction into a clinical symptom. During pregnancy it may be difficult to assess if a specific symptom is an expression of a gastrointestinal disease or if it is caused by the pregnancy itself that simply adds on the preexisting subclinical gastrointestinal abnormalities. The aim of every healthcare provider is to identify gastrointestinal symptoms during pregnancy, refuse the idea that all of them are simple “normal” side effects of being pregnant, and, through them, identify prepregnancy subclinical conditions and to address the best treatment options, focusing particularly on nutritional mechanisms.

As our understanding of the pathogenesis of autoimmune diseases is growing, new therapies are being developed to target disease-specific pathways. Since the introduction of etanercept in 1998, several biotechnological agents have been developed, most of them indicated in the treatment of rheumatoid arthritis, but also psoriatic arthritis. Most currently available molecules target TNF-alfa with different strategies (i.e., etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol), IL-6 (tocilizumab), CTLA-4 (abatacept), and B cells (rituximab, belimumab) as they are key mediators in the cascade of inflammation. Further, small molecules have been recently developed to target intracellular signaling, such as Janus Kinases for tofacitinib, the first FDA-approved small molecule for rheumatoid arthritis. Most novel treatments are being developed for arthritis with specific differences between rheumatoid and psoriatic arthritis, as well as for systemic lupus erythematosus, following the approval of belimumab. Finally, biologic therapies are effective also in gout, mainly targeting interleukin-1 to block the inflammasome. This review article describes the new and upcoming treatment options for rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and gout to dissect what we should be aware of when discussing these new and promising molecules.

Background The serum anti-phospholipid antibody (aPLs) prevalence in the general population and the association with cardiovascular disease and risk factors remain unclear. Objectives To test serum samples from a population study for aPLs and determine the presence of cardiovascular and metabolic comorbidities in a Northern Italian city. Methods We performed a cross-sectional study on 1712 adult subjects (median age 47 year-old, interquartile range 37–61, 49.8% women), randomly enrolled in 2010 from the voting lists of a 32.000-population city in the Lombardia region. All subjects completed a questionnaire for medical history and ongoing/past medications and underwent physical examination and abdomen and carotid ultrasound. Anti-cardiolipin (aCL), anti-beta2 glycoprotein I (aGPI), anti-phosphatidylserine-prothrombin (aSP) IgG, IgM, and IgA antibodies were tested in all subjects by ELISA. Results At least one aPL was positive in 258 (15.1%), at high titer in 56 (3.3%) subjects; 35 (2%) were positive for two or more aPL, 15 (0.9%) at high titer. Serum aCL were positive in 26 (1.5%) subjects, at high titer in 17 (1%), without additional aPL in 2; IgG in 15 (0.9%; at high titer in 11), IgM in 18 (1.1%, at high titer in 10), IgA at high titer in 4 (0.2%). Serum aGPI were positive in 73 (4.3%) subjects, at high titer in 48 (2.8%), without additional aPL in 4; IgG in 20 (1.2%; at high titer in 3), IgM in 28 (1.6%, at high titer in 6), IgA in 35 (2%, at high titer in 12). Serum aSP were positive in 201 (11.7%) subjects, at high titer in 29 (1.7%), without additional aPL in 167; IgG in 157 (9.2%, at high titer in 19), IgM in 65 (3.8%, at high titer in 12). Women represented 53.1% of aPL positive subjects, with higher incidence for aGPI, especially IgA, and aSP. Among aPL positive subjects, there were 10 cases of acute myocardial infarction, 7 strokes, 17 peripheral arteriopathy and 22 increased intimal-medial-thickness. Positivity for aPL was associated with older age, particularly for aGPI and aSP, while high-titer aCL IgG and aSP IgG were associated with tobacco smoking. Hypertension and hypercholesterolemia were significantly associated to aGPI IgG and IgM positivity, respectively. Hyperhomocystinemia was significantly associated with high titer multiple aPLs. Hyperuricemia was associated with aSP IgG positivity. Subjects with positive aPL had significantly higher frequency of thyroid disease (p=0.02 for high titer), peripheral arteriopathy (crude odds ratio –OR- 2; 95% confidence interval –CI- 1.2–3.6; isolated aCL crude OR 25.1; 95% CI 1.6–405.4), myocardial infarction (isolated aCL crude OR 28.5; 95%CI 1.8–460.5). Importantly, adjusted ORs for cardiovascular risk factors were not statistically significant. Conclusions We confirm that serum aPL are common in the general population, particularly at older age and possibly in association with smoking. Serum aPL is associated with common cardiovascular risk factors and specific events, however this latter effect needs to be clarified in the follow-up study to determine the real impact of aPL on the risk of cardiovascular events. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) susceptibility is linked to HLA DR4 and DR1. T cells in RA recognize the DR4/DR1-restricted epitope 261-273 of the human type II collagen, whereas B cells recognize the epitope 359-369. These epitopes can undergo post-translational modifications such as carbamylation and citrullination and both processes are involved in RA pathogenesis. Objectives To investigate the role of B and T cell epitopes and their post-translational modifications on the adaptive immune response in the unique model of DR4 carrying monozygotic twins discordant for RA. Methods PBMCs were obtained from a treatment-naive HLA-DR4 positive woman with early RA (rheumatoid factor +, anti-CCP -, elevated CRP, bilateral wrist arthritis for 3 months) and from her healthy monozygotic twin sister (autoantibody-negative, normal CRP). Cells were cultured for 3 days with the native form of the collagen T epitope, its K264 carbamylated form (homocitT), the native form of the collagen B epitope, its R360 citrullinated form (citB) or a combination of the native and modified epitopes. After the stimulation, cells were analyzed by flow cytometry for activation, apoptosis, and cytokine polarization. Results The activation of CD4 T cells was induced only with the modified B and T epitope stimulation in the RA twin (CD4+CD154+ in RA vs healthy; unstimulated: 1 vs 0.4%; T: 0.9 vs 1.6%; homocitT: 1.5 vs 0.7; B: 1 vs 0.6%; citB: 1.7 vs 0.1%, T + B: 0,5 vs 0,3%; homocitT + citB: 0,9 vs 0,4%). The antigen-activated CD4 T cells in the RA twin were significantly less apoptotic compared to unstimulated cells and the healthy twin (RA vs healthy; unstimulated: 37.5 vs 40%; T: 25 vs 24.1%; homocitT: 17 vs 50%; B: 30.8 vs 28%; citB: 13.9 vs 83.3%; T + B: 12.3 vs 63.6%; homocitT + citB: 19 vs 50%). Opposite from what observed in RA, the healthy twin manifested a higher increase in Th2 cells (CD4+CD154+IL4+ in RA vs healthy; unstimulated: 1.7 vs 2.1%; T: 2.9 vs 5.7%; homocitT: 3.6 vs 5.8%; T + B: 4 vs 4.9%; homocitT + citB: 3.9 vs 2.9%) compared to Th17 cells (CD4+CD154+IL17+ in RA vs healthy; unstimulated: 2.7 vs 1.7%; T: 4.1 vs 3.1%; homocitT: 4.5 vs 3.2%; T + B: 4.8 vs 3.5%; homocitT + citB: 5.5 vs 3%). In the healthy twin the Th2 increase was observed also in the antigen-activated CD8 T cells while B cell activation increased after different stimulations, but in all conditions activated B cells were apoptotic in 80% of the cases. Cytokine B cell production was not substantially altered with the epitope stimulations in the RA twin, while in the healthy twin there was a general increase in all cytokines. Conclusions Our data obtained in the unique model of discordant monozygotic twins suggest that the exposure of collagen self-epitopes to lympocytes induces changes with pathogenic or protective effects that appear to be independent on DR4 and on post-translational antigen modifications. Further, this is associated with a greater Th17 shift in the antigen-activated CD4 T cells and with their enhanced resistance to spontaneous apoptosis in RA, while a greater Th2 shift is observed in the healthy twin. Carbamylation and citrullination of collagen epitopes may promote the activation of CD4 T cells. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4278