Raquel Faria

Fetal outcome in autoimmune diseases

The impact on fetal outcome in women with autoimmune diseases is a result of a several conditions. Fetal success depends on early immunological changes in the mother, which rely in modifications of the innate and adaptative immune system, inducing tolerance to the semi-allogenic fetus. Others crucial factors are maternal disease activity, severity of organ damage, circulating antibodies, and drug treatment. Although fetal outcome is becoming better still it has a worse prognosis in comparison with healthy women. Diseases like antiphospholipid syndrome, systemic lupus erythematosus and vasculitis have the higher risk while rheumatoid arthritis and spondiloarthopaties the least. In the majority of the diseases the risk of poor fetal outcome directly correlates with the activity of disease. While there are no pathognomonic autoantibodies for fetal outcome, antiphospholipid and anti-thyroid antibodies have been implicated in unsuccessful pregnancies and anti-Ro and, to a lesser extent, anti-La antibodies may result in neonatal lupus syndrome congenital heart block. There is increasingly the hope that fetal outcome will be good if the disease is well controlled prior to pregnancy, and with a specialized interdisciplinary support.

Systemic sclerosis refractory disease: from the skin to the heart.

Systemic sclerosis or scleroderma (SSc) is an heterogeneous disease involving the connective tissue and the microvasculature with fibrosis and vascular occlusion. It is difficult to define refractory SSc once it is itself a paradigm of a refractory condition: there is no evidence of when to act to stop the progression to fibrosis and irreversible microvascular damage. There is no definition of refractory disease in SSc and to propose a definition we used mainly the Medsger severity index and the EULAR 2009 treatment recommendations from the skin to the heart through peripheral vascular, musculoskeletal, gastrointestinal, renal, pulmonary hypertension and interstitial lung disease. We used some clinical setting reflecting the different reasoning when there is probable refractory disease and finally we briefly pointed out some available treatment options to refractory disease. With this reflection, we would like to open paths to a broader discussion.

Safety of Anti-TNF Therapies in Immune-Mediated Inflammatory Diseases: Focus on Infections and Malignancy.

Preclinical Research

MDMA in Adolescent Male Rats

Abstract:  Long‐term behavioral consequences of the neurotoxicity produced by 3,4‐methylenedioxymethamphetamine (MDMA) in the adolescent rat are still mostly unknown. Here, adolescent male rats (postnatal day 45 PND [45]) were exposed to 10 mg/kg of MDMA, intraperitoneally, every 2 h for 6 h. Controls were given 0.9% saline in the same protocol. Ten days after exposure, the behavioral effects of MDMA were assessed in the elevated plus‐maze (n= 6 per group). After behavioral testing, animals were sacrificed and the amygdalae were dissected and processed for HPLC determination of dopamine (DA), serotonin (5‐HT), and metabolites. Results showed a significant decrease in the 5‐HT content (P < 0.05), but no significant alterations in DA or its metabolites. Behavioral observation in the elevated plus‐maze showed a decreased number of entries in the unprotected arms (P < 0.05), which were correlated to the number of entries and time spent in the central platform. Rearing was also decreased (P < 0.05). No differences were observed in head dips, grooming, or number of entries in the protected arms of the apparatus. Therefore, we conclude that, as in the adult rat, exposure to MDMA in the adolescent rat is associated to long‐term depletion of the 5‐HT content and increased anxiety‐like behavior.

Ustekinumab: The "New Kid on the Block" in the Treatment of Psoriatic Arthritis.

Preclinical Research

Infection and Malignancy Risk in Patients Treated with TNF Inhibitors for Immune-Mediated Inflammatory Diseases

BACKGROUND Infectious and malignant events are responsible for morbidity and mortality in patients with Immune-Mediated Inflammatory Diseases (IMIDs). Anti-tumor necrosis factor (Anti-TNF) agents appear to have an impact, however the individual effect of these agents in the different conditions is still unclear. OBJECTIVE The aim of this study is to estimate the Incidence Rates (IR) of infections and malignancies in patients treated with anti-TNFs across different IMIDs, as well as potential risk factors. METHODS IR/100 patient-years were evaluated in adult patients treated for any IMID with an anti-TNF between January 2000 and December 2014. Predictors were tested with bivariate and multivariate statistical analysis. RESULTS The IR/100 patient-years of serious infections was 4.02 (95% CI 3.20-5.04) with significant differences across IMIDs and anti-TNF agents. The most frequent site of serious infection was the gastrointestinal system. Five cases [IR of 0.28 (95% CI 0.12-0.66) /100 patient-years] of tuberculosis were diagnosed, exclusively in patients treated with monoclonal antibodies. Three (60%) of those were extrapulmonary. The IR/100 patient-years of malignancy was 1.75 (95% CI 1.24-2-47). CONCLUSION There is significant variability in the IR of infections across indications and agents. Thus, physicians should be thoughtful when generalizing data from literature regarding the use of an anti-TNF agent in a specific IMID. Further studies are necessary to clear aspects regarding the safety of individual anti-TNF biologics and to clarify their impact in the different IMIDs.

Lucky to meet RS3PE

We present a florid case of remitting seronegative symmetrical synovitis with pitting edema that was actually a paraneoplastic syndrome of an asymptomatic undiagnosed adenosquamous lung cell carcinoma. The arthritis led to a screening for lung cancer and an early enough diagnosis for a curative intervention.

Invasive pneumococcal disease complicated by cerebral vasculitis, transient diabetes insipidus and spondylodiscitis

Invasive pneumococcal disease (IPD) is a potential life-threatening situation that requires immediate recognition and treatment. Cerebrovascular complications are uncommon and have been reported less frequently in adults than in children. We report a case of 59-year-old man with IPD complicated by cerebral vasculitis, transient central diabetes insipidus and spondylodiscitis. Each of these complications is rare and needs specific approach. Their association is even rarer and to the best of our knowledge this is the first case reported.

Opportunistic Infections and Autoimmune Diseases

Abstract Infections are common causes of morbidity and mortality in autoimmune diseases, and opportunistic infections are the tip of this problem, emerging as one main causes of morbidity in these patients. Opportunistic infections are defined as infection caused by non-pathogenic microorganisms which become pathogenic when the immune system is impaired by an unrelated disease. Use of immunosuppressors in the treatment of autoimmune diseases has increased opportunistic infections related to therapy, although disease itself and comorbilities can also be factors affecting susceptibility. Some opportunistic infections are more common and related to specific immunological deficits, such as Mycobacterium tuberculosis and anti-TNF biologic therapies, progressive multifocal leukoencephalopathy and natalizumab or rituximab exposure. Herpes zoster is one of the most common opportunistic infections related to immunosuppression. The distinction between infection and a flare-up of disease can be difficult to distinguish or can coexist, and therefore poses a real challenge to physicians.

She could no longer wear a hat: Paget's disease

In the 1980s, a woman in her 40s started noticing that her hats were not fitting. She also reported suffering from headache, hearing loss and tinnitus. Alkaline phosphatase and urinary hydroxyproline levels were raised in the beginning. She was diagnosed with Pagets disease. She was started on calcitonin treatment and when available, a few years later, bisphosphonates.1 Pagets disease is a localised disorder of bone remodelling that typically begins with excessive bone resorption followed by an increase in bone formation. …