Heparin challenge test in patients undergoing cardiac surgery: dealing with heparin allergy.

: A history of heparin hypersensitivity in patients undergoing cardiopulmonary bypass surgery poses the dilemma of which anticoagulant to use. Here, we report the successful use of a heparin challenge test in a 66-year-old female candidate for coronary artery bypass graft surgery with a past medical history of enoxaparin type I hypersensitivity after pulmonary embolism. Challenge and desensitization protocols are effectively used for essential antibiotics in patients with severe infections and/or allergies, or patients with aspirin intolerance requiring revascularization for coronary disease. A successful use of desensitization protocols to unfractionated heparin has been previously described in four patients undergoing cardiac surgery with various schemes. However, our case report indicates that a challenge test may also offer a quick, safe and effective approach in patients with a history of hypersensitivity reactions to heparin with inconclusive diagnostic tests and/or whenever the use of alternative heparins is tricky.

Bronchiolitis obliterans organizing pneumonia in patients with autoimmune rheumatic diseases.

Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by buds of granulation tissue within lung distal airspaces. The diagnosis requires the histopathologic evidence of organizing pneumonia along with a suggestive clinical and radiographic pattern. This disorder is characterized by a good response to corticosteroids and an excellent prognosis. It can occur in association with a broad spectrum of clinical conditions or can be isolated, in this last case named cryptogenic organizing pneumonia. We searched for BOOP in patients with autoimmune rheumatic diseases (ARD) in the literature, and we found 32 well-documented cases. We reported here demographic features, manifestations, treatment and outcome of patients with BOOP associated with ARD. Notably, BOOP can be the presenting feature in some patients with ARD; thus, a close follow-up of patients with BOOP is recommended.

Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases.

Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per µl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.

Predictors of maternal and fetal complications in SLE patients: a prospective study.

The aim of the study was to evaluate predictors of disease flares during pregnancy and obstetric and fetal complications in a cohort of systemic lupus erythematosus (SLE) patients. One hundred and thirty-two pregnancies in 96 SLE patients were prospectively followed by monthly clinical and laboratory evaluations. Predictors of lupus flares, fetal and obstetric complications during pregnancy were identified performing stepwise logistic regression analysis. Maternal lupus flares occurred in 57 % of pregnancies and were being best predicted by the number of flares before conception. Manifestations during flares were best predicted by the same features occurred before conception: dermatological flares by skin rash, renal flares by nephritis, and hematological flares by hematological abnormalities. There were 110 live births and 22 fetal losses. Among live newborns, 22 % were premature. Fetal loss was best predicted by hypertension at conception; miscarriages by the amount of steroids taken during the last year before conception; stillbirth by the number of flares during the last year before conception; preterm birth by the coexistence of anti-phospholipid antibody syndrome and anti-double-stranded DNA antibody levels before conception; premature rupture of membranes by high ECLAM score during the 6 months before conception, small for gestation age by hypertension at conception; and preeclampsia by positive lupus anticoagulant. Some independent predictors of lupus flares and fetal and obstetric complications were identified, which can help the risk assessment of pregnancy in SLE patients.

Vitamin D: a new anti-infective agent?

Before the antibiotic era, treatment of tuberculosis patients was restricted to sun exposure in sanatoria. Years later, it was found that 1,25-dihydroxyvitamin D3 stimulates production of cathelicidins, a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes. Cathelicidins serve a critical role in innate immune defense, which plays an important role in the suppression of Mycobacterium infections and other pathogens. It is believed that the increased incidence of the common cold and pneumonia during winter is related, in part, to decreased exposure to sunlight, resulting in a decreased synthesis of 1,25-dihydroxyvitamin D3. An association has been established between low levels of vitamin D and upper respiratory and enteric infections, pneumonia, otitis media, Clostridium infections, vaginosis, urinary tract infections, sepsis, influenza, dengue, hepatitis B, hepatitis C, and HIV infections. Accumulating evidence suggests that 1,25-dihydroxyvitamin D3 exerts protective effects during infections by upregulating the expression of cathelicidin and ß-defensin 2 in phagocytes and epithelial cells. Vitamin D may be acting as a panaceal antibiotic agent and thus may be useful as an adjuvant therapy in diverse infections.

Myositis autoantibodies and clinical phenotypes.

Autoantibodies are powerful diagnostic tools in idiopathic inflammatory myopathies, especially for confirming the diagnosis and contributing to the definition of disease subsets. They are present in over 80 % of patients with immuno-mediated myositis and directed towards ubiquitously expressed intracellular complexes. Most of these autoantibodies are reported also in other autoimmune diseases, while some are considered myositis-specific. Myositis autoantibodies are traditionally categorized in two groups, based on their diagnostic accuracy: myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA), the latter mostly occurring in myositis-overlap syndromes. Besides the so-called traditional MSA, including anti-synthetases, anti-SRP and anti-Mi-2 antibodies, additional newly conceived immune targets have been recently identified, mostly in patients with severe forms of dermatomyositis or necrotizing myopathy. They mainly encompass enzymatic proteins essentially involved in the regulation of gene transcription or post-translational modifications, i.e., TIF1-γ, NXP-2, MDA5, SAE and HMGCR. Among the MAA, anti-PM/Scl and anti-Ku characterize an overlap polydermatomyositis/systemic sclerosis syndrome with severe interstitial lung involvement.

Autoantibodies in polymyositis and dermatomyositis.

Inflammatory myopathies are a group of acquired diseases, characterized by immunoflogistic processes primarily involving the skeletal muscle. According to recent classification criteria, four major diseases have been identified: polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myositis (NAM). Autoantibodies can be found in the sera of most patients with myositis. Myositis-specific autoantibodies (MSAs) are markers of very specific disease entities within the spectrum of myositis, and target proteins involved in key processes of protein synthesis. Myositis autoantigens comprise the well-defined aminoacyl-tRNA synthetases, the Mi-2 helicase/histone deacetylase protein complex, and the signal recognition particle (SRP) ribonucleoprotein, together with novel targets such as TIF1-γ, MDA5, NXP2, SAE, and HMGCR. Recent studies suggest that autoantigens drive a B cell antigen-specific immune response in muscles. Interestingly, an increased expression of Jo-1 and Mi-2 in regenerating fibers in muscle biopsies from PM and DM patients compared to normal was demonstrated. Myositis autoantigen up-regulation was observed in neoplastic tissues, thus representing a potential link between cancer and autoimmunity in myositis. Non-immunological mechanisms seem to participate to the pathogenesis of inflammatory myopathies; induction of endoplasmic reticulum stress response in response to abnormal muscle regeneration and inflammation has recently been reported in patients with myositis. This review article provides an update of new emerging insights about the clinical and pathophysiologic role of principal autoantibodies in myositis.

Rituximab in refractory idiopathic inflammatory myopathies and antisynthetase syndrome: personal experience and review of the literature.

In this paper, we report our experience with the use of rituximab (RTX) in the treatment of refractory idiopathic inflammatory myopathies (IIM) and review the literature on this topic. Six adult patients (5 female, 1 male) with active IIM, as defined by persistent proximal muscle weakness, elevated serum muscle enzymes, muscle magnetic resonance imaging, electromyographic and histological abnormalities, refractory to at least one immunosuppressant, including methotrexate, were treated with RTX (1,000 mg twice, 2 weeks apart). Patients were regularly followed up for serial assessment of muscle strength by manual muscle test 8 and creatine kinase serum levels. Three patients were affected with polymyositis (PM) and three with anti-t-RNA synthetase syndrome (ASS). A complete B-cell depletion was observed in all patients by 3 months after RTX. A significant clinical improvement was observed in 5 out of 6 cases 6 months after RTX. Only one mild infusion reaction and one case of Herpes zoster infection were observed. A review of the literature to find all the available cases of refractory patients affected with IIM from 1980 to 2012, using the PubMed database, was performed. We were able to find 27 papers, 18 on PM and dermatomyositis and 9 on ASS, including 88 and 40 patients, respectively. A significant improvement was observed in 80% of patients overall and the drug was well tolerated in the majority of cases. In conclusion, RTX can be considered a therapeutic option in refractory IIM.