A comprehensive review of myelodysplastic syndrome patients with autoimmune diseases

Primary myelodysplastic syndromes (MDS) are heterogeneous clonal hemopoietic disorders clinically presented with a varying degree of peripheral cytopenias and an increased probability of leukemic evolution. A distinct subset of MDS patients manifests overt autoimmune-inflammatory manifestations, the underlying pathogenesis and prognostic significance of which still remain controversial. In this review we attempt to analyze clinical aspects of MDS-related rheumatoid disease, and discuss pathophysiologic associations between autoimmunity and distorted BM function in preleukemic states in light of recent findings, in vivo and in vitro. We further explore the potential of recent biological and molecular advances to forward therapeutic targeting against both autoimmune and malignant process.     

The duality of chemokines in heart failure

The failing human heart is a bustling network of intra- and inter-cellular signals and related processes attempting to coordinate a repair mechanism for the injured or diseased myocardium. While our understanding of signaling by mode of cytokines is well understood on a systemic level, we are only now coming to elucidate the role of cytokines in cardiac self-regulation. An increasing number of studies are showing now that cardiomyocytes themselves have not only the ability but also the mandate to produce signals, and play direct roles in how these signals are interpreted. One of the families of cytokines employed by distressed cardiac tissue are chemokines. By regulating the movement of pro-inflammatory cell types to sites of injury, we see now how the myocardium responds to stress. Herein we review the participation of these inflammatory mediators and explore the delicate balance between their protective roles and damaging functions.     

Risk factors for renal disease in systemic lupus erythematosus and their clinical implications

Lupus nephritis is one of the most common severe manifestations of systemic lupus erythematosus and is associated with significant morbidity and mortality. Genetic, ethnic and hormonal factors may influence the presence and severity of renal involvement and therefore affect the outcome and overall prognosis of patients. In this review, we will discuss the association of known lupus risk factors in developing renal disease and explore the recent literature to identify potential risk factors and their clinical implications in terms of diagnostic vigilance, management and prognosis.     

Psoriasis and lasting implications

Psoriasis is a chronic immunological disorder that affects the joints and skin. The disease is strongly correlated with genetic predisposition and environmental factors that can act as triggers of the innate and adaptive immune response. Once this immune response has begun many different signaling factors lead to inflammation and plaques which are visible throughout the body. As psoriasis progresses, it strongly affects the mental and physical health of the individual. This article reviews the different types of psoriasis, genetic and environmental triggers of psoriasis, the molecular progression of psoriasis, and current and future therapies.     

The rise of biosimilars: potential benefits and drawbacks in rheumatoid arthritis

Although biologic agents are effective in the treatment of rheumatoid arthritis, the high price of drugs and restricted health care budgets have restricted easy access to biologics. Eventually, the use of biologic disease-modifying antirheumatic drugs might be inversely associated with disease activity in countries with low gross domestic product. The EMA approved an infliximab biosimilar for the first time in September 2013. The first approval of a biosimilar monoclonal antibody by a major regulatory authority provided a global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars. Biosimilars with a highly similar quality and efficacy profile at an acceptable lower cost would significantly increase affordability of biologic disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis. Here, we will review the current status of first biosimilar antibody agent and the potential discussion points raised against biosimilars. In addition, the importance of awareness on biosimilars for stakeholders is discussed.     

Cytokine immunomodulation for the treatment of infectious diseases: lessons from primary immunodeficiencies

Traditionally, management of infectious diseases focuses on identification of the causative microbe and the use of pathogen-targeted therapy. With increasing antimicrobial resistance, novel approaches are required. One strategy is to modulate those natural host immune responses that critically mediate resistance to specific microbes. Clinically, this host-directed tactic could be used either alone or in combination with antimicrobial therapy. While conceptually attractive, there is potential concern that the pathways governing host resistance to pathogens in animal models may not extrapolate linearly to humans. Targeting these immune processes clinically may precipitate damaging, epiphenomenal responses. The field of Primary Immunodeficiencies focuses on the characterization of humans with inborn errors of immunity. These rare conditions permit the identification of those molecular and cellular processes that are central to human susceptibility to microbes. In efforts to compensate for defective host responses, this field has also provided a wealth of clinical experience in the effective use of cytokines to treat various active infections, while demonstrating their safety. In this review, we provide a historical perspective of the treatment of infectious diseases, evolving from a focus on the microbe, to an understanding of human immunity; we then outline the growing contribution of Primary Immunodeficiencies to the rational use of adjunctive cytokine immunotherapy in the management of infections.     

Ragweed allergy immunotherapy tablet MK-3641 (Ragwitek®) for the treatment of allergic rhinitis

ABSTRACT

Introduction: Allergic rhinitis (AR) is among the most common chronic conditions affecting both children and adults. It is the cause of significant morbidity from the symptoms and interference with sleep. It results in major impairment of performance both at school and at work. In the U.S. and certain parts of Europe, ragweed pollen is a major cause of seasonal AR. In 2014, the U.S. Food and Drug Administration (FDA) approved a sublingual ragweed tablet (MK-3641) for use in adults with ragweed-induced AR.

Areas covered: This paper will review the impact of ragweed-induced AR and available treatments including subcutaneous immunotherapy and studies with MK-3641. The principal search method was PubMed.

Expert commentary: One dosing finding, two 28-day safety and two 52-week safety and efficacy studies have been conducted with MK-3641. The 12-U (12μg Amb a 1) tablet was the most effective. Local application site reactions were common but usually not serious. Only one, non-serious systemic reaction was reported in four safety studies. MK-3641 is a safe and effective treatment for ragweed-pollen-induced AR when treatment is initiated ≥ 12 weeks prior to the onset of the ragweed pollen season.     

Golimumab in the treatment of psoriatic arthritis

ABSTRACT

Introduction: Psoriatic arthritis (PsA) is an inflammatory arthritis that can be aggressive and destructive, resulting in significant morbidity. While many new agents have been approved for the treatment of PsA over the past decade, TNF inhibitors (TNFi)remain an anchor treatment, in part based on extensive clinical experience. Recently, the TNFi golimumab was approved for intravenous use in PsA.

Areas covered: This expert review presents an overview of the currently available treatment options for PsA with a focus on the evidence from clinical trials supporting the use of golimumab in PsA. This information is placed in context with recent advances in the understanding of PsA pathogenesis and treatment.

Expert commentary: The rapid growth of treatment options available for PsA has brought the prospect of personalized treatment selection closer to reality but improved understanding of the domains of PsA and new biomarkers may be needed before such changes reach the clinic. Until patients who are most likely to benefit from a given agent can be identified and then treated accordingly, TNFi will likely remain a central option and their further development, such as the introduction of an intravenous form of golimumab, remains an important part of treatment improvement.     

Bridging past and present: Embodied intergenerational trauma and the implications for dance/movement therapy

This paper explores the role of the body in intergenerational transmission of trauma using examples of wartime sexual violence (WSV) during World War II in Germany. It is argued that traumatic memory held in the body is transmitted between generations in a similar fashion to how implicit body memory is passed on from body to body. In relationship, the body shapes subjectivity and intersubjectivity and therefore represents a vessel for transmission of trauma on a familial and cultural level. Silence and culture as source of perpetuation of trauma are taken into account. Furthermore, the severe long-term effects of rape, underlying body defences and relational consequences are outlined. Somatic implications for descendents of WSV survivors are unknown and require research. Dance/movement therapy is offered as a body-focused modality to help transform intergenerational trauma caused by WSV. Implications for further research in body-to-body transmission of trauma are highlighted.