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Journal: Expert review of clinical immunology

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Psoriasis has a profound impact on patients' lives, but adherence to topical treatment of psoriasis is still poor. Biologic treatment has revolutionized the management of psoriasis, but adherence to treatment may still be a barrier for some patients. Areas covered: A PubMed search was conducted in August 2017 using the terms “biologics psoriasis adherence” and “biologics psoriasis survival.” Additional articles were obtained by perusing the references of articles identified in the original PubMed search. Articles that did not specifically mention “survival,” “adherence,” or “persistence” were not included. We review the measures used to assess adherence to biologics for psoriasis and the factors impacting drug survival and adherence rates for biologics in psoriasis. Expert commentary: Drug survival and adherence rates for biologic therapy is less than ideal but may be modifiable. Means that may improve adherence and drug survival include individualized choice of biologic and providing additional support for patients who are at increased risk for prematurely stopping treatment.

Concepts: Illness, Impact event, PubMed

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The Tropics is very appropriate to test the hypotheses raised to explain the increasing trends of allergy and other inflammatory diseases worldwide. The absence of parasite infection as a possible cause of the increase of allergic diseases was proposed by J. Gerrard a long time ago; however, the idea that helminth infections, which induce a strong Th2 could reduce allergy symptoms seems counterintuitive; but the fact is that they have a dual effect: they increase the Th2 responses but also exert immunosuppression and both effects influence the symptoms of allergy. Basic experimentation has provided valuable information about the mechanisms of allergic inflammation and more recently, about its control by helminth induced immunomodulation, discovering helminth molecules with anti-inflammatory properties that are meant to replace the live helminth therapeutic approaches. The immunosuppressive power of helminths makes them excellent candidates to be considered in the hygiene hypotheses. Future comprehensive studies evaluating simultaneously the role of microbial infections, helminth infections, microbiota, pollution and biodiversity will help to elucidate the causes of the increasing trends of allergic disorders. Doing this in the tropics, where all these variables are still present could be difficult but no doubt that will be more informative.

Concepts: Immunology, Intestinal parasite, Asthma, Infection, Anti-inflammatory, Inflammation, Allergy, Immune system

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Although multiple sclerosis (MS) remains incurable, interferon beta (IFNβ) has been at the forefront of treatment for many years. Different formulations of IFNβ allow for different levels of exposure: low-dose/frequency with some agents, and high-dose/frequency with others. Areas covered: This review article discusses existing and emerging efficacy and safety data for IFNβ in MS. Clinical evidence of IFNβ efficacy has been generated and accumulated over many decades. During this time, key clinical trials have demonstrated the benefits of high-dose and/or high-frequency dosing of IFNβ-1a or β-1b, compared with lower levels of exposure, on outcome measures such as relapse rates, disability progression, disease progression and magnetic resonance imaging lesion outcomes. IFNβ therapy is well tolerated and has one of the best characterized safety profiles of all first line therapies. The overall severity of adverse events (AEs) does not appear to be affected by different IFNβ exposures. Typical AEs that patients may experience with IFNβ are mild, reversible and manageable. Expert Commentary: IFNβ is one of the best characterized treatments for MS, with a large body of clinical and real-world evidence supporting the risk-benefit profile. High-dose/frequency regimens may provide better long-term outcomes.

Concepts: Avicenna, Interferon beta-1a, Interferon, Adverse event, Therapy, Clinical trial, Magnetic resonance imaging, Multiple sclerosis

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Interstitial lung disease (ILD) is the most serious complication of systemic sclerosis (SSc). There is no accepted guidance as to which clinical, radiological or physiological thresholds should prompt initiation or changes in treatment. Furthermore, some patients with extensive disease remain stable without the need for intervention whilst others with limited disease at the outset, experience a precipitous decline. Areas Covered: In this article, evidence for the integration of a number of disease-specific and patient-related domains are discussed and proposed. Introduction and maintenance of therapy requires a nuanced understanding of these factors and is crucial when weighing up the risks and benefits of immunomodulation. The evidence for the existing treatment modalities is discussed and the future directions for management of patients with SSc-ILD, which may include antifibrotic or biologic therapy, are explored. Expert Commentary: In the management of SSc-ILD, a multidisciplinary team approach which integrates physiology and radiology with the patient at the centre of the process is crucial for effective management and provision of the best outcomes.

Concepts: Rheumatology, Pulmonology, Patient, Avicenna, Systemic scleroderma, Cancer, Scleroderma, Physiology

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Hypereosinophilic syndromes (HES) encompass a group of disorders defined by sustained peripheral blood hypereosinophilia >1500/mm3 and evidence of eosinophilia-associated organ impairment. Approximately 10% of HES patients may harbor a cryptic deletion on chromosome 4 leading to formation of the FIP1L1-PDGFRA (F/P) fusion gene; these patients are diagnosed as F/P-mutated myeloid/lymphoid neoplasms with eosinophilia (MLN-eo). The results of numerous studies on the efficacy of tyrosine kinase inhibitor, imatinib mesylate (IM), in patients with HES have been published in the literature. Areas covered: This review discusses the results of IM treatment in HES depending on mutation status. The literature on IM therapy in HES by searching PubMed for the terms “imatinib mesylate”, “hypereosinophilic syndromes” and “FIP1L1-PDGFRA” has been reviewed. The author’s publications as well as his own experience in the field of HES treatment remain a significant contribution to this work. Expert Commentary: Imatinib mesylate, a first generation tyrosine kinase inhibitor, has revolutionized the therapeutic approach to patients with hypereosinophilic syndromes and detectable F/P fusion gene. The response to IM in F/P-mutated MLN-eo is universal with minimal side effects. IM at 100mg per day induces complete molecular remission and even lower doses can be efficient to maintain durable response. Some patients may remain in continued remission after IM discontinuation. Resistance to IM is associated with dismal prognosis. IM is less effective in F/P-unmutated HES with short-lived response.

Concepts: Hypereosinophilic syndrome, Mesylate, Philadelphia chromosome, Protein kinase, Tyrosine kinase, DNA, Chromosome, Imatinib

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Haematopoietic stem cell transplantation (HSCT) is an established curative treatment for many primary immunodeficiencies. Advances in donor selection, graft manipulation, conditioning and treatment of complications, mean that survival for many conditions is now around 90%. Next generation sequencing is identifying new immunodeficiencies, many of which are treatable with HSCT. Challenges remain however with short and long-term sequalae. This article reviews latest developments in HSCT for conventional primary immunodeficiencies and presents data on outcome for emerging diseases, Areas covered: This article reviews recently published literature detailing advances, particularly in conditioning regimens and new methods of T-lymphocyte depletion, as well as new information regarding approach and out come of transplanting patients with conventional primary immunodeficiencies. The article reviews data regarding transplant outcomes for newly described primary immunodeficiencies, particularly those associated with gain-of-function mutations. Expert commentary: New methods of graft manipulation have had significant impact on HSCT outcomes, with the range of PIDs treated using T-lymphocyte depletion significantly expanded. Outcomes for newly described diseases with variable phenotypes and clinical features, transplanted when the diagnosis was unknown are beginning to be described, and will improve as patients are identified earlier, and targeted therapies such as JAK inhibitors are used as a bridge to transplantation.

Concepts: Thymus, Bone marrow, Organ transplant, Hematopoietic stem cell, Immunodeficiency, Hematopoietic stem cell transplantation, Primary immunodeficiency, Immune system

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Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory arthritis characterised by a range of musculoskeletal conditions including enthesitis, dactylitis and synovitis as well as skin and nail manifestations. The foot is a complex mixture of tissues, all of which can be involved in this disease and is frequently the presenting feature. Areas covered: In this under-researched area, articles were reviewed from the authors' publications as well as from other known authors. This review will discuss how PsA affects the foot and ankle with a particular focus on synovitis, tenosynovitis, enthesitis, dactylitis, bone erosion and psoriatic skin and nail disease. The use of imaging is discussed. Conventional radiography is consistently used, however magnetic resonance imaging and ultrasound should be used routinely to diagnose, assess and monitor the disease appropriately. The complex nature of PsA in the foot and ankle should be considered when managing the condition and treatment should be individualized to relieve pain, maintain mobility and improve quality of life. Expert commentary: The foot and ankle remains a neglected area in PsA. Problems with the foot and ankle should be prioritised as they can significantly impact on patients' quality of life. Focussing treatment on the foot and ankle can significantly improve outcome.

Concepts: Ultrasound, Rheumatology, Arthritis, Foot, Medical imaging, Magnetic resonance imaging, Rheumatoid arthritis, Psoriatic arthritis

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Interstitial lung diseases (ILDs) are among the most serious complications associated with systemic rheumatic diseases, and lead to significant morbidity and mortality; they may also be the first manifestation of connective tissue diseases (CTDs). The aim of this narrative review is to summarise the data concerning the pathogenesis of CTD/ILD and its distinguishing features in different rheumatic diseseas. Areas covered: The pathogenesis, clinical aspects and treatment of ILD associated with rheumatic systemic diseases and CTDs were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1995 and February 2017 using combinations of words or terms. Articles not written in English were excluded. Expert Commentary: The management of CTD-ILD is challenging because of the lack of robust data regarding the treatments used, the heterogeneity of the diseases themselves, and the scarcity of well-defined outcome measures. Treatment decisions are often made clinically on the basis of functional, radiographic progression, and exacerbating factors such as age and the burden of comorbidities. Given the complexities of diagnosis and the paucity of treatment trials, the management of CTD patients with ILD requires multidisciplinary collaboration between rheumatologists and pulmonologists in CTD-ILD clinics.

Concepts: Immune system, Diseases and disorders, Pneumothorax, MEDLINE, Rheumatoid arthritis, Medicine, Rheumatology, Pulmonology

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X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton’s Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype.

Concepts: Infection, Disease, Genetics, Bruton's tyrosine kinase, Protein kinase, Immune system, Bacteria, X-linked agammaglobulinemia

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Allergy to Hymenoptera (Apis mellifera, Vespula species, Polistes species, Vespa crabro) venom can be safely and effectively treated by venom immunotherapy (VIT), which in the 40 years since its introduction has been able to prevent reactions to stings, and to treatment as well, though systemic reactions, occasionally severe, are possible. Areas covered: We reviewed the recent literature on VIT by searching in PubMed for the terms “venom immunotherapy” and “Hymenoptera venom immunotherapy” to highlight the current status of VIT and the likely development in the coming years. Expert commentary: VIT, provided the correct choice of the venom and adequate venom preparations and maintenance doses are used, is a treatment of great value in preventing systemic reactions to Hymenoptera stings. A 5-year duration ensures a prolonged tolerance to stings following VIT discontinuation, unless patients suffer from mastocytosis. In fact, due to reports of fatal reactions after stopping VIT, patients with mastocytosis, or with very severe reactions to stings, need an indefinite duration of treatment.

Concepts: Insect, Immunology, Vespoidea, Asian giant hornet, Immune system, Asthma, Mast cell, Allergy