Introduction Immune checkpoint inhibitors (ICIs) have proved to be groundbreaking in the field of oncology and immunotherapy. However, immune system overactivation from ICIs has introduced a novel medical entity known as immune related adverse events (irAEs), that can affect any organ or tissue. ICI-induced inflammatory arthritis (ICI-IIA) is the most common musculoskeletal irAE and can lead to significant

Introduction Between 5 and 25% of patients with cutaneous lupus erythematosus (CLE) can progress to systemic lupus erythematosus (SLE) during the course of the disease. There is no clear predictive guideline for the progression of CLE to SLE. Areas covered Lupus erythematosus (LE), a chronic autoimmune disease, has a wide spectrum of manifestations. On one side of the spectrum is CLE, in which patients

Introduction Although mounting evidence has linked environmental factors with childhood allergies, some specific key issues still remain unclear: what is the main environmental factor? what is the critical timing window? And whether these contribute to the development of disease? Areas covered This selective review summarizes recent epidemiological studies into the association between early-life exposure

Introduction With a complex and often misunderstood etiology, acute Charcot neuroarthropathy (ACN) is a devastating complication of peripheral neuropathy. In patients with diabetes, timely diagnosis of ACN in the foot and ankle is essential to prevent loss of both limb and life. Areas covered Herein, the authors evaluate the growing body of evidence in identifying targeted pathways for future therapeutic

Introduction Dietary elimination therapy has long been an option for patients with eosinophilic esophagitis (EoE). Multiple diets have been reported, with variable efforts involved, efficacy rates, costs, and long-term management plans. Although the pros and cons of dietary elimination therapy have been described, a clear method for deciding on who is the right candidate for a diet, and which diet

Introduction Ixekinumab (IXE) is a high affinity IgG4 approved for the treatment of ankylosing spondylitis (AS). Recently, two phase III randomized clinical trials (COAST-V, COAST-W) showed significant and sustained improvements in signs and symptoms of AS as evaluated by ASAS40 response. Areas covered: The authors performed a comprehensive literature search on this topic, by a review of published

Introduction Main clinical manifestations of SARS-CoV-2 infection are characterized by fever, cough, dyspnoea and interstitial pneumonia frequently evolving in an acute respiratory distress syndrome (ARDS). Areas covered Features of coronavirus disease 2019 (COVID-19) pneumonia presents some common points with interstitial lung disease (ILD) both idiopathic and related to rheumatoid arthritis (RA)

Introduction During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the

Introduction Dupilumab is a treatment option newly licensed for adolescents with moderate to severe atopic dermatitis (AD). It reduces type 2 inflammation by blocking the shared receptor subunit for IL-4 and IL-13 and thereby inhibits receptor signaling downstream the JAK-STAT-pathway. Dupilumab affects three important disease mechanisms in atopic dermatitis: the skin barrier, the Th2-cell differentiation

Introduction Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition. Teprotumumab is a human insulin-like growth factor-I receptor monoclonal inhibitor antibody which indicated for treating thyroid eye disease. Areas covered The authors performed a systematic review of the literature using the PubMed database, and the following keywords were used: ‘teprotumumab’

Introduction Noninfectious uveitis represents one of the leading causes of blindness in developed Countries, compromising patients’ quality of life and social functioning. The main treatment goals are the control of ocular inflammation, to avert and treat sight-threatening complications, thus preserving and/or restoring visual function. Areas covered This manuscript deals with systemic therapy with

(2020). Reducing lupus flares: should we be more careful about stopping glucocorticoids? Expert Review of Clinical Immunology: Vol. 16, No. 6, pp. 539-542.

(2020). Food allergy severity prediction: quite a way to go yet? Expert Review of Clinical Immunology: Vol. 16, No. 6, pp. 543-546.

Introduction Interstitial lung disease (ILD) is a leading cause of death in patients with systemic sclerosis (SSc). Nonspecific immunosuppressants have been the first-line treatment for SSc-associated ILD (SSc-ILD). Nintedanib, an oral triple kinase inhibitor targeting profibrotic pathways, has been employed for the treatment of idiopathic pulmonary fibrosis and has recently received marketing approval

Introduction Allergies affect 20-30% of the population and respiratory allergies are mostly due to pollen grains from anemophilous plants. One to 5% of people suffer from food allergies and clinicians report increasing numbers of pollen-food allergy syndrome (PFAS), such that the symptoms have broadened from respiratory to gastrointestinal, and even to anaphylactic shock in the presence of cofactors

Introduction Allergic contact dermatitis is an inflammatory skin disease which accounts for up to 20% of all childhood dermatitis. Childhood allergic contact dermatitis is more frequent than previously thought and today early diagnosis is considered very important. Patch testing represents the gold standard method used to confirm the diagnosis of allergic contact dermatitis. The knowledge of the most

Introduction Biologics have revolutionized the therapy of moderate-to-severe plaque psoriasis. Despite their greater efficacy over conventional systemic therapies their high cost has represented a burden for health-care systems, which limited their use. The availability of biosimilars at low cost is changing the place in therapy of biologics for psoriasis. Areas covered The role of TNF- α inhibitors

Introduction Psoriasis is a very common chronic inflammatory skin disease affecting up to 3% of the general population with 75% of the psoriasis subjects being affected by a mild form of disease. Hence, topical therapy is the most frequent employed treatment in psoriasis also because it can be easily combined with systemic therapy. In this context, calcipotriol/betamethasone dipropionate (Cal/BD) fixed-dose

Introduction Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease. Early referral and treatment are key to the effective management of the disease. This makes imperative the identification of biomarkers and of pathobiological endotypes. Areas covered This review describes recent efforts to integrate large-scale datasets for the identification of disease endotypes for precision medicine

Objective Currently published papers regarding the relationship between integrin alpha V (ITGAV) gene polymorphisms and rheumatoid arthritis (RA) are contradictory. The aim of this meta-analysis was to evaluate the associations between the ITGAV gene polymorphisms and RA risk. Methods Comprehensive literature search based on four electronic databases was applied to retrieve all related data. Two independent

Objectives Human Ficolin-3 (FCN3) is an oligomeric-structured lectin encoded by the FCN3 gene with a pivotal role in the lectin complement pathway. It has anti-microbial activities against bacterial and viral infections and restrains opportunistic pathogens. Mutation in the FCN3 gene is associated with variable clinical manifestations particularly immunologic (infections and autoimmunity) and neurologic

Introduction Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific

Introduction Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression. Areas covered This collaborative work proposes practical management and follow-up

Introduction Secondary immunodeficiency is becoming a greater medical concern as the usage of immunosuppressive and biological treatments has increased. Individuals with certain medical conditions, such as hematological malignancies, can also have secondary immunodeficiency. Immunoglobulin replacement therapy (IGRT), which has been used for decades in inherited or primary immunodeficiency, provides

Introduction Alpha-gal Syndrome (AGS) is a unique allergy to non-primate mammalian meat (and derived-products) that is associated with tick bites and is due to a specific IgE antibody to the oligosaccharide galactose-α-1,3-galactose (alpha-gal). AGS has many novel features that broaden the paradigm of food allergy, including that reactions are delayed 3-6 hours after exposure and patients have frequently

Introduction Treatment of colorectal cancer as one of the most commonly diagnosed and a frequent cause of cancer-related deaths is of great challenges in health-related issues. Areas covered Immunotherapy is the fourth pillar of cancer treatment which provides more novel therapeutic options with expanding investigational potentials. One of the modalities in immunotherapy is the use of bispecific antibodies

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects almost every organ system and it is treated with immunomodulation and immunosuppression. SLE patients have an intrinsically dysfunctional immune system which is exacerbated by disease activity and leaves them vulnerable to infection. Treatment with immunosuppression increases susceptibility to infection, while hydroxychloroquine

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects almost every organ system and it is treated with immunomodulation and immunosuppression. SLE patients have an intrinsically dysfunctional immune system which is exacerbated by disease activity and leaves them vulnerable to infection. Treatment with immunosuppression increases susceptibility to infection, while hydroxychloroquine

Introduction Hematopoietic cell transplantation (HCT) is a curative treatment for an expanding number of primary immunodeficiencies (PIDs). Malignancies are more common in patients with PID than in the general population, and this review will discuss whether a successful HCT is expected to abolish or alter this risk. Second malignancy post HCT for a malignant disease is well known to occur, but generally

Introduction For several years now, medicine has been benefiting from the contribution of nanoparticles (NPs) technology for both diagnosis and therapy. They can be used as adjuvants, being capable per se of immune-modulating activity, or as carriers for molecules to be transported to a specific target, eventually loaded with specific ligands favoring specific uptake. Areas covered The review focuses

Introduction High mobility group protein box 1 (HMGB1) is a protein belonging to the alarmin family. HMGB1 has a relevant role in starting the inflammatory cascade by means of receptors, such as RAGE and TLR. HMGB1 supports transcription of many genes in interactions with many transcription factors, including NF-kB. The axis HMGB1-RAGE-NF-kB has, therefore, a pivotal role in the inflammatory cascade

Introduction Psoriasis is a chronic-immune-mediated disease affecting 2–4% of the western population. The disease is associated with several co-morbidities including an increased risk of cancer. Concerns have been raised whether psoriasis itself, the psoriasis-associated risk factors, or the treatment of psoriasis might lead to an increased risk of cancer. Areas covered We reviewed the literature on

Introduction: Since the identification of HIV, several studies reported the unusual case of small groups of subjects showing natural resistance to HIV infection. These subjects are referred to as HIV-1-exposed seronegative (HESN) individuals and include people located in different areas, with diverse ethnic backgrounds and routes of exposure. The mechanism/s responsible for protection from infection

Introduction: Diagnostic and therapeutic strategies in eosinophilic esophagitis (EoE) are constantly evolving. Recently, the improved understanding of EoE pathogenesis has led to identification of a variety of other potential targets that have never been considered before.Areas covered: In September 2019, we performed structured literature searches in Medline and PubMed, Cochrane meta-analyses, and

Introduction: Metabolic Syndrome (MetS) is strictly interconnected with systemic inflammation, and increased evidence has described a close link between this condition and Psoriatic Arthritis (PsA).Areas covered: This review summarizes main studies exploring clinical aspects and prevalence of MetS in PsA cohorts. Further, there is accumulating evidence showing shared inflammatory pathways between MetS

Introduction: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease, characterized by the production of autoantibodies. Numerous mechanisms contribute to the pathogenesis and autoimmunity in SLE. One of the most important mechanisms is the defective function of the early complement components that are involved in clearing the immune-complexes and apoptotic debris. Major evidence supporting

Introduction: A genetic biomarker to select which drug will work best for which patients with rheumatic diseases is a goal of pharmacogenetic precision medicine approaches and one that patients and the public support. However, studies to date have yielded inconsistent findings with no robustly replicated or clinically useful genetic biomarkers emerging.Areas covered: Using studies investigating biomarkers

Introduction: The clinical manifestations of cutaneous adverse drug reactions are variable with different severity. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs) majorly caused by drugs and mediated by cytotoxic T cells.Areas covered: In this review, we focus on risk factors that contribute to the development of SJS/TEN

Introduction: Ruxolitinib is an oral selective JAK1/JAK2 inhibitor, initially approved by the FDA for the treatment of intermediate-2 or high-risk myelofibrosis and patients with polycythemia vera who have had an inadequate response or are intolerant to hydroxyurea.Areas covered: Accumulating evidence supports the role of JAK1/JAK2 pathways in the pathogenesis of graft-versus-host disease (GVHD), and

(2020). Genomic opportunities for drug repositioning in systemic seropositive rheumatic diseases. Expert Review of Clinical Immunology: Vol. 16, No. 4, pp. 343-346.

Objective: To assess the correlation of serum protein biomarkers with disease activity across different domains of psoriatic arthritis (PsA).Material and methods: A cross-sectional cohort of 45 adult patients with PsA fulfilling the classification for psoriatic arthritis (CASPAR) criteria was recruited from University of California San Diego (UCSD) Arthritis Clinics. Clinical data and serum samples

Objectives: To systematically review the risk of sustained amenorrhoea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate the efficacy of gonadotropin releasing hormone agonists (GnRHa) to reduce this risk.Methods: Systematic search for papers reporting the incidence of sustained amenorrhoea ≥ 12 months in ARD following: IV cyclophosphamide; or GnRHa and IV cyclophosphamide

Introduction: The development of new biologic agents has provided definite therapeutic advances but, like with any new medications, safety remains a concern.Areas covered: Using PubMed, we reviewed the literature on the adverse effects (AE) to five biologics approved for asthma and/or allergic diseases: one anti-IgE (omalizumab), three anti-IL5 (mepolizumab, reslizumab, benralizumab), and one anti-IL4

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory airway disease characterized as tight junction loosening, inflammation, and mucosal remodeling. Epithelial cells form a barrier against allergens, bacteria, and proteases, and can also trigger or enhance the immune response by releasing various inflammatory mediators including cytokines, chemokines, and secreted proteins

Introduction: Stevens-Johnson syndrome (SJS) and its severe phenotype, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucosa. Approximately 50% of SJS/TEN patients diagnosed by dermatologists and in burn units suffer from severe ocular complications (SOC) in the acute stage.Areas covered: Earlier studies on patients with SJS/TEN with SOC identified

Introduction: The International Dermatology Outcome Measures (IDEOM) identified 'Psoriatic Arthritis (PsA) Symptoms' as a core domain to be measured in psoriasis clinical trials. This domain includes the measurement of pain, patient global and physical function. Herein, we evaluated the quality (i.e. measurement properties) of five candidate 'PsA Symptoms' measures: Patient Global Assessment (PGA)

Introduction: Palmoplantar pustulosis (PPP) is a chronic, relapsing and refractory disease characterized by sterile pustules appearing on the palms and/or soles, accompanied by erythema, blistering, scales and/or keratinization. The overall burden of PPP in terms of its clinical impact, effect on patients and families, and economic consequences has not previously been investigated in a structured manner

Introduction: Generalized pustular psoriasis (GPP) is characterized by widespread erythema and edema, superficial sterile coalescing pustules, and lakes of pus. Although the impact of GPP is thought to be substantial, emerging literature on its clinical, humanistic, and economic burden has not previously been described in a structured way.Areas covered: A structured search focused on the identification

(2020). Should patients with rheumatic diseases take pain medication in order to engage in exercise? Expert Review of Clinical Immunology: Vol. 16, No. 3, pp. 235-237.

(2020). The case for narcolepsy as an autoimmune disease. Expert Review of Clinical Immunology: Vol. 16, No. 3, pp. 231-233.

Introduction Biomarkers may help influence long-term outcomes of psoriatic disease by improving the objective assessment of the presence and severity of psoriatic arthritis (PsA) and by guiding treatment selection. However, there are no validated biomarkers for PsA. Areas covered Beginning with a brief overview of the clinical features of PsA and concepts about biomarkers and risk prediction in medicine

Introduction HAE is a very debilitating disease that causes significant distress for patients not only during an acute attack but also constant fear for a subsequent attack. It is important to address long-term prophylactic (LTP) therapy to prevent attacks, decrease morbidity and increase the quality of life. When discussing LTP, the drug burden, convenience and efficacy must be taken into account

ABSTRACT Introduction At the end of 2019, Wuhan, a city in China with a population of about 11 million, witnessed the outbreak of unusual pneumonia. As of 29 March 2020, the disease has spread to more 199 countries and territories worldwide. The 2019 novel coronavirus, 2019-nCoV, is known as the probable causative agent of the illness. Areas covered Here, the epidemiological dynamics of the coronavirus

(2020). Placebo responses in ankylosing spondylitis patients worldwide: variations and possible explanations. Expert Review of Clinical Immunology: Vol. 16, No. 5, pp. 447-450.

(2020). Avoiding infections in transplant recipients: does the gut microbiota have a key role? Expert Review of Clinical Immunology: Vol. 16, No. 2, pp. 113-115.

(2020). The potential of fecal microbiota transplantation in systemic sclerosis. Expert Review of Clinical Immunology: Vol. 16, No. 2, pp. 117-118.

Introduction: Certolizumab pegol (CZP) is an Fc-free PEGylated TNF-α inhibitor approved for the treatment of psoriatic arthritis (PsA) and plaque psoriasis in many countries. It demonstrated favorable results in PsA in terms of improvement in peripheral arthritis, dactylitis, and enthesitis in a phase III trial (RAPID-PSA) and in real-life experiences. Recently, three phase III randomized clinical

Introduction: Adult-onset Still's disease (AOSD) is a rare multisystem autoinflammatory disorder of unknown etiology, with clinical and biological similarities with the juvenile form (sJIA).The pivotal role of interleukin (IL)-1 gives rise to the use of IL-1 inhibitors in treating resistant cases.Areas covered: This review focuses on canakinumab, a fully human anti-IL-1β antibody, as treatment for

Introduction: The goal of immunosuppressive therapy post-transplantation in pediatric renal transplant recipients is to prevent acute and chronic rejection while minimizing drug side effects. Most therapies alter immune response mechanisms but are not immunologically specific, and a careful balance is required to find the dose that prevents rejection of the graft, while minimizing the risks of over-immunosuppression

Introduction: 'Chronic inflammatory immune-related skin disease' (ISDs) is an umbrella term grouping together heterogeneous entities characterized by chronic inflammation potentially involving the whole skin. We are not covering all ISDs in this review, but take a few as the most representative, including nonbullous and bullous diseases. The question we are aiming to address can be summarized as follows: