Journal: Clinical reviews in allergy & immunology
Raynaud’s phenomenon often precedes the diagnosis of systemic sclerosis and is the first symptom of the disease in many cases. Antinuclear antibody positivity can assist in the early identification of cases of isolated Raynaud’s phenomenon likely to progress to systemic sclerosis. However, the specific differences between rate of progression for different scleroderma hallmark antibodies is less clear. We review the predictive potential of ANA positivity and nailfold capillaroscopy for identifying cases of Raynaud’s phenomenon which may progress to connective tissue diseases. We also have reviewed data from our own large scleroderma cohort to explore the relationship between antibody subtype and time to development of SSc. Duration of pre-existing Raynaud’s phenomenon may be an important determinant of the profile of systemic sclerosis cases identified through screening. Ninety-five percent of our patients with isolated Raynaud’s phenomenon, negative autoimmune serology on more than one visit and normal capillaroscopy score showed no progression to connective tissue disease. Duration of antecedent Raynaud’s phenomenon differs between disease subsets and scleroderma-specific ANA patterns.
Familial Mediterranean fever (FMF) is a recessive, autosomal, auto-inflammatory disorder characterised by brief, recurring, self-limited episodes of fever and serositis resulting in abdominal, chest, joint and muscular pain; it is the most common of the periodic hereditary fevers and mostly affects Mediterranean populations. Daily administration of colchicine, a tricyclic alkaloid with anti-microtubule and anti-inflammatory properties, prevents the recurrence of FMF attacks and the development of secondary (AA) amyloidosis, the major long-tem complication of FMF. Colchicine is generally safe and well-tolerated; nevertheless, 5-10 % of FMF patients do not respond to conventional treatment, while another 2-5 % of patients are colchicine-intolerant because of toxicity issues, leading physicians to search for alternative therapeutic strategies. Recent new insights into the mechanisms of auto-inflammation add further proof to the efficacy of IL-1 targeting drugs in colchicine non-responder/intolerant FMF patients. A systematic study of relevant literature through PubMed/Medline was performed in order to identify publications reporting IL-1β biological treatment of FMF. Treatment methods, comorbidities, clinical response and side effects in literature case reports were analysed, as well as recent advances in the pathogenesis of auto-inflammation mechanisms in FMF and the causes of colchicine resistance or toxicity in common clinical practice. The paradigmatic experience of an FMF patient with severe FMF mutations (M694V/M694V) suffering from colchicine toxicity and successfully treated with anakinra is also reported. The present data show that anti-IL-1β biological treatment is actually a therapeutic option for FMF patients unresponsive or intolerant to colchicine or in FMF patients with concomitant vasculitis.
Raynaud’s phenomenon and digital ulcers (DUs) are frequent among systemic sclerosis (SSc) patients. Our aim was to investigate the diagnostic and predictive value for DU of endothelial dysfunction biomarkers (flow-mediated dilatation (FMD), serum levels of endothelin-1 (ET-1), and ADMA), angiogenic/angiostatic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin), and nailfold videocapillaroscopy (NVC). We compared our results with a literature review. In a cohort study of 77 SSc patients, we followed two groups of patients: (i) naïve DU patients (39) and (ii) active DU at baseline (38 patients) for 3 years. Telangiectasia (p < 0.001) and diffuse disease subset (p = 0.001) were significantly more frequent in patients with active DU at enrolment. Additionally, NVC late scleroderma pattern (AUC 0.846, 95%CI 0.760-0.932), lower values of FMD (AUC 0.754, 95%CI 0.643-0.864), increased serum levels of ET-1 (AUC 0.758, 95%CI 0.649-0.866), ADMA (AUC 0.634, 95%CI 0.511-0.757), and endoglin as well as low VEGF serum levels (AUC 0.705, 95%CI 0.579-0.830) were significantly associated to new DU events in the 3-year follow-up. Cox regression analysis showed that FMD > 9.41 % (HR 0.37, 95%CI 0.14-0.99); ET-1 >11.85 pmol/L (HR 3.81, 95%CI 1.41-10.26) and late NVC pattern (HR 2.29, 95%CI 0.97-5.38) were independent predictors of DU recurrence. When estimating the probability of occurrence of first DU in naïve DU patients, only late NVC pattern (HR 12.66, 95%CI 2.06-77.89) was an independent predictor factor. In conclusion, late scleroderma patterns in NVC are the best independent predictors of SSc patients who are at risk of developing DU. Endothelial dysfunction assessed by FMD and ET-1 was also found to be an independent predictor of DU recurrence in a 3-year follow-up.
Histamine fish poisoning, also known as scombroid poisoning, is the most common cause of ichythyotoxicosis worldwide and results from the ingestion of histamine-contaminated fish in the Scombroidae and Scomberesocidae families, including mackerel, bonito, albacore, and skipjack. This disease was first described in 1799 in Britain and re-emerged in the medical literature in the 1950s when outbreaks were reported in Japan. The symptoms associated with histamine fish poisoning are similar to that of an allergic reaction. In fact, such histamine-induced reactions are often misdiagnosed as IgE-mediated fish allergy. Indeed, histamine fish poisoning is still an underrecognized disease. In this review, we discuss the epidemiology, pathophysiology, evaluation, and treatment of scombroid disease. Because more than 80 % of fish consumed in the USA is now imported from other countries, the disease is intimately linked with the global fish trade (National Marine Fisheries Service, 2012). Preventing future scombroid outbreaks will require that fishermen, public health officials, restaurant workers, and medical professionals work together to devise international safety standards and increase awareness of the disease. The implications of scombroid poisoning go far beyond that of fish and have broader implications for the important issues of food safety.
The “Bermuda triangle” of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics.
TNF inhibitors have been used in psoriasis (Pso) and psoriatic arthritis (PsA), which were associated with increased risk of cardiac and cerebrovascular events. However, whether TNF inhibitors reduce cardiovascular event is still unclear. Therefore, we aimed to evaluate the effect of TNF inhibitors on adverse cardiovascular events (CVEs) in Pso with or without PsA. We undertook a meta-analysis of clinical trials identified in systematic searches of MEDLINE, EMBASE, Wanfang database, Cochrane Database, and Google scholar through December 31, 2015. Five studies (49,795 patients) were included. Overall, compared with topical/photo treatment, TNF inhibitors were associated with a significant lower risk of CVE (RR, 0.58; 95 % CI, 0.43 to 0.77; P < 0.001; I (2) = 66.2 %). Additionally, compared with methotrexate (MTX) treatment, risk of CVE was also markedly decreased in the TNF inhibitor group (RR, 0.67; 95 % CI, 0.52 to 0.88; P = 0.003; I (2) = 9.3 %). Meanwhile, TNF inhibitors were linked to reduced incidence of myocardial infarction compared with topical/photo or MTX treatment (RR, 0.73; 95 % CI, 0.59 to 0.90; P = 0.003; I (2) = 56.2 % and RR, 0.65; 95 % CI, 0.48 to 0.89; P = 0.007; I (2) = 0.0 %, respectively). Furthermore, there was a trend of decreased rate of mortality in the TNF inhibitor group compared with other therapy (RR, 0.90; 95 % CI, 0.54 to 1.50; P = 0.68; I (2) = 70.9 %). TNF inhibitors appear to have net clinical benefits with regard to adverse cardiovascular events in Pso and/or PsA. Rigorous randomized controlled trials will need to evaluate whether TNF inhibitors truly result in reduction of cardiovascular diseases.
Tattoos are defined as the introduction of exogenous pigments into the dermis in order to produce a permanent design. This process may occur unintentional or may be deliberately administered for cosmetic or medical reasons. Tattoos have been around for over 5000 years and over time have evolved to represent a common cosmetic practice worldwide. Currently, adverse reactions are relatively rare and generally unpredictable and predominantly include immune-mediated reactions and skin infections. Along with better healthcare standards and more stringent public health mandates such as the provision of disposable needles, major infectious complications related to hepatitis and human retroviral infections have decreased significantly. When they do occur, skin infections are most frequently associated with Staphylococcus aureus or Streptococcus pyogenes. The aim of this study is to review the types and rates of medical complications of permanent tattoos. PubMed search and search dates were open ended. Acute local inflammation is the most common complication, but infections, allergic contact dermatitis, and other inflammatory or immune responses that are not well-characterized may occur. As many patients with immune reactions to tattoos do not react on skin or patch testing, it is postulated that the antigens contained in dyes or pigments are such small molecules that they need to be haptenized in order to become immunogenic. Red ink is associated more frequently with long-term reactions, including granulomatous and pseudolymphomatous phenomena or morphea-like lesions and vasculitis. Exacerbation of preexisting psoriasis, atopic dermatitis, and pyoderma gangrenosum may occur after tattooing. There is no well-defined association between cancer and tattoos. The treatment of tattoo-related complications may include local destructive measures (cryotherapy, electro-surgery, dermabrasion, chemical destruction, ablative laser destruction), surgical excision, and thermolysis of the pigment using Q-switched laser therapy.
Food allergy is defined as an adverse immune response towards food proteins or as a form of a food intolerance associated with a hypersensitive immune response. It should also be reproducible by a double-blind placebo-controlled food challenge. Many reported that food reactions are not allergic but are intolerances. Food allergy often presents to clinicians as a symptom complex. This review focuses on the clinical spectrum and manifestations of various forms of food allergies. According to clinical presentations and allergy testing, there are three types of food allergy: IgE mediated, mixed (IgE/Non-IgE), and non-IgE mediated (cellular, delayed type hypersensitivity). Recent advances in food allergy in early childhood have highlighted increasing recognition of a spectrum of delayed-onset non-IgE-mediated manifestation of food allergy. Common presentations of food allergy in infancy including atopic eczema, infantile colic, and gastroesophageal reflux. These clinical observations are frequently associated with food hypersensitivity and respond to dietary elimination. Non-IgE-mediated food allergy includes a wide range of diseases, from atopic dermatitis to food protein-induced enterocolitis and from eosinophilic esophagitis to celiac disease. The most common food allergies in children include milk, egg, soy, wheat, peanut, treenut, fish, and shellfish. Milk and egg allergies are usually outgrown, but peanut and treenut allergy tends to persist. The prevalence of food allergy in infancy is increasing and may affect up to 15-20 % of infants. The alarming rate of increase calls for a public health approach in the prevention and treatment of food allergy in children.
Taxanes (a class of chemotherapeutic agents) are an important cause of hypersensitivity reactions (HSRs) in cancer patients. During the last decade, the development of rapid drug desensitization has been key to allow patients with HSRs to taxanes to be safely re-treated although the mechanisms of these HSRs are not fully understood. Earlier studies suggested that solvents, such as Cremophor EL used to solubilize paclitaxel, were responsible for HSRs through complement activation, but recent findings have raised the possibility that some of these HSRs are IgE-mediated. Taxane skin testing, which identifies patients with an IgE-mediated sensitivity, appears as a promising diagnostic and risk stratification tool in the management of patients with HSRs to taxanes. The management of patients following a HSR involves risk stratification and re-exposure could be performed either through rapid drug desensitization or graded challenge based on the severity of the initial HSR and the skin test result. Rapid drug desensitization has been shown to be an effective and safe method to re-introduce taxanes in hundreds of patients, including those with life-threatening HSRs. Patients with non-severe delayed skin HSRs may benefit from rapid drug desensitization since they may be at increased risk for an immediate HSR upon re-exposure. This review focuses on the clinical presentation, diagnosis, and novel mechanisms of immediate HSRs to taxanes. A new management strategy for HSRs to taxanes based on skin testing and rapid drug desensitization is proposed.
Propolis, a waxy substance produced by the honeybee, has been adopted as a form of folk medicine since ancient times. It has a wide spectrum of alleged applications including potential anti-infection and anticancer effects. Many of the therapeutic effects can be attributed to its immunomodulatory functions. The composition of propolis can vary according to the geographic locations from where the bees obtained the ingredients. Two main immunopotent chemicals have been identified as caffeic acid phenethyl ester (CAPE) and artepillin C. Propolis, CAPE, and artepillin C have been shown to exert summative immunosuppressive function on T lymphocyte subsets but paradoxically activate macrophage function. On the other hand, they also have potential antitumor properties by different postulated mechanisms such as suppressing cancer cells proliferation via its anti-inflammatory effects; decreasing the cancer stem cell populations; blocking specific oncogene signaling pathways; exerting antiangiogenic effects; and modulating the tumor microenvironment. The good bioavailability by the oral route and good historical safety profile makes propolis an ideal adjuvant agent for future immunomodulatory or anticancer regimens. However, standardized quality controls and good design clinical trials are essential before either propolis or its active ingredients can be adopted routinely in our future therapeutic armamentarium.