Allergy and asthma proceedings最新文献

Primary antibody deficiencies are characterized by the inability to effectively produce antibodies and may involve defects in B-cell development or maturation. Primary antibody deficiencies can occur at any age, depending on the disease pathology. Certain primary antibody deficiencies affect males and females equally, whereas others affect males more often. Patients typically present with recurrent sinopulmonary and gastrointestinal infections, and some patients can experience an increased risk of opportunistic infections. Multidisciplinary collaboration is important in the management of patients with primary antibody deficiencies because these patients require heightened monitoring for atopic, autoimmune, and malignant comorbidities and complications. The underlying genetic defects associated with many primary antibody deficiencies have been discovered, but, in some diseases, the underlying genetic defect and inheritance are still unknown. The diagnosis of primary antibody deficiencies is often made through the evaluation of immunoglobulin levels, lymphocyte levels, and antibody responses. A definitive diagnosis is obtained through genetic testing, which offers specific management options and may inform future family planning. Treatment varies but generally includes antibiotic prophylaxis, vaccination, and immunoglobulin replacement. Hematopoietic stem cell transplantation is also an option for certain primary antibody deficiencies.

Primary immunodeficiencies, also commonly called inborn errors of immunity (IEI), are commonly due to developmental or functional defects in peripheral blood cells derived from hematopoietic stem cells. In light of this, for the past 50 years, hematopoietic stem cell transplantation (HSCT) has been used as a definitive therapy for IEI. The fields of both clinical immunology and transplantation medicine have had significant advances. This, in turn, has allowed for both an increasing ability to determine a monogenic etiology for many IEIs and an increasing ability to successfully treat these patients with HSCT. Therefore, it has become more common for the practicing allergist/immunologist to diagnose and manage a broad range of patients with IEI before and after HSCT. This review aims to provide practical guidance for the clinical allergist/immunologist on the basics of HSCT and known outcomes in selected forms of IEI, the importance of pre-HSCT supportive care, and the critical importance of and guidance for life-long immunologic and medical monitoring of these patients.

Immunoglobulin replacement is donor-derived pooled immunoglobulin G, which provides passive immunity to patients with antibody deficiency or dysfunction. It may be administered via either intravenous or subcutaneous routes. Intravenous immunoglobulin is administered at higher doses every 3-4 weeks, whereas most forms of subcutaneous immunoglobulin are administered at lower doses, usually every 1-2 weeks. Benefits and risks, including adverse effects, convenience, and cost vary according to route of administration. Immunoglobulin products also differ in their composition, so patient-specific comorbidities are important to consider when selecting an immunoglobulin product. We discuss adverse effects associated with immunoglobulin therapy, their associated risk factors, treatment, and ways to mitigate these risks. Finally, the laboratory monitoring and vaccination recommendations for patients on immunoglobulin replacement therapy are reviewed.

Immunodeficiency disorders pose substantial burdens on the health-care system and the patients affected. Broadly, immunodeficiencies can be divided into primary immunodeficiency disorders (PIDDs) and secondary immunodeficiency disorders. This review will focus on PIDDs. The overall prevalence for PIDDs is estimated to be ∼1-2% of the population but may be underestimated due to underdiagnosis of these conditions. PIDDs affect males slightly more often than females. The mortality rates differ based on the specific condition but can be extremely high if the condition is left undiagnosed or untreated. The most common causes of death are infections, respiratory complications, and cancers (e.g., lymphoma). Comorbidities and complications include infection, chronic lung disease, granulomatous lymphocytic interstitial lung disease, and autoimmune disorders. The disease burden of patients with common variable immunodeficiency (CVID) is estimated to be greater than patients with diabetes mellitus and chronic obstructive pulmonary disease. PIDDs have a serious impact on the quality of life of the patients, including sleep disturbance, anxiety, and social participation as well as other psychosocial burdens associated with these disorders. The financial cost of PIDDs can be substantial, with the cost of untreated CVID estimated to be $111,053 per patient per year. Indirect costs include productivity loss and time lost due to infusion and hospital visits. Secondary immunodeficiency is not fully discussed in this review but likely contributes equally to the burden of overall immunodeficiency disorders. Management of patients with PIDDs should use a comprehensive approach, including medical, nursing, psychiatric, and quality of life, to improve the outcome.

The primary immunodeficiency diseases are often accompanied by autoimmunity, autoinflammatory, or aberrant lymphoproliferation. The paradoxical nature of this association can be explained by the multiple cells and molecules involved in immune networks that interact with each other in synergistic, redundant, antagonistic, and parallel arrangements. Because progressively more immunodeficiencies are found to have a genetic etiology, in many cases, a monogenic pathology, an understanding of why immunodeficiency is really an immune dysfunction becomes evident. Understanding the role of specific genes allows us to better understand the complete nature of the inborn error of immunity (IEI); the latter is a term generally used when a clear genetic etiology can be discerned. Autoimmune cytopenias, inflammatory bowel disease, autoimmune thyroiditis, and autoimmune liver diseases as well as lymphomas and cancers frequently accompany primary immunodeficiencies, and it is important that the practitioner be aware of this association and to expect that this is more common than not. The treatment of autoimmune or immunodysregulation in primary immunodeficiencies often involves further immunosuppression, which places the patient at even greater risk of infection. Mitigating measures to prevent such an infection should be considered as part of the treatment regimen. Treatment of immunodysregulation should be mechanism based, as much as we understand the pathways that lead to the dysfunction. Focusing on abnormalities in specific cells or molecules, e.g., cytokines, will become increasingly used to provide a targeted approach to therapy, a prelude to the success of personalized medicine in the treatment of IEIs.

The complement system is an important component of innate and adaptive immunity that consists of three activation pathways. The classic complement pathway plays a role in humoral immunity, whereas the alternative and lectin pathways augment the innate response. Impairment, deficiency, or overactivation of any of the known 50 complement proteins may lead to increased susceptibility to infection with encapsulated organisms, autoimmunity, hereditary angioedema, or thrombosis, depending on the affected protein. Classic pathway defects result from deficiencies of complement proteins C1q, C1r, C1s, C2, and C4, and typically manifest with features of systemic lupus erythematosus and infections with encapsulated organisms. Alternative pathway defects due to deficiencies of factor B, factor D, and properdin may present with increased susceptibility to Neisseria infections. Lectin pathway defects, including Mannose-binding protein-associated serine protease 2 (MASP2) and ficolin 3, may be asymptomatic or lead to pyogenic infections and autoimmunity. Complement protein C3 is common to all pathways, deficiency of which predisposes patients to severe frequent infections and glomerulonephritis. Deficiencies in factor H and factor I, which regulate the alternative pathway, may lead to hemolytic uremic syndrome. Disseminated Neisseria infections result from terminal pathway defects (i.e., C5, C6, C7, C8, and C9). Diagnosis of complement deficiencies involves screening with functional assays (i.e., total complement activity [CH50], alternative complement pathway activity [AH50], enzyme-linked immunosorbent assay [ELISA]) followed by measurement of individual complement factors by immunoassay. Management of complement deficiencies requires a comprehensive and individualized approach with special attention to vaccination against encapsulated bacteria, consideration of prophylactic antibiotics, treatment of comorbid autoimmunity, and close surveillance.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

Background: There is controversy on whether allergic contact dermatitis (ACD) is associated with atopy. Research on eczema and the risk of ACD is mixed, and there is sparse literature on other atopic conditions. Objective: Our study examined the prevalence of several atopic conditions, including allergic rhinitis, eczema, asthma, and food allergies in patients with ACD, and compared these to patients without ACD. Methods: We retrospectively reviewed adult patients ages ≥ 18 years with ACD (n = 162) with positive patch testing results and documented any history of atopy, including childhood eczema, asthma, allergic rhinitis, and immunoglobulin E-mediated food allergy. The prevalence of atopic conditions was compared between our ACD cohort and controls without ACD (n = 163) from our electronic medical records system (age and gender matched). Results: Among our patients with ACD, 53 (33%) had allergic rhinitis, 22 (14%) had childhood eczema, 32 (20%) had asthma, and 8 (5%) had food allergies. We observed that the odds of atopy overall (n = 76) in the ACD group compared with the control group were increased (odds ratio [OR] 1.88; p = 0.007). Allergic rhinitis was the highest risk factor (n = 53) with an OR of 12.64 (p < 0.001). Childhood eczema (n = 22) was also increased in the ACD group (OR 2.4; p = 0.026). The odds of asthma and food allergy in the ACD group were also increased; however, the difference was not statistically significant from the control group (OR 1.76 [p = 0.071] and OR 2.76 [p = 0.139], respectively). Conclusion: Patients with ACD had increased odds of eczema, allergic rhinitis, and atopic conditions overall. Asthma and food allergies were not found to have a statistically significant correlation. Larger studies that delve into atopic risk factors in ACD would be important to confirm these findings.

Background: The normally acidic skin pH changes in atopic dermatitis (AD) to alkaline, which contributes to the associated skin-barrier dysfunction. Hence, acidic cleansers would be preferred, but such information is scarce. Objective: Guiding health-care providers and patients on selecting skin cleansers with a pH optimal for AD. Methods: A total of 250 products were tested: 37 soaps (32 bars, 5 liquid) and 213 syndets (14 bars, 199 liquid); 10% solutions were tested for pH by using a pH meter; pH values 6.65-7.35 were considered neutral. Results: The pH of the tested skin cleansers varied widely (3.59-10.83). All 37 soaps were highly alkaline. In the 14 syndet bars, the pH was neutral in 6, alkaline in 8, and acidic in none. In the 199 syndet liquids, the pH was acidic in 84.9%, neutral in 11.1%, and alkaline in 4.0%. The product's pH was disclosed in none of the 37 soaps and in only 32 syndets (15%) , of which 9 bars were labeled "balanced," whose measured pH was neutral in 6 and alkaline in 3. Of the other 23 syndets, the labeled pH was referred to as "balanced" in 20 whose measured pH was neutral in 2 (6.80, 6.88) and acidic in 18 (3.59-6.59). The pH in the other three syndets was 4.25-6.00. Conclusion: All tested soaps had undesirable pH, whereas 84.9% of the liquid syndets were acidic (which is desirable) and 11.1% were neutral (which could be acceptable). Only 12.8% of the products disclosed the pH, an issue in need of improvement.

Background: Hereditary angioedema (HAE) is a rare genetic condition characterized by painful and often debilitating swelling attacks. Little is known about the differences in outcomes between patients with HAE types I or II (type I: HAE caused by C1 esterase inhibitor deficiency; type II: HAE caused by C1 esterase inhibitor dysfunction), with decreased or dysfunctional C1 esterase inhibitor (C1-INH), and those with normal C1-INH (nC1-INH-HAE). Objective: To compare physician- and patient-reported real-world outcomes in patients with HAE types I/II versus patients with nC1-INH-HAE. Methods: Data were drawn from the Adelphi HAE Disease Specific Programme^TM a real-world, cross-sectional survey of HAE-treating physicians and their patients in the United States conducted between July and November 2021. Physicians reported patient disease activity and severity, and recent attack history. Patient-reported outcomes were collected. Bivariate tests used were either the Student's t-test, the Fisher exact test, or Mann-Whitney U test. Results: Physicians (N = 67) provided data on 368 patients (92.4% HAE types I/II and 7.6% nC1-INH-HAE). Physicians reported that a higher proportion of patients with nC1-INH-HAE had moderate or high disease activity and moderate or severe disease severity both at diagnosis and at data collection versus those with HAE types I/II. Patients with nC1-INH-HAE versus patients with HAE types I/II experienced increased attack severity (34.6% versus 4.4%) and hospitalization rate during the most recent attack (39.3% versus 6.6%), and reported lower health status and quality of life, via the European Quality of Life 5 Dimension 5 Level (US tariff) and Angioedema Quality of Life, respectively. On average, 25% of the patients with nC1-INH-HAE reported absenteeism and work or activity impairment due to HAE compared with 2.7% of patients with HAE types I/II. Both patient groups reported improvements in disease activity and severity from diagnosis to the time of data collection. Conclusion: These real-world findings suggest that patients with nC1-INH-HAE have increased disease activity and severity, and experience greater impairment to their quality of life, work, and daily functioning than patients with HAE types I/II. Powered statistical analyses are required to confirm these findings.