ABSTRACT
Background: Clinical testing, including food-specific skin and serum IgE level tests, provides limited accuracy to predict food allergy. Confirmatory oral food challenges (OFCs) are often required, but the associated risks, cost, and logistic difficulties comprise a barrier to proper diagnosis. Objective: We sought to utilize advanced machine learning methodologies to integrate clinical variables associated with peanut allergy to create a predictive model for OFCs to improve predictive performance over that of purely statistical methods. Methods: Machine learning was applied to the Learning Early about Peanut Allergy (LEAP) study of 463 peanut OFCs and associated clinical variables. Patient-wise cross-validation was used to create ensemble models that were evaluated on holdout test sets. These models were further evaluated by using 2 additional peanut allergy OFC cohorts: the IMPACT study cohort and a local University of Michigan cohort. Results: In the LEAP data set, the ensemble models achieved a maximum mean area under the curve of 0.997, with a sensitivity and specificity of 0.994 and 1.00, respectively. In the combined validation data sets, the top ensemble model achieved a maximum area under the curve of 0.871, with a sensitivity and specificity of 0.763 and 0.980, respectively. Conclusions: Machine learning models for predicting peanut OFC results have the potential to accurately predict OFC outcomes, potentially minimizing the need for OFCs while increasing confidence in food allergy diagnoses.
ABSTRACT
BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergy. Prior studies demonstrate significant differences among food-allergic individuals across race, ethnicity, and socioeconomic groups. Disparities in OIT have not been evaluated. OBJECTIVE: We assessed disparities in the use of OIT in patients with peanut allergy based on race, ethnicity, and socioeconomic status at a single academic medical center. METHODS: We identified 1028 peanut-allergic patients younger than 18 years receiving care in the University of Michigan food allergy clinics. Of these, 148 patients who underwent peanut OIT (treatment group) were compared with the 880 patients who avoided peanut (control group). Pertinent demographic and socioeconomic characteristics were compared. RESULTS: There were no differences in gender or ethnicity between the OIT and control groups. However, Black patients comprised 18% of the control group but only 4.1% of the OIT treatment group (P < .0001). The proportion of patients with private insurance was significantly higher in the treatment group compared with the control group (93.2% vs 82.2%, P = .0004). Finally, the neighborhood affluence index, a census-based measure of the relative socioeconomic prosperity of a neighborhood, was significantly higher in the OIT group than the control group (0.51 ± 0.18 vs 0.47 ± 0.19, P = .015), whereas the neighborhood disadvantage index, a census-based measure of the relative socioeconomic disadvantage of a neighborhood, was significantly lower (0.082 ± 0.062 vs 0.10 ± 0.093, P = .020). CONCLUSIONS: Significant racial and economic disparities exist at our institution between peanut-allergic individuals who receive OIT and those who do not. Efforts to understand the basis for these disparities are important to ensure that patients have equitable access to OIT.
Subject(s)
Desensitization, Immunologic , Healthcare Disparities , Peanut Hypersensitivity , Socioeconomic Factors , Humans , Peanut Hypersensitivity/therapy , Male , Female , Child , Desensitization, Immunologic/methods , Child, Preschool , Administration, Oral , Adolescent , Arachis/immunology , Infant , Social Class , Socioeconomic Disparities in HealthABSTRACT
BACKGROUNDFood allergy (FA) is a growing health problem requiring physiologic confirmation via the oral food challenge (OFC). Many OFCs result in clinical anaphylaxis, causing discomfort and risk while limiting OFC utility. Transepidermal water loss (TEWL) measurement provides a potential solution to detect food anaphylaxis in real time prior to clinical symptoms. We evaluated whether TEWL changes during an OFC could predict anaphylaxis onset.METHODSPhysicians and nurses blinded to the TEWL results conducted and adjudicated the results of all 209 OFCs in this study. A study coordinator measured TEWL throughout the OFC and had no input on the OFC conduct. TEWL was measured 2 ways in 2 separate groups. First, TEWL was measured using static, discrete measurements. Second, TEWL was measured using continuous monitoring. Participants who consented provided blood samples before and after the OFCs for biomarker analyses.RESULTSTEWL rose significantly (2.93 g/m2/h) during reactions and did not rise during nonreacting OFCs (-1.00 g/m2/h). Systemic increases in tryptase and IL-3 were also detected during reactions, providing supporting biochemical evidence of anaphylaxis. The TEWL rise occurred 48 minutes earlier than clinically evident anaphylaxis. Continuous monitoring detected a significant rise in TEWL that presaged positive OFCs, but no rise was seen in the OFCs that resulted in no reaction, providing high predictive specificity (96%) for anaphylaxis against nonreactions 38 minutes prior to anaphylaxis onset.CONCLUSIONSDuring OFCs, a TEWL rise anticipated a positive clinical challenge. TEWL presents a monitoring modality that may predict food anaphylaxis and facilitate improvements in OFC safety and tolerability.
Subject(s)
Anaphylaxis , Food Hypersensitivity , Humans , Anaphylaxis/diagnosis , Anaphylaxis/etiology , Food Hypersensitivity/diagnosis , Food , AllergensABSTRACT
BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy treated by trigger food avoidance and supportive care. Whether the prevalence of different trigger foods is changing with evolving food introduction patterns is unknown. The rate and nature of subsequent reactions after initial diagnosis have not been fully studied. OBJECTIVE: We sought to characterize how trigger foods have changed over time and investigate the nature of subsequent reactions after initial diagnosis. METHODS: We collected data regarding patients' FPIES reactions from 347 patients seen in the University of Michigan Allergy and Immunology clinic for FPIES from 2010 to 2022. Inclusion criteria consisted of pediatric patients diagnosed with FPIES by an allergist based on international consensus guidelines. RESULTS: Most foods including less commonly cited FPIES triggers increased in frequency over time. The most common index trigger was oat. A total of 32.9% (114 of 347) patients experienced a subsequent reaction after education on trigger avoidance and safe home introduction of new foods, with 34.2% (41 of 120) of subsequent reactions to new triggers at home and 45% (54 of 120) to known triggers at home. Of patients reacting subsequently, 28% (32 of 114) experienced a subsequent reaction necessitating an emergency department visit. The most common new subsequent reaction triggers were egg and potato, whereas peanut most commonly triggered reactions on oral food challenge. CONCLUSIONS: The risk profile of FPIES triggers may be evolving over time, though high-risk FPIES foods remain common. The subsequent reaction rate after counseling indicates that home food introduction poses risk. This study highlights the need for improved safety of new food introduction and/or prediction methods for FPIES to help prevent potentially dangerous home FPIES reactions.
Subject(s)
Enterocolitis , Food Hypersensitivity , Child , Humans , Infant , Food Hypersensitivity/diagnosis , Food Hypersensitivity/epidemiology , Syndrome , Food/adverse effects , Enterocolitis/diagnosis , Enterocolitis/epidemiology , Allergens , Dietary Proteins/adverse effectsABSTRACT
BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).
Subject(s)
Anaphylaxis , Desensitization, Immunologic , Peanut Hypersensitivity , Child, Preschool , Humans , Infant , Allergens/adverse effects , Anaphylaxis/etiology , Arachis/adverse effects , Desensitization, Immunologic/adverse effects , Desensitization, Immunologic/methods , Peanut Hypersensitivity/complications , Peanut Hypersensitivity/therapy , Administration, CutaneousABSTRACT
Background: Allergic reactions have been reported with mRNA vaccines for COVID-19 prevention. Patients perceived to be at higher risk for a reaction may be referred to an allergist, although evaluation strategies may differ between allergists. Objective: Our aim was to determine outcomes of COVID-19 vaccinations in patients evaluated by an allergist using different approaches. Methods: We conducted a retrospective case series evaluation of 98 patients seen at the University of Michigan Allergy Clinic for concerns regarding COVID-19 vaccination. Of these 98 patients, 34 underwent skin testing with polyethylene glycol (PEG) 2000 with or without PEG 3350/polysorbate 80 testing. Results: Of the 34 patients on whom skin testing was performed, 16 underwent testing before vaccination and 18 underwent testing after a reported vaccine-related event. One patient had a positive skin testing result in response to PEG 3350 following a vaccination reaction and natural infection and was advised against a second dose. One patient with a significant history concerning of anaphylaxis in response to PEG had positive results of testing to identify allergy to PEG 2000, PEG 3350, and polysorbate 80 and was advised against vaccination. Of the 98 patients, 63 (64%) tolerated COVID-19 vaccination without complication after evaluation by an allergist. Conclusion: No significant differences were found between vaccination counseling with and without skin testing to excipients. Patients who presented before the first dose of vaccination were more likely to proceed with COVID-19 vaccination and tolerate vaccination without complication.
Subject(s)
Anaphylaxis , Anaphylaxis/diagnosis , Anaphylaxis/etiology , Child , Epinephrine/therapeutic use , Hospitalization , HumansABSTRACT
BACKGROUND: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. OBJECTIVE: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. METHODS: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. RESULTS: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. CONCLUSIONS: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.
Subject(s)
Peanut Hypersensitivity , Administration, Oral , Adolescent , Allergens , Arachis , Child , Desensitization, Immunologic , Double-Blind Method , Humans , Peanut Hypersensitivity/therapyABSTRACT
Food allergies consist of aberrant immunologic, typically immunoglobulin E mediated, reactions that involve food proteins. A clinical history with regard to the suspected food, temporal associations, the duration of symptoms, characteristic symptom complex, and reproducibility in some cases is the key to making an accurate diagnosis. The differential diagnosis includes, for example, other immunologic adverse food reactions, nonimmunologic adverse food reactions, and reactions that involve nonfood items. Skin and blood immunoglobulin E testing for the suspected food antigen can aid the diagnosis in the context of a supportive clinical history. Immunoglobulin E testing for food components may further enhance diagnostic accuracy. Novel testing modalities are under development but are not yet ready to replace the current paradigm. Thus, double-blinded placebo controlled oral food challenge is considered the criterion standard of testing, although unblinded oral food challenges are usually confirmatory.
ABSTRACT
Symptoms of esophageal dysfunction such as food impaction are consistent with, but not diagnostic for eosinophilic esophagitis (EoE) without obtaining histology. We conducted a retrospective study to characterize patients with food impaction at a tertiary center. We hypothesized that many patients with food impaction may be lost to follow-up and that many have features suggestive of EoE. Adult patients presenting to the emergency department with esophageal food impaction were identified from an endoscopic database. Electronic medical records were manually abstracted. We examined associations between demographics, comorbid conditions, and follow-up with biopsy findings. Of 220 patients who presented to the emergency department for food impaction, 74.1% were men. Adequate follow-up was not documented in 120 (54.5%). Those lost to follow-up did not differ significantly by gender, age at symptom onset, or distance from hospital compared to those with follow-up. Esophageal biopsies were obtained in 158 (71.8%), and those with ≥15 eos/HPF were more likely to be lost to follow-up than those with <15 eos/HPF (52.8% vs. 34.8%, P < 0.05). Of those never biopsied, 79.0% were lost to follow-up and had intermediate proportions of males, food allergy, and asthma when compared to those with and without eosinophilic inflammation. Patients with food impaction commonly have EoE but are often lost to follow-up. Among those never biopsied, demographic and clinical features suggest that many may have undiagnosed EoE. Strategies for increasing use of biopsies in patients with food impaction and improving follow-up are needed to diagnose and manage EoE.
Subject(s)
Eosinophilic Esophagitis/surgery , Esophagus/injuries , Food/adverse effects , Foreign Bodies/surgery , Lost to Follow-Up , Adult , Aged , Biopsy , Eosinophilic Esophagitis/complications , Esophagoscopy/statistics & numerical data , Esophagus/pathology , Female , Foreign Bodies/complications , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).
Subject(s)
Allergens/administration & dosage , Arachis/adverse effects , Biological Products/administration & dosage , Desensitization, Immunologic/methods , Peanut Hypersensitivity/therapy , Plant Proteins/administration & dosage , Administration, Oral , Adolescent , Adult , Age Factors , Allergens/adverse effects , Biological Products/adverse effects , Biological Products/immunology , Child , Child, Preschool , Desensitization, Immunologic/adverse effects , Dose-Response Relationship, Immunologic , Double-Blind Method , Female , Gastrointestinal Diseases/etiology , Humans , Male , Middle Aged , Plant Proteins/adverse effects , Plant Proteins/immunology , Young AdultABSTRACT
PURPOSE OF REVIEW: This review provides an overview of food allergy among children and adolescents in the context of its impact on psychosocial functioning, and quality of life (QoL). RECENT FINDINGS: The prevalence of food allergy is increasing. The burden of day to day management of food allergy is significant and can have a negative impact on QoL for both parents of those with food allergy, and the children themselves. This can impact social functioning, academic functioning, and mental health. Children with food allergy experience more bullying than peers. Greater internalizing of symptoms has been identified in adolescents with food allergy. Typical developmental considerations in the transition from adolescence to adulthood can be impacted significantly. Those caring for children with food allergy should consider the impact of food allergy on the individual and family level within the context of social and emotional development.
Subject(s)
Food Hypersensitivity/psychology , Mental Disorders/etiology , Adolescent , Bullying , Child , Humans , Mental Disorders/diagnosis , Mental Disorders/therapy , Psychiatry , Quality of Life/psychologyABSTRACT
PURPOSE OF REVIEW: There are no established guidelines for evaluating and treating hypogammaglobulinemia in patients with rheumatic disease who receive B-cell depleting agents. The purpose of this article is to review findings in the work-up and treatment of common variable immunodeficiency (CVID) that can guide our evaluation of patients with autoimmune disease who develop hypogammaglobulinemia after rituximab/B-cell depleting therapy. RECENT FINDINGS: Infection rates are higher in rheumatic disease patients who develop hypogammaglobulinemia than those who do not. However, not all patients who develop hypogammaglobulinemia are at increased risk of developing infection after B-cell depleting therapy. Recent consensus statements have helped refine the diagnosis of impaired immune responses in patients with CVID, and can provide guidance for the diagnostic work-up and therapeutic decision making for patients with secondary drug induced hypogammaglobulinemia. SUMMARY: Based on findings in studies of CVID, assessment of vaccine response in patients with hypogammglogulinemia after rituximab therapy in the setting of recurrent infections can help predict propensity for infection and thus guide decision making with regards to intravenous immunoglobulin supplementation and retreatment with rituximab.
Subject(s)
Agammaglobulinemia , B-Lymphocytes/immunology , Immunity, Cellular , Rituximab/administration & dosage , Agammaglobulinemia/diagnosis , Agammaglobulinemia/drug therapy , Agammaglobulinemia/immunology , Humans , Immunologic Factors/administration & dosageABSTRACT
BACKGROUND: Our previous pilot study conducted at the University of Michigan Health Services showed that fewer than 25% of the non-university allergen immunotherapy (AIT) prescribers adhered to AIT labeling guidelines which impacted both patients and healthcare personnel involved in AIT administration. OBJECTIVES: We expand our study to characterize AIT labeling compliance and impact of practice variability at the "Big 10" University Health Services, and investigate prescribers motives for nonadherence to practice parameter guidelines. METHODS: Three online surveys were distributed: AIT Administrator and Manager surveys for healthcare personnel at the "Big 10"; University Health Services and Physician Survey for physician members of the AAAAI. Data were analyzed using frequency/bivariate analysis and logistic regression. RESULTS: 21 AIT administrators from 10 University Health Services responded. 90.4% (20/21) felt labels containing all recommended practice parameter guidelines, components would decrease error; and standardization of labels, buildup and missed dose schedules would increase workflow efficiency (76%; 16/21). 90% (17/19) felt standardized protocols for treatment of systemic reactions would increase patient safety, workflow efficiency and comfort level of administrators. Only 28.6% of AIT extract vial labels at University Health Services were in accordance with practice parameter guidelines. Despite familiarity with the guidelines (91.5%; 697/762), only 64% (488/762) of surveyed physicians had practice parameter adherent AIT extracts labels with higher odds of a complete label when physicians were in group practice (odds ratio 1.51; [95% confidence interval, 1.06-2.15]; P=0.02). Reasons for nonadherence included having personalized labeling systems (55.4%, 174/314), unfamiliarity (14%, 44/314) and disagreement (9%, 29/314) with practice parameter guidelines. CONCLUSION: Poor adherence with AIT practice parameters labeling guidelines is an important concern in nonallergy offices. It is imperative that allergists comply with the highest recommended standards to provide the best clinical outcomes and ensure excellent and efficient care in both allergy and non-allergy offices.
Subject(s)
Allergists/statistics & numerical data , Desensitization, Immunologic/standards , Guideline Adherence/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Student Health Services , Attitude of Health Personnel , Clinical Competence , Humans , Logistic Models , Practice Guidelines as Topic , Surveys and Questionnaires , WorkflowABSTRACT
BACKGROUND: Few interventions have focused on the difficulties that African American women face when managing asthma. OBJECTIVE: To evaluate a telephone-based self-regulation intervention that emphasized African American women's management of asthma in a series of 6 sessions. METHODS: A total of 422 African American women with persistent asthma were randomly assigned to either an intervention or control group receiving usual care. Behavioral factors, symptoms and asthma control, asthma-related quality of life, and health care use at baseline and 2 years after baseline were assessed. Generalized estimating equations were used to assess the long-term effect of the intervention on outcomes. RESULTS: Compared with the control group, those who completed the full intervention (6 sessions) had significant gains in self-regulation of their asthma (B estimate, 0.73; 95% CI, 0.17-1.30; P < .01), noticing changes to their asthma during their menstrual cycle (B estimate, 1.42; 95% CI, 0.69-2.15; P < .001), and when having premenstrual syndrome (B estimate, 1.70; 95% CI, 0.67-2.72; P < .001). They also had significant reductions in daytime symptoms (B estimate, -0.15; 95% CI, -0.27 to -0.03; P < .01), asthma-related hospitalization (B estimate, 0.51; 95% CI, 0.00-1.02; P < .05), and improved asthma control (B estimate, 1.34; 95% CI, 0.57-2.12; P < .001). However, neither grouped changed over time in outcomes. CONCLUSION: Despite high comorbidity, African American women who completed a culturally responsive self-management program had improvements in asthma outcomes compared with the control group. Future work should address significant comorbidities and psychosocial issues alongside asthma management to improve asthma outcomes in the long term. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT01117805.
Subject(s)
Asthma/prevention & control , Black or African American , Culture , Patient Education as Topic , Asthma/diagnosis , Asthma/drug therapy , Case-Control Studies , Female , Follow-Up Studies , Humans , Outcome Assessment, Health Care , Patient Acceptance of Health Care , Quality of Life , Self CareABSTRACT
PURPOSE OF REVIEW: Because rituximab is increasingly used in systemic autoimmune diseases, alone or in combination with other immunosuppressive medication, secondary reduction of normal immune defenses has become a more significant clinical problem. RECENT FINDINGS: The goal of rituximab treatment of immune-mediated conditions is complete depletion of circulating B cells. Studies have suggested that lack of complete B-cell depletion is associated with nonresponse, and B-cell repletion can predict relapse. The resulting prolonged B-cell depletion is associated with risk of adverse effects including hypogammaglobulinemia, increased risk of infection, failure to develop immune responses after vaccination, and neutropenia. Pre-existing hypogammaglobulinemia has been linked to increased risk of reduction of IgG levels and serious infections after rituximab therapy, and concomitant cyclophosphamide therapy has been associated with an increased risk of developing hypogammaglobulinemia. SUMMARY: Although rituximab therapy is effective in the treatment of many systemic autoimmune diseases and has an acceptable safety profile, treating physicians need to keep in mind that pre-existing hypogammaglobulinemia and likely also use of additional immunosuppressive agents can increase the risk of prolonged hypogammaglobulinemia and infection. In keeping with current recommendations for rheumatoid arthritis, we recommend that all patients who undergo rituximab therapy have baseline IgG, IgM, and IgA measurements and also have immunoglobulin levels monitored periodically during treatment.
Subject(s)
Arthritis, Rheumatoid , B-Lymphocytes/immunology , Immunity, Cellular/drug effects , Immunosuppressive Agents/therapeutic use , Rituximab/therapeutic use , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , B-Lymphocytes/drug effects , Humans , RecurrenceABSTRACT
OBJECTIVE: African American women are disproportionately burdened by asthma morbidity and mortality and may be more likely than asthma patients in general to have comorbid health conditions. This study sought to identify the self-management challenges faced by African American women with asthma and comorbidities, how they prioritize their conditions and behaviors perceived as beneficial across conditions. METHODS: In-depth interviews were conducted with 25 African-American women (mean age 52 years) with persistent asthma and at least one of the following: diabetes, heart disease or arthritis. Information was elicited on women's experiences managing asthma and concurrent health conditions. The constant-comparison analytic method was used to develop and apply a coding scheme to interview transcripts. Key themes and subthemes were identified. RESULTS: Participants reported an average of 5.7 comorbidities. Fewer than half of the sample considered asthma their main health problem; these perceptions were influenced by beliefs about the relative controllability, predictability and severity of their health conditions. Participants reported ways in which comorbidities affected asthma management, including that asthma sometimes took a "backseat" to conditions considered more troublesome or worrisome. Mood problems, sometimes attributed to pain or functional limitations resulting from comorbidities, reduced motivation for self-management. Women described how asthma affected comorbidity management; e.g. by impeding recommended exercise. Some self-management recommendations, such as physical activity and weight control, were seen as beneficial across conditions. CONCLUSIONS: Multiple chronic conditions that include asthma may interact to complicate self-management of each condition. Additional clinical attention and self-management support may help to reduce multimorbidity-related challenges.
Subject(s)
Asthma/embryology , Asthma/therapy , Black or African American/statistics & numerical data , Self Care/statistics & numerical data , Adult , Affect , Black or African American/psychology , Arthritis/drug therapy , Arthritis/epidemiology , Asthma/psychology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Chronic Disease , Cognition Disorders/epidemiology , Depression/epidemiology , Depression/psychology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Female , Humans , Middle Aged , Motivation , Pain/epidemiology , Pain/psychology , Qualitative Research , Quality of Life , Self Care/psychology , Socioeconomic Factors , TelephoneABSTRACT
We present a 50-year-old woman with progressive dyspnea, cough, and nasal congestion. Evaluation revealed positive skin tests (IgE) to trees and dust mites, early glottic closure on spirometry, and sinus opacities on CT. Diagnostic considerations included allergic and nonallergic rhinitis, asthma, aspirin-exacerbated respiratory disease, vocal cord dysfunction, chronic sinusitis secondary to gastroesophageal reflux disease, and systemic inflammatory and immunologic diseases, including vasculitis. Progresson of her symptoms prompted further investigation, and a biopsy yielded an unexpected diagnosis.