A retrospective study of a novel 3-session rush venom immunotherapy protocol.

BACKGROUND: Venom immunotherapy (VIT) is an effective treatment for life-threatening stinging-insect hypersensitivity. Rush VIT protocols allow patients to reach maintenance dosing faster, thus conferring protection sooner. The published protocols vary in dosing regimens, monitoring parameters, and safety profiles. OBJECTIVE: To describe a novel 3-session outpatient rush VIT protocol with full therapeutic dosing achieved at the end of session 3. METHODS: We conducted a retrospective chart review of adult patients treated with rush VIT in an outpatient university allergy/immunology clinic. Demographic and clinical data, including the type of sting reaction, the number of venom allergens, and any systemic reactions (SRs) during VIT, were analyzed. RESULTS: Over a 14-year period, 55 patients (28 females and 27 males) with a median age of 47 years underwent our VIT protocol. A total of 46 patients (84%) tolerated the procedure without SR, and 53 (96%) attained full maintenance dosing. All reactions during rush were Brown anaphylaxis criteria grade 1 or 2. Although the most common venom allergy was yellow jacket, most patients had multiple venom allergies and received therapy with more than 1 venom. Furthermore, 10 patients were re-stung while on maintenance with only 1 patient having a mild SR. CONCLUSION: Our 3-session outpatient rush VIT protocol is effective and safe. Most patients had no SR and attained maintenance dosing. Compared with other 3-session rush protocols, our protocol requires non-invasive monitoring, and patients achieved monthly maintenance dosing immediately on completion.

Clinical implications of C6 complement component deficiency.

Background: Terminal complement component deficiencies are risk factors for neisserial infections. Objective: To review the clinical characteristics, the diagnosis and the management of patients with a terminal complement component deficiency. Methods: Pertinent articles were selected and reviewed in relation to a case presentation of C6 deficiency. Results: A case of a 56-year old patient with a history of meningitis, chronic rash, and C6 deficiency was presented, followed by discussion of clinical characteristics, diagnosis, and management of terminal complement component deficiencies. Clinical pearls and pitfalls were reviewed for the practicing allergist/immunologist and fellow-in-training. Conclusion: C6 deficiency is the most common terminal complement component deficiency and can present later in age with N. meningitidis infections. Patients can be screened for terminal complement component deficiency by checking CH50.

A 72-year-old woman with periorbital swelling.

As allergists, we are frequently consulted to evaluate patients with swelling presumed to be angioedema. Patients with presumed angioedema can have multiple possible underlying triggers. We present the case of a hospitalized 72-year-old woman with a history of hypertension and metastatic chordoma who developed marked periorbital swelling that precluded eye opening 2 days after a neurosurgical operation (chordoma resection and T10-11 hardware repair). After a detailed evaluation of her swelling, a broad differential diagnosis was made; she did not respond to high-dose antihistamines, systemic steroids, icatibant and angiotensin-converting enzyme inhibitor cessation. Ultimately, computed tomography imaging confirmed a specific diagnosis. The differential diagnosis for swelling is complex, and this case illustrated the importance of considering alternative causes of swelling when evaluating cases of possible angioedema.

Detrimental Association of Hypogammaglobulinemia With Chronic Lung Allograft Dysfunction and Death Is Not Mitigated by On-Demand Immunoglobulin G Replacement After Lung Transplantation.

BACKGROUND:: Hypogammaglobulinemia (HGG), immunoglobulin G (IgG) <700 mg/dL, is associated with infections, chronic lung allograft dysfunction, and death following lung transplantation. This study evaluates the use of on-demand intravenous IgG in lung transplant recipients with HGG. MATERIALS AND METHODS:: This single-center retrospective cohort study of adult lung recipients evaluated 3 groups, no, untreated (u), or treated (t) HGG at first IgG administration or a matched time posttransplant. Primary outcome was freedom from allograft dysfunction. Secondary outcomes included development of advanced dysfunction, rejection, infection burden, and mortality. RESULTS:: Recipients included 484 (no HGG: 76, uHGG: 192, tHGG: 216). Freedom from chronic allograph dysfunction was highest in the non-HGG group 2 years post-enrollment (no HGG 77.9% vs uHGG 56.4% vs tHGG 52.5%; P = .002). Freedom from advanced dysfunction was significantly different 2 years post-enrollment (no HGG 90.5% vs uHGG 84.7% vs tHGG 75.4%; P = .017). Patients without HGG and those with uHGG had less mortality at 2 years post-enrollment (no HGG 84.2% vs uHGG 81.3% vs tHGG 64.8%; P < .001). Gram-negative pneumonias occurred more often in the tHGG group ( P = .02). CONCLUSIONS:: Development of chronic lung allograft dysfunction, patient survival, rejection burden, and key infectious outcomes in lung transplant recipients were still problematic in the context of on-demand IgG therapy. Prospective studies are warranted.

A 10-year experience of a novel and safe modified environmental rush immunotherapy protocol.

BACKGROUND: Allergen immunotherapy (AIT) is an effective treatment option for allergic rhinitis. Although conventional AIT takes 6 months to reach maintenance dosing, rush AIT accelerates the build-up period and reaches the maintenance dose months earlier. However, accelerated schedules of AIT carry an increased risk of systemic reactions (SR). OBJECTIVE: We aimed to describe a novel 1-day, eight-step modified environmental rush immunotherapy (MERIT) protocol, characteristics of the patients who underwent this therapy, and the safety of this procedure. We also compared distinguishing features of those patients with SRs. METHODS: We retrospectively analyzed demographic and clinical data of 362 adult patients seen in an outpatient university allergy clinic, from January 2005 to January 2015, and who underwent MERIT protocol treatment for allergic rhinitis. RESULTS: In a univariate analysis, the factors significantly associated with SR were lower body mass index (BMI); younger age; a higher number of allergens in the extracts; and the presence of cat, dust mite, and certain weed pollens. In a multivariate analysis, cat, dust mite, and mugwort were significantly associated with SRs. Over the 10-year period, 50 patients experienced SRs (13.81%), with a total number of 68 SRs. Only 4.7% of the SRs occurred on the MERIT day. Most SRs occurred >30 minutes and were mild. Our MERIT protocol continuation rate for all the patients was 49.2% and did not seem to be influenced by having an SR versus no SR. CONCLUSION: We present a modified rush AIT protocol that seems to be effective and safe. Most patients tolerated therapy, and only a minority of patients developed SRs, which generally were mild. We identified novel risk factors for SRs that may help determine optimal dosing to decrease the risk of SRs. Ultimately, future studies will be needed to compare the safety of our MERIT protocol with traditional AIT.

The morbidity and cost of vocal cord dysfunction misdiagnosed as asthma.

BACKGROUND: Vocal cord dysfunction (VCD) is frequently misdiagnosed and mistreated as asthma, which leads to morbidity secondary to unnecessary medication use and increased health care utilization. OBJECTIVE: We identified discriminating symptoms and triggers, and analyzed the costs, morbidity, and health care burden associated with misdiagnosis of VCD as asthma. We sought to determine if current measures of asthma control contributed to these findings. We evaluated if a simple set of breathing exercises would be an effective low-cost treatment option for those with VCD. METHODS: We compared the demographics, comorbidities, clinical symptoms, and symptom triggers of subjects with VCD misdiagnosed as asthma compared with those not misdiagnosed as asthma. Costs secondary to asthma misdiagnosis were quantified, and the effectiveness of breathing exercises as a treatment option was evaluated. RESULTS: We identified symptoms of shortness of breath, wheezing, chest tightness, and a trigger of exercise as being more common in the subjects with VCD misdiagnosed as asthma. Asthma medication use and health care utilization and costs were also higher in this group. The subjects with VCD had Asthma Control Questionnaire scores that labelled them as having uncontrolled asthma. Breathing exercises appeared to offer an inexpensive and effective treatment option for subjects with VCD. CONCLUSION: Misdiagnosis of VCD as asthma leads to significant morbidity and increased costs, and misuse of measures of asthma control may be contributing to these findings. Timely and accurate diagnosis of VCD and the use of breathing exercises have the potential to eliminate or minimize the burdens on the patient and the health care system.

Successful desensitization to brentuximab vedotin after hypersensitivity reaction.

Monoclonal antibodies (mAb) have become the standard of care for numerous diseases. However, side effects including infusion and hypersensitivity reactions experienced by patients continue to be a limiting factor in their use. In the therapy of cancer, treatment choices are frequently limited and minimizing side effects of a life-saving or life-prolonging therapy becomes of the utmost importance. We report the successful use of a rapid desensitization protocol in a patient with NHL, treated with a novel antibody-drug conjugate, chimeric monoclonal antibody linked to the antimitotic agent monomethyl auristatin E (MMAE) Brentuximab vedotin, who had previously developed a hypersensitivity reaction.

A retrospective analysis comparing subjects with isolated and coexistent vocal cord dysfunction and asthma.

Vocal cord dysfunction (VCD) is often misdiagnosed as asthma or complicates coexisting asthma. This study aimed to identify distinguishing clinical characteristics in patients with VCD, asthma, and coexisting VCD and asthma. We conducted a retrospective analysis of demographic and clinical data from 292 patients with VCD, asthma, coexisting VCD and asthma, and control subjects from an outpatient university asthma/allergy clinic. Concomitant asthma was present in 32.6% of VCD subjects. Overall, 42.4 % of all VCD subjects were previously misdiagnosed as having asthma for an average of 9.0 years. Upper airway symptoms were more prevalent in the VCD population and nocturnal apnea was more prevalent in comorbid VCD and asthma compared with either condition alone. Irritable bowel syndrome and chronic pain were identified as new comorbidities associated with VCD. VCD subjects who had been misdiagnosed with asthma had significantly more health care and asthma medication use compared to VCD subjects who had not mimicked asthma. There was no difference in asthma severity between those with and without VCD. Comorbid VCD and asthma led to an increase in long-acting ß-agonist use only, but no difference in health care usage, compared with asthma alone. These findings suggest that the main morbidity associated with VCD may not lie in its inherent disease process, but instead in its ability to mimic asthma.

A Safe and Novel Outpatient Subcutaneous Vitamin B12 Desensitization Protocol in A Patient with Crohn's Disease and Vitamin B12 Allergy: A Case Report.

INTRODUCTION: Although rare, some patients may have a vitamin B12 allergy. Crohn's disease commonly leads to significant vitamin B12 deficiency, especially in those patients that have undergone ileal resection. In these difficult cases, vitamin B12 desensitization may be required. CASE PRESENTATION: Here, we report a successful case of a serial outpatient subcutaneous vitamin B12 desensitization protocol in a 35-year-old female with a past medical history of Crohn's disease status post ileal resection, subsequent vitamin B12 deficiency, and allergy to subcutaneous vitamin B12. CONCLUSION: This is the first subcutaneous vitamin B12 desensitization protocol reported to have been safely performed in the outpatient setting.

Factors Associated with Self-Reported Drug Allergies in a Large Chronic Spontaneous Urticaria Cohort.

INTRODUCTION: Chronic spontaneous urticaria (CSU) is characterized by recurrent hives without a known trigger. While certain drugs are associated with urticaria exacerbations, the overall drug allergy incidence in CSU is unknown. We hypothesized that the incidence of drug allergy in CSU would be greater than the general population and that there would be distinguishing clinical features of drug-allergic CSU patients. METHODS: 362 adult CSU patients seen over a 10-year period at a University Allergy/Asthma clinic were identified. Patients reported no drug allergies or any drug allergy. Multiple drug allergies were defined as allergies to ≥ 2 chemically unrelated drugs. Using Chi-square or Wilcoxon analysis, we compared demographic features of CSU with and without drug allergy and with multiple vs. single drug allergy. RESULTS AND DISCUSSION: Overall, 202 CSU patients (56%) reported drug allergy. Drug allergic CSU patients were older, with a greater proportion of whites and higher BMI vs. CSU without drug allergy (p=0.002, p=0.047, p=0.004, respectively). Penicillin was the most common drug allergy, with urticaria the most frequently reported reaction. Female sex, white race, older age at the visit, and co-existing asthma were more common in multiple drug allergy (n=115) vs. single drug allergy (p=0.002, p=0.02, p=0.03, p=0.0002, respectively). CONCLUSION: In CSU, the prevalence of self-reported drug allergies was higher than the general population. Drug allergy is associated with older age, white race and higher BMI, while multiple drug allergy was also associated with asthma. These CSU sub-populations should be studied to avoid the potential for morbidity associated with less efficacious and more costly drugs.

Antibody Deficiency, Chronic Lung Disease, and Comorbid Conditions: A Case-Based Approach.

New emerging pulmonary phenotypes associated with antibody deficiency, such as neutrophilic asthma, frequent exacerbations of chronic obstructive pulmonary disease, and unexplained interstitial lung disease, particularly in younger adults, are discussed in this review through a case-based approach. Also discussed in similar fashion are antibody deficiency syndromes that lead to end-stage lung disease and the indications for lung transplantation in primary immunodeficiency disease. These challenging cases require timely and individualized strategies for genetic and immunologic diagnosis, decisions about therapeutic approaches, and long-term monitoring.

Vocal Cord Dysfunction: The Spectrum Across the Ages.

Vocal cord dysfunction (VCD) is an upper airway disorder characterized by exaggerated and transient glottic constriction causing respiratory and laryngeal symptoms. Although the origin of VCD symptoms is in the upper airway, it is frequently misdiagnosed as asthma resulting in significant morbidity. VCD can coexist with asthma or mimic allergic conditions affecting the upper airway. VCD may be difficult to diagnose, because patients are intermittently symptomatic and VCD awareness in the medical community is underappreciated. Once VCD is diagnosed and treated, most patients report significant improvement in their symptoms as well as a decrease in asthma medication use.

Co-existence of vocal cord dysfunction with pulmonary conditions other than asthma: A case series.

BACKGROUND: Vocal cord dysfunction (VCD) is defined as inappropriate movement of the vocal cords resulting in functional airway obstruction and symptoms including cough, wheezing, and dyspnea. VCD is often misdiagnosed with asthma but can also co-exist with asthma. The association of VCD with other serious pulmonary conditions has not been described to date. CASE REPORTS: We describe the first case series of two adult patients evaluated at a university asthma clinic who in addition to having VCD also had significant pulmonary pathology other than asthma. Patient 1 had VCD and pulmonary veno-occulsive disease which necessitated a lung transplant. Patient 2 had VCD and a patent ductus arteriosis who necessitated surgical closure. CONCLUSION: It is important to recognize that VCD can exist with pulmonary conditions other than asthma. Lack of improvement in respiratory symptoms after appropriate treatment for VCD should alert the clinician to evaluate for additional conditions.