An 82-year-old man with new skin lesions after COVID-19 vaccination.

Background: During the height of the SARS CoV-2 (severe acutre respiratory syndrome coronavirus disease 2019 [COVID 19]) pandemic, there have been numerous case reports of cutaneous reactions shortly after COVID-19 vaccine administration. Most reported cases are local injection-site reactions, whereas persistent or delayed cutaneous reactions have not been as common. Methods: We present the case of an 82-year-old man with persistent rash after the second COVID-19 vaccination. Results: A specific diagnosis was confirmed after the third skin biopsy. Conclusion: Patients are frequently referred to an allergist for various cutaneous reactions that occurred after vaccination, concerned about a possible drug allergy. This case emphasizes the importance of keeping a broad differential diagnosis when encountering a persistent skin rash not resolved by oral antihistamines or steroids.

Histamine-releasing factor in severe asthma and rhinovirus-associated asthma exacerbation.

BACKGROUND: Histamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma. OBJECTIVE: We aim to present data analysis from 3 separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus [RV]-infected individuals, and sera samples from patients with RV-induced asthma exacerbation) and 1 mouse sample to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations. METHODS: Total IgE and HRF-reactive IgE/IgG as well as HRF in sera from patients with mild/moderate asthma or severe asthma (SA) and healthy controls (HCs) were quantified by ELISA. HRF secretion in culture media from RV-infected adenovirus-12 SV40 hybrid virus transformed human bronchial epithelial cells and in nasal washings from experimentally RV-infected subjects was analyzed by Western blotting. HRF-reactive IgE/IgG levels in longitudinal serum samples from patients with asthma exacerbations were also quantified. RESULTS: HRF-reactive IgE and total IgE levels were higher in patients with SA than in HCs, whereas HRF-reactive IgG (and IgG1) level was lower in asthmatic patients versus HCs. In comparison with HRF-reactive IgElow asthmatic patients, HRF-reactive IgEhigh asthmatic patients had a tendency to release more tryptase and prostaglandin D2 on anti-IgE stimulation of bronchoalveolar lavage cells. RV infection induced HRF secretion from adenovirus-12 SV40 hybrid virus transformed bronchial epithelial cells, and intranasal RV infection of human subjects induced increased HRF secretion in nasal washes. Asthmatic patients had higher levels of HRF-reactive IgE at the time of asthma exacerbations associated with RV infection, compared with those after the resolution. This phenomenon was not seen in asthma exacerbations without viral infections. CONCLUSIONS: HRF-reactive IgE is higher in patients with SA. RV infection induces HRF secretion from respiratory epithelial cells both in vitro and in vivo. These results suggest the role of HRF in asthma severity and RV-induced asthma exacerbation.

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.

Development of New White Fish Allergy after Bone Marrow Transplantation from a Non-atopic Donor.

Background: Transplant-acquired food allergy has become increasingly recognized in solid organ and bone marrow transplantation. As food allergy has no cure and causes considerable impact on the lives of patients who require strict avoidance of foods to avoid potentially severe or fatal reactions, it is crucial for physicians to better understand the risk factors and mechanisms driving development of food allergy post-transplant. We report a case of new food allergy to whitefish in an elderly patient post-bone marrow transplant in which neither donor nor recipient had a history of atopy. Methods: A 70-year-old man experienced an anaphylactic reaction to Swai whitefish (Pangasius hypophthalmus) 6 months post-transplant that he had previously tolerated on multiple occasions both pre-transplant and in the preceding months post-transplant. This allergy was investigated by commercial serum specific IgE testing and fresh prick-to-prick skin test to Swai whitefish. Results: Fresh prick-to-prick demonstrated large positive reaction to the Swai whitefish with wheal of 10 mm and flare of 22 mm compared to positive histamine control with a wheal/flare of 5x8mm. Serum specific IgE testing to commercial whitefish was negative (specific IgE <0.10kU/L). The patient continues to strictly avoid Swai whitefish but tolerates all other fish and shellfish. Conclusions: The unique development of specific Swai whitefish allergy in an elderly man after bone marrow transplant where both donor and recipient had no prior history of atopy strongly supports transplant-related immunomodulation as a major mechanism for transplant-acquired allergy and suggests that that absence of atopy or advanced age may not necessarily be protective.

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.

Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma.

Rationale: Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation and IL-1ß secretion from monocytes and cause airway epithelial cell injury, but the role of eDNA, NETs, and IL-1ß in asthma is uncertain. Objectives: To characterize the role of activated neutrophils in severe asthma through measurement of NETs and inflammasome activation. Methods: We measured sputum eDNA in induced sputum from 399 patients with asthma in the Severe Asthma Research Program-3 and in 94 healthy control subjects. We subdivided subjects with asthma into eDNA-low and -high subgroups to compare outcomes of asthma severity and of neutrophil and inflammasome activation. We also examined if NETs cause airway epithelial cell damage that can be prevented by DNase. Measurements and Main Results: We found that 13% of the Severe Asthma Research Program-3 cohort is "eDNA-high," as defined by sputum eDNA concentrations above the upper 95th percentile value in health. Compared with eDNA-low patients with asthma, eDNA-high patients had lower Asthma Control Test scores, frequent history of chronic mucus hypersecretion, and frequent use of oral corticosteroids for maintenance of asthma control (all P values <0.05). Sputum eDNA in asthma was associated with airway neutrophilic inflammation, increases in soluble NET components, and increases in caspase 1 activity and IL-1ß (all P values <0.001). In in vitro studies, NETs caused cytotoxicity in airway epithelial cells that was prevented by disruption of NETs with DNase. Conclusions: High extracellular DNA concentrations in sputum mark a subset of patients with more severe asthma who have NETs and markers of inflammasome activation in their airways.

A Safe and Novel Desensitization Protocol with Ferric Carboxymaltose to Treat Iron Deficiency Anemia.

INTRODUCTION: Worldwide, iron deficiency anemia is the most common nutritional disorder. Treatment with oral iron supplementation may not be well tolerated due to gastrointestinal side effects. Therapy with Intravenous (IV) iron supplementation is more effective and better tolerated, especially in patients with underlying Inflammatory Bowel Disease (IBD) or malignancy. However, Hypersensitivity Reactions (HSR) and anaphylaxis to IV iron have been described. METHODS: We evaluated the literature and developed an eleven step desensitization protocol for ferric carboxymaltose to be administered in high risk patients. RESULTS: We present the first case series demonstrating the safety of ferric carboxymaltose desensitization in patients with a history of anaphylaxis to IV iron and iron deficiency anemia. CONCLUSION: While there are many IV iron formulations available, ferric carboxymaltose can replenish iron stores with fewer doses. Ferric carboxymaltose is contraindicated in patients with prior hypersensitivity reactions to iron formulations. This novel eleven step desensitization protocol was well tolerated without any adverse reactions and allowed the patients to receive iron supplementation when limited therapeutic options existed.

Desensitization protocol for rituximab-induced serum sickness.

Rituximab, a chimeric anti-CD20 monoclonal antibody, is used to treat rheumatologic and hematologic diseases. Serum sickness, a Type III delayed hypersensitivity reaction, has been reported with rituximab treatment. Traditionally, drug desensitization has been used to treat Type I IgE-mediated hypersensitivity reactions. We report the first case of successful drug desensitization to rituximab in a patient with medication-induced serum sickness. In our case, a 37-year-old woman with Sjogren's syndrome and papillary thyroid carcinoma developed serum sickness 72 hours following rituximab infusion for gastric mucosal associated lymphoma tissue (MALT). Her MALT progressed after stopping rituximab. She underwent a rapid 12-step intravenous rituximab desensitization without recurrence of serum sickness. Following the completion of 4 rituximab desensitizations, she had gastric MALT remission. She received 25 maintenance rituximab doses using this desensitization protocol quarterly without complications. This is the first report documenting rituximab desensitization for the treatment of delayed drug reactions like serum sickness.

A novel scoring system to distinguish vocal cord dysfunction from asthma.

BACKGROUND: Vocal cord dysfunction is often misdiagnosed and mistreated as asthma, which can lead to increased and unnecessary medication use and increased health care utilization. OBJECTIVE: To develop a valid scoring index that could help distinguish vocal cord dysfunction from asthma. METHODS: We compared the demographics, comorbidities, clinical symptoms, and symptom triggers of subjects with vocal cord dysfunction (n = 89) and those with asthma (n = 59). By using multivariable logistic regression, we identified distinguishing features associated with vocal cord dysfunction, which were weighted and used to generate a novel score. The scoring index also was tested in an independent sample with documented vocal cord dysfunction (n = 72). RESULTS: We identified symptoms of throat tightness and dysphonia, the absence of wheezing, and the presence of odors as a symptom trigger as key features of vocal cord dysfunction that distinguish it from asthma. We developed a weighted index based on these characteristics, the Pittsburgh Vocal Cord Dysfunction Index. By using a cutoff of ≥4, this index had good sensitivity (0.83) and specificity (0.95) for the diagnosis of vocal cord dysfunction. The scoring index also performed reasonably well in the independent convenience sample with laryngoscopy-proven vocal cord dysfunction and accurately made the diagnosis in 77.8% of subjects. CONCLUSION: The Pittsburgh Vocal Cord Dysfunction Index is proposed as a simple, valid, and easy-to-use tool for diagnosing vocal cord dysfunction. If confirmed by a prospective evaluation in broader use, it may have significant clinical utility by facilitating a timely and accurate diagnosis of vocal cord dysfunction, thereby preventing misdiagnosis and mistreatment as asthma. Future prospective validation studies will need to be performed.

Prostaglandin D2 pathway upregulation: relation to asthma severity, control, and TH2 inflammation.

BACKGROUND: Bronchoalveolar lavage (BAL) fluid prostaglandin D2(PGD2) levels are increased in patients with severe, poorly controlled asthma in association with epithelial mast cells (MCs). PGD2, which is generated by hematopoietic prostaglandin D synthase (HPGDS), acts on 3 G protein-coupled receptors, including chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTH2) and PGD2 receptor 1 (DP1). However, much remains to be understood regarding the presence and activation of these pathway elements in asthmatic patients. OBJECTIVE: We sought to compare the expression and activation of PGD2 pathway elements in bronchoscopically obtained samples from healthy control subjects and asthmatic patients across a range of disease severity and control, as well as in relation to TH2 pathway elements. METHODS: Epithelial cells and BAL fluid were evaluated for HPGDS (quantitative real-time PCR/immunohistochemistry [IHC]) and PGD2 (ELISA/liquid chromatography mass spectrometry) in relation to levels of MC proteases. Expression of the 2 inflammatory cell receptors DP1 and CRTH2 was evaluated on luminal cells. These PGD2 pathway markers were then compared with asthma severity, level of control, and markers of TH2 inflammation (blood eosinophils and fraction of exhaled nitric oxide). RESULTS: Confirming previous results, BAL fluid PGD2 levels were highest in patients with severe asthma (overall P = .0001). Epithelial cell compartment HPGDS mRNA and IHC values differed among groups (P = .008 and P < .0001, respectively) and correlated with MC protease mRNA. CRTH2 mRNA and IHC values were highest in patients with severe asthma (P = .001 and P = .0001, respectively). Asthma exacerbations, poor asthma control, and TH2 inflammatory markers were associated with higher PGD2, HPGDS, and CRTH2 levels. CONCLUSION: The current study identifies coordinated upregulation of the PGD2 pathway in patients with severe, poorly controlled, TH2-high asthma despite corticosteroid use.