Effect of Gender and Special Considerations for Women in Mastocytosis and Anaphylaxis.

This article reviews the effects of gender on anaphylaxis in general and focuses on mastocytosis-specific issues. Incidence of anaphylaxis is increased in female compared with male patients during the pubertal years through the fifth decade of life, in which these disparities decrease. Estrogen is thought to increase the severity of anaphylaxis through increased endothelial nitric oxide synthase release. Despite this, all-cause fatal anaphylaxis does not appear to show a gender predilection. Systemic mastocytosis incidence is higher in women; however, mortality is increased in men owing to increased molecular and cytogenetic abnormalities.

Mastocytosis in Pregnancy.

Mastocytosis is a rare neoplastic disorder of the mast cell lineage resulting in unregulated proliferation and activation of mast cells. Symptoms worsen in about one-third of pregnant patients. Treatment focuses on management of symptoms with antimediator therapy (H1 & H2 antihistamines, glucocorticoids, and epinephrine, if required). Medication selection requires care during labor and delivery. Although it is generally considered safe to use a medication patient tolerated before, some common medications may need to be avoided or used with caution (eg, codeine, morphine, nonsteroidal antiinflammatory drugs, vancomycin) if the patient does not have any history of exposure to them.

Vaccination counseling with and without excipient skin testing in patients with suspected allergic reactions to mRNA COVID-19 vaccines and patients with atopy.

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.

Clinical Profile and Treatment in Hypereosinophilic Syndrome Variants: A Pragmatic Review.

BACKGROUND: Hypereosinophilic syndrome (HES) is a group of rare hematologic disorders leading to eosinophil-driven tissue damage and dysfunction. Better understanding of HES variants may facilitate improved patient management. OBJECTIVE: To describe disease characteristics, treatment, and outcomes of patients with idiopathic (I-HES), myeloproliferative (M-HES), lymphocytic (L-HES), and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) among HES case reports and aggregate data where available. METHODS: Relevant articles published between January 1, 2000, and March 20, 2020, were retrieved via PubMed; those reporting secondary, associated/reactive, overlap/single-organ, or familial HES were excluded. RESULTS: Of 188 articles included, 171 contained data on 347 separate HES cases (152 I-HES, 121 M-HES, 62 L-HES, 12 CEL-NOS). Based on individual data, mean age at diagnosis was 43 to 48 years for patients with all HES variants. Males accounted for 90% to 91% of M-HES/CEL-NOS and 55% to 65% of I-HES/L-HES cases. Cardiac symptoms were frequently observed for all HES variants (13%-22% of patients). Respiratory symptoms (I-HES), splenomegaly (M-HES and CEL-NOS), and skin conditions (L-HES) were also frequently observed. Bone marrow, heart, lung, spleen, liver, skin, and lymph nodes were commonly involved. Most patients with I-HES, L-HES, and CEL-NOS received corticosteroids (65%-85%), whereas most with M-HES received imatinib (81%); those with CEL-NOS also received interferon alpha (42%). CONCLUSIONS: Collective analysis of HES case reports supports and extends current understanding of HES variants, highlighting differences in signs and symptoms, organ involvement, and treatment approaches. Improved characterization of HES variants may facilitate the development of novel treatments.

Case report of heart transplantation for giant cell myocarditis in a patient with common variable immunodeficiency.

BACKGROUND: Solid-organ transplantation in patients with common variable immunodeficiency (CVID) is controversial due to the risk for severe and recurrent infections. Determining transplantation candidacy in CVID patients is further complicated by the presence of CVID-related non-infectious complications that can reduce overall survival and also recur in the transplanted organ. Data regarding solid organ transplantation in patients with CVID are limited, particularly in heart transplantation. CASE SUMMARY: A 32-year-old female with CVID presented with new heart failure after 3 months of dyspnoea on exertion. Her echocardiogram showed severe global systolic dysfunction with an ejection fraction of approximately 10%, and her right heart catheterization revealed severe biventricular pressure overload and severely reduced cardiac output. Endomyocardial biopsy revealed giant cells and mononuclear infiltrate consistent with giant cell myocarditis (GCM). Despite medical management, she developed progressive cardiogenic shock and underwent uncomplicated orthotopic heart transplantation on hospital Day 38. After 2 years of follow-up, she has had no major infectious complications and continues to have normal graft function with no recurrence of GCM. CONCLUSION: We report a case of successful heart transplantation for GCM in a patient with CVID, with no major infectious complications after 2 years of follow-up. CVID should not be considered an absolute contraindication for heart transplantation.

Gastrointestinal Manifestations of Hypereosinophilic Syndromes and Mast Cell Disorders: a Comprehensive Review.

Hypereosinophilic syndrome and mastocytosis are relatively rare proliferative diseases encountered in the general population. However, allergists frequently consider these disorders in the differential of patients presenting with gastrointestinal, pulmonary, cutaneous, and allergic symptoms. Gastrointestinal symptoms are some of the most frequent and/or debilitating aspects of both disease states and in many cases lead to poor quality of life and functional limitation for the patient. They are the third most common clinical manifestation in hypereosinophilic syndrome and have been found to be the most distressful aspect of the disorder in those with systemic mastocytosis. Both eosinophils and mast cells play integral parts in normal gut physiology, but when and how exactly their effector functionality translates into clinically significant disease remains unclear, and the available literature regarding their pathophysiology remains sparse. Eosinophils and mast cells even, in fact, may not necessarily function in isolation from each other but can participate in bidirectional crosstalk. Both are affected by similar mediators and can also influence one another in a paracrine fashion. Their interactions include both production of soluble mediators for specific eosinophil and mast cell receptors (for example, eosinophil recruitment and activation by mast cells releasing histamine and eotaxin) as well as direct physical contact. The mechanistic relationship between clonal forms of hypereosinophilia and systemic mastocytosis has also been explored. The nature of gastrointestinal symptomatology in the setting of both hypereosinophilic syndrome and mast cell disease is frequently manifold, heterogeneous, and the lack of better targeted therapy makes diagnosis and management challenging, especially when faced with a substantial differential. Currently, the management of these gastrointestinal symptoms relies on the treatment of the overall disease process. In hypereosinophilia patients, systemic corticosteroids are mainstay, although steroid-sparing agents such as hydroxyurea, IFN-α, methotrexate, cyclosporine, imatinib, and mepolizumab have been utilized with varying success. In mastocytosis patients, anti-mediator therapy with antihistamines and mast cell stabilization with cromolyn sodium can be considered treatments of choice, followed by other therapies yet to be thoroughly studied, including the role of the low-histamine diet, corticosteroids, and treatment of associated IBS symptoms. Given that both eosinophils and mast cells may have joint pathophysiologic roles, they have the potential to be a combined target for therapeutic intervention in disease states exhibiting eosinophil or mast cell involvement.

Management of Mastocytosis in Pregnancy: A Review.

In this article, the authors present a case of pregnancy complicated by the need for management of indolent systemic mastocytosis. The diagnosis of mastocytosis is reviewed, as well as subtypes of mastocytosis and management options particularly in pregnancy. A table of pregnancy/lactaction categories for common medications used in mastocytosis is presented.

Eosinophilia.

Eosinophilia is defined as elevation of eosinophils in the bloodstream (450-550 cell/µL). There are many reasons for eosinophilia to exist, including parasitic disease, allergic disease, autoimmune, connective tissue disease, rheumatologic disease, primary eosinophilia such as hypereosinophilic syndrome, and as part of a malignant state. Primary care physicians should have an understanding of the variety of diseases or situations that can produce eosinophilia and know in what setting referral to specialty care may be warranted.

Eosinophilia in mast cell disease.

Eosinophils and mast cells coexist in clonal and nonclonal disorders. The interplay between these cells is complex and not fully understood. Discussed are both allergic/nonclonal disorders in which both cell types are increased in number are likely to play a role in pathogenesis and clonal disorders in which both cell types are affected and play key roles in pathogenesis. Finally, some treatment options, keeping both disorders in mind, are discussed. Future directions in thinking about these disorders are also briefly explored.