Idiopathic, Refractory Sweet's Syndrome Associated with Common Variable Immunodeficiency: a Case Report and Literature Review.

PURPOSE OF REVIEW: Sweet's syndrome (SS) is classically considered a hypersensitivity reaction often associated with autoimmune disorders and malignancy. SS has also been increasingly reported to occur with immunodeficiencies. We present a case of treatment-refractory, systemic SS as the initial manifestation in a young child with common variable immunodeficiency (CVID). We also review current literature about SS and concurrent immunodeficiencies and autoimmunity in CVID patients. RECENT FINDINGS: Few case reports exist regarding the co-occurrence of Sweet's syndrome and primary immunodeficiencies. SS is characterized by a pro-inflammatory state with a neutrophil predominance resulting in a spectrum of clinical manifestations. CVID is a multifactorial antibody deficiency that can be associated with autoimmunity, which some studies have proposed to be secondary to altered CD21 expression. SS occurring in patients with CVID has been infrequently reported, and one case study demonstrated improvement of Sweet's associated skin lesions with immunoglobulin replacement. In our case, the patient had multi-system SS refractory to multiple immunomodulatory therapies. To our knowledge, this is the first report of the effective and safe use of intravenous tocilizumab and oral lenalidomide to treat SS in a child with CVID. Immunoglobulin replacement reduced the frequency of infections and may have contributed to the opportunity to wean the immunosuppressive therapies for Sweet's syndrome. Sweet's syndrome as an initial manifestation of co-occurring immunodeficiencies is rare, and providers need a high index of suspicion. In addition, treatment of SS associated with an immunodeficiency can be a challenge. Treatment with immunoglobulin replacement reduces the frequency of infections, and in some patients with concurrent SS may improve skin lesions and reduce the need for immunomodulator therapy. Further study is necessary to better understand the pathogenesis of CVID in patients with SS and to identify possible biomarkers that predict who with SS are at risk for developing hypogammaglobulinemia.

Update on peanut allergy: Prevention and immunotherapy.

Background: The prevalence of food allergy is steadily increasing, and the burden of food allergy has become significant. However, treatments for food allergy remain experimental. Objective: To review advances in the past 18 months for the prevention and treatment of food allergies, with a particular focus on peanut allergy. Methods: Recently published trials on the use of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) as well as updates on the implementation of the early introduction of peanut guidelines were identified. Results: To address the slow implementation of the early introduction of peanut guidelines, addendum guidelines were published by the National Institute of Allergy and Infectious Diseases, which provide broader and more practical guidelines across a wider range of patients. Well-known studies of OIT have supported its efficacy. Recent studies have shown the potential for sustained unresponsiveness (SU) in up to 50% of subjects after peanut OIT and an even higher proportion in toddlers who received peanut OIT. Adjustments in the protocol to address practicality and safety have shown potential for lower maintenance doses and faster buildups. Longer durations of peanut SLIT have shown successful desensitization to moderate amounts of peanut and may also show the potential for SU. EPIT has maintained an excellent safety profile with statistically significant response rates in children <11 years of age. Conclusion: Advances in food immunotherapy have continued to push the field forward and provided a better understanding of the safety and efficacy of OIT, SLIT, and EPIT. These treatments remain experimental, although phase III studies are currently underway.

Peptide and Recombinant Allergen Vaccines for Food Allergy.

Food allergy is a significant public health problem, with no suitable treatments available for patients. Currently, patients are limited to avoidance and the use of readily available emergency medications. Immunotherapy is an appealing therapeutic strategy for inducing tolerance. Studies with whole native allergens have demonstrated the efficacy of immunotherapy for food allergy; however, the risk of IgE-mediated reactions with such treatment is significant. Advances in molecular biology techniques, including purification, sequencing, and cloning, have allowed researchers to identify specific allergen components and T cell binding epitopes. Support for the use of recombinant and peptide vaccines for food allergy comes from prior studies involving aeroallergens and hymenoptera venom. By manipulating allergen structure and IgE binding, allergenicity can be reduced, thereby reducing systemic reactions, making recombinant and peptide vaccines a safe and effective form of immunotherapy. Pre-clinical studies using in vitro and murine models demonstrated a more tolerant state following the use of these therapies. Studies with human subjects will be necessary to characterize the effects of recombinant and peptide food allergy vaccines and to demonstrate a safe treatment option for patients.