Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review.

INTRODUCTION: Allergic and nonallergic hypersensitivity reactions to iodinated contrast media (ICM) and gadolinium-based contrast media are classified as immediate or non-immediate hypersensitivity reactions (IHR and NIHR), respectively. Skin tests and provocation tests are recommended for the evaluation of hypersensitivity reactions to contrast agents; however provocations are not common in clinical practice. METHODS: A MEDLINE search was conducted to investigate studies comprising both skin tests and provocation tests that evaluated hypersensitivity reactions to ICM. RESULTS: Nineteen studies were identified that reported on skin tests, followed by provocations. In the case of IHR to ICM, 65/69 (94%) patients with a positive skin test for the culprit media tolerated a challenge with a skin-test-negative alternative ICM. In IHR to ICM with a negative skin test for the culprit media, provocations were positive in 3.2%-9.1% patients. In the case of a NIHR to ICM with a positive skin test, provocation with a skin-test-negative agent was tolerated in 75/105 (71%) of cases. In NIHR with a negative skin test for the culprit agent, re-exposure to the culprit or an alternative was positive in 0%-34.6% patients. Provocations with the same ICM in skin test positive patients with IHR or NIHR were positive for a majority of the patients, although such provocation tests were rarely performed. Data on hypersensitivity reactions, skin tests and provocations with gadolinium-based contrast media were limited; however, they exhibited a pattern similar to that observed in ICM. CONCLUSION: In both ICM and gadolinium-based contrast media, the risk of an immediate repeat reaction is low when skin tests are negative. In contrast, a provocation with a skin-test-positive contrast medium showed a high risk of an immediate repeat hypersensitivity reaction. Therefore, a thorough medical history is necessary, followed by skin tests. A provocation is recommended, for diagnostic work-up, when the diagnosis is uncertain.

The treatment outcomes in IgG4-related orbital disease: a systematic review of the literature.

IgG4-related disease (IgG4-RD) is an immune-mediated systemic fibro inflammatory disease. Treatment of IgG4-related orbital disease (IgG4-ROD) is often indicated to relieve the symptoms and to prevent complications. For IgG4-ROD, no international formal treatment guidelines are available and the optimal treatment strategy is uncertain. In this systematic review, we describe the efficacy of conventional and biologic disease-modifying antirheumatic drugs (DMARDs) in IgG4-ROD. A systematic search of Embase, Medline, Web-of-Science, PubMed publisher, Cochrane and Google Scholar was performed for treatment outcomes in IgG4-ROD. Relevant articles on treatment of IgG4-ROD were retrieved to last date of inclusion 3 January 2018. The following inclusion criteria were used: articles in English or English translation, studies evaluating the use of DMARDs (conventional and biologic) in the treatment of IgG4-ROD. Meta-analysis and review articles were excluded. A final selection after full-text evaluation was made by independent reviewers, based on treatment of IgG4-ROD with DMARDs and the availability of treatment outcomes. With this systematic review, we identified 35 studies and case reports/series on IgG4-ROD, describing 95 patients, treated with conventional and/or biologic DMARDs. The success of conventional DMARDs varies between 36% and 75% in patients with IgG4-ROD, while rituximab is successful in the majority (93%) of the patients. Based on this systematic review, rituximab is the most effective DMARD in IgG4-ROD, while the efficacy of conventional DMARDs is limited. We propose early initiation of rituximab in case of refractory and organ- or life-threatening disease.

Expansion of blood IgG4+ B, TH2, and regulatory T cells in patients with IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG4+ plasma cells in tissue are hallmarks of the disease, and IgG4-RD is associated with increased IgG4 serum levels. However, disease pathogenesis is still unclear, and these cellular and molecular parameters are neither sensitive nor specific for the diagnosis of IgG4-RD. OBJECTIVE: Here we sought to develop a flow cytometric gating strategy to reliably identify blood IgG4+ B cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis. METHODS: Sixteen patients with histologically confirmed IgG4-RD, 11 patients with sarcoidosis, and 30 healthy subjects were included for 11-color flow cytometric analysis of peripheral blood for IgG4-expressing B cells and TH subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG4-expressing B cells, and IgG4 transcripts were analyzed for somatic hypermutations. RESULTS: Cellular and molecular analyses revealed increased numbers of blood IgG4+ memory B cells in patients with IgG4-RD. These cells showed reduced expression of CD27 and CXCR5 and increased signs of antibody maturation. Furthermore, patients with IgG4-RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21low B cells, as well as TH2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG4-RD. CONCLUSION: These results provide new insights into the dysregulated IgG4 response in patients with IgG4-RD. A specific "peripheral lymphocyte signature" observed in patients with IgG4-RD, could support diagnosis and treatment monitoring.