Omalizumab Use in Chronic Spontaneous Urticaria during Pregnancy and a Four Years' Follow-Up: A Case Report.

Chronic spontaneous urticaria (CSU) is a benign skin disorder usually responsive to treatment; however, at times it can be difficult to control and become very debilitating. We discuss the case of a woman with CSU that was unresponsive to H1-antihistamines who was treated with omalizumab and became pregnant during omalizumab treatment. We also considered the follow-up of the mother and newborn for 4 years after delivery. Our case report confirms that omalizumab is a safe and effective therapeutic option, after careful evaluations in terms of cost-effectiveness, in pregnant and lactating women with severe chronic urticaria. Assessment throughout follow-up confirmed a regular progression of pregnancy parameters and no adverse reaction was documented in the child from birth to 4 years of age.

Anti-Neutrophil Cytoplasmic Antibodies Positivity and Anti-Leukotrienes in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Monocentric Study on 134 Italian Patients.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. OBJECTIVE: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. METHOD: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca' Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. RESULTS: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. CONCLUSION: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects.

Tryptase as a marker of severity of aortic valve stenosis.

BACKGROUND: Severe aortic valve stenosis is one of the most common cause of mortality in adult patients affected with metabolic syndrome, a condition associated with an active inflammatory process involving also mast cells and their mediators, in particular tryptase. The aim of this study was to characterize the possible long-term prognostic role of tryptase in severe aortic valve stenosis. CASE PRESENTATION: The baseline serum tryptase was measured in 5 consecutive patients admitted to our Hospital to undergo aortic valve replacement for severe acquired stenosis. Within 2 years after, the patients were evaluated for the occurrence of major cardiovascular events (MACE). The tryptase measurements were higher in patients experiencing MACE (10.9, 11.7 and 9.32 ng/ml) than in non-MACE ones (5.69 and 5.58 ng/ml). CONCLUSIONS: In patients affected with severe aortic stenosis, baseline serum tryptase may predict occurence of MACE. Further studies are needed to demonstrate the long-term prognostic role of this biomarker.

Mite-Induced Asthma and IgE Levels to Shrimp, Mite, Tropomyosin, Arginine Kinase, and Der p 10 Are the Most Relevant Risk Factors for Challenge-Proven Shrimp Allergy.

BACKGROUND: Shrimp sensitization is common in the general population, but the presence of symptoms is only moderately related to sensitization. A point still at issue is which in vivo and/or in vitro tests (food challenge, component-resolved diagnosis, house dust mite [HDM] sensitization) can help in distinguishing shrimp-allergic subjects from subjects that are sensitized but tolerant. METHODS: The aim of this study was to evaluate the role of IgE to the different shrimp and mite allergens in distinguishing shrimp challenge-positive from challenge-negative patients. Subjects with suspected hypersensitivity reactions to shrimp, positive skin prick tests (SPTs), and/or anti-shrimp IgE were submitted to open and double-blind placebo-controlled food challenges (DBPCFC). Specific IgE to shrimp, mites, and the recombinants rPen a 1, rDer p 1, 2, and 10 were tested using ImmunoCAP-FEIA. IgE immunoblotting was performed to identify the patients' allergenic profiles. RESULTS: In total, 13 out of 51 (25.5%) patients with reported reactions to shrimp were truly shrimp allergic (7 DBPCFC positive and 6 with documented severe reactions). These patients had significantly higher skin test wheal diameters than nonallergic patients, as well as higher levels of IgE to rPen a 1 and rDer p 10. HDM-induced asthma and the simultaneous presence of anti-nDer p 1, 2, and 10 IgE levels increased the risk of true shrimp allergy. CONCLUSION: Food challenge tests are mandatory for the diagnosis of shrimp allergy. Tropomyosin is associated with clinical reactivity. HDM-induced asthma and anti-mite IgE are risk factors for shrimp allergy.

Tolerated drugs in subjects with severe cutaneous adverse reactions (SCARs) induced by anticonvulsants and review of the literature.

BACKGROUND: Anticonvulsant hypersensitivity syndrome represents a rare but potentially fatal kind of adverse drug reaction. This clinical picture often hampers the flexibility with which alternative anticonvulsants or even other classes of drugs are prescribed in these patients, negatively affecting the efficacy of treatment and the course of the disease. The aim of this study was to analyse a group of six patients with severe cutaneous drug reactions induced by anticonvulsants and to report which alternative antiepileptic drugs and which drugs of other classes were tolerated. CASE PRESENTATION: A total of six patients (2 males and 4 females, age 11-73 years) are described in this study. In all the patients the onset of the severe cutaneous drug reactions was 2-4 weeks after initiating the anticonvulsant therapy: 2 out of 6 patients presented with a drug reaction with eosinophilia and systemic symptoms under therapy with phenytoin; 2 out of 6 presented with Stevens-Johnson syndrome under therapy with lamotrigine; and 2 out of 6 presented with a toxic epidermal necrolysis, one of them under therapy with valproic acid, and the other one under therapy with lamotrigine. Alternative anticonvulsants tolerated after the reaction were: clonazepam, levetiracetam, diazepam, delorazepam and lormetazepam. CONCLUSIONS: In our cases we observed that non aromatic anticonvulsants and benzodiazepines were well tolerated as alternative treatments in six patients with reactions to aromatic anticonvulsivants and that the risk of hypersensitivity reactions to other drug classes was not increased as compared to general population.

Identification of risk factors of severe hypersensitivity reactions in general anaesthesia.

BACKGROUND: Hypersensitivity reactions to anaesthetic agents are rare but often severe, with a mortality ranging from 4 to 9% in IgE-mediated events. Identification of the risk factors may contribute to limit the incidence of these reactions. The aim of our study was to search for possible risk factors of severe perioperative hypersensitivity reactions in our study population. METHODS: For this study we retrospectively reviewed data from 193 patients who experienced drug hypersensitivity reactions during general anaesthesia. The diagnostic protocol consisted of 1) history of the reaction, 2) measurement of serum baseline tryptase and specific IgE-assays for latex, beta-lactams and succinylcholine, 3) skin tests for the agents listed in the anaesthesia chart and for others likely to be safe for future use, latex, and others medications administered during the perioperative period (i.e. antibiotics), 4) subdivision of our patients on the basis of two criteria: a) grade of severity of clinical reactions according to the Ring and Messmer classification; b) results of skin tests and/or serum specific IgE-assays. RESULTS: One hundred of 193 patients had reactions of grade I, 32/193 patients had reactions of grade II, 55/193 patients had reactions of grade III and 6/193 patients had reactions of grade IV. A diagnosis of IgE-mediated reaction was established in 55 cases (28.50%); the most common causes were neuromuscular blocking agents, followed by latex and beta-lactams. Severe reactions were associated with older age (p = 0.025), asthma (p = 0.042), history of hypertension (p = 0.001), intake of serum angiotensin converting enzyme inhibitor medication (p = 0.012) or serum angiotensin II antagonist (p = 0.033), higher levels of basal tryptase (p = 0.0211). Cardiovascular symptoms (p = 0.006) and history of hypersensitivity to antibiotics (p = 0.029) were more frequently reported in IgE-mediated reactions. CONCLUSIONS: We confirmed the relevance of several clinical features as risk factors for anaphylactic reactions induced by anaesthetic agents: older age, asthma, hypertension and antihypertensive drugs. We observed increased levels of serum basal tryptase in severe reactions: this finding may signify that this biomarker is useful for the identification of patients at risk.

Anti-Amoxicillin Immunoglobulin E, Histamine-2 Receptor Antagonist Therapy and Mast Cell Activation Syndrome Are Risk Factors for Amoxicillin Anaphylaxis.

BACKGROUND: ß-Lactam antibiotics (mainly amoxicillin, AX) are the drugs that most frequently induce systemic drug allergy reactions. OBJECTIVE: We attempted to identify the risk factors associated with systemic reactions to AX. METHODS: All patients who were referred to our department for suspected hypersensitivity reactions to AX over a 6-month period were evaluated for anti-AX immunoglobulin E (IgE) levels and skin-test positivity for ß-lactams. Age, sex, concomitant diseases, therapies, total IgE, serum tryptase levels and signs and symptoms suggesting mast cell activation syndrome (MCAS) were analyzed in relation to the severity of the reaction in accordance with the Mueller classification. RESULTS: Sixty-seven patients were selected: 39 with mild reactions such as cutaneous or gastrointestinal symptoms (grades I and II) and 28 with severe systemic reactions (grades III and IV). Anti-AX IgE levels and total IgE were significantly higher in severe reactions than in mild ones (p < 0.00005, p = 0.0037). Treatment with histamine-2 receptor antagonists (anti-H2) was significantly related to severe reactions (p = 0.007). No significant correlations were found between the severity of the reactions and dyslipidemia or levels of angiotensin-converting enzyme and tryptase. CONCLUSION: Anti-AX IgE levels were the most significant immunological parameter distinguishing patients who presented with severe reactions to AX and those with mild reactions. Higher values of total IgE, the use of gastroprotective drugs and signs and symptoms suggesting an MCAS significantly increased the odds ratio of having a severe reaction. The risk of serious adverse reactions to AX increased in older patients and in males, but this trend was not significant.

Rice allergy demonstrated by double-blind placebo-controlled food challenge in peach-allergic patients is related to lipid transfer protein reactivity.

BACKGROUND: The risk factors for sensitisation to rice and the involved allergens are still partially unknown. In this study we evaluated the clinically relevant aspects of rice allergy in DBPCF-positive patients, the major rice allergens, the severity of peach- and rice-induced symptoms in respect to Pru p 3 sensitisation and the role of anti-rPru p 3 IgE levels as a risk factor for rice allergy. METHODS: In 148 peach-allergic subjects, patients with allergic reactions to rice and rice-positive serum IgE were selected. Symptoms were verified by double-blind placebo-controlled food challenges (DBPCFCs), performed at a maximum dosage of 25 g. Rice allergens, identified by IgE immunoblotting, were characterised by N-terminal amino acid sequencing. The relationship between anti-rPru p 3, 1 and 4 IgE levels and rice symptoms were statistically analysed. RESULTS: Eight out of 10 recruited rice-allergic patients had positive DBPCFCs, while 2 patients were not challenged due to their previously documented severe reactions. All patients with rice-induced symptoms were Pru p 3 positive and presented with higher anti-rPru p 3 levels than the rice-sensitised but tolerant patients. A 9-kDa lipid transfer protein, which was highly homologous to Pru p 3, was identified as the major rice allergen and elicited a positive response in all of the patients. Five patients reacted to a putative 15- to 17-kDa rice allergenic protein, and 3 patients reacted to an [alpha]-amylase/subtilisin inhibitor that was approximately 20 kDa. CONCLUSION: Rarely, allergic reactions to rice can arise in patients with peach allergies who are sensitised to Pru p 3, particularly in patients with high anti-rPru p 3 IgE levels.