A Patient Charter for Chronic Urticaria.

Chronic urticaria (CU) is the recurring development of wheals (aka "hives" or "welts"), angioedema, or both for more than 6 weeks. Wheals and angioedema occur with no definite triggers in chronic spontaneous urticaria, and in response to known and definite physical triggers in chronic inducible urticaria. Approximately 1.4% of individuals globally will have CU during their lifetime. The itching and physical discomfort associated with CU have a profound impact on daily activities, sexual function, work or school performance, and sleep, causing significant impairment in a patient's physical and mental quality of life. CU also places a financial burden on patients and healthcare systems. Patients should feel empowered to self-advocate to receive the best care. The voice of the patient in navigating the journey of CU diagnosis and management may improve patient-provider communication, thereby improving diagnosis and outcomes. A collaboration of patients, providers, advocacy organizations, and pharmaceutical representatives have created a patient charter to define the realistic and achievable principles of care that patients with CU should expect to receive. Principle (1): I deserve an accurate and timely diagnosis of my CU; Principle (2): I deserve access to specialty care for my CU; Principle (3): I deserve access to innovative treatments that reduce the burden of CU on my daily life; Principle (4): I deserve to be free of unnecessary treatment-related side-effects during the management of my CU; and Principle (5): I expect a holistic treatment approach to address all the components of my life impacted by CU. The stated principles may serve as a guide for healthcare providers who care for patients with CU and translate into better patient-physician communication. In addition, we urge policymakers and authors of CU treatment guidelines to consider these principles in their decision-making to ensure the goals of the patient are achievable.

Case series: expanding diagnostic markers in postorgasmic illness syndrome.

Introduction: Postorgasmic illness syndrome (POIS) is a rare condition in which individuals develop generalized and flu-like symptoms after ejaculation. Several mechanisms and treatments for this disorder have been proposed but many questions remain. Aims: We sought to present a summary of literature to date and highlight common symptoms, associated features, comorbidities, and laboratory findings in a clinical sample of patients with POIS. Methods: We conducted a retrospective chart review of 6 patients with POIS in our clinic and presented compiled results. Results: We identified newly described non-flu-like presentations, onset of symptoms with high states of arousal without ejaculation, and presence of psychiatric comorbidity in a majority of patients. We did not identify a postorgasm allergic response with bloodwork available. Conclusion: POIS remains a poorly understood condition that likely comprises a number of different clinical entities. Further research on a larger clinical sample is necessary to better characterize POIS and understand its biological and psychological basis.

Transitioning subcutaneous immunoglobulin 20% therapies in patients with primary and secondary immunodeficiencies: Canadian real-world study.

BACKGROUND: Real-world data on transitioning to Immune Globulin Subcutaneous (Human) 20% solution (Ig20Gly) are limited. This study aimed to assess infusion parameters and experience of patients with primary (PID) or secondary immunodeficiencies (SID) transitioning to Ig20Gly in clinical practice in Canada. METHODS: Patients with PID or SID who received subcutaneous immunoglobulin (SCIG) for ≥ 3 months before transitioning to Ig20Gly were eligible for this multicenter (n = 6), phase 4, non-interventional, prospective, single-arm study. Ig20Gly infusion parameters, dosing, and adverse events were collected from patient medical records at Ig20Gly initiation and 3, 6, and 12 months post-initiation. Patient satisfaction and quality of life were assessed 12 months post-initiation using validated questionnaires. RESULTS: The study included 125 patients (PID, n = 60; SID, n = 64; PID + SID, n = 1). Median volume per infusion was 30.0 ml at initiation, and 40.0 ml at 6 and 12 months post-initiation. Most patients administered Ig20Gly weekly and used two infusion sites (primarily abdomen). At each time point, median infusion duration was ≤ 1 h. At 12 months, 61% of infusions were administered via a pump and 39% manually. Headache and infusion-site reactions were the most reported adverse events of interest. Patients expressed overall satisfaction with Ig20Gly at 12 months post-initiation, with all respondents indicating they would like to continue Ig20Gly. CONCLUSIONS: This study provides a detailed description of Ig20Gly infusion parameters, tolerability, and quality of life in clinical practice among patients with PID or SID switching to Ig20Gly from another SCIG and confirms the feasibility of infusing Ig20Gly via pump or manual administration. Trial registration NCT03716700, Registered 31 August 2018, https://clinicaltrials.gov/ct2/show/NCT03716700.

The use of dupilumab in severe atopic dermatitis during pregnancy: a case report.

BACKGROUND: Atopic dermatitis is a common chronic skin disease that can occur in pregnancy. Current treatments include topical and systemic glucocorticoids and cyclosporine. Presently, the only biologic approved for atopic dermatitis is dupilumab with limited data available regarding its safety profile in pregnancy. CASE PRESENTATION: We report a case of severe atopic dermatitis treated safely with dupilumab with no adverse maternal or fetal outcomes and resolution of atopic dermatitis postpartum in the absence of maintenance dupilumab therapy. CONCLUSION: Here we demonstrate the safe use of dupilumab in pregnancy. Further research is needed to elucidate the role of dupilumab in the management of atopic dermatitis during pregnancy.

Cannabis-related allergies: An international overview and consensus recommendations.

Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.

Demographic and clinical characteristics of patients with hereditary angioedema in Canada.

BACKGROUND: Data on the clinical and demographic features of Canadian patients with hereditary angioedema (HAE) are lacking. OBJECTIVE: To describe the clinical and demographic features in a large Canadian HAE cohort and compare them with patients with HAE in other countries. METHODS: An online questionnaire was distributed to the members of 2 Canadian HAE patient groups to collect information on demographics and HAE clinical characteristics. All participants 18 years of age or older with HAE type I or II were eligible. Frequency, location, prodromes, and triggers of HAE attacks, including types of HAE treatment, were characterized. RESULTS: Among the 90 participants who completed the online survey, 57% self-identified as having HAE type 1 and 26% HAE type II. The average diagnostic delay was 11 years. In the preceding 6 months, 24% of the participants had no attacks and 35% experienced greater than 5 attacks. The most frequently affected regions of the body were the abdomen (83%), arms orlegs (63%), face (41%), and larynx or throat (41%). Approximately 87% of the participants reported having access to C1 inhibitor at home, and 69% reported using it for long-term prophylaxis. CONCLUSION: Canadian patients with HAE share common clinical characteristics with patients with HAE in other countries. They had a delay in HAE diagnosis and a high burden of disease, as indicated by the high frequency of attacks in the preceding 6 months. This study provides a better understanding of the demographic and clinical characteristics of Canadian patients with HAE.

Malignancy and immune disorders in patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is an inherited condition manifesting as recurrent angioedema episodes which is caused by deficiency or dysfunction of C1 inhibitor. Although complement dysregulation has historically been shown to be associated with various malignancy and immune disorders, it is currently not known if HAE patients are at an increased risk of developing malignancy or autoimmune conditions. CASE PRESENTATION: We reviewed the charts of 49 HAE patients and identified 6 patients who had a co-existing malignancy diagnosis (two with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer and one with cervical dysplasia) and 6 patients who had a diagnosis of a co-existing immune disorder (two with rheumatoid arthritis, two with ulcerative colitis, one with chronic urticaria with hypothyroidism and one with Sjogren's syndrome). Nearly all malignancy cases occurred in older HAE patients (> 50 years) and malignancy was diagnosed before HAE in 3 of the patients. CONCLUSIONS: Our case series identified multiple hereditary angioedema (HAE) patients with co-existing malignancy and immune disorders. Based on these findings, we would advocate that physicians managing HAE patients should maintain a high index of suspicion for these conditions and that in patients with angioedema, C1 inhibitor deficiency and malignancy, a diagnosis of HAE should still be considered in addition to acquired angioedema (AAE).

The role of C1 inhibitor and complement as acute phase reactants: are we missing the diagnosis of hereditary angioedema?

BACKGROUND: C1 inhibitor (C1-INH) and complement 4 (C4) have historically been referred to as positive acute phase reactants, however this has never been evaluated in hereditary angioedema (HAE) patients. Low function of C1-INH and low levels of C4 are important in the diagnosis of HAE type 1 and 2. If C1-INH and/or C4 are significant acute phase reactants, their levels may be falsely "normal" in patients with HAE when measured during times of infection or inflammation resulting in missed or delayed diagnosis. CASE PRESENTATION: We present a case series of four HAE patients who had C4, C1-INH, c-reactive protein (CRP) and ferritin measured at baseline and again during a self-reported upper respiratory tract infection (URTI) or flu-like illness. We did not identify any HAE patients who had a significant change in their C1-INH functional level in the context of a mild infection. However, the C4 level did increase into the normal range on three occasions (2 patients, with 1 patient having elevation during two separate illnesses). CONCLUSIONS: C1 inhibitor may not be a clinically significant acute phase protein and appears to still be a reliable diagnostic marker of hereditary angioedema, even in times of modest acute inflammation, unlike complement C4 which can be elevated in this setting.

Impact of lanadelumab in hereditary angioedema: a case series of 12 patients in Canada.

BACKGROUND: Hereditary angioedema (HAE) is a rare autosomal dominant disease resulting in recurring episodes of swelling, leading to considerable patient morbidity and mortality. Lanadelumab is a plasma kallikrein inhibitor that is approved as 1st line therapy in Canada for long term prophylaxis of HAE attacks. OBJECTIVE: To describe our clinical findings from a case series of adult patients with HAE type 1/2 who have been initiated on lanadelumab. METHODS: A chart review of HAE type 1/2 patients at three academic centers in Canada was undertaken with demographic and clinical data extracted. Patients were included if they had been receiving lanadelumab for at least 6 months. Patients with other causes of angioedema were excluded. RESULTS: 12 patients meeting enrollment criteria were identified. Compared to pre-lanadelumab, patients had mean reductions of 72% and 62% in attack rate and treated attack rate respectively. 3 patients reported complete remission from attacks after starting lanadelumab. Most patients had significant improvements in HAE impact on social outings. CONCLUSION: Our case series findings support the 2019 International/Canadian HAE guideline that lanadelumab is an effective therapy for long term prophylaxis. In our patient population, initiation of lanadelumab improved disease control, minimized the burden of treatment and improved HAE impact on social outings.

Selective cannabis strain allergy in a patient presenting with a local allergic reaction.

BACKGROUND: Cannabis use is growing domestically due to recent legalization in many jurisdictions. There are two main species of cannabis, Cannabis sativa and Cannabis indica, and thousands of different commercially available cannabis strains. Although there are multiple reports of cannabis allergy in the literature, to our knowledge, there is no prior published report of selective cannabis strain allergy. CASE PRESENTATION: A 31-year-old male was referred for allergy assessment due to several episodes of localized pruritus and erythema after direct contact with various strains of cannabis. He had noted that the severity of his reaction appeared to be strain dependent. He developed a severe local reaction involving bilateral periorbital edema shortly after coming into direct contact with one particular strain of cannabis. He denied any adverse symptoms after inhalation of cannabis. Fresh skin prick testing was performed to various strains of cannabis and had positive testing to the three of the five tested strains. CONCLUSIONS: We believe this is the first reported case of selective cannabis strain allergy based on patient history and skin prick testing. This case report outlines the variability in different strains of cannabis and stresses the importance of further research into cannabis allergen identification. Multiple cannabis allergens should be included and incorporated into commercial extracts when they become routinely available.

Quality of life in patients with hereditary angioedema in Canada.

BACKGROUND: Hereditary angioedema (HAE) is associated with decreased quality of life (QoL), which has typically been measured using a generic non-disease-specific questionnaire. OBJECTIVE: We aimed to assess the QoL in patients with HAE type I and II in Canada using a previously validated HAE-specific questionnaire. METHODS: An online questionnaire was sent to the members of two Canadian HAE patient groups to collect data on demographics, HAE clinical course, and QoL scores. All patients 18 years of age or older with HAE type I or II were eligible. The impact of the available clinical factors on the QoL scores was evaluated. Multiple linear regression was performed using clinically relevant factors to predict HAE QoL outcome. RESULTS: Among the 72 patients in the study, the mean total HAE QoL score was 102 (±23) (SD) on a scale of 25 to 135, with higher scores indicating better QoL. Although the total QoL scores correlated positively with patients' level of satisfaction and perceived control (P < .001 for both), it correlated negatively with the number of acute attacks (P = .03). Yet, the types of treatment did not have an impact on the QoL. Predictors, including sex, comorbidities, and the number of attacks, only explained 12% of the variance in the total QoL scores. CONCLUSION: HAE continues to impair QoL in Canadian patients despite receiving recommended treatment. Although the frequency of attacks affects QoL, patients' experience with their HAE care also affects QoL substantially. The study highlights the importance of considering patients' experience with their HAE care as physicians develop an appropriate management plan.

Natural history, prognostic factors and patient perceived response to treatment in chronic spontaneous urticaria.

BACKGROUND: Although the diagnosis and management of chronic spontaneous urticaria (CSU) is well documented in the literature, some aspects of the disease remain unclear. We aimed to further describe the natural history, prognostic factors, humanistic burden and uptake of traditional and alternative therapies in patients with CSU. METHODS: This was a prospective, cross-sectional analysis at a single centre. We reviewed patient medical records and conducted a survey in patients with CSU. RESULTS: 72 patients participated in the study with a median duration of CSU of 48 months. 30% of patients had symptoms that resolved in under 2 years with these patients trending towards an older age of onset of CSU (48 ± 17 years). 16% of patients had symptoms lasting 10 years or longer with these patients trending towards a younger age of onset (22 ± 16 years). Patients with a relapsing/remitting disease course (31%) and those with co-existing angioedema (57%) trended towards a longer median duration of CSU (96 and 50 months respectively) and were observed to have a higher proportion of patients reporting CSU duration of 10 years or longer (33% and 25%, p = 0.033 and p = 0.036 respectively). Patients with co-existing autoimmune/thyroid disease (19%) trended towards a shorter median duration of CSU (37 months). 54 patients (75%) reported sleep disturbance and 29 patients (43%) required emergency room visit(s) for symptomatic control. 84% of patients who trialed second generation antihistamines reported a response to treatment, while 73% of patients who trialed omalizumab reported a response to treatment. Patients using alternative medicine such as acupuncture, traditional Chinese medicine and naturopathic medicine had lower reported response rates (20-29%) to treatment. CONCLUSIONS: The natural history of CSU may be longer than previously reported with our study finding a median duration of symptoms of nearly 4 years with one-third of patients reporting a relapsing/remitting disease course. Younger age of onset, a relapsing/remitting disease course and angioedema may predict a longer duration of CSU, whereas older age of onset and co-existing autoimmune/thyroid disease may predict a shorter duration of CSU. Reported symptomatic benefit was higher from guidelines based pharmacologic therapy versus various alternative medicines.

Correction to: The International/Canadian Hereditary Angioedema Guideline.

[This corrects the article DOI: 10.1186/s13223-019-0376-8.].

Development of the Hereditary Angioedema Rapid Triage Tool.

BACKGROUND: Patients with hereditary angioedema (HAE) present to the emergency department (ED), where their symptoms are often incorrectly attributed to common allergic and gastrointestinal conditions, resulting in major delays in diagnosis and treatment. OBJECTIVE: To develop a rapid triage HAE (Hereditary AngioEdema Rapid Triage [HAE-RT]) tool for ED settings. METHODS: A mixed-methods approach was used in 3 phases: Phase 1: A literature review on the current management of patients with HAE in the ED. Phase 2: A Delphi study with HAE specialists (N = 9) and Patient Advocacy Group Members (N = 3) to reach consensus on the predictor variables (PVs) to be included in the HAE-RT tool. Phase 3: A retrospective chart review to assess the performance of the PVs for HAE. RESULTS: The literature review informed the final list of PVs included in the HAE-RT prototype. Nine experts participated in the Delphi study. Of 8 identified HAE-specific PVs, 3 reached consensus: (1) absence of urticaria, (2) recurrent abdominal pain/swelling, and (3) lack of response to allergic-directed therapy. The retrospective study included 107 patients (N = 66 with HAE; N = 41 non-HAE). Patients with HAE were more likely to have a family history of HAE (71%; P < .0001), previous recurrent angioedema (96%; P < .002), and previous recurrent abdominal pain (77%; P < .0001), and only 6% responded to allergy treatments (P < .0001). The HAE-RT tool had 98% sensitivity and specificity. CONCLUSIONS: Expert consensus led to the identification and prioritization of variables that when incorporated into an HAE-RT tool were associated with a high level of sensitivity and specificity when applied to known patients.

The International/Canadian Hereditary Angioedema Guideline.

This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.

Review of cold-induced urticaria characteristics, diagnosis and management in a Western Canadian allergy practice.

BACKGROUND: Cold-induced urticaria is a significant condition, especially among young females. Despite the morbidity of this disease, studies that fully characterize the disease are limited. METHODS: We analyzed the characteristics of patients diagnosed with cold-induced urticaria at a community-based allergy practice in Vancouver, BC, Canada between 2003 and 2016. Detailed patient history, diagnostic measures and treatment were evaluated. RESULTS: A total of 50 patients were found to have active cold-induced urticaria with a median age of 28.5 (range 2-67) years and 35 patients (70%) were female. 16 patients (32%) had co-occurring physical urticarias while 26 patients (52%) had secondary allergic diagnoses and 3 patients (6%) were thought to have a provoking factor. Of those with a clinical history of suspected cold-induced urticaria that were evaluated with ice cube testing, a positive test was obtained in 84.7% of patients. Treatment was largely with non-sedating antihistamines, with the majority of patients receiving this modality. CONCLUSIONS: Cold-induced urticaria is a complex disease with significant overlap with other chronic inducible urticarias and other allergic diseases. Diagnostic testing shows inconsistent results and the mainstay of treatment consists of non-sedating antihistamines, with other options available for those who do not respond.

The diagnosis of hereditary angioedema with C1 inhibitor deficiency: a survey of Canadian physicians and laboratories.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease resulting in random and unpredictable attacks of swelling. The swelling in C1-INH-HAE is a result of impaired regulation of bradykinin production. The fact that the array of tests needed to diagnose HAE is not always available to the treating physicians is challenging for them and their patients. METHODS: The data for this article were extracted from two distinct surveys. The first survey was conducted among HAE treating physicians and aimed to determine the availability and utilization of the various assays performed to help the diagnosis of C1-INH-HAE. The second survey was conducted with the various laboratories across Canada that performs the assays used in the diagnosis of HAE. The aim of this survey was to determine the availability and profile of the various assays used in the diagnosis of C1-INH-HAE in Canada, thereby ultimately bringing a rational basis for the biological testing. RESULTS: C1-INH functional assay was widely available in Canada (93%), but was only offered by a small numbers of hospitals meaning that there could be longer delays in the analysis of these samples that may explain why the physicians expressed a lower level of confidence in this assay (59%). Antigenic C1-INH was available to the vast majority of the physicians treating C1-INH-HAE (93%) and was considered reliable by 96% of the respondents. Antigenic C4 was found available to all Canadian physicians and, although with limited specificity, was considered very reliable by all the participants. This study revealed that 81% of physicians were able to order the antigenic C1q and the confidence in this assay was moderate (70%). Concerning genetic testing, the survey revealed that most of the CHAEN members never had to or couldn't order this test. CONCLUSION: This study highlights the need for improved education and knowledge exchange, about biological assays available to Canadian physicians and their performance in proper diagnosis of C1-INH-HAE to improve confidence and access to relevant tests.

Urticaria and angioedema.

Urticaria (hives) is a common disorder that often presents with angioedema (swelling that occurs beneath the skin). It is generally classified as acute or chronic. Second-generation, non-sedating, non-impairing histamine type 1 (H1)-receptor antihistamines represent the mainstay of therapy for both acute and chronic urticaria. Angioedema can occur in the absence of urticaria and can be broadly divided into histamine-mediated and non-histamine-mediated angioedema. Histamine-mediated angioedema can be allergic, pseudoallergic or idiopathic. Non-histamine mediated angioedema is largely driven by bradykinin and can be hereditary, acquired or drug-induced, such as with angiotensin-converting enzyme inhibitors. Although bradykinin-mediated angioedema is often self-limited, laryngeal involvement can lead to fatal asphyxiation. The mainstay of management for angioedema is to avoid specific triggers, if possible. For hereditary angioedema, there are specifically licensed treatments that can be used for the management of acute attacks, or for prophylaxis in order to prevent attacks. In this article, the authors will review the causes, diagnosis and management of urticaria (with or without angioedema) and isolated angioedema. The diagnostic and therapeutic approaches to these two conditions are considerably different, and this review is designed to highlight these differences to the reader.