Food-dependent and food-exacerbated symptomatic dermographism: New variants of symptomatic dermographism.

BACKGROUND: Symptomatic dermographism (SD) is the most common form of chronic inducible urticaria. The criterion standard for diagnosing SD and disease activity assessment in SD is provocation testing. As of now, if and what cofactors have an impact on provocation test results is unknown. OBJECTIVE: We sought to determine whether the induction of signs and symptoms of SD is affected by the intake of food. METHODS: We performed standardized skin provocation testing with a dermographometer (FricTest) before and after the intake of food. Patients were off antihistamine treatment for at least 3 days before testing. In total, 17 patients were tested after not having eaten for at least 4 hours (preprandial) on one volar forearm and 60 minutes after a carbohydrate-rich meal (postprandial) on the other. FricTest responses (wheals, itch) at trigger thresholds were assessed at 5 and 30 seconds as well as at 1, 2, 5, and 10 minutes. RESULTS: We identified 7 patients with SD who showed faster onset of FricTest-induced whealing and/or lower trigger thresholds after the intake of food, that is, food-exacerbated SD. In 5 other patients, FricTest provocation testing resulted in a positive response only after the intake of food, but not before. Three of these 5 patients with food-dependent SD had comorbid chronic spontaneous urticaria and 1 had cholinergic urticaria. CONCLUSIONS: We describe 2 previously unknown subtypes of SD, food-exacerbated SD and food-dependent SD. The prevalence and underlying pathomechanisms of food-exacerbated SD and food-dependent SD need to be investigated, and the impact of food intake on other forms of chronic inducible urticaria should be explored.

Angioedema without wheals: a clinical update.

Angioedema without wheals (urticaria) represents a heterogeneous group of clinically indistinguishable diseases of hereditary or acquired etiology. Hereditary angioedema is a rare inherited condition leading to recurrent, sometimes life-threatening angioedema attacks in subcutaneous tissues and gastrointestinal and oropharyngeal mucosa dating back to childhood or adolescence. Most of these patients have mutations in the SERPING1 gene, causing either low C1 inhibitor production (hereditary angioedema with C1 inhibitor deficiency type I) or the production of dysfunctional C1 inhibitor (hereditary angioedema with C1 inhibitor deficiency type II). Hereditary angioedema with normal C1 inhibitor has been defined later. Although C1 inhibitor concentration and function are in the normal range, it leads to typical hereditary angioedema symptoms owing to mutations in FXII, PLG, ANGPT1, KNG1, and MYOF genes. Patients who exhibit none of these genetic mutations despite having a similar clinical presentation are classified as having unknown hereditary angioedema. Fewer than 1 in 10 patients with C1 inhibitor deficiency have acquired angioedema with C1 inhibitor deficiency. The clinical presentation is very similar to that of hereditary angioedema, making it difficult to distinguish these 2 conditions clinically. Unlike hereditary angioedema, there are no genetic mutations, and family history and symptoms tend to appear later in life. Acquired angioedema with C1 inhibitor deficiency is commonly associated with lymphoproliferative and autoimmune diseases. Angioedema attacks might start 1 year before the underlying disease in acquired angioedema with C1 inhibitor deficiency. Approximately half of the patients admitted to the hospital for acute angioedema are patients receiving angiotensin-converting enzyme (ACE) inhibitor therapy. Angioedema typically occurs on the lips, tongue, mouth, pharynx, and subglottic regions. Patients may require hospitalization and intensive care monitoring owing to airway involvement. Idiopathic histaminergic acquired angioedema may be diagnosed only when any possible causes of histaminergic angioedema are excluded (foods, drugs, animal dander, aeroallergens, insect stings, latex, and others), and the symptoms respond well to antihistamine treatment. Idiopathic nonhistaminergic acquired angioedema should be considered when all other types of recurrent angioedema have been ruled out and patients do not respond to high-dose antihistamines. The lack of a standard biochemical laboratory test for patients with idiopathic histaminergic acquired angioedema, idiopathic nonhistaminergic acquired angioedema, angiotensin-converting enzyme inhibitor-induced acquired angioedema, and hereditary angioedema with normal C1 inhibitor makes the diagnosis more challenging. Future efforts should focus on increasing awareness of all the rare types of angioedema among physicians and developing more straightforward and more accessible diagnostic methods.

A Comparison of the United States and International Perspective on Chronic Urticaria Guidelines.

Urticaria is a heterogeneous skin disorder that may be acute or chronic and is defined by the appearance of wheals, angioedema, or both. The European perspective is expressed in a recent international guideline and the American perspective has been based on the US Joint Task Force chronic urticaria practice parameter published in 2014. Both the international guideline (initiated by the European societies European Academy of Allergology and Clinical Immunology [EAACI]/Global Allergy and Asthma European Network [GA2LEN]/European Dermatology Forum [EDF] in collaboration with the World Allergy Organization [WAO]) and the US (American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology) guideline have been developed to help direct primary care physicians and specialists in the management of their patients with urticaria. The EAACI/GA2LEN/EDF/WAO guideline applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to developing consensus recommendations and these were then discussed in a Delphi conference including more than 250 specialists in the field and have been endorsed by more than 40 international societies. In contrast, the US Joint Task Force CU practice parameter made recommendations based on scientific evidence whenever possible; however, when there was insufficient evidence, recommendations were based on expert consensus opinion. Although both agree on most points regarding the definition, general evaluation, and treatment, there are some differences that exist between the 2 guidelines. Most of these differences pertain to recommendations based on expert opinion because of weak scientific evidence. Within this document, we compare the recommendations of these 2 groups, highlighting the key similarities and differences.

Chronic Urticaria: Comparisons of US, European, and Asian Guidelines.

PURPOSE OF REVIEW: Chronic urticaria is a common dermatological condition that has significant impact on quality of life. Multiple international societies have published guidelines, and although these guidelines generally agree on the definition of urticaria, as well as approach to diagnosis and management, there have been notable differences to date. These differences have been reconciled by the recent publication of the 2017 revision and update published by the EAACI/GA2LEN/EDF/WAO. RECENT FINDINGS: The 2017 revision and update to the guidelines for chronic urticaria are the most comprehensive consensus document to date, and reconcile previously existing differences between the US, European, and Asian guidelines. The purpose of our review is to present basic background on urticaria and discuss classification, diagnosis, and most importantly, management. We present differences from previous US, European, and Asian guidelines and reconcile the previous differences by summarizing the 2017 revision and update published by the EAACI/GA2LEN/EDF/WAO.

[Is it possible for chronic urticaria diagnostic approach to be simplified? A clinical data checklist]. / ¿Es posible simplificar el abordaje diagnóstico de urticaria crónica? Una lista de verificación de información clínica.

BACKGROUND: Existing clinical guidelines do not offer an efficient alternative for the collection of data on relevant clinical traits during history and physical of the patient with chronic urticaria. OBJECTIVE: Our aim was to provide a clinical data checklist together with its guide to allow for thorough information to be obtained and for a physical exam that identifies the main features and triggering factors of the disease to be carried out. METHODS: A search was conducted for relevant literature on chronic urticaria in Medline, the Cochrane library and PubMed. RESULTS: We developed an easy-to-use clinical data checklist with its corresponding clinical guide, comprised by 42 items based on two components: essential clues for history taking and chronic urticaria diagnosis (typical symptoms according to subgroups, etiology and laboratory results). Some components are the time of disease onset, wheals' duration, shape, size, color and distribution, associated angioedema, atopy, triggering factors and others. CONCLUSION: The clinical data checklist and its guide constitute a tool to focus, guide and save time in medical consultation, with the main purpose to aid physicians in providing better diagnosis and management of the disease.

Antecedentes: Las guías clínicas existentes no ofrecen una alternativa eficiente para la recolección de rasgos clínicos relevantes durante la anamnesis y el examen físico del paciente con urticaria crónica. Objetivo: Proporcionar una lista de verificación de información clínica y una guía que permitan obtener información completa y realizar un examen físico que identifique las características principales de la enfermedad y los factores desencadenantes. Métodos: Se realizó una búsqueda de literatura relevante sobre urticaria crónica en Medline, la Biblioteca Cochrane y PubMed. Resultados: Desarrollamos una lista de verificación de información clínica fácil de usar, con su respectiva guía clínica, integrada por 42 elementos basados en 2 componentes: pistas esenciales para la anamnesis y el diagnóstico de la urticaria crónica (síntomas típicos según sus subtipos, etiología y resultados de laboratorio). Algunos componentes son el tiempo de aparición de la enfermedad, duración, forma, tamaño, color y distribución de las erupciones; angioedema aso-ciado, atopia, factores desencadenantes y otros. Conclusiones: La lista de verificación de información clínica y su guía constituyen una herramien-ta para enfocar, orientar y ahorrar tiempo en la consulta médica, con el fin principal de que los médicos realicen un mejor diagnóstico y manejo de la enfermedad.

Autoinflammatory Diseases in Pediatric Dermatology-Part 1: Urticaria-like Syndromes, Pustular Syndromes, and Mucocutaneous Ulceration Syndromes. / Enfermedades autoinflamatorias en dermatología pediátrica. Parte 1: síndromes urticariformes, síndromes pustulosos y síndromes con ulceraciones cutáneo-mucosas.

Monogenic autoinflammatory diseases are a heterogeneous emergent group of conditions that are currently under intensive study. We review the etiopathogenesis of these syndromes and their principal manifestations. Our aim is to propose a classification system based on the clinicopathologic features of typical skin lesions for routine clinical use in dermatology. Our focus is on diagnosis in pediatric practice given that this is the period when the signs and symptoms of these syndromes first appear. In Part 1 we discuss the course of urticaria-like syndromes, which include cryopyrin-associated periodic conditions and hereditary periodic fever syndromes. Pustular syndromes are also covered in this part. Finally, we review the range of therapies available as well as the genetic mutations associated with these autoinflammatory diseases.

Delayed effort-induced swelling with myofasciitis and systemic manifestations: A so far unrecognized type of pressure-induced urticaria.

Diseases characterized by recurrent symptoms with prolonged intervals without any clinical manifestations can pose diagnostic difficulties. Some diagnoses will be obvious but other situations can be very challenging.To nosologically delineate a new entity characterized by recurrent flares of induration of the forearms and legs with swelling of the extremities accompanied by intense fatigue and variable other symptoms.Retrospective observational study of patients recorded from 2000 to 2015. All patients included were seen during a consultation at the Dermatology Department of the University Hospital of Strasbourg, France. We retrieved the medical records from patients seen and recorded over the last 16 years having induration of the extremities, the forearm and the legs occurring between 4 and 12 hours after a physical effort accompanied by systemic signs that lasted for a few days. We analyzed in detail the clinical and biological features, evolution, and treatments of these patients.We included 6 males, with a mean age of 47 years; mean age at disease onset was 42. All patients were initially misdiagnosed as having rheumatic disorders. The mean delay before diagnosis was 5 years. The main complaint was painful induration or muscle soreness of the forearms and the legs associated with transient functional impairment and prolonged asthenia for a mean duration of 3.5 days. Induration of the deep soft tissues was very suggestive of myofasciitis. The delay between the triggering physical effort and the swelling was between 6 and 12 hours. Physical effort as triggering factor was never spontaneously mentioned. Two patients had partial response to high dose antihistamines and 2 other patients to the interleukin-1 inhibitor anakinra. One patient responded to hydroxychloroquine.The very stereotypical presentation in those 6 patients suggests that this is a recognizable entity characterized by effort-induced induration of forearms and/or legs, due to deep edematous myofascial involvement, occurring a few hours after a physical effort. We suggest to name this entity delayed effort-induced swelling with myofasciitis and systemic manifestations.

Proposed ICDRG Classification of the Clinical Presentation of Contact Allergy.

The International Contact Dermatitis Research Group proposes a classification for the clinical presentation of contact allergy. The classification is based primarily on the mode of clinical presentation. The categories are direct exposure/contact dermatitis, mimicking or exacerbation of preexisting eczema, multifactorial dermatitis including allergic contact dermatitis, by proxy, mimicking angioedema, airborne contact dermatitis, photo-induced contact dermatitis, systemic contact dermatitis, noneczematous contact dermatitis, contact urticaria, protein contact dermatitis, respiratory/mucosal symptoms, oral contact dermatitis, erythroderma/exfoliative dermatitis, minor forms of presentation, and extracutaneous manifestations.

Inducible urticaria: Case series and literature review.

Inducible urticaria is a heterogeneous group of skin disorders characterized by the appearance of wheals, pruritus and/or angioedema, sometimes accompanied by systemic symptoms caused by innocuous stimuli (cold, heat, pressure, etc.). This group of disorders compromises people's quality of life and most of the literature in this regard comes from case reports and case series since its epidemiology has been poorly studied and some cases are very rare. The aim of this review is to show an up-to-date overview of the available literature for various types of inducible urticarias, always beginning with an illustrative case and then describing their pathophysiological mechanisms, clinical manifestations, and treatment.

Questions and answers in chronic urticaria: where do we stand and where do we go?

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. In 2011, a report of the GA(2) LEN task force on urticaria outlined important and unanswered questions in chronic urticaria (CU). These included, but were not limited to, questions on the epidemiology and course of chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], the resources allocated for the diagnosis and treatment of CSU, whether patients with angioedema as an isolated symptom can be regarded as a subgroup of CSU, and the efficacy and long-term safety of therapies. Many of these questions have been addressed by recent studies. Some of the answers obtained raise new questions. Here, we summarize some of the key insights on CU obtained over recent years, and we discuss old and new unmet needs and how to address them with future studies. We need to analyze the influence of recent advances in understanding of the burden of CU on patients and society, disease management and the CU patient journey. Our increased understanding of urticarial pathophysiology and consideration of the patient as a whole will need to be translated to better treatment algorithms and protocols. Actions to address these challenges include the 5th International Consensus Meeting on Urticaria, which will take place later this year. The formation of a global network of Urticaria Centers of Reference and Excellence over the next few years has also been proposed, with the aim of providing consistent excellence in urticaria management and a clear referral route, furthering knowledge of urticaria through additional research and educating/promoting awareness of urticaria.

Dermatoses of pregnancy: Nomenclature, misnomers, and myths.

The most recent reclassification of dermatoses of pregnancy includes polymorphic eruption of pregnancy, atopic eruption of pregnancy, and pemphigoid gestationis; intrahepatic cholestasis of pregnancy, strictly not a dermatosis, was included in specific dermatoses of pregnancy for working purposes. Another dermatosis, pustular psoriasis of pregnancy, could be included for similar reasons. The nomenclature of these pregnancy-specific eruptions has been revised several times, generating potential confusion among practitioners. Clouding the picture further are misnomers that have been used to describe dermatoses of pregnancy. In addition, several cutaneous conditions that are associated with, but not specific to, pregnancy, have been misunderstood, which has resulted in certain myths among patients and physicians. In this contribution, we describe how the nomenclature of each dermatosis of pregnancy has evolved to fit the current classification scheme. We then identify several misnomers that have generated confusion within the scheme. Finally, we debunk several myths that have developed around cutaneous conditions outside of this scheme, in both mother and newborn.

Urticaria inducible: serie de casos y revisión de la literatura

Las urticarias inducibles constituyen un grupo heterogéneo de trastornos cutáneos caracterizados por la aparición de habones, prurito o angioedema, que en ocasiones se acompañan de síntomas sistémicos causados por estímulos inocuos para la mayoría de la población, como el frío, el calor, la presión, etc., y que comprometen la calidad de vida de los pacientes. La mayor parte de la literatura médica pertinente proviene de reportes y series de casos, ya que su epidemiología se ha estudiado poco. El objetivo de esta revisión es ofrecer una visión actualizada de la información disponible sobre varios tipos de urticaria inducida, mediante la presentación de un caso clínico ilustrativo y la descripción de los mecanismos fisiopatológicos, las manifestaciones clínicas y el tratamiento de cada condición.

Inducible urticaria is a heterogeneous group of skin disorders characterized by the appearance of wheals, pruritus and/or angioedema, sometimes accompanied by systemic symptoms caused by innocuous stimuli (cold, heat, pressure, etc.). This group of disorders compromises people´s quality of life and most of the literature in this regard comes from case reports and case series since its epidemiology has been poorly studied and some cases are very rare. The aim of this review is to show an up-to-date overview of the available literature for various types of inducible urticarias, always beginning with an illustrative case and then describing their pathophysiological mechanisms, clinical manifestations, and treatment.

Diamine oxidase levels in different chronic urticaria phenotypes.

BACKGROUND: Diamine oxidase (DAO) is a polyamine-degrading enzyme also implicated in histamine metabolism. Chronic urticaria (CU) has a wide spectrum of clinical presentations and causes. Anisakis sensitisation associated chronic urticaria (CU+) has been characterised as a phenotype with different clinical and immunological characteristics and possibly associated with previous acute parasitism. We aimed to analyse serum DAO levels in different CU phenotypes. We further analysed the possible association of DAO with fish eating habits. METHODS: We studied 35 CU+ patients and 39 non-sensitised CU patients (CU-) as well as 19 controls. We analysed fish-eating frequency as well as fish intake associated exacerbation of CU (FIAE) or gastro-intestinal complaints (GI). DAO levels were further analysed with respect to lymphoproliferative responses, cytokine and specific IgE production. RESULTS: DAO levels were not different between CU and controls, but were significantly higher in CU+ than in CU-. CU+ patients with FIAE had lower DAO levels, but no differences were detected in patients with GI. DAO levels correlated positively with oily and canned fish consumption in CU-. In CU+, DAO levels correlated positively with specific Anisakis IgE, percentages of proliferation in Anisakis stimulated peripheral blood lymphocytes, serum IL-2 and IL-6, but correlated negatively with mitogen stimulated TGF-ß in supernatants. CONCLUSIONS: DAO levels in CU depend on fish-eating habits and in CU+ on the amount of specific IgE production. In the CU+ phenotype, lower levels of DAO predispose to urticaria exacerbation after fish intake, probably due to a relative insufficient enteric availability of this enzyme.

A Review and Proposed Approach to the Neutrophilic Dermatoses of Childhood.

Neutrophilic dermatoses (NDs) are inflammatory skin conditions that are not associated with infection. The classification and clinical approach to these conditions in children is poorly described. This review classifies these conditions into five nosological subtypes: Sweet's syndrome, pyoderma gangrenosum, aseptic pustules, neutrophilic urticarial dermatoses, and Marshall's syndrome. In addition, we review the various secondary diseases that need to be excluded in the clinical management of the NDs of childhood, with a focus on the autoinflammatory conditions that the reader may not be familiar with. We propose a practical clinical approach to these disorders.

Validation of an ICD-9-based claims algorithm for identifying patients with chronic idiopathic/spontaneous urticaria.

BACKGROUND: There is no specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for chronic idiopathic urticaria or spontaneous urticaria (CIU/CSU), a skin condition characterized by hives and angioedema lasting at least 6 weeks with no known cause. OBJECTIVE: To validate an ICD-9-CM-based algorithm for identification of patients with CIU/CSU and thus facilitate claims-based research. METHODS: Patient records were reviewed at 4 US practices. Patients included in the study were from a random sample of those identified by their physician as having CIU/CSU or because they met the following diagnosis-based algorithm: (1) at least 2 outpatient ICD-9-CM diagnosis codes 708.1, 708.8, or 708.9 at least 6 weeks apart or (2) 1 outpatient diagnosis of 708.1, 708.8, or 708.9 and 1 diagnosis of 995.1 at least 6 weeks apart. Data collected included ICD-9-CM codes, diagnoses of urticaria and allergy-related conditions, and medication use. Sensitivity and positive predictive value were calculated. The study was approved by the Western Institutional Review Board. RESULTS: One hundred forty-nine patient records were reviewed (mean age 41.1 years; 73.8% were women; 69.1% were white): 115 were identified with the diagnosis-based algorithm, 90 were patients with "known CIU/CSU", and 56 were in the 2 groups. The mean duration of CIU/CSU was 2.9 to 3.1 years. The 2 cohorts most frequently had diagnoses of idiopathic urticaria, unspecified urticaria, and other specified urticaria. The diagnosis-based algorithm had a positive predictive value of 90.4% and a sensitivity of 71.1%. CONCLUSION: The high positive predictive value suggests that patients identified using the algorithm are highly likely to have CIU/CSU. The 71.1% sensitivity suggests that most patients with CIU/CSU will be identified. The validation statistics support the use of the diagnosis-based algorithm in claims-based research, although future studies could refine the algorithm further.