Celiac disease (CD) is an immune-mediated enteropathy caused by gluten ingestion, affecting approximately 1% of the worldwide population. Extraintestinal symptoms may be present as the first signs of CD, years before the CD diagnosis is made. A great variety of extraintestinal manifestations may be associated with CD. Cutaneous manifestations represent the main extraintestinal manifestations, with dermatitis herpetiformis being the most common in patients with CD. In adults, it has been demonstrated that the role of a gluten-free diet is crucial not only for the recovery of signs and symptoms associated with CD but also for cutaneous manifestations, which often improve after gluten avoidance. In children with CD, the association with skin disorders is well documented regarding dermatitis herpetiformis, but studies considering other dermatological conditions, such as psoriasis and atopic dermatitis, are few. The prevalence and manifestations of dermatological disorders in celiac children are often different from those in adults, explaining the gap between these populations. In addition, the therapeutic role of a gluten-free diet in the improvement in skin alterations is not fully understood in children and in adult population except for dermatitis herpetiformis. Therefore, cutaneous CD symptoms need to be known and recognized by physicians despite their specialties to improve early CD diagnosis, which is critical for a better prognosis. This review describes the current scientific evidence on skin manifestations associated with CD in the pediatric population.

Abdominal pain is one of the most common conditions leading people to the emergency department. An uncommon but well described cause of abdominal pain is angioedema of the gastrointestinal tract due to recurrent angioedema without wheals. Abdominal involvement is very common in hereditary angioedema (HAE), but it is also described in acquired angioedema and allergic forms. In patients with HAE, the involvement of gastrointestinal tract with resultant abdominal pain occurs in 43-93% of cases. Attacks can involve the entire gastrointestinal tract, such as the oropharynx, small intestine, colon, liver, or pancreas. Pain is the most common gastrointestinal symptom, and it may occur for many years even without cutaneous or respiratory symptoms. The case report we included in this article emphasizes the importance of accurate evaluation of personal and family history in patients with a long history of acute, severe, and unexplained abdominal pain, and it gives an example of how diagnostic delay may be longer if gastroenterological symptoms are the predominant clinical presentation. Furthermore, sometimes the simultaneous presence of concomitant gastrointestinal disorders and HAE may cause difficulties in differential diagnosis. Gastroenterologists and other physicians should add HAE to their list of potential causes of unexplained abdominal pain. The initiation of appropriate prophylaxis and treatment will prevent needless suffering and useless surgical and medical procedures.

Gluten, a protein found in wheat, rye, and barley, is known to cause an immune reaction in patients with celiac disease (CD) resulting in small bowel villous atrophy and impaired nutrient absorption and cutaneous manifestations in patients with dermatitis herpetiformis (DH). It is common that patients associate skin conditions with their diet, and the advantages of a gluten-free diet (GFD) are brought up frequently. Indeed, there is evidence that certain dermatologic conditions can respond to a GFD, especially for those with concomitant CD and DH. In the last decade, new data have become available on the significance of gluten in skin disease. Herein, we review the role of gluten and a GFD on various cutaneous diseases beyond DH.

Celiac disease (CD) is an autoimmune enteropathy that primarily affects the small intestine and is characterized by atrophy of intestinal villi. The manifestations of the disease improve following a gluten-free diet (GFD). CD is associated with various extra-intestinal diseases. Several skin manifestations are described in CD patients. The present paper reviews all CD-associated skin diseases reported in the literature and tries to analyze the pathogenic mechanisms possibly involved in these associations. Different hypotheses have been proposed to explain the possible mechanisms involved in every association between CD and cutaneous manifestations. An abnormal small intestinal permeability seems to be implicated in various dermatological manifestations. However, most of the associations between CD and cutaneous diseases is based on case reports and case series and a few controlled studies. To better assess the real involvement of the cutaneous district in CD patients, large multicentric controlled clinical trials are required.

Cutaneous manifestations of intestinal diseases are increasingly reported both in the adult and in the children, and this association cannot longer be considered a simple random. Besides the well-known association between celiac disease (CD) and dermatitis herpetiformis (DH), considered as the cutaneous manifestation of gluten-dependent enteropathy, is more frequently reported also the association with other mucocutaneous diseases. Among these there are both autoimmune, allergic, and inflammatory diseases, but also a more heterogeneous group called miscellaneous. The knowledge about pathogenic, epidemiological, clinical, and diagnostic aspects of CD is increasing in recent years as well as those about DH, but some aspects still remain to be defined, in particular the possible pathogenetic mechanisms involved in the association between both CD and DH and CD and other immunological skin diseases. The aim of this paper is to describe the skin diseases frequently associated with CD, distinguishing them from those which have a relationship probably just coincidental.

Urticaria affects nearly 25% of the population at some time in their lives. In a subset of children, urticaria will develop into a chronic condition that can greatly affect quality of life. Although numerous causes and triggers are proposed for chronic urticaria (CU) in children, ranging from infections, allergens, and medications to physical factors and autoimmune disease, the exact etiology is not always identifiable. Accordingly, a large subset of cases are designated "chronic idiopathic urticaria." Because of the clinical complexities of CU, as well as the confusing literature on this topic, we have developed a conceptual framework based on the cumulative evidence to assist with the categorization, clinical evaluation, and treatment of CU in children.

Hereditary angioedema is a rare, autosomal dominant disease inherited. The cause is a quantitative or qualitative congenital deficit in C1 inhibitor. Various clinical symptoms, in particular of sub-cutaneous, upper airways and digestive origin, have been described. Life threatening conditions may be observed. Little information is available on digestive tract localization corresponding to intestinal intussusception associated with hereditary angioedema in children. We report a case of hereditary angioedema observed in a 15-years-old girl who presented such features. We propose a review of the literature and discuss the curative treatment of digestive crisis in children with hereditary angioedema.

Idiopathic chronic urticaria (ICU) is a chronic relapsing cutaneous disease. Some case reports or studies on small series of celiac disease (CD) patients have suggested a possible association between CD and ICU. The aim of this study was to assess the prevalence of CD in a population of adults ICU patients with respect to healthy controls. We consecutively enrolled 80 patients affected by ICU and 264 blood donors as the control population without a history of ICU. Serum anti-transglutaminase IgG and anti-endomysium IgA antibodies were evaluated in all subjects. In the case of positivity to serology, diagnosis was confirmed by duodenal biopsy. One of 80 (1.25%) ICU patients were positive to both anti-transglutaminase and anti-endomysium antibodies. Duodenal biopsy showed partial villous atrophy. One control of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between the two groups. ICU patients do not seem to bear a greater risk for CD compared to the general population.

Celiac disease (CD) and chronic urticaria (CU) are both sustained by immune mechanisms, but there are so far few data on their clinical association. We performed a case-control study to determine the occurrence of CD in urticaria and matched control children, and to assess the clinical relevance of this association. Children and adolescents were diagnosed to have severe chronic idiopathic urticaria in the presence of hives for more than 6 wk poorly or not responsive to oral antihistamines. Other known causes of urticaria had to be excluded. A matched control group without urticaria was enrolled. In both groups, the presence of CD was searched by assaying antitransglutaminase and antiedomysial antibodies, and confirmed with endoscopic intestinal biopsy. Results. CD was diagnosed and confirmed in 4/79 (5.0%) of children with CU and in 17/2545 (0.67%) of the controls (p = 0.0003). In the four children with urticaria and CD the gluten free diet (GFD) lead to complete remission of urticaria within 5-10 wk, whereas the disappearance of serological markers occurred in longer times (5-9 months).

The presence of CD in children with CU was significantly more frequent than in controls. GFD resulted in urticaria remission. CD may be regarded in such subjects as a cause of CU.

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

The Hungarian HAE Center was established in 1994, in Budapest. Assignments of the Center include diagnostic work-up of patients with angioedema; developing national guidelines for the recognition, treatment of patients with HAE; maintaining the registry, patient education, supply patients with info-card and C1-INH concentrate, follow-up of patients, telephone 'hot-line' service, under- and postgraduate education as well as pursues scientific activities. Established in 1996, the Hungarian HAE Patients' Association a foundation to support HAE patients; and a Hungarian HAE website. Hungarian HAE Working Group is the main organizer of the European C1-INH Deficiency Workshops to be held at two-year intervals from 1999.