Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

Oral Immunotherapy and Risk of Eosinophilic Esophagitis in Children: 15 Years' Experience.

OBJECTIVES: Oral immunotherapy (OIT) is an effective treatment for children with persistent food allergy, and has concerns about its safety, including eosinophilic esophagitis (EoE). The aim of this study was to evaluate the prevalence of EoE in a large cohort of children who underwent OIT in our center, and to determine if there were any clinical, endoscopic, or histologic differences depending on the food employed for the OIT. METHODS: A retrospective study was performed over a 15-year period (2005-2020). Children who underwent cow's milk (CM), egg, and/or peanut OIT and developed EoE were included. RESULTS: Six hundred and seven OIT were carried out (277 CM-OIT, 322 egg-OIT, and 8 peanut-OIT). Seventeen patients (2.8%) had a confirmed histologic diagnosis of EoE with a higher prevalence for patients who underwent CM-OIT (3.9%) than egg-OIT (2.2%). Symptoms suggestive of EoE and a confirmed diagnosis occurred at median times of 25 and 36 months, respectively, after the build-up phase of the OIT was completed. Choking, abdominal pain, and dysphagia were the most frequent symptoms and lamina propria fibrosis was observed in 41.2% of patients. No significant differences in clinical symptoms, endoscopic, or histologic findings between patients under CM or egg-OIT were found. One-third of patients reported mild symptoms suggestive of EoE before the OIT. CONCLUSIONS: EoE appears to be a rare but important adverse event that can occur even years after OIT. Validated questionnaires to screen EoE before the OIT and in the follow-up of these patients may be the main tool for an early diagnosis.

Poor prognosis of food protein-induced enterocolitis syndrome to fish.

BACKGROUND: Fish is the most common causative food of food protein-induced enterocolitis syndrome (FPIES) in Southern Europe. In children with FPIES, the development of tolerance varies according to the culprit food and specifically fish seems to have a poorer prognosis than other solid foods. We sought to evaluate the fish-FPIES resolution rate in children. METHODS: A descriptive retrospective analysis of children with fish-FPIES, followed during the last 20 years, was performed. The offending fish, age and symptoms at onset, the coexistence of atopic diseases and FPIES to other foods were registered. All the children included had undergone an oral food challenge (OFC) with the offending fish. We recorded those children that overcame their fish-FPIES and those that did not outgrow the disease. RESULTS: Seventy children were enrolled in this study (median age: 9 yo; IQR 6.4-13.8). Forty-two (60%) achieved tolerance to the offending fish with a median age of 4 years (IQR: 3-5). Among children ≤5 yo (n = 40), 35 (87.5%) developed tolerance; among 6-8yo (n = 14), 40% developed tolerance; and only 12.5% among those ≥9 yo (n = 16) developed tolerance. Twenty-eight children did not outgrow the disease (median age: 8.9 yo; IQR: 9-13.8). We did not find any statistical differences regarding the offending fish, presence of single vs multiple fish-FPIES, symptoms at the beginning, coexistence of other atopic diseases or the coexistence of other FPIES, between the children who overcame the disease and those who did not. CONCLUSION: One in five children with FPIES to fish will not overcome the disease during childhood.

Oral Food Challenge in Food Protein-Induced Enterocolitis Syndrome by Fish: Is There Any Room for Improvement?

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow's milk or soy. Among the solid foods, rice is one of the most causative foods worldwide, but it varies depending on the geographic area. In the Mediterranean countries, fish is one of the most important triggers of FPIES. There is not a specific biological marker for the disease that allows us to confirm the diagnosis or to predict when tolerance to the offending food has been achieved, so all patients with a FPIES diagnosis undergo an oral food challenge (OFC) at least once. The OFC is a risky procedure and many patients develop severe symptoms. OBJECTIVE: We sought to evaluate the safety of a new OFC protocol in children with fish-FPIES. METHODS: A retrospective study was performed over a 22-year period (1996-2018). We compared two methodologies used in the OFC: Method 1 that consisted in giving several doses during the same day versus Method 2 that consisted in giving a unique dose per day on 2 or three non-consecutive days. RESULTS: A total of 75 positive OFC with fish done in 40 children were included. Forty-three (57.3%) OFC were performed following Method 1 and 32 (42.7%) with Method 2.The severity of the symptoms of the OFC done with Method 1 was mostly moderate (41.9%) followed by severe (39.5%) and mild (18.6%). The adverse reactions with Method 2 were mostly mild (68.8%) and only 18.8 and 12.5% presented moderate or severe symptoms, respectively. CONCLUSIONS: OFC performed in children with fish-FPIES are risky and many patients develop moderate or severe symptoms after this procedure. We propose a new protocol that has demonstrated to improve safety.

Stevens Johnson Syndrome versus Jarisch Herxheimer Reaction in an HIV Positive Patient with Secondary Syphilis.

BACKGROUND: HIV positive patients can suffer many complications due to infectious diseases. A sever drug reaction to some of the drugs involved in the treatment can overlap the symptoms of the infections, making the diagnosis very difficult. We present the case of a 28-year-old-man, HIV positive, with secondary syphilis, who developed a Stevens Johnson Syndrome (SJS) caused by one of the many drugs he received. The SJS was overlapped with a possible Jarisch Herxheimer Reaction, which complicated the diagnosis of the skin reaction. OBJECTIVE: In HIV+ patients, the overlapping of severe drug reactions and infectious diseases could be fatal, thus an accurate diagnosis is mandatory. MATERIAL AND METHODS: A Rapid Plasma Reagin Test (RPR), an ELISA test, a blood laboratory test, chest radiography and a skin biopsy were realized in order to diagnose the infectious disease and the cause of skin lesions. Intradermal tests and double blind challenge tests were realized in the allergy study. RESULTS: The laboratory tests confirmed the diagnosis of syphilis; the skin biopsy confirmed the cause of lesions, a severe allergic reaction as a SJS. The allergy study discharged all the drugs involved, except dypirone which wasn't proved in the study because of the severity of reaction, the high possibility to be the causative drug and the alternative of other similar drugs available. For the inflammatory response, HIV+ patients are especially susceptible to severe reaction, both infectious and allergic, as in this case. Thus, recent patents emphasize the interest in inflammatory molecules that cause inflammatory symptoms. CONCLUSIONS: Although the diagnose of SJS has established criteria, the possibility of overlapping with infectious illness and/or with its treatment, may complicate the diagnosis.

Immediate reactions to iodinated contrast media.

BACKGROUND: Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients. OBJECTIVE: To study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period. METHODS: Demographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM. RESULTS: A total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test-based CCT identified an alternative non-cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%). CONCLUSION: This study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non-cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results.

Atrial Fibrillation in Anaphylaxis.

BACKGROUND: The relationship between anaphylaxis and cardiovascular events has been reported in the past. While skin and respiratory symptoms are usually the most common and the first to appear, cardiovascular complications play a key role and represent the leading cause of death in anaphylaxis. METHODS: We report 3 episodes of atrial fibrillation triggered by anaphylaxis. Allergy and cardiology studies were performed. In both patients, the etiological agent was identified: Anisakis simplex hypersensitivity and food allergy. RESULTS: The heart is the source and target of chemical mediators released during an allergic reaction. In the heart, there are plenty of mast cells, and they are predominantly located around the coronary adventitia and in close contact with small vessels in the muscle wall. The release of mediators can influence ventricular function, heart rate, and coronary artery tone. Anaphylaxis can trigger any kind of arrhythmia. In these cases, the very interesting point of discussion was: which should be first, treating anaphylaxis or cardiac events? The other controversial point was the use of epinephrine, the first line of treatment for anaphylaxis. Recommendations about epinephrine in cardiac patients during an anaphylactic event are still a major dilemma. CONCLUSIONS: We emphasize the importance of the priority of establishing protocols between cardiologist and allergist in treatment of cardiac complications during anaphylaxis, and we warn about the correct diagnosis of arrhythmias in anaphylaxis in order to treat them as soon as possible, to prevent other consequences and complications.

[Cereal-dependent exercise-induced anaphylaxis]. / Anafilaxia dependiente de cereales inducida por ejercicio.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is increasing. In vitro test such as omega-5-gliadin levels are useful in the diagnosis, while oral single blind challenge tests (OCT) with wheat plus exercise continuous being the gold standard diagnostic method. This paper reports the case of a 38-year-old woman, with several episodes of anaphylaxis after eating different foods and doing exercise after ingestion. An allergy study was performed with positive skin prick tests for wheat, barley and rye. Total IgE 238.0KU/L, positive specific IgE (>100KU/L) to wheat, barley and rye, and negative to rTri-a-19 omega-5 gliadin. OCT with bread and exercise was positive. In this case of wheat-dependent exerciseinduced anaphylaxis (WDEIA) with negative serum specific IgE to omega-5-gliadin, negative results with gamma, alpha, bheta y omega-gliadin doesn't exclude the diagnosis of WDEIA.

La anafilaxia inducida por ejercicio dependiente de trigo (WDEIA por sus siglas en inglés de wheat-dependent-exercise-induced-anaphylaxis) es una entidad cada vez más frecuente. La detección de IgE frente a omega-5-gliadina in vitro se usa como método diagnóstico, pero la provocación oral controlada simple ciego (POC) con el alimento, junto con la realización de ejercicio físico, es el método diagnóstico patrón de referencia. Se comunica el caso de una paciente de 38 años de edad, con antecedente de episodios de anafilaxia relacionados con la ingestión de alimentos y la realización de actividad física. Se realizó un estudio alergológico. Las pruebas cutáneas fueron positivas a harina de trigo, cebada y centeno. IgE total: 238.0 kU/L, IgE específica positiva (mayor de 100 kU/L) a trigo, cebada, centeno y negativa a rTri-a-19omega-5 gliadina. La provocación oral controlada con pan de trigo y ejercicio físico fue positiva. En este caso con anafilaxia inducida por ejercicio dependiente de trigo sin sensibilización omega-5 gliadina la ausencia de IgE frente gamma, alfa, beta yomega-gliadina no excluiría el diagnóstico de esta enfermedad.