eosinophilic colitis an update on pathophysiology and treatment pdf

Eosinophilic Colitis An Update On Pathophysiology And Treatment Pdf

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Eosinophilic colitis EC is a rare disease in which a type of white blood cell, the eosinophil, appears in elevated numbers in the large intestine. This in turn causes injury and inflammation. When seen in infancy, it is mostly a benign disease, resolving by early childhood once an offending food is eliminated and outgrown.

Eosinophilic Colitis: University of Minnesota Experience and Literature Review

Abdulrahman A. Alfadda, Martin A. Storr, Eldon A. Primary eosinophilic gastrointestinal disorders, a spectrum of inflammatory conditions, occurs when eosinophils selectively infiltrate the gut in the absence of known causes for such tissue eosinophilia. These may be classified into eosinophilic esophagitis, eosinophilic gastroenteritis and eosinophilic colitis EC.

This review focuses on EC: its pathogenesis, epidemiology, clinical presentation, diagnosis and current approach to treatment. A literature review published in English was performed using Pubmed, Ovid, Google scholar search engines with the following keywords: eosinophilic gastrointestinal disorder, EC, eosinophils, colitis and gastrointestinal. The basis for primary EC appears related to increased sensitivity to allergens, principally as a food allergy in infants and a T lymphocyte-mediated event in adults.

Endoscopic changes are generally modest, featuring edema and patchy granularity. Clear clinical and pathological diagnostic criteria of EC and its management strategy. Intestinal involvement of EC is primarily mucosal, presenting as a mild self-limited proctitis in infants and self-limited colitis in young adults.

Therapeutic approaches based on case reports tend to use either elimination diets to avoid a presumed allergen; agents traditionally used in inflammatory disease or targeted drugs like anti-histamines or leukotriene receptor antagonists. Prospective randomized controlled trials addressing the disease natural history, possible preventive methods and effective medical approach and long-term prognosis are required.

Eosinophils are bilobed granulocytes that stain brick red when stained with eosin. They are less commonly termed acidophils i. These white blood cells arise from pluripotent stem cells in the bone marrow under the influence of cytokines like interleukin IL -5 along with IL-3 and the granulocyte-macrophage colony-stimulating factor GM-CSF. IL-5 is the most specific to the eosinophil lineage; it causes selective expansion and bone marrow release of eosinophils.

Eosinophils reside in the bone marrow and spend about 8 days while undergoing maturation. Here they are found in the submucosa throughout the gastrointestinal tract except for the esophagus that normally is devoid of eosinophils. Their location in the intestines allows ready access for these white blood cells to combat multicellular parasites, likely an evolutionary survival tool.

Translocation from blood to tissue entails adhesion and diapedesis. The chemokine termed CC family eotaxin-1, -2 and -3 are highly specific, binding the CCR-3 receptor that is strongly expressed on eosinophils. Eosinophils harbor an array of cytotoxins whose release by degranulation and activation yield a host defense against helminthic infestations. They also produce tissue damage in inflammatory and allergic diseases. The result is lysosomal, oxidative and cytotoxic damage: acting on extracellular targets like parasites and yielding inflammatory mediators.

Eosinophils thus acutely produce cytokines, leukotrienes and lipid mediators of inflammation; they also trigger the release of histamine from basophils and mast cells. The result can be a hypersensitivity reaction.

Furthermore, eosinophils may contribute to chronic inflammation and fibrosis. Thus, eosinophil function can be beneficial killing parasites and viruses or detrimental causing chronic inflammation like asthma.

IL-5 may be a particularly important mechanism by supporting the terminal differentiation and proliferation of eosinophilic precursors while maintaining the viability of mature eosinophils. Thus the pathogenesis of eosinophilic colitis EC appears based on genetic factors but is elicited by environmental exposure, acting through adaptive T-cell immunity that involves IL expression and the chemokine, eotaxin. Whether gut eosinophilic disorders are IgE or non-IgE mediated is unclear.

Some reports suggest that IgE is responsible for mast cells accumulating in the colonic interstitium. Eosinophilia, often construed as an increase in circulating eosinophils, is a common accompaniment of hematological malignancies e. An excess of eosinophils in general can result from increased bone marrow production eosinophilopoesis accompanied by their subsequent appearance in the peripheral circulation, and in certain instances, their accumulating in specific tissues.

Eosinophilic infiltration of specific organs frequently is associated with inflammation: pulmonary, cutaneous, renal, cardiac, transplant rejection and gastrointestinal diseases. In eosinophilic gastrointestinal disorders EGID , eosinophils infiltrate various sites along the gastrointestinal tract to a variable depth. The clinical presentation of EGID depends upon the segment of the gastrointestinal tract affected, the depth to which the eosinophils infiltrate the wall and the local tissue response.

Some overlap exists particularly in the pediatric aged group, concerning the extent of gut involvement tract distal to the esophagus. Moreover, EGID frequently occurs independent of peripheral blood eosinophilia, the best examples being eosinophilic esophagitis and EC.

In HES, the primary end-organs affected are the heart and skin, while the gut appears to be a rather innocent bystander, being merely infiltrated without exhibiting marked dysfunction. The esophagus normally lacks resident eosinophils but can attract these inflammatory cells, the best example being gastroesophageal reflux disease and sometimes as part of an allergic reaction often food-related. Primary eosinophilic esophagitis is likely not an IgE-mediated disease but rather represents a distinct condition that manifests as dysphagia often with food bolus impaction and retrosternal chest pain.

Only a few have a history of true food anaphylaxis. Eosinophilic gastroenteritis seems to be an inaccurate sub-classification, as eosinophils can involve the whole gastrointestinal system including the biliary system in EGID. Nonetheless, there has been an exponential rise in EC recognition, yielding cases reported over the past decade Fig.

EC can present primarily as a separate entity or can be a secondary manifestation of other disease affecting the gut. The diagnosis of EC is more challenging as it lacks a clear definition. No guidelines exist. PubMed search on case reports and series for EC from the period — A surge of case publications have been taken place in the last 10 years with scant publications before the year Food allergy is part of this atopic syndrome and represents an adverse immune response towards certain food proteins.

Each category has its unique spectrum of clinical features. IgE-mediated food allergies typically have a rapid onset following ingestion of specific foods and can affect multiple organ systems, yielding dermatological and respiratory reactions like urticaria, laryngospasm and an acute asthmatic attack.

Such immediate hypersensitivity transpires when food-specific IgE antibodies residing on mast cells and basophils come in contact with and bind to circulating food allergens. This then activates these inflammatory cells, releasing potent mediators and cytokines. In contrast, non-IgE-mediated food allergies present as more delayed hypersensitivity reactions, featuring more subacute or chronic symptoms that most commonly target the gastrointestinal tract. The precise etiology of primary EC is however unclear.

Eosinophilic proctocolitis of infancy occurs in infants either being breast-fed or receiving a protein hydrolysate formula. Although an allergen-free diet represents one therapeutic strategy for EGID, this is only occasionally successful.

Adults with EC likely differ: food-related anaphylaxis is uncommon. EC has a bimodal age distribution affecting infants and young adults, each with somewhat different clinical presentations. Its characteristic intense eosinophilic infiltration can involve specific segments of the colon or can be pan-colonic. Different clinical manifestations of EC depend mainly on the colonic layer s most affected by the eosinophilic infiltration. Mucosa predominant EC, the most common form, is associated with mucosal injury and presents with malabsorption, diarrhea and protein losing enteropathy.

Transmural disease, reported to a lesser extent, presents more dramatically with colonic wall thickening and features of acute intestinal obstruction intussusception or cecal volvulus or even perforation. Several conditions can prompt eosinophils to infiltrate the colon. Important secondary causes include parasitic helminthic infections trichuris trichiura , enterobius vermicularis and strongyloides stercoralis 30—33 and drugs like clozapine, 29 carbamizipine 27 rifampicin, gold, 34 , 35 naproxen 36 , 37 and calcineurin inhibitor e.

Tacrolimus use in solid organ transplant recipients. Allergic skin testing has its limitations in eosinophilic disorders as these lack sensitivity and specificity. A negative skin prick test SPT is quite useful for excluding an IgE-mediated food allergy; a negative SPT has value in conjunction with clinical presentations and laboratory findings for infants with eosinophilic proctocolitis in whom IgE is presumably important for disease activity.

Conversely, a positive test response cannot ensure diagnosis but merely confirms some evidence for a food-induced allergy in the appropriate clinical setting with a clear history. Endoscopic changes are rather modest and not characteristic, sometimes evident as patchy erythematous changes, loss of vascular pattern and superficial ulceration. In other cases the mucosa appears quite normal Fig. Essential is a biopsy diagnosis to demonstrate eosinophilic involvement of the colon.

Biopsies will typically reveal sheets of eosinophils infiltrating the lamina propria, often with extension through the muscularis mucosa into the submucosa and occasionally into the muscularis propria. Crypt abscesses and lymphonodular hyperplasia also may be evident Fig.

Multiple biopsies are necessary. Not only is the distribution patchy in EC but also the eosinophil count normally has a broad range in different segments of the colon, exhibiting a proximal-to-distal distribution: cecum 35 eosinophils per high power field to the rectum 8—10 per high power field.

Two patients diagnosed with eosinophilic colitis histologically with two different endoscopic findings. The arrows indicate eosinophils. Eosinophilic proctocolitis milk-protein proctocolitis is an entity that has been described classically in infants associated with ingestion of soy protein and cow's milk.

The onset of bleeding is initially erratic over several days, and then wanes to occasional streaks of blood. In some, bloody diarrhea is pronounced and may lead to anemia. The infants otherwise are quite healthy and the colitis tends to be self-limiting. The abdominal examination is usually normal. Fecal smear may show an increased polymorphonuclear cell count.

Sigmoidoscopy may reveal modest inflammatory changes with focal erythema and friability. Enlarged lymphoid nodules, associated with transmural eosinophilic infiltration of the colon is best visualized by cross sectional imaging.

Elimination, oligoantigenic and elemental amino-acid based diets can provide symptomatic relief in many patients with EC, particularly infants with proctitis. Such a diet can be effective in some instances but its poor palatability commonly diminishes compliance. In more severe cases, medical therapy becomes clinically warranted. Limited information is available concerning any benefit from medical therapies; EC is quite rare, precluding randomized clinical trials.

Glucocorticoids therapy has been tried on the basis of case reports and medical experience. Maintenance corticosteroids at lower doses have been used in more relapsing, chronic disease. Immunomodulatory agents like azathioprine or 6-mercaptopurine down regulate or inhibit eosinophil growth factors, reducing eosinophilic infiltration and improving symptoms. They are worth trying in severe, refractory or steroid-dependent EC. Montelukast at 10—40 mg for several months can successfully maintain clinical remission in steroid-dependant patients with eosinophilic gastroenteritis, yielding a safe and effective steroid-sparing therapy.

Ketotifen, a second-generation H 1 -antihistamine, works as a mast cell stabilizer and thereby prevents the release of histamine.

Diagnosing Eosinophilic Colitis: Histopathological Pattern or Nosological Entity?

Eosinophilic gastrointestinal disorders EGID are a group of disorders that compromise the gastrointestinal tract. The best known is eosinophilic esophagitis while eosinophilic colitis which was first reported in the literature in is less well-known. Eosinophilic colitis is characterized by functional digestive disorders, most importantly diarrhea. Although there are no clear diagnostic criteria, blood should be tested for eosinophils and biopsies taken by colonoscopies should be studied for histological findings of eosinophilic infiltration. Eosinophilic colitis especially affects neonates and young adults and has been linked to genetic and allergic causes. Initial treatment consists of the suspension of allergens.

Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. Read article at publisher's site DOI : Rothenberg ME. N Engl J Med, 22 Annu Rev Immunol,

Eosinophilic colitis: an update on pathophysiology and treatment.

Eosinophilic colitis EC is a rare inflammatory disease included in the chapter of eosinophilic gastrointestinal disorders EGIDs , diagnosed by the presence of primary eosinophilic infiltrate in the colon wall in symptomatic patients. While the etiology of primary colonic eosinophilia is unknown, several conditions are involved in the pathogenesis of secondary eosinophilic colonic infiltrate food allergens, parasitic infections, drugs , which have to be excluded in order to correctly diagnose the primary form of the disease. Up to now, EC is lacking of codified guidelines regarding diagnostic criteria especially eosinophil threshold values and treatment, thus a correct approach to EC remains very challenging. Imaging, laboratory tests and endoscopy might be helpful in ruling out other mimic conditions, but EC is still a diagnosis of exclusion.

Abdulrahman A. Alfadda, Martin A. Storr, Eldon A.

Eosinophilic colitis: clinical review and 2020 update

Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI:

Eosinophilic colitis is a rare inflammatory disorder of the digestive tract with chronic evolution and unknown pathophysiological mechanisms. The article describes the case of a year old woman with a history of asthma and hypereosinophilia, who presented to a surgical department for persistent abdominal pain in the past 4 months, weight loss and malabsorption. She was diagnosed with eosinophilic colitis based on the colonoscopic result indicating extensive eosinophilic infiltration of the colonic mucosa correlated with the laboratory data and abdominal CT scan results. Following the colonoscopy, the patient developed fever, hypotension and diarrhea and was transferred to an Infectious Diseases Department with a presumptive diagnosis of abdominal sepsis. Treatment with ertapenem was immediately started. Metronidazole was also added due to a PCR positive stool test for Clostridioides difficile toxins encoding-genes.

Wolfgang B. Gaertner, Jennifer E. MacDonald, Mary R. Eosinophilic colitis is a rare form of primary eosinophilic gastrointestinal disease that is poorly understood. Neonates and young adults are more frequently affected.

Pathogenesis

Javascript is currently disabled in your browser. Several features of this site will not function whilst javascript is disabled. Received 24 September Published 5 June Volume Pages — Review by Single anonymous peer review.

Alan W. There is no consensus over its diagnosis and management, and uncertainty is compounded by the use of the same term to describe an idiopathic increase in colonic eosinophils and an eosinophilic inflammatory reaction to known aetiological agents such as parasites or drugs. In patients with histologically proven colonic eosinophilia, it is important to seek out underlying causes and careful clinicopathological correlation is advised. Because of the variability of eosinophil density in the normal colon, it is recommended that histological reports of colonic eosinophilia include a quantitative morphometric assessment of eosinophil density, preferably across several sites. As no correlation has been shown between colonic eosinophil density and symptoms in older children or adults, it is suggested that treatment should be directed towards alleviation of symptoms and response to treatment assessed clinically rather than by histological estimates of intramucosal eosinophils.

Через пять гудков он услышал ее голос. - Здравствуйте, Это Сьюзан Флетчер. Извините, меня нет дома, но если вы оставите свое сообщение… Беккер выслушал все до конца. Где же. Наверняка Сьюзан уже начала волноваться. Уж не уехала ли она в Стоун-Мэнор без .

Кардинальное отличие Монокля заключалось не в его миниатюрном дисплее, а в системе ввода информации. Пользователь вводил информацию с помощью крошечных контактов, закрепленных на пальцах. Контакты соединялись в определенной последовательности, которую компьютер затем расшифровывал и переводил на нормальный английский.

 Неужели так. - Утечка информации! - кричал кто-то.  - Стремительная.

 Коммандер? - позвала Сьюзан. Свет внутри исходил лишь от светящихся компьютерных мониторов Стратмора.  - Коммандер! - повторила.  - Коммандер.

Он решил было обратиться в полицию - может быть, у них есть данные о рыжеволосых проститутках, - но Стратмор на этот счет выразился недвусмысленно: Вы должны оставаться невидимым. Никто не должен знать о существовании кольца. Может быть, стоит побродить по Триане, кварталу развлечений, и поискать там эту рыжую девицу. Или же обойти все рестораны - вдруг этот тучный немец окажется .

Беккер с трудом приподнял голову. Неужели в этой Богом проклятой стране кто-то говорит по-английски. На него сверху вниз смотрел прыщавый бритоголовый коротышка. Половина головы красная, половина - синяя.

 Вы заплатили ему десять тысяч долларов? - Она повысила голос.  - Это грязный трюк. - Трюк? - Теперь уже Стратмор не мог скрыть свое раздражение.  - Это вовсе не трюк. Да я вообще слова ему не сказал о деньгах.

Он исходил из самых патриотических соображений, но все пошло вкривь и вкось. Результатом стали смерть и предательство. Теперь начнутся судебные процессы, последуют обвинения, общественное негодование. Он много лет служил своей стране верой и правдой и не может допустить такого конца. Я просто добивался своей цели, - мысленно повторил .

Он не знал, каким образом она поняла, что ему нужно кольцо, но был слишком уставшим, чтобы терзаться этим вопросом. Его тело расслабилось, он представил себе, как вручает кольцо сияющему заместителю директора АНБ.

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    Eosinophilic colitis: an update on pathophysiology and treatment of eosinophils (>15/high powered field) although consensus guidelines are.

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