The role of histopathology in the diagnosis and management of coeliac disease and other malabsorptive conditions

Abstract

Most absorption of nutrients takes place in the proximal small intestine, and the most common disorders leading to malabsorption are associated with a morphological abnormality in the duodenal mucosa that is appreciable in histological sections of biopsy specimens. Coeliac disease is the most well‐known example, causing intraepithelial lymphocytosis, inflammation and villous atrophy in the duodenum. Remarkably similar inflammatory changes can be induced by other processes, including medications, e.g. angiotensin II receptor blockers and immune checkpoint inhibitors, immune dysregulation disorders, e.g. common variable immunodeficiency and autoimmune enteropathy, infections, collagenous sprue, and tropical sprue. However, there are often subtle histological differences from coeliac disease in the type of inflammatory infiltrate, the presence of crypt apoptosis, and the extent and type of inflammation beyond the duodenum. The clinical setting and serological investigation usually allow diagnostic separation, but some cases remain challenging. Histopathology is also important in assessing the response to treatment, such as the change in villous architecture caused by a gluten‐free diet, or the response to cessation of a potentially causative medication. This review examines the practical role that histopathology of duodenal biopsy specimens plays in the assessment and management of inflammatory malabsorptive processes of the proximal small intestine, with a particular emphasis on coeliac disease.

Small and Large Intestine (I): Malabsorption of Nutrients

“…The typically rapid clinical improvement with folate helps to establish the diagnosis. Complete histological improvement generally follows treatment with doxycycline, although this may take several months [101,102].…”

“…Lamina propria inflammation and intraepithelial lymphocytosis are sometimes seen. The diagnosis can be confirmed by breath test analysis or, more definitively, by microbial analysis of jejunal aspirates [102,112]. Although symptom relief can be achieved through multiple-antibiotic regimens, the correction of underlying etiology, if possible, is necessary for long-lasting cure.…”

Histological Features of Celiac-Disease-like Conditions Related to Immune Checkpoint Inhibitors Therapy: A Signal to Keep in Mind for Pathologists

“…Numerous disorders can cause a damage of the intestinal mucosa with similar histological features. Some of these conditions including immunodeficiency disorders (i.e., IgA deficiency, common variable immunodeficiency, HIV enteropathy), a variety of infections, (i.e., HP, Giardia, Cryptosporidium, Cyclospora ), and drug enteropathies (NSAIDs, recently approved antineoplastic agents, angiotensin II antagonists, immunosuppressive medications such as methotrexate, azathioprine, and mycophenolate mofetil) have rarely been associated with severe villous blunting, showing only a more or less pronounced increase of intraepithelial lymphocytes [ 41 , 42 , 43 , 44 , 45 ]. These conditions characterized by intraepithelial lymphocytosis without villous blunting fall into the category of so-called “microscopic enteritis”.…”

“…Microscopic enteritis is an “umbrella term” proposed by the Bucharest Consensus [ 46 ], to indicate a group of heterogeneous conditions that represent a challenge for the gastroenterologist, and the strict collaboration between the clinician and the pathologist is mandatory to achieve a correct diagnosis [ 47 ]. In some cases, histological features such as neutrophil crypt abscess, prominent crypt apoptosis, prominent eosinophil infiltration, plasma cells absence, and crypt distortion can help in the differential diagnosis [ 42 ]. In contrast, duodenitis is a reactive condition to the injurious effect of gastric acid.…”

Modern understanding of adult celiac disease

“…Так, стандартным в скрининга на целиакию является определение высокочувствительных АТ к тТТГ IgA (98%) и IgG (70%) с учетом возможного дефицита общего Ig A. Единственным устойчивым диагностическим индикатором целиакии является высокий уровень tTG, хотя имеется широкий диапазон (0-88%) положительных результатов у пациентов с глютеновой болезнью с типом 1 типа Марша [35,36]. Однако повышение уровня тТГ менее одной нормы по сравнению с верхним пределом нормы, было зарегистрировано у 17% пациентов, у которых не доказано, что они страдают целиакей [37]. Стоит отметить, что низкие титры антител против tTG могут быть обнаружены у пациентов с аутоиммунным заболеванием, хроническим заболеванием печени, застойной сердечной недостаточностью, гипергаммаглобулинемией, некоторыми лимфомами и кишечными инфекциями [38].…”