Atypical HUS and Crohn’s disease—interference of intestinal disease activity with complement-blocking treatment

Background In atypical hemolytic-uremic syndrome (aHUS), various defects of the complement system have been reported to explain pathophysiology. Therapeutic options for complement inhibition are well-recognized; however, the links between various immune-derived diseases and aHUS are unclear, and their interference with treatment efficacy during long-term complement-blocking therapy is scarcely known. Case-diagnosis/treatment We present a pediatric patient who developed aHUS with acute kidney injury in parallel with the onset of Crohn’s disease (CD), and who required long-term complement-blocking therapy with eculizumab (ECU). Unexpectedly, during the 6-year ECU treatment, an important intra-patient variation of the degree of complement inhibition was observed. In spite of continuous and stable doses of complement-blocking therapy, periods of incomplete blockade were observed in strong association with relapses of CD. When conventional and later biological therapy with adalimumab was introduced, with CD going into remission, complement blockade became complete again. Despite periodically low ECU levels and insufficient complement inhibition, no clinical or hematological signs of aHUS recurrence were detected during CD relapses. Conclusion In aHUS cases secondary to CD, close monitoring of both complement inhibition and serum ECU levels is needed as intestinal disease can interfere with complement-blocking treatment. Increased doses of ECU may be necessary to maintain therapeutic blood levels of ECU and full complement blockade, especially if the intestinal disease is not under control.

Leukocyte numbers and intestinal mucosal morphometrics in horses with no clinical intestinal disease

Healthy horses and other animals have large numbers of resident leukocytes in the intestinal wall, but there is scant information regarding which and how many leukocytes are normally present in the equine intestinal wall. Our aim was to provide a reference range of leukocytes in the intestinal mucosal and submucosal propria of normal horses. We included in our study intestinal tissues from 22 Thoroughbred racehorses with no clinical intestinal disease, which had been euthanized because of catastrophic musculoskeletal injuries. Neutrophils, lymphocytes, eosinophils, macrophages, and plasma cells were counted in 5 random 17,600-µm2 areas of villus lamina propria of the duodenum, jejunum, and ileum, and deep lamina propria of the duodenum, jejunum, ileum, right ventral colon, left ventral colon, left dorsal colon, right dorsal colon, and small colon. Other features investigated in the same intestinal segments included villus height and width (small intestine), presence of ciliated protozoa, Paneth cells number, subcryptal leukocyte layers (number of leukocyte layers between the bottom of the crypts and the muscularis mucosae), and submucosal leukocytes. Lymphocytes were the most numerous cells in all segments analyzed, followed by plasma cells, eosinophils, macrophages, and neutrophils. Eosinophil numbers were significantly higher in both lamina propria and submucosa of the large intestine than in the small intestine. The duodenum had shorter and thinner villi than either jejunum or ileum. The data provided from our study will be useful for diagnosticians examining inflammatory processes in the intestinal tract of horses.

Treating chronic diarrhea: A systematic review on Immunoproliferative Small Intestinal Disease (IPSID)

Immunoproliferative Small Intestinal Disease (IPSID) is a disease characterized by extra-nodal marginal zone B-cell lymphoma with villous atrophy in the small intestine, causing chronic intermittent non-bloody diarrhea. Although originally associated with the Mediterranean region, this disease is present in many countries worldwide and may have been underreported due to its complicated diagnosis and scarce scientific literature, especially in regards to treatment. This study aims to review IPSID clinical features, therapeutic options, and treatment outcomes to help physicians identify and treat IPSID. Using PRISMA guidelines, a systematic review of articles was conducted on PubMed database with search terms including IPSID, therapy, treatment, and outcomes. Inclusion and exclusion criteria were used to select 33 English language articles published from the year 2000–2020 that included relevant clinical information about IPSID treatment. Data were extracted independently by at least two authors to reduce the introduction of potential bias. There were 22 case reports, 7 reviews, 1 research article, 1 prospective study, 1 letter to the editor and 1 memoriam in which 76 patients were identified. Epidemiological analysis showed a mean patient age of 32 years old, 2.4:1 mal to female ratio and heterogeneous ethnicities, with 16 Europeans (43.2%) and 12 Asians (32.4%). Chief symptoms included chronic diarrhea (53/76, 69.7%), weight loss (49/76, 64.4%), malabsorption (38/76, 50%), abdominal pain (32/76, 42.1%), and finger clubbing (24/76, 31.6%). Patients stratified into the early disease stage (Galian A) were treated with tetracycline antibiotics, corticosteroids, and non-pharmacological supplements with mostly with complete or partial remission. Late stages (Galian B or C), were treated mostly with anthracycline-based chemotherapy, and occasionally surgery, radiotherapy, or rituximab. This work offers a targeted approach to diagnosing and treating IPSID to aid physicians and serve as a treatment guideline recommendation for future public policies and clinical studies.

A clinical case of difficult diagnosis of systemic lupus erythematosus

The paper presents a clinical case of a patient diagnosed with systemic lupus erythematosus, which had a vague clinical picture and required a combined examination for differential diagnosis with intestinal disease (Crohn’s disease with extraintestinal manifestations). Data of instrumental, laboratory studies during hospitalization and data of pathoanatomic examination after death of the patient from the developed complications are presented.

Comparison of the Fecal Microbiota of Horses with Intestinal Disease and Their Healthy Counterparts

(1) Background: The intestinal microbiota plays an essential role in maintaining the host’s health. Dysbiosis of the equine hindgut microbiota can alter the fermentation patterns and cause metabolic disorders. (2) Methods: This study compared the fecal microbiota composition of horses with intestinal disease and their healthy counterparts living in Korea using 16S rRNA sequencing from fecal samples. A total of 52 fecal samples were collected and divided into three groups: horses with large intestinal disease (n = 20), horses with small intestinal disease (n = 8), and healthy horses (n = 24). (3) Results: Horses with intestinal diseases had fewer species and a less diverse bacterial population than healthy horses. Lactic acid bacteria, Lachnospiraceae, and Lactobacillaceae were overgrown in horses with large intestinal colic. The Firmicutes to Bacteroidetes ratio (F/B), which is a relevant marker of gut dysbiosis, was 1.94, 2.37, and 1.74 for horses with large intestinal colic, small intestinal colic, and healthy horses, respectively. (4) Conclusions: The overgrowth of two lactic acid bacteria families, Lachnospiraceae and Lactobacillaceae, led to a decrease in hindgut pH that interfered with normal fermentation, which might cause large intestinal colic. The overgrowth of Streptococcus also led to a decrease in pH in the hindgut, which suppressed the proliferation of the methanogen and reduced methanogenesis in horses with small intestinal colic.