Intestinal Abnormalities in Patients With SARS-CoV-2 Infection: Histopathologic Changes Reflect Mechanisms of Disease.

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.

Case Report: Molecular Diagnosis of Cystoisospora belli in a Severely Immunocompromised Patient with HIV and Kaposi Sarcoma.

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting trimethoprim-sulfamethoxazole, her diarrhea and eosinophilia improved, and she had undetectable Cystoisospora belli DNA on repeat stool quantitative polymerase chain reaction. This case highlights the importance of a thorough workup for diarrhea, including parasites, especially for immunocompromised patients. Antibiotic prophylaxis is recommended in patients with Cystoisospora belli and HIV/AIDS.

Eosinophilic colitis: an infrequent disease with difficult diagnose.

Eosinophilic colitis (EC) is a rare entity. It is part of eosinophilic gastroenteritis, a rare inflammatory disorder characterised by eosinophilic infiltration of tissues that can affect any segment of the digestive tract. The diagnosis is established by the presence of an increased eosinophilic infiltrate in the colon wall in symptomatic patients. There is no characteristic clinical picture of EC. It can be associated with abdominal pain, changes in bowel movements, diarrhoea and rectal bleeding. Biopsies are mandatory if EC is suspected and despite visualising a normal mucosa. Although there are no protocol guidelines in this regard, steroid treatment is the first option in controlling the disease. Increasing the knowledge of clinicians and pathologists of this disorder and the recording its real incidence and population impact, could improve the understanding and treatment of the disease.

Unique features of non-IgE-mediated gastrointestinal food allergy during infancy in Japan.

PURPOSE OF REVIEW: An increase in incidence of unique phenotypic non-IgE-mediated gastrointestinal food allergies (non-IgE GIFAs) has occurred in Japan ahead of Western countries. There are differences in clinical features of non-IgE GIFAs in Western and Japanese patients. As this phenotype has now come to be recognized internationally, we describe it in this review. RECENT FINDINGS: A large number of Japanese patients with non-IgE GIFAs present with vomiting accompanied by bloody stool, putting them between food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis. Some neonates and early infants with non-IgE GIFAs who present with fever and elevated C-reactive protein have symptoms consistent with severe systemic bacterial infections (e.g., sepsis). Some of these cases have now been defined in international guidelines as chronic FPIES. Eosinophils might be involved in the inflammatory process observed. The incidence of FPIES and food protein-induced allergic proctocolitis is increasing in Western countries and likely worldwide, after it has increased in Japan. SUMMARY: The phenotype observed in Japan shows distinct clinical features compared with the classical phenotype, that is, increased levels of eosinophils, suggestive of 'eosinophilic shift' alongside symptomatic differences, making it difficult to categorize.

Fatal nosocomial hemorrhagic enterocolitis probably caused by adenovirus. Report of one case.

Adenovirus (ADV) is a recognized cause of severe disease among immunocompromised patients. We report a previously healthy 39-year-old female, admitted with influenza pneumonia and evolving with lung hemorrhage and acute renal failure requiring mechanical ventilation and hemodialysis. She received high corticosteroid doses due to an initial suspicion of alveolar hemorrhage. Lymphopenia already present before steroid use (567/µL), was maintained during the whole hospital stay (mean 782/µL). From the second week of admission she presented a high-volume diarrhea (mean 2.5 L/day) associated to intermittent bloody stools. An ulcerative enterocolitis was confirmed by CT images and colonoscopy. ADV was detected in a colonic tissue sample by real time PCR but not by a commercial filmarray test. Cidofovir-probenecid and racecadotril therapy were indicated without changing the clinical course of diarrhea and the patient finally died.

Fatal nosocomial hemorrhagic enterocolitis probably caused by adenovirus: report of one case / Enterocolitis hemorrágica fatal nosocomial probablemente causada por adenovirus: informe de un caso

ABSTRACT Adenovirus (ADV) is a recognized cause of severe disease among immunocompromised patients. We report a previously healthy 39-year-old female, admitted with influenza pneumonia and evolving with lung hemorrhage and acute renal failure requiring mechanical ventilation and hemodialysis. She received high corticosteroid doses due to an initial suspicion of alveolar hemorrhage. Lymphopenia already present before steroid use (567/μL), was maintained during the whole hospital stay (mean 782/μL). From the second week of admission she presented a high-volume diarrhea (mean 2.5 L/day) associated to intermittent bloody stools. An ulcerative enterocolitis was confirmed by CT images and colonoscopy. ADV was detected in a colonic tissue sample by real time PCR but not by a commercial filmarray test. Cidofovir-probenecid and racecadotril therapy were indicated without changing the clinical course of diarrhea and the patient finally died.

Adenovirus (ADV) es una causa reconocida de enfermedades graves en pacientes inmunocomprometidos. Informamos el caso de una mujer de 39 años, previamente sana, que ingresó por neumonía grave por influenza, evolucionando con hemorragia pulmonar y falla renal aguda, requiriendo ventilación mecánica y hemodiálisis. Recibió altas dosis de corticoides por la sospecha inicial de una hemorragia alveolar. Tuvo linfopenia durante toda su estadía (promedio 782/μL), la que ya estaba presente antes del uso de los corticoides (567/μL). Desde la segunda semana de hospitalización, presentó una diarrea de alto volumen (promedio 2,5 L/día) asociada a la presencia de sangre en deposiciones en forma intermitente. Se confirmó una enterocolitis ulcerativa por tomografía computada y colonoscopía. Se detectó ADV en muestras de biopsia colónica por PCR en tiempo real pero no por un test de PCR múltiples automatizado comercial. Fue tratada con cidofovir-probenecid y racecadrotrilo sin impacto clínico y la paciente finalmente falleció.

A unique phenotype of acquired Glanzmann thrombasthenia due to non-function-blocking anti-αIIbß3 autoantibodies.

Essentials Acquired Glanzmann thrombasthenia (aGT) is generally caused by function-blocking antibodies (Abs). We demonstrated a unique aGT case due to marked reduction of αIIbß3 with anti-αIIbß3 Abs. The anti-αIIbß3 Abs of the patient did not inhibit platelet function but reduced surface αIIbß3. Internalization of αIIbß3 induced by the Abs binding may be responsible for the phenotype. SUMMARY: Background Acquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function-blocking anti-αIIbß3 autoantibodies. Aim We characterize an unusual case of aGT caused by marked reduction of surface αIIbß3 with non-function-blocking anti-αIIbß3 antibodies (Abs). Methods A 72-year-old male suffering from immune thrombocytopenia since his 50s showed exacerbation of bleeding symptom despite mild thrombocytopenia. Platelet aggregation was absent with all agonists but ristocetin. Analysis of αIIbß3 expression and genetic analysis were performed. We also analyzed effects of anti-αIIbß3 Abs of the patient on platelet function and αIIbß3 expression. Results Surface αIIbß3 expression was markedly reduced to around 5% of normal, whereas his platelets contained αIIbß3 to the amount of 40-50% of normal. A substantial amount of fibrinogen was also detected in his platelets. There were no abnormalities in ITGA2B and ITGB3 cDNA. These results indicated that reduced surface αIIbß3 expression caused a GT phenotype, and active internalization of αIIbß3 was suggested. Anti-αIIbß3 IgG Abs were detected in platelet eluate and plasma. These Abs did not inhibit PAC-1 binding, indicating that the Abs were non-function-blocking. Surface αIIbß3 expression of a megakaryocytic cell line and cultured megakaryocytes tended to be impaired by incubation with the patient's Abs. After 2 years of aGT diagnosis, his bleeding symptom improved and surface αIIbß3 expression was recovered to 20% of normal with reduction of anti-αIIbß3 Abs. Conclusion We demonstrated a unique aGT phenotype due to marked reduction of surface αIIbß3. Internalization induced by anti-αIIbß3 Abs may be responsible in part for the phenotype.

Histologic Features of Gastrointestinal Tract Biopsies in IgA Vasculitis (Henoch-Schönlein Purpura).

Immunoglobulin A (IgA) vasculitis or Henoch-Schönlein purpura (HSP) typically occurs in the pediatric population, although rare cases also occur in adults. Gastrointestinal (GI) involvement is common. The "classic" histologic finding in IgA vasculitis (HSP) is leukocytoclastic vasculitis (LCV); other histologic features in biopsies of IgA vasculitis (HSP) have only been rarely described. The pathology archival files at our institution were searched for GI biopsies from patients with IgA vasculitis (HSP). Slides were retrieved and histologic and clinical features were reviewed. We identified 16 patients with IgA vasculitis (HSP) with a GI biopsy series, including both adult and pediatric patients. The most common histologic abnormality was lamina propria hemorrhage (all cases) with many cases also showing lamina propria fibrin deposition with red cell sludging and nuclear debris (7 cases). Twelve of the 16 duodenal biopsies had acute duodenitis; 3 of which were severe and erosive. Several also had an eosinophilic infiltrate. Seven of the 9 jejunal and/or ileal biopsies had acute jejunitis or ileitis. An acute colitis or proctitis was observed in 9/12 colorectal biopsies. Four biopsies contained LCV; in each of these cases, the involved vessels were small capillaries within the lamina propria. Only 1 biopsy contained deeper submucosal vessels, but they were uninvolved. Sites involved by LCV included the colorectum (2 cases), colorectum and terminal ileum, terminal ileum only, duodenum, and jejunum (1 case each). All patients presented with abdominal pain; 13/16 developed a rash, 1 following the index biopsy. Other presenting symptoms included diarrhea and/or hematochezia (8 cases), nausea/vomiting (5 cases), and intussusception (1 case). Four patients had concurrent skin biopsies showing LCV; only 1 of these patients had LCV on GI biopsy. Indications for biopsy included nonspecific presenting symptoms, absence of rash at presentation, and/or failure to respond adequately to steroid therapy. Biopsies are commonly performed in patients with or without suspected IgA vasculitis (HSP) to rule out infection, inflammatory bowel disease, and less commonly, vasculitis. In general, vasculitis is not commonly observed in GI biopsies of patients with IgA vasculitis (HSP), and the spectrum of findings includes neutrophilic infiltrate within the small bowel and colon, with the duodenum most commonly affected. While the clinical and histologic findings may mimic early inflammatory bowel disease, the presence of predominant small bowel involvement, especially erosive duodenitis, should raise suspicion for IgA vasculitis (HSP). Biopsies should be obtained before steroid therapy is initiated, if possible.

Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment.

AIM: To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM). METHODS: We selected a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not relieve completely after routine therapy or cannot adhere to the therapy, and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT, and GM composition was assessed for infants and donors using 16S rDNA sequencing analysis. RESULTS: After FMT treatment, AC symptoms in 17 infants were relieved within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to follow-up. During follow-up, one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover, Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4) were enriched in some AC infants after FMT treatment, but the relative abundances of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and Klebsiella (n = 8) decreased dramatically. CONCLUSION: FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.

[Immunological balance of CD8+CD28+/CD8+CD28- T lymphocytes can predict gastrointestinal hemorrhage in patients with inflammatory bowel disease].

OBJECTIVE: To evaluate the sensitivity and specificity of CD8+CD28+/CD8+CD28- T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD). METHODS: Forty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8+CD28+ and CD8+CD28- T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8+CD28+/CD8+CD28- T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8+ T lymphocytes and the factors were analyzed. RESULTS: The utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8+CD28+T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8+CD28+T cells, CD8+CD28- T cells, and especially CD8+CD28+/CD8+CD28- ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ2=9.730, P=0.002; Χ2=15.981, P=0.000). CD8+CD28+/CD8+CD28- ratio was significantly related to both BA (P=0.009) and surgery (P=0.038). CONCLUSION: Both decreased CD8+CD28+T cells and elevated CD8+CD28-T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.

Deposiciones sanguinolentas iniciadas en los primeros días de vida / Bloody stools started in the first days of life

La proctocolitis alérgica del lactante es un trastorno caracterizado por la presencia de deposiciones mucosanguinolentas en los dos primeros meses de vida, pudiendo aparecer en los primeros días de vida. Anteriormente, relacionado con niños alimentados con lactancia artificial, en los últimos años se observa un aumento de la incidencia en niños alimentados con lactancia materna exclusiva debido al paso de proteínas de leche de vaca a la leche de la madre. Recién nacido a término, alimentado con lactancia materna exclusiva inicia a los dos días de vida deposiciones con hebras de sangre de forma intermitente. Todos los estudios realizados resultan normales. La clínica mejora progresivamente tras la eliminación de las proteínas de leche de vaca de la dieta de la madre, por lo que se diagnostica de proctocolitis alérgica. El diagnóstico se basa en la clínica, la desaparición de los síntomas al retirar las proteínas de leche de vaca de la dieta, y en la reaparición de éstos al reintroducirla. Los niños mantienen buen estado general en todo momento, siendo la gran mayoría tolerantes a la leche de vaca al año de vida, por lo que se considera una patología de buen pronóstico.

Allergic colitis is a pathology characterized by blood in faeces, appeared in first two months of life, but it can also appear during the first days of life. Previously it was related with children with non breastfeeding, however in the last years incidence is increasing in children with breastfeeding. This is explained with the presence of cow’s milk proteins in human’s milk. Newborn term, fed with exclusive breastfeeding, starts at second day of life blood in faeces, intermittently. The studies done are normal. The symptoms improve progressively after removing the cow’s milk proteins of the mother’s diet, so the child is diagnosed with allergic protocolitis. Diagnosis is based on the symptoms, the improvement with the removal of the cow’s milk protein of the diet, and the worsening when they are reintroduced. The children conserve good general condition every moment, almost all of them tolerate cow’s milk when they are one year old, and so it is considered pathology of well prognosis.

A case of multiple recurrence of Clostridium difficile infection with severe hematochezia in an immunocompromised host.

Clostridium difficile infection (CDI) is increasing in incidence and severity. Clinically, diarrhea frequently occurs, but severe hematochezia is rarely seen with CDI. We describe here a hematopoietic stem cell transplantation (HSCT) recipient who experienced life-threatening gastrointestinal bleeding due to severe CDI. Subsequent stool surveillance and molecular typing observed the patient who had two episodes of recurrence with a new strain of C. difficile distinct from the initial infection. We analyze C. difficile strains obtained from the patient, and also discuss the diagnosis and treatment of this case.

Strain differences in intestinal toxicity of warfarin in rats.

Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5mg/l) led to mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values of prothrombin time were noted at low WF dose (0.35mg/l) in the former strain. Leukocyte infiltration in intestine noted at this dose in both strains was associated with oxidative injury and more pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cell proliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats, represent different strategies to protect vulnerable intestine from harmful immune responses.

[SYSTEMIC CYTOKINOTHERAPY, USING BETALEUKIN IN A COMPLEX TREATMENT OF AN ACUTE GASTRODUODENAL ULCER BLEEDING].

Results of surgical treatment for an acute ulcer gastroduodenal bleeding in 120 patients, ageing 16-75 yrs old, were analyzed. In 20 of them a gastric ulcer was a cause of bleeding, while in 84--a duodenal ulcer, and in 16--a coexistent gastroduodenal ulcer. The bleeding activity was estimated in accordance to J. Forrest classification. In 57 patients (a comparison group) preoperatively and postoperatively a complex of a standard basal conservative therapy without immunocorrection was conducted, and in 63 (the main group)--a systemic cytokinotherapy (SCKTH), using betaleukin, was applied postoperatively additionally in a complex of therapy. A content of CD3+, CD4+, CD8+, CD19+, IgA, IgM, IgG was estimated in dynamics, as well as circulating immune complexes, phagocytic index, phagocytic number. There was established, that a dysbalance depth in the immune status have had depended upon the blood loss severity. The SCKTH application is pathogenetically substantiated, it promotes the immune status normalization, as well as a more favorable course of postoperative period and the results of treatment improvement.

Short article: Etiologic profile and endoscopic findings in immunocompromised children and adolescents with gastrointestinal bleeding.

BACKGROUND: Gastrointestinal bleeding (GIB) is one of the potential causes of increased morbidity and mortality in immunocompromised patients, but data on characteristics of GIB in immunocompromised children are sparse. OBJECTIVES: This study aimed to identify the etiology, endoscopic, and histologic findings of GIB in immunocompromised children. DESIGN: This was a retrospective descriptive study. PATIENTS: We identified 33 patients (aged<20 years) and 45 GIB episodes related to GIB between January 2007 and April 2015 from a tertiary care and teaching hospital. RESULTS: The mean age at endoscopy was 10.7±4.6 years. Most common indications for endoscopy were melena in upper GIB and hematochezia in lower GIB. The median delay of duration between GIB presentation to endoscopy was 3 days. All except one child had at least one endoscopic abnormality. The most common cause of upper GIB was cytomegalovirus (CMV)-related gastrointestinal disease (35%), followed by esophageal varices (26%), and the most common cause of lower GIB was CMV-related gastrointestinal disease (55%). Fourteen percent of patients died during upper GIB episodes and 15% died during lower GIB episodes. CONCLUSION: Among immunocompromised individuals aged younger than 20 years presenting with GIB, CMV-related gastrointestinal disease is the most prevalent in our study population. However, the etiology of immunocompromised state needs to be taken into consideration when evaluating these children presenting with GIB.