Primary classic Hodgkin lymphoma of the gastrointestinal tract represents a rare occurrence. A full patient's work-up is essential in order to exclude a secondary intestinal involvement. Histologically Epstein-Barr virus mucocutaneous ulcer closely resembles Hodgkin lymphoma. The differential diagnosis between these two entities is relevant, since both the therapeutic approach and the clinical behavior are different. Herein, we describe a case of primary classic Hodgkin lymphoma arising in the ileum and a case of Epstein-Barr virus mucocutaneous ulcer of the colon, focusing on the main clinicopathological differences.
Colonic Diseases/pathology , Epstein-Barr Virus Infections/pathology , Hodgkin Disease/pathology , Ileal Neoplasms/pathology , Opportunistic Infections/pathology , Ulcer/pathology , Adult , Aged, 80 and over , Biomarkers, Tumor/analysis , Biopsy , Colonic Diseases/immunology , Colonic Diseases/virology , Diagnosis, Differential , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , Female , Hodgkin Disease/drug therapy , Hodgkin Disease/metabolism , Humans , Ileal Neoplasms/chemistry , Ileal Neoplasms/drug therapy , Immunocompromised Host , Immunohistochemistry , Immunosuppressive Agents/adverse effects , Male , Methotrexate/adverse effects , Opportunistic Infections/immunology , Opportunistic Infections/virology , Predictive Value of Tests , Ulcer/immunology , Ulcer/virology
The aim of the study was to use in silico and in vitro techniques to evaluate whether a triple formulation of antiretroviral drugs (tenofovir, darunavir, and dapivirine) interacted with P-glycoprotein (P-gp) or exhibited any other permeability-altering drug-drug interactions in the colorectal mucosa. Potential drug interactions with P-gp were screened initially using molecular docking, followed by molecular dynamics simulations to analyze the identified drug-transporter interaction more mechanistically. The transport of tenofovir, darunavir, and dapivirine was investigated in the Caco-2 cell models and colorectal tissue, and their apparent permeability coefficient (Papp), efflux ratio (ER), and the effect of transporter inhibitors were evaluated. In silico, dapivirine and darunavir showed strong affinity for P-gp with similar free energy of binding; dapivirine exhibiting a ΔGPB value -38.24 kcal/mol, darunavir a ΔGPB value -36.84 kcal/mol. The rank order of permeability of the compounds in vitro was tenofovir < darunavir < dapivirine. The Papp for tenofovir in Caco-2 cell monolayers was 0.10 ± 0.02 × 10-6 cm/s, ER = 1. For dapivirine, Papp was 32.2 ± 3.7 × 10-6 cm/s, but the ER = 1.3 was lower than anticipated based on the in silico findings. Neither tenofovir nor dapivirine transport was influenced by P-gp inhibitors. The absorptive permeability of darunavir (Papp = 6.4 ± 0.9 × 10-6 cm/s) was concentration dependent with ER = 6.3, which was reduced by verapamil to 1.2. Administration of the drugs in combination did not alter their permeability compared to administration as single agents. In conclusion, in silico modeling, cell culture, and tissue-based assays showed that tenofovir does not interact with P-gp and is poorly permeable, consistent with a paracellular transport mechanism. In silico modeling predicted that darunavir and dapivirine were P-gp substrates, but only darunavir showed P-gp-dependent permeability in the biological models, illustrating that in silico modeling requires experimental validation. When administered in combination, the disposition of the proposed triple-therapy antiretroviral drugs in the colorectal mucosa will depend on their distinctly different permeability, but was not interdependent.
ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry , Darunavir/chemistry , Pyrimidines/chemistry , Tenofovir/chemistry , Anti-HIV Agents/chemistry , Anti-HIV Agents/therapeutic use , Caco-2 Cells , Colonic Diseases/prevention & control , Colonic Diseases/virology , Darunavir/therapeutic use , HIV Infections/prevention & control , Humans , Molecular Docking Simulation , Pyrimidines/therapeutic use , Tenofovir/therapeutic use
Antiviral Agents/therapeutic use , Colonic Diseases/drug therapy , Cytomegalovirus Infections/drug therapy , Ganciclovir/therapeutic use , Granuloma, Plasma Cell/drug therapy , Kidney Transplantation/adverse effects , Biopsy , Colonic Diseases/diagnosis , Colonic Diseases/virology , Colonoscopy , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/virology , Granuloma, Plasma Cell/diagnosis , Granuloma, Plasma Cell/virology , Humans , Immunohistochemistry , Male , Middle Aged , Remission Induction , Time Factors , Treatment Outcome
Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. The gastrointestinal (GI) tract is a common site involved, but non-specific signs and symptoms often delay the diagnosis. We report a case of EBV-associated GI-PTLD in a 68-year-old kidney transplant patient who received the kidney ten months earlier. He presented with chronic diarrhea and developed massive pneumo-peritoneum secondary to multiple colonic perforations.
Colonic Diseases/etiology , Epstein-Barr Virus Infections/etiology , Kidney Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , Aged , Biopsy , Chronic Disease , Colectomy , Colonic Diseases/diagnosis , Colonic Diseases/surgery , Colonic Diseases/virology , Diarrhea/etiology , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/virology , Fatal Outcome , Humans , Intestinal Perforation/etiology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/surgery , Lymphoproliferative Disorders/virology , Male , Pneumoperitoneum/etiology , Risk Factors , Time Factors , Treatment Outcome
Colonic Diseases/virology , Cytomegalovirus Infections/complications , Cytomegalovirus/immunology , Enterocolitis/virology , Ileal Diseases/virology , Leukemia/complications , Ulcer/virology , Aged , Antibodies, Viral/analysis , Colonic Diseases/diagnosis , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/virology , Diagnosis, Differential , Endoscopy, Gastrointestinal , Enterocolitis/diagnosis , Female , Humans , Ileal Diseases/diagnosis , Leukemia/diagnosis , Tomography, X-Ray Computed , Ulcer/diagnosis
We present the case of a 58-year-old woman with a long-standing history of systemic lupus erythematosus (SLE) who developed a cytomegalovirus (CMV) infection with colonic perforation and subsequent purulent peritonitis whilst using combined immunosuppressive therapy. The pathogenesis and the clinical presentation of this unique case is discussed in detail. Opportunistic infection should always be kept in mind in SLE patients presenting with fever. Viral serology should be routinely performed in these patients, especially when immunosuppressive therapy is given, to avoid delay in instituting adequate management and therapy.
Colonic Diseases/virology , Cytomegalovirus Infections/chemically induced , Cytomegalovirus Infections/virology , Immunosuppressive Agents/adverse effects , Intestinal Perforation/virology , Lupus Erythematosus, Systemic/drug therapy , Opportunistic Infections/chemically induced , Opportunistic Infections/virology , Antiviral Agents/therapeutic use , Colectomy , Colonic Diseases/diagnosis , Colonic Diseases/therapy , Colostomy , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/therapy , Female , Humans , Intestinal Perforation/diagnosis , Intestinal Perforation/therapy , Middle Aged , Opportunistic Infections/diagnosis , Opportunistic Infections/therapy , Peritonitis/chemically induced , Peritonitis/virology , Treatment Outcome
Colitis/complications , Colitis/virology , Colonic Diseases/virology , Cytomegalovirus Infections/complications , Cytomegalovirus , Liver Abscess/virology , Aged , Antiviral Agents/therapeutic use , Biopsy , Colectomy , Colitis/therapy , Colon/pathology , Colon/surgery , Colon/virology , Colonic Diseases/therapy , Constriction, Pathologic/virology , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/therapy , Female , Ganciclovir/therapeutic use , Humans , Liver Abscess/therapy , Treatment Outcome
Colonic Diseases/virology , Epstein-Barr Virus Infections/etiology , Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor , Iatrogenic Disease , Immunoglobulin Heavy Chains/genetics , Immunosuppressive Agents/adverse effects , Lymphoproliferative Disorders/virology , Skin Ulcer/virology , Aged, 80 and over , Fatal Outcome , Female , Hodgkin Disease/pathology , Humans , Lymphoproliferative Disorders/pathology
Colonic Diseases/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Retinitis/diagnosis , Immunocompetence , Intestinal Obstruction/virology , Colonic Diseases/diagnosis , Colonic Diseases/surgery , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/immunology , Cytomegalovirus Retinitis/drug therapy , Female , Humans , Infant, Newborn , Intestinal Obstruction/diagnosis , Intestinal Obstruction/surgery
Cytomegalovirus Infections/diagnosis , Cytomegalovirus/genetics , Gastrointestinal Diseases/virology , Organ Transplantation/pathology , Colonic Diseases/virology , Cytomegalovirus/isolation & purification , Duodenal Diseases/virology , Gastrointestinal Diseases/epidemiology , Humans , Jejunal Diseases/virology , Polymerase Chain Reaction/methods , Stomach Diseases/virology
A 27-week-old infant developed symptoms of bowel obstruction when full enteral feeds were started. Laparotomy revealed strictures in the ascending and proximal transverse colon. Right hemicolectomy was performed. Histological examination of the resected large bowel demonstrated the presence of Cytomegalovirus inclusion bodies. Cytomegalovirus infections of the gut are extremely rare in neonates. This case report alerts neonatologists and microbiologists to consider Cytomegalovirus infection as a possible cause of bowel obstruction and necrotising enterocolitis like symptoms.
Colonic Diseases/virology , Cytomegalovirus Infections/complications , Cytomegalovirus/isolation & purification , Infant, Premature, Diseases/virology , Intestinal Obstruction/virology , Colon, Ascending , Colon, Transverse , Colonic Diseases/pathology , Cytomegalovirus Infections/virology , Female , Histocytochemistry , Humans , Inclusion Bodies, Viral , Infant, Newborn , Infant, Premature, Diseases/pathology , Intestinal Obstruction/pathology , Laparotomy , United Kingdom
BACKGROUND: Several studies have shown an association between vaccination with the rotavirus vaccine and the development of intussusception. We evaluated the plausibility of a causal association between natural rotavirus infection and intussusception. METHODS: We performed ultrasound measurements, in infants with confirmed rotavirus infection and in healthy control subjects, of the ileum wall thickness and mesenteric lymph nodes, at enrollment and 1 month later. RESULTS: Thirteen pairs of patients with rotavirus infection and control subjects were enrolled. The mean distal ileum wall thickness at the first examination was 3.0 mm in patients with rotavirus infection and 2.0 mm in control subjects (P = .037). The maximum lymph node size in patients with rotavirus infection was 11.6 mm at the first examination and 7.4 mm at the second examination (P = .017). Nodal aggregates and free fluid were also observed more commonly among patients with rotavirus infection (54% vs. 9%; P = .033 for both). CONCLUSION: Rotavirus infection was associated with increased distal ileum wall thickness and lymphadenopathy during the illness period. These changes suggest a plausible mechanism by which rotavirus infection could cause intussusception.
Colonic Diseases/virology , Ileal Diseases/virology , Ileum/pathology , Intussusception/virology , Rotavirus Infections/pathology , Rotavirus/growth & development , Case-Control Studies , Cohort Studies , Colonic Diseases/diagnostic imaging , Colonic Diseases/pathology , Female , Humans , Ileal Diseases/diagnostic imaging , Ileal Diseases/pathology , Ileum/diagnostic imaging , Ileum/virology , Infant , Infant, Newborn , Intussusception/diagnostic imaging , Intussusception/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymph Nodes/virology , Male , Pilot Projects , Prospective Studies , Rotavirus Infections/diagnostic imaging , Rotavirus Infections/virology , Rotavirus Vaccines/adverse effects , Ultrasonography
BK Virus/isolation & purification , Colonic Diseases/virology , Intestinal Mucosa/virology , Polyomavirus Infections/virology , Tumor Virus Infections/virology , Ulcer/virology , Adult , Colonic Diseases/pathology , Colonic Diseases/therapy , Female , Humans , Immunosuppressive Agents/adverse effects , Intestinal Mucosa/pathology , Kidney Transplantation/adverse effects , Polyomavirus Infections/pathology , Polyomavirus Infections/therapy , Treatment Outcome , Tumor Virus Infections/pathology , Tumor Virus Infections/therapy , Ulcer/pathology , Ulcer/therapy