Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality.

Herpes simplex virus 1 (HSV-1), a leading cause of genital herpes, infects oral or genital mucosal epithelial cells before infecting the peripheral sensory nervous system. The spread of HSV-1 beyond the sensory nervous system and the resulting broader spectrum of disease are not well understood. Using a mouse model of genital herpes, we found that HSV-1-infection-associated lethality correlated with severe fecal and urinary retention. No inflammation or infection of the brain was evident. Instead, HSV-1 spread via the dorsal root ganglia to the autonomic ganglia of the enteric nervous system (ENS) in the colon. ENS infection led to robust viral gene transcription, pathological inflammatory responses, and neutrophil-mediated destruction of enteric neurons, ultimately resulting in permanent loss of peristalsis and the development of toxic megacolon. Laxative treatment rescued mice from lethality following genital HSV-1 infection. These results reveal an unexpected pathogenesis of HSV associated with ENS infection.

Toxic megacolon and human Cytomegalovirus in a series of severe ulcerative colitis patients.

BACKGROUND: Human Cytomegalovirus (HCMV) infection has been reported to be a cause of refractory ulcerative colitis (UC). Toxic megacolon (TM) is a rare but severe complication of an acute attack of UC. OBJECTIVES: Aim of this study is to evaluate in a case-control study the association between HCMV and TM. STUDY DESIGN: All patients who were admitted at Medicine Department of V. Cervello Hospital in Palermo (tertiary referral center) for a severe UC flare-up complicated by the onset of TM (diameter of the transverse colon>6 cm) between January 1990 and November 2011 were identified through the electronic database. A total of 24 consecutive patients (16 male/8 female) with TM were identified. Each case of TM were individually matched by sex, age, extent of the underlying disease to 24 severe UC controls who did not develop TM. A further non matched control population of 48 severe UC was included. Haematoxilin and eosin stain, immunohistochemical procedure and nested polymerase chain reaction were performed to detect HCMV genes and proteins on rectal biopsies or surgical specimens. Pp65 antigenemia was performed in order to diagnose any possible systemic infection. HCMV frequency was compared between patients with and without TM during follow-up, using Fisher's Exact test. RESULTS AND CONCLUSIONS: HCMV was detected in histological specimens of 11 patients (46%) with TM compared to 2 (9%) severe UC matched controls (P = 0.0078) and 7 (14%) unmatched controls (p = 0,003). In severe colitis the presence of HCMV is more frequently associated with TM.

A young leukemic patient with unusual catastrophic intestinal complication.

A 14-year-old child with acute lymphoblastic leukemia who had completed induction chemotherapy presented with fever and diffuse musculoskeletal pains which was thought to be a constellation of myositis, arthralgias and arthritis. Investigations revealed initially showed normal peripheral blood counts but had pancytopenia and pre-terminally blasts were seen in the peripheral blood smear. He had bone marrow necrosis. Disseminated intravascular coagulation was suspected with a positive fungal serology. At autopsy, he had evidence of disease relapsed in lymph nodes, liver, spleen, testes and kidneys. There was extensive pseudomembranous colitis and appendicitis with changes of toxic megacolon.

Toxic megacolon after abdominoplasty: a case report.

After an accepted technique of abdominoplasty, a 66-year-old woman developed Clostridium difficile-associated diarrhea, leading to toxic megacolon and subsequent subtotal colectomy. The presumed etiology is chronic use of a proton pump inhibitor. This was addressed in a 2012 "white paper" warning issued by the Food and Drug Administration. This article presents the course of this case as well as a review of the pertinent literature.

Recent advances in understanding ulcerative colitis.

Ulcerative colitis, one of the two main forms of inflammatory bowel disease, is characterized by inflammation of the large bowel with constant involvement of the rectum, and a possible continuous retrograde distribution up to the cecum. Typical macroscopic lesions are mucosal ulcerations, with immune cell infiltration and cryptic abscesses at histology. Ulcerative colitis usually manifests with bloody diarrhea, is associated with a number of extra-intestinal manifestations, and may be acutely complicated by toxic megacolon. Longstanding disease may predispose to the development of colorectal cancer. Therapeutic options include mesalazine, corticosteroids, immunomodulators and biologic agents; however, if these treatments fail, the only available therapeutic choice remaining is the surgical removal of the colon. This review emphasizes novel concepts in the basic aspects of ulcerative colitis, and, in addition to the current clinical and diagnostic knowledge, it also describes new treatment options for this condition.

Toxic megacolon complicating a Clostridium difficile infection in a pregnant woman.

Clostridium difficile infection (CDI) in non-hospitalized patients has been reported with increased frequency, whereas an association between CDI and pregnancy has not been highlighted. We report a case of toxic megacolon complicating a severe CDI during the second trimester of pregnancy in a patient without traditional risk factors, such as antibiotic use, immunodeficiency, and prolonged and recent hospitalization.

Un caso de megacolon tóxico por salmonella / Case report of a toxic megacolon due to salmonella infection

Se presenta el caso de un paciente masculino de 59 años de edad, con antecedentes de colitis ulcerosa, que luego de la ingesta de agua no potable se internó por diarrea de una semana de evolución con más de veinte deposiciones acuosas diarias. Al momento de la internación se realizó rectosigmoidoscopía que no reveló actividad de su enfermedad intestinal de base. Se solicitaron estudios para descartar diversas etiologías infecciosas, obteniéndose en coprocultivo desarrollo de Salmonella species por lo que se indicó tratamiento antibiótico con ciprofloxacina.

[Toxic megacolon and jejunal perforation due to cytomegalovirus]. / Megacolon tóxico y perforación yeyunal por citomegalovirus.

Cytomegalovirus (CMV) infection is a frequent disease in immunocompromised patients and can affect the gastrointestinal tract in 50% of patients, giving rise to colitis due to CMV. However, a perforated jejunum is not frequent. We present the case of an immunocompromised patient who was diagnosed with colitis due to CMV infection after bowel perforation. Outcome was favorable after surgery and antiviral treatment.

Invasive aspergillosis localised to the colon presenting as toxic megacolon.

Primary gut involvement by Aspergillus is an exceedingly rare and often a fatal complication of intensive chemotherapy in patients with acute leukaemia. We report a 46-yr-old patient with granulocytic sarcoma of the testis. He received acute myeloid leukaemia type treatment with ADE chemotherapy (Cytosine Arabinoside, Daunorubicin and Etoposide). While neutropenic he presented with pyrexia, abdominal pain and massive abdominal distention. He was treated with intravenous antibiotics and antifungals according to our usual institutional protocol without any response. He was found to have toxic megacolon on plain X-ray and subsequently underwent total colectomy and ileostomy. The colon histology showed Aspergillus fungal hyphae infiltrating the bowel wall. There was no any evidence of pulmonary, hepatic, splenic or renal lesions on the computerised tomography scan. Following colectomy, he was treated with 2 wk of antifungal treatment. He recovered well and was discharged home. The increased awareness, high degree of clinical suspicion of unusual presentation and early surgical intervention with aggressive antifungal treatment, has a key role in the management of these rare and often fatal cases.

Current indications for blow-hole colostomy:ileostomy procedure. A single center experience.

BACKGROUND AND AIMS: Because of improved medical care and surgical techniques blow-hole colostomy with loop ileostomy is now rarely performed to reduce operative risks in patients with toxic megacolon related to inflammatory bowel disease (IBD). We reviewed patient charts to identify continuing indications for this procedure. PATIENTS AND METHODS: Seventeen patients underwent blow-hole colostomy procedure with ( n=15) or without ( n=2) ileostomy (8 men, 9 women; median age 51 years, range 21-79) during the past 18 years (1983-2001). RESULTS: The indications for the procedure were: toxic megacolon related to IBD ( n=6), toxic megacolon related to IBD and associated with pregnancy ( n=2), Clostridium difficile colitis ( n=3), adult Hirschsprung's disease ( n=1), pancreatitis with obstructing pseudocyst ( n=1), and palliation for malignant bowel obstruction with metastases ( n=4). Patients were discharged home after a median stay of 10 days (range 4-32 days). The 4 patients who underwent a palliative blow-hole procedure had died secondary to their underlying disease by the time of follow-up. Of the remaining 13 patients 12 had their alimentary tract reconstituted, and one still awaits a definitive procedure. CONCLUSION: The blow-hole colostomy-ileostomy procedure is still indicated for select patients with toxic megacolon and large-bowel obstruction. The procedure acts as a bridge to definitive operation for toxic patients with benign disease and palliates those with malignant obstructions and metastasis.