Punched-out Ulcers Research Articles

1904 Multiple Facets of CMV-Related Gastrointestinal Disease: From Top to Bottom

INTRODUCTION: Cytomegalovirus (CMV) primarily affects immunocompromised patients, and has multiple manifestations in the gastrointestinal (GI) tract. The incidence of CMV-related GI disease has decreased since the advent of antiretroviral therapy (ART) for HIV. This, along with varied and nonspecific symptoms, makes it difficult to diagnose. CASE DESCRIPTION/METHODS: We report a 34-year-old man with AIDS (CD4 count 114 cells/µL) on ART presenting with five days of fevers. He was admitted to the ICU for sepsis and stabilized. His course was complicated by pulmonary embolism, recurrent fevers, and development of biopsy proven pyoderma gangrenosum. He also reported odynophagia, and was empirically treated for candida esophagitis with fluconazole. On hospital day 37, he developed massive hematochezia. An urgent esophagogastroduodenoscopy (EGD) did not reveal the source of bleeding, but showed a 5-cm linear esophageal scar, which appeared to be a healing tear. Sigmoidoscopy revealed a solitary rectal ulcer with a visible vessel, which was clipped for hemostasis. His bleeding resolved. The patient’s odynophagia persisted, significantly limiting his ability to tolerate oral intake. Repeat EGD revealed a large, cratered, non-bleeding esophageal ulcer which was biopsied. The same day, the patient developed hematochezia; repeat sigmoidoscopy showed a deeply cratered rectal ulcer with a visible vessel successfully treated with hemostatic clips. Esophageal biopsies returned positive for CMV; valganciclovir was initiated. His odynophagia improved after starting treatment and he had no further GI bleeding. Given the clinical response, the rectal ulcers were presumed to be due to CMV, making this a case of extensive CMV-related GI disease. DISCUSSION: This is a case of extensive CMV-related GI disease which eluded diagnosis during a prolonged and complicated hospitalization. CMV-related GI disease has varied presentations, most commonly affecting the esophagus, but has also been noted to manifest with gastritis, duodenitis, pancreatitis, and colitis. The most common endoscopic findings for esophageal involvement are discrete, shallow, punched-out ulcers surrounded by normal appearing mucosa. Clinical manifestations of colonic CMV include abdominal pain and diarrhea, while discrete ulceration causing bleeding is less commonly reported. This case highlights the importance of a high index of suspicion for CMV in immunocompromised patients with multiple, unexplained GI symptoms to avoid a delay in diagnosis and management.

3069 CMV Colitis Presenting as Chronic Non-Remitting Diarrhea and Anemia

INTRODUCTION: Cytomegalovirus (CMV) is a common infection in immunocompromised patients including solid organ transplant patients. CMV infection of the GI tract can present in various ways. We present a case of chronic diarrhea of one-year duration associated with anemia. CASE DESCRIPTION/METHODS: A 56 year old female with a past medical history of hypertension, end stage renal disease with renal transplant in 2004 (maintained on cyclosporine, mycophenolate mofetil and prednisone) presented to the emergency room with generalized weakness of 4-days duration. The patient further endorsed significant weight loss and gradually progressive watery diarrhea that initially was postprandial and had been present for about one year. The symptoms persisted despite treatment with anti-diarrheal agents. The patient was also found to have anemia that began around a similar time as the diarrhea, and required multiple admissions for blood transfusions. She denied melena, hematochezia, fevers or chills. During prior admissions, fecal occult blood tests were negative and stool studies were unrevealing. On admission, the patient was found to have hemoglobin (Hgb) of 5.4 g/dL, acute kidney injury and metabolic acidosis. Fecal occult blood test was positive. Colonoscopy revealed diffuse pan colonic erythematous inflamed mucosa with rectal sparing and no evidence of punched-out ulcers (see Figures 1 and 2). Qualitative CMV polymerase chain reaction study was positive. Hematoxylin and Eosin stained biopsies were inconclusive for inclusion bodies. Immunohistochemical staining for CMV was positive for scattered reactive cells. CMV colitis was diagnosed. Patient was treated with oral valganciclovir leading to complete symptom resolution, improvement of anemia and weight gain. DISCUSSION: CMV colitis in immunocompromised patients typically presents with diarrhea associated with abdominal pain, fever, leukopenia and frank hematochezia. This case represents an unusual disease manifestation with an atypical timeline of disease duration, lack of aforementioned symptoms and non-characteristic endoscopic findings, making the diagnosis challenging. Furthermore, delayed CMV infection in organ transplant patients is quite unusual, as most typically, CMV infection presents shortly after initiation of immunosuppressive therapy.

1597 An Unexpected Cause of Colonic Ulcers in a Young Chinese Male Resulting in a Total Colectomy—Intestinal Behcet's Disease

INTRODUCTION: Behçet's disease (BD) is an uncommon immune-mediated inflammatory disorder. Gastrointestinal (GI) BD may affect any part of the GI tract but most commonly manifests in the ileocecal region. The diagnosis of GIBD is challenging and complications can be severe. CASE DESCRIPTION/METHODS: A 32-year-old Chinese male with HLA-B27 positive spondyloarthropathy was undergoing treatment with golimumab and methotrexate. He had a history of retinal vasculitis, erythema nodosum and was taking isoniazid for latent tuberculosis (TB). He was admitted for 1 day of right iliac fossa pain with occasional tongue ulcers but no fever or bloody stools. Abdominal computed tomography scan (CTAP) showed inflammatory changes in the ileocecal region. Colonoscopy with biopsies revealed an inflamed terminal ileum but no other colonic abnormalities; TB and cytomegalovirus biopsies were negative. He was discharged with antibiotics. He re-presented 4 weeks later with recurrent abdominal pain and 7-kg weight loss. CTAP showed worsening ileocecal thickening. The patient declined a colonoscopy only to be readmitted 5 days later for similar symptoms. Repeat colonoscopy showed large discrete round punched-out ulcers with overlying slough in the cecum, transverse, and left colon, with intervening normal mucosa. Biopsies showed extensive ulceration, acute inflammatory infiltrate with 1 non-caseating granuloma and intraluminal thrombi in submucosal arterioles/venules, raising the suspicion of gut vasculitis. Intravenous hydrocortisone and heparin were started. He developed worsening abdominal pain and a repeat CTAP showed pneumoperitoneum. Emergency surgery revealed multiple colonic perforations with feculent peritonitis necessitating total colectomy with end ileostomy. Histology revealed acute mucosal ulceration, areas of transmural necrosis, inflammation at perforation sites and luminal thrombi in the blood vessels around inflamed areas. A diagnosis of GIBD was made based on his constellation of symptoms. Treatment included prednisolone, cyclophosphamide, and he was later transitioned to azathioprine. DISCUSSION: In this immunosuppressed host with arthropathy presenting with abdominal pain, the key differentials of TB, Crohn's disease and GIBD are challenging to distinguish as there is significant clinical overlap. Endoscopic features may be helpful but are not pathognomonic of GIBD. This case highlights the diagnostic and management difficulties in GIBD and need for heightened awareness as outcomes in GIBD are potentially catastrophic.

Can endoscopists differentiate cytomegalovirus esophagitis from herpes simplex virus esophagitis based on gross endoscopic findings?

Differential diagnosis between herpes simplex virus (HSV) esophagitis and cytomegalovirus (CMV) esophagitis is challenging because there are many similarities and overlaps between their endoscopic features. The aims of this study were to investigate the implications of the endoscopic findings for the diagnosis of HSV and CMV esophagitis, and to develop a predictive model for differentiating CMV esophagitis from HSV esophagitis.Patients who underwent endoscopic examination and had pathologically-confirmed HSV or CMV esophagitis were eligible. Clinical characteristics and endoscopic features were retrospectively reviewed and categorized. A predictive model was developed based on parameters identified by logistic regression analysis.During the 8-year study period, HSV and CMV esophagitis were diagnosed in 85 and 63 patients, respectively. The endoscopic features of esophagitis were categorized and scored as follows: category 1 (-3 points): discrete ulcers or ulcers with vesicles, bullae, or pseudomembranes, category 2 (-2 points): coalescent or geographic ulcers, category 3 (1 points): ulcers with an uneven base, friability, or with a circumferential distribution, category 4 (2 points): punched-out, serpiginous, or healing ulcers with yellowish exudates. And previous history of transplantation (2 point) was included in the model as a discriminating clinical feature. The optimal cutoff point of the prediction model was 0 (area under receiver operating characteristic curve: 0.967), with positive scores favoring CMV esophagitis. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 89.4%, 92.6%, 87.3%, and 97.5%, respectively.The predictive model based on endoscopic and clinical findings appears to be accurate and useful in differentiating CMV esophagitis from HSV esophagitis.

Primary Herpes Simplex Virus-1 Infection Manifesting as Severe Esophagitis in an Adult Immunocompetent Host With Eosinophilic Esophagitis

While a common cause for infectious esophagitis in the immunocompromised, primary herpes esophagitis rarely affects immunocompetent hosts. Meanwhile, incidence of eosinophilic esophagitis (EoE) has increased over the past several decades, with a majority of those affected being young males. Several cases have been reported in the pediatric population, but we describe a case of an immunocompetent adult with known EoE who presented with a primary herpes simplex virus 1 (HSV1) infection manifesting as severe esophagitis. A 20-year-old male with known EoE complicated by prior esophageal food impactions presented to the emergency department with severe odynophagia and solid food dysphagia. The diagnosis of EoE was based on esophageal biopsies showing greater than 50 eosinophils per high powered field. He had been prescribed courses of swallowed aerosolized fluticasone in the past for symptomatic EoE, but had not required treatment in several years. The preceding week, he experienced fevers, chills, ear pain, pharyngitis, and a pustular lesion on his genitalia. He reported difficulty maintaining oral intake, and was found to have a mild leukocytosis. EGD was performed which showed multiple nonbleeding medium sized punched-out ulcers in the mid and distal esophagus. Biopsies of ulcer periphery demonstrated viral cytopathic effect and confirmed HSV by immunohistochemical staining. Histology also confirmed presence of eosinophils, up to 6 per high powered field. The patient was treated with a course of acyclovir with subsequent resolution of his symptoms. Initial HSV serologies were negative, but repeat testing several weeks later showed HSV seroconversion (HSV-1 IgG: 9.08). The patient tested negative for HIV and other sexually transmitted infections. This case adds to the few, but growing number of young immunocompetent hosts with EoE who present with primary HSV esophagitis. One potential reason why such patients are at risk for infectious esophagitis is the need for topical steroid therapy, but as illustrated above, our patient had not been on this treatment for many years. Rather, perhaps the impaired esophageal mucosal integrity present in EoE allows for increased susceptibility to HSV infection at this location. Recognition of this association allows for earlier detection and more targeted treatment.1773_A Figure 1. Severe HSV esophagitis, distal esophagus.1773_B Figure 2. HSV ulcers, mid esophagus.

Recurrent upper gastrointestinal bleed in a 26 year old female

According to recent society guidelines, upper gastrointestinal bleed initial approach includes assessment of hemodynamic status, fluid resuscitation if necessary, transfusion strategy to target hemoglobin above 7 (g/dL), use of intravenous proton pump inhibitor and generally upper endoscopy within 24 hours. We present a case of a 26-year-old woman who sought treatment after one episode of hematemesis and pre-syncope. She had a similar presentation three months earlier and received interventional radiology-guided mesenteric angiography and the use of multiple coils to embolize a 1.5-cm deep punched-out duodenal ulcer. Migration of the coil was noted on endoscopy within the previously described ulcer. Coil migration is expected to occur in up to 3% of cases of endovascular embolization. However, migration into the duodenum is uncommon and could have actually been a contributing factor to the current bleed.

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Three Cases with Punched-out Skin Ulcers during Anti-EGFR Monoclonal Antibody Drug Administration

Three Cases with Punched-out Skin Ulcers during Anti-EGFR Monoclonal Antibody Drug Administration

Eczema Herpeticum

A 27-year-old woman with a history of systemic lupus erythematosus and eczema presented to the emergency department with a progressive, pruritic facial rash of 4 days' duration. Examination revealed “punched-out” ulcers to the forehead, cheeks, chin, and upper and lower cutaneous lips, some coalescing into larger lesions with scalloped borders and honey-colored serous crust (Figure 1A). Curiously, the punched-out ulcers fluoresced under a Wood's lamp (Figure 1B). The patient was given i.v. acyclovir and clindamycin for impetiginized eczema herpeticum, and admitted to the hospital. A swab subsequently confirmed the presence of herpes simplex virus-1 (HSV-1) via polymerase chain reaction (PCR). The patient was continued on i.v. clindamycin and acyclovir until hospital day 5, when all the lesions had crusted over, at which point she was transitioned to oral valacyclovir, oral doxycycline, and topical mupirocin before discharge. Two weeks after her initial presentation, the rash had improved greatly, but significant scarring was present (Figure 1C).

Hailey-Hailey Disease Complicated by Herpes Simplex Viral Infection

A 51-year-old man with a history of Hailey-Hailey disease presented to clinic due to worsening discomfort from a rash in his groin. Physical examination of the inguinal area and scrotum revealed grouped, punched-out ulcers on a base of macerated, erythematous plaques. Viral culture from the ulcers was positive for HSV-2. The patient had no known history of Herpesvirus infection. Treatment with oral valacyclovir resulted in marked clinical improvement. Although cases of Hailey-Hailey herpeticum are much less common than the better-studied eczema herpeticum, it is important for physicians to be aware that any disease that disrupts the stratum corneum increases the risk of superimposed HSV infection, which constitutes a medical emergency. Prompt treatment with antiviral agents can hasten patient recovery and optimize outcomes.

Hailey-Hailey Disease Complicated by Herpes Simplex Viral Infection

A 51-year-old man with a history of Hailey-Hailey disease presented to clinic due to worsening discomfort from a rash in his groin. Physical examination of the inguinal area and scrotum revealed grouped, punched-out ulcers on a base of macerated, erythematous plaques. Viral culture from the ulcers was positive for HSV-2. The patient had no known history of Herpesvirus infection. Treatment with oral valacyclovir resulted in marked clinical improvement. Although cases of Hailey-Hailey herpeticum are much less common than the better-studied eczema herpeticum, it is important for physicians to be aware that any disease that disrupts the stratum corneum increases the risk of superimposed HSV infection, which constitutes a medical emergency. Prompt treatment with antiviral agents can hasten patient recovery and optimize outcomes.

The Association Between CMV Viremia or Endoscopic Features and Histopathological Characteristics of CMV Colitis in Patients with Underlying Ulcerative Colitis

Cytomegalovirus (CMV) infection has been shown to be related to severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this study was to evaluate the endoscopic and pathological characteristics of CMV colitis in patients with UC and to assess the predictive value of the endoscopic and pathological features of CMV colitis. A total of 50 consecutive UC patients with CMV infection who were admitted to Peking Union Medical College Hospital from 2010 to 2015 were enrolled in this study. Twenty-five UC patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%, respectively. A higher proportion of endoscopic punched-out ulcers, irregular ulcers, and cobblestone-like appearance were observed among the patients in the CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%, 60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of CMV inclusion bodies per high-power field was significantly higher in those with punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of pathological inflammation was observed in the CMV colitis group than in the control group (68.0% versus 44.0%). Characteristic endoscopic features with punch-out ulcers and high CMV viremia load may be useful for predicting the presence of CMV colitis in histology. Punch-out ulcers were found to be associated with a higher number of inclusion bodies on histology, suggesting a role of targeted biopsy for endoscopist.

Analysis of Recent Cases of Postbulbar Duodenal Ulcer in Japan

Although the incidence of postbulbar duodenal ulcers is low, many complications occur, such as hemorrhage, stenosis and perforation, and there are many points to be paid attention to with regard to its pathology. A high acid level has been pointed out as a cause, but this is not conclusive, and its association with Helicobacter pylori (Hp) infection is also unclear. We investigated chronic cases excluding acute cases such as acute duodenal mucosal lesion we encountered between 2001 and 2015. Five cases corresponded, accounting for 1.4% of all chronic duodenal ulcer cases, and there were more male patients (four patients were male), as previously reported. All cases were solitary punched-out ulcer on the medial side near the superior duodenal flexure, and many complications were observed such as melena in all patients, narrowing in 2, and penetration in 1. No specific pathology, such as Crohn’s disease, vasculitis, or Zollinger-Ellison syndrome, was noted, no patient was previously medicated with NSAIDs or low dose aspirin, and 3 patients were infected with Hp. All cases were healed by proton pump inhibitor administration or gastric acid secretion-suppressing treatment with selective proximal vagotomy. Recurrence after Hp eradication occurred in all of the 3 Hp-infected patients, suggesting that involvement of Hp in the cause of disease is unlikely.

Tongue Ulcers, Abdominal Pain, and Fever in a Kidney Transplant Recipient

Tongue Ulcers, Abdominal Pain, and Fever in a Kidney Transplant Recipient

Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis.

To identify characteristic endoscopic findings and risk factors for cytomegalovirus (CMV)-associated colitis in patients with active ulcerative colitis (UC). A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis. Multivariate analysis indicated independent associations with the extent of disease (pancolitis) and use of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC (odds ratio = 12.672, 95%CI: 4.210-38.143). Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.

A Rare Case of Ecthyma Gangrenosum Caused by Proteus vulgaris and Candida albicans in a Patient with Castleman Disease.

Ecthyma gangrenosum (EG) is an ulcerative pyoderma of the skin that extends into the dermis and subdermal tissue with necrotic changes, and is generally described as a round, deep, punched-out ulceration with a central black eschar surrounded by an erythematous halo [[1]]. Development of EG is most commonly associated with Pseudomonas aeruginosa and is often seen in immunocompromised patients. However, cases of EG caused by other bacterial, viral, and fungal pathogens have been reported in the literature, albeit rarely. Prompt surgical debridement with appropriate antibiotic therapy is crucial for lowering the mortality rate in EG patients [[1]]. We describe an interesting case of EG caused by Proteus vulgaris (P. vulgaris) and Candida albicans (C. albicans) in a patient with multicentric Castleman disease (MCD), which involves hyperactivation of the immune system and multiple organ system dysfunction. Our patient showed extensive lesions involving necrotic ulcerative changes on the lower abdomen and on the right upper arm. To the best of our knowledge, this was a rare case of EG associated with P. vulgaris and C. albicans.

A case of acquired immunodeficiency syndrome with ileocecal ulcer

We report a case of a patient with acquired immunodeficiency syndrome (AIDS) and ileocecal ulcer. A 31-year-old man was admitted with chief complaints of decreased body weight and abdominal pain. Colonoscopy revealed a round punched-out ulcer on the ileocecal valve. Initially, we suspected entero-Behçet's disease and simple ulcer as the cause of the ileocecal ulcer. However, after histologic examination of tissue biopsies obtained during colonoscopy, we diagnosed the patient as having cytomegalovirus (CMV) enteritis. Based on the patient's white blood cell depletion and CMV enteritis, we performed a human immunodeficiency virus (HIV) antibody test. The test was positive, and the diagnosis of AIDS was established. The number of patients with AIDS has been increasing in Japan; thus, we should consider the possibility of CMV enteritis and AIDS in young adult patients affected by ileocecal ulcer with no notable history.

Lipschütz Disease and Epstein-Barr Virus

Lipshutz disease (LD), also known as ulcus vulvae acutum, Epstein-Barr virus (EBV) vulvitis, or reactive nonsexually related acute genital ulcers, typically presents as multiple self-limited, punched-out, and painful ulcers on the labia minora of young, nonsexually active females. These ulcers are commonly associated with EBV, but also with cytomegalovirus (CMV), influenza, mumps, toxoplasmosis, mycoplasma, and salmonella. These authors explored histology in a retrospective review of seven …

A Painful Perianal Lesion

Gastroent Question: A 54-yearold white man with a history of infection with human immunodeficiency virus complicated with disseminated bartonellosis infection was recently diagnosed with multicentric Castleman disease. He was treated with 4 weekly doses of rituximab 375 mg/m and methylprednisone 4 mg/d. His further treatment consisted of ritonavir boosted daranuvir, emtricitabin, and tenofovir. His CD4 count was 100/ mL, and his viral load 151 copies/mL. During his second course of chemotherapy, he developed complaints of anal pain and rectal bleeding. On physical examination, he had a deep, solitary, punched-out perianal ulcer with granulating base and raised indurated edges (Figure A). His leukocyte count was 3400/mL, with 59% neutrophils and 34% lymphocytes. Serological testing was negative for Bartonella henselae immunoglobulin M enzyme-linked immunosorbent assay and Treponema pallidum rapid plasma reagent. Tissue cultures of the ulcer were negative for fungi, mycobacteria and pathogenic bacteria, as was the polymerase chain reaction (PCR) for Chlamydia trachomatis and Neisseria gonorrhoeae and the direct immunofluorescence assay for Herpes simplex types 1 and 2. Biopsies from the border of the ulcer showed a mixed inflammatory infiltrate (mainly consisting of neutrophils, without granuloma formation) in the basal layer of the stratified squamous epithelium (Figure B, arrow). Specific staining could not demonstrate any acid-fast bacilli, fungi, or herpesvirus antigens. What are major differential diagnoses, and how may you proceed? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Herpes simplex esophagitis: Report of 4 pediatric cases in immunocompetent patients

Although herpetic infection is considered in the differential diagnosis of a patient who is immunocompromised with esophagitis, it is less thought of in the immunocompetent patient. There are few reports of esophagitis caused by herpes simplex virus in immunocompetent children and adolescents. We are reporting four cases in this age group who have been identified to have herpes simplex esophagitis. The first patient was nine-year-old boy who presented with chest pain, fever, and diarrhea. The second patient was a six-year-old boy who presented severe chest pain and had a negative endoscopy four months prior. The third was an 18-year-old young man with history of vomiting, odynophagia, and recent weight loss of 25 lbs. The fourth patient was a six-year-old girl admitted for dehydration and febrile illness three days after tonsillectomy, complaining of chest pain and epigastric abdominal.Their endoscopic findings varied from punched-out ulceration only to erosive esophagitis or both. They were all diagnosed by PCR analysis and not by pathology. All had biopsies suggestive of esophagitis. They all responded well to acyclovir. Based on testing and available follow up, all patients appeared to be immunocompetent, although one case refused HIV testing. Herpes simplex esophagitis in children can have variable presentations. High level of suspicion is warranted even in the immunocompetent patient. This is especially important when the history of acute gastrointestinal symptoms includes a triad of fever, chest pain, and odynophagia, but also even if these symptoms are recurrent. Viral cultures and PCR of the esophageal biopsies should be performed in addition to pathology looking for Cowdry Type A bodies.