Cytomegalovirus Inclusions Research Articles

A case of cytomegalovirus cystic lung disease and review of literature.

A 31-week gestation male infant with respiratory distress since day of delivery had lobectomy at 8 weeks of age for symptomatic, suspected congenital pulmonary airway malformation (CPAM). Histology of resected lung showed cytomegalovirus (CMV) inclusion bodies and emphysematous changes. The infant was treated with antiviral therapy with improvement in symptoms. CMV infection of the lung should be considered in any neonate presenting with lung cysts.

NAVIGATING THE UNCHARTED WATERS: MANAGING CONCURRENT CYTOMEGALOVIRUS MYOCARDITIS AND ALLOGRAFT REJECTION IN A PATIENT WITH HEART TRANSPLANTATION

Abstract A 49–year–old female with hypertrophic cardiomyopathy underwent orthotopic heart transplantation. She was cytomegalovirus(CMV)–positive and received a heart from a CMV–negative donor, so prophylaptic therapy was not administered. Initial immunosuppression included cyclosporine and induction with Basiliximab in a steroid–free regimen. The first routine biopsy (EMB) showed mild focal cellular rejection (grade 1A) and C4d positivity with granular aspect. Mycophenolate mofetil (MMF) was added. The second EMB, 7 days later, showed mild diffuse cellular rejection (grade 1B) and diffuse C4d positivity. Anti–HLA donor–specific antibodies (DSA) had increased anti–B13 levels (MFI=21298) compared to pre–transplantation tests. Echocardiography showed a normal ejection fraction (LVEF) and mild concentric hypertrophy (LVH). Treatment included pulse methylprednisolone therapy (1 g/day for three days) followed by oral prednisone with a slow tapering regimen, and increased MMF. CMV count weekly monitored was negative. The next two EMBs performed one week apart from each other described a grade 1A mild focal pattern while the 5th EMB (1 month and 2 weeks post–transplant) showed a grade 1A rejection together with focal mild fibrosis and eosinophils, so we replaced cyclosporine with tacrolimus, increased MMF and prednisone. At this time, the patient had no overt clinical signs of CMV infection but a CMV–PCR of 100847 IU/mL so ganciclovir 5 mg/Kg bid was started and CMV–PCR decreased to 42308 IU/mL after 1 week. Subsequently, she developed sinus tachycardia, mildly reduced LVEF, moderate LVH and diastolic dysfunction. Troponin was elevated. A new EMB revealed interstitial edema, diffuse ischemic injury, and eosinophilic inclusions suggesting CMV myocarditis. Treatment involved down–titrating MMF and Prednisone, administering standard intravenous immunoglobulin (IVIG), and high–dose Ganciclovir (7.5 mg/Kg bid). Leukopenia subsequently led to Ganciclovir down–titration. In the next days, the patient improved, CMV cleared, and leukocyte count normalized. She was discharged on Tacrolimus, MMF, Prednisone and Valganciclovir. Subsequent tests showed no cellular or antibody–mediated rejection (AMR), no CMV inclusions, recovered cardiac function, and markedly reduced anti–B13 DSA (MFI 3000). This case raises some concerns: in this context, the use of IVIG in the treatment of CMV infection and AMR appears reasonable, in support of antiviral and immunosuppressive therapy.

Management of cytomegalovirus reactivation in patient with immunotherapy-induced gastritis.

We present the case of a 52-year-old woman diagnosed with stage IV clear cell renal cell carcinoma who received combination of surgery and systemic therapy with nivolumab (anti-PD1) and ipilimumab (anti-CTLA-4). During treatment, patient presented oral intolerance, vomiting and abdominal pain. Computed tomography (CT) and gastroscopy (EGD) were performed, identifying findings suggestive of severe gastro-duodenitis with friability and diffuse oedema of the mucosa and deep ulcers. A gastrointestinal immunotherapy-induced toxicity was suspected so patient was managed with proton pump inhibitors (PPIs) and intravenous corticosteroids 1mg/Kg. Three weeks later, corticosteroid treatment failed. EGD was repeated and gastric biopsies were taken for histological and microbiological tests. Gastric biopsies revealed the presence of cytomegalovirus (CMV) inclusion bodies by immunohistochemistry (IHC). CMV viral load by quantitative PCR in plasma was 2,000 IU/mL so intravenous ganciclovir was prescribed. Then, the patient presented poor clinical course with persistent vomiting due to a failure of first-line corticosteroid and antiviral treatment. Another EGD was performed. Last IHC reveals a low CMV viral load. Second-line treatment with Anti-TNF was performed using a single-dose regimen of intravenous infliximab 5 mg/Kg. Finally, the patient presented a clinical and endoscopic response and a negative CMV DNA test in the blood after completing the antiviral treatment.

Cytomegalovirus esophagitis associated with arytenoid cyst in an immunocompetent host

CMV esophagitis is usually encountered in immunocompromised individuals and esophagus is rarely affected in immunocompetent individuals. CMV esophagitis associated with arytenoid cyst has not yet been reported in literature to the best of my knowledge and can be considered in case of recurrence of cyst following excision. The objective of this study is to report the unique presentation of CMV in an immunocompetent patient. A middle-aged immunocompetent lady presenting with dysphagia was diagnosed to have arytenoid cyst. Biopsy from upper esophagus revealed cytomegalovirus inclusion bodies and immunological test were performed to confirm the pathology. The cyst excision lead to recurrence. It was excised again followed by a course of intravenous ganciclovir. Currently, the role of antiviral in treatment of CMV esophagitis in immunocompetent individual is not well established. We have obtained good result in this patient with a course of Ganciclovir following excision of the cyst. The rarity of cytomegaloviral upper esophageal involvement, its association with arytenoid cyst and the utility of antivirus in treatment of an immunocompetent host makes this case report unique and interesting.

Utility of Machine Learning to Detect Cytomegalovirus in Digital Hematoxylin and Eosin–Stained Slides

Rapid and accurate cytomegalovirus (CMV) identification in immunosuppressed or immunocompromised patients presenting with diarrhea is essential for therapeutic management. Due to viral latency, however, the gold standard for CMV diagnosis remains to identify viral cytopathic inclusions on routine hematoxylin and eosin (H&E)–stained tissue sections. Therefore, biopsies may be taken and “rushed” for pathology evaluation. Here, we propose the use of artificial intelligence to detect CMV inclusions on routine H&E–stained whole-slide images to aid pathologists in evaluating these cases. Fifty-eight representative H&E slides from 30 cases with CMV inclusions were identified and scanned. The resulting whole-slide images were manually annotated for CMV inclusions and tiled into 300 × 300 pixel patches. Patches containing annotations were labeled “positive,” and these tiles were oversampled with image augmentation to account for class imbalance. The remaining patches were labeled “negative.” Data were then divided into training, validation, and holdout sets. Multiple deep learning models were provided with training data, and their performance was analyzed. All tested models showed excellent performance. The highest performance was seen using the EfficientNetV2BO model, which had a test (holdout) accuracy of 99.93%, precision of 100.0%, recall (sensitivity) of 99.85%, and area under the curve of 0.9998. Of 518,941 images in the holdout set, there were only 346 false negatives and 2 false positives. This shows proof of concept for the use of digital tools to assist pathologists in screening “rush” biopsies for CMV infection. Given the high precision, cases screened as “positive” can be quickly confirmed by a pathologist, reducing missed CMV inclusions and improving the confidence of preliminary results. Additionally, this may reduce the need for immunohistochemistry in limited tissue samples, reducing associated costs and turnaround time.

Importance of using tissue PCR to diagnose CMV colitis in ulcerative colitis

Objective: To show the importance of tissue Cytomegalovirus (CMV) PCR to diagnose CMV infection in patients with treatment-resistant ulcerative colitis.
 Methods: Fifteen patients who had previously been diagnosed as ulcerative colitis with clinical, endoscopic, histological, and radiological criteria and who had referred to our clinic with acute exacerbation who were diagnosed with CMV colitis and received CMV treatment, were evaluated retrospectively. After the demographic and clinical characteristics of the patients were noted, Mayo scores were evaluated to determine ulcerative colitis activity. Patients' age, gender, laboratory values, type of colitis, and Mayo scores were recorded. Biopsy results, CMV IgM, serum, and tissue CMV DNA levels were noted. Descriptive statistical parameters of the demographical data were calculated.
 Results: Eleven of the patients were male, and four were female. The mean age of the patients was 42±11,3. The mean duration of the disease was 28±46 months. Twelve patients had pancolitis, and three patients had distal colitis. All patients' Mayo score was 12 points. All patients were steroid-resistant, and none had previously received biological agent therapy. 7 of 15 patients had serum CMV DNA levels over 1000 copies/mL. Tissue CMV DNA levels of 8 patients were found higher than 250 copies/mg, although serum CMV DNA levels were below 1000 copies/mL. Pathology samples of 11 patients were evaluated, and CMV inclusion bodies were not detected. All patients received ganciclovir for CMV treatment. After treatment, CMV DNA of all patients was negative, and diarrhea and inflammation markers were reduced.
 Conclusion: For the diagnosis of CMV, CMV-PCR in colon tissue specimens should also be considered in addition to endoscopic appearance and serum CMV DNA levels.

Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report

BackgroundThe coinfection between cytomegalovirus (CMV) and either human herpesvirus‐6 (HHV‐6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV‐8 coinfection after renal transplantation.Case presentationA 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi’s sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved.ConclusionsWe report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

S2018 Concurrent CMV Colitis and GI Amyloidosis as Initial Presentation of Multiple Myeloma: A Case Report

Introduction: Prior associations with Cytomegalovirus (CMV) colitis and multiple myeloma (MM) or amyloidosis are only described in immunocompromised patients undergoing treatments like transplantation, monoclonal antibodies, or chemotherapy. The concurrent presentation of gastrointestinal (GI) amyloidosis with CMV colitis is rarely reported and should be considered more readily in the hospital. Case Description/Methods: 67-year-old male was admitted to the hospital with bilateral lower extremity deep vein thromboses after transurethral resection of the prostate 8 days prior. He was started on anticoagulation, but due to onset of hematuria, anticoagulation was stopped and an IVC filter was placed. The patient then developed bright red blood per rectum with diarrhea and GI was called. On exam, vitals were stable, and abdomen was non-distended and non-tender. Digital rectal exam showed brown stool. A colonoscopy displayed discontinuous areas of ulcerated, erythematous mucosa with loss of vascular pattern (Figure A). A histologic examination showed terminal ileal mucosa with lymphoid aggregates (Figure B), positive Congo red stain with apple green birefringence and cytomegalovirus inclusions in the colon (Figure C). Subsequent immunology testing demonstrated elevated free lambda light chains with a free kappa to lambda ratio of 0.019. A bone marrow biopsy confirmed lambda restriction and >20% CD138-positive plasma cells, consistent with MM. The patient was started on valganciclovir but showed no improvement of symptoms, which was attributed to his confounding amyloidosis. The patient’s clinical status continued to worsen, and he ultimately expired from cardiac causes. Discussion: It is noteworthy that CMV colitis occurred concurrently with amyloidosis. Immune dysfunction and hypogammaglobinemia in amyloidosis lead to susceptibility to infection, but the inciting organisms usually are H. influenzae, S. pneumoniae, and E. coli. The use of immunosuppressing therapies such as transplantation or chemotherapy increases the likelihood of opportunistic infections. Besides these scenarios, CMV has rarely been reported in patients with amyloidosis or MM. We suggest GI amyloidosis and CMV should be considered and treated rapidly in patients presenting with non-specific GI symptoms. However, our case also highlights the difficulty in measuring effectiveness of antiviral treatment for CMV in GI amyloidosis due to overlap of symptoms between both conditions.Figure 1.: A) skiped areas of ulcerated, friable colon. B) immunohistochemistry CMV viral inclusions, C) Colonic epithelium with amyloidosis.

S2722 Cytomegalovirus Colitis in an Immunocompetent Patient Presenting With New Onset Ulcerative Colitis: A Clinical Vignette

Introduction: Cytomegalovirus (CMV) colitis is a rare disease among immunocompetent patients presenting with inflammatory bowel disease (IBD). CMV can cause steroid-refractory IBD, which may require antiviral and infliximab (IFX) combination therapy. Case Description/Methods: A 23-year-old woman was admitted for dehydration and poor oral intake in the setting of eight bloody bowel movements per day, tenesmus, and weight loss. She presented to an outside hospital 5-weeks prior with abdominal cramps and bright red blood per rectum. The CT scan showed bowel wall thickening and mucosal enhancement in the rectosigmoid and descending colon. A colonoscopy 2-weeks prior to admission was suggestive of severe ulcerative colitis (UC) and she was started on mesalamine/budesonide. Due to poor clinical response, she was switched to prednisone 40 mg for 5 days. Outpatient medical management failed and, upon admission, she was converted to methylprednisolone 20 mg every eight hours. Serum CMV PCR was positive at 1,758 IU/mL and colonic biopsies showed scattered CMV inclusions by immunohistochemical staining. She was started on ganciclovir 5mg/kg/dose IV in addition to the steroid regimen and IFX infusions were deferred. By day 2 of ganciclovir IV and day 7 of methylprednisolone IV, IBD symptoms began to resolve. On discharge at hospital day 12, patient was transitioned to twice daily oral valganciclovir 900 mg for a 3-week course and an oral prednisone taper. CMV PCR was 1,185 IU/mL on discharge and < 100 IU/mL at one week follow up. IFX therapy was initiated 45 days post discharge with improved symptoms, as characterized by a 17-lb weight gain at 3-month follow-up. (Figure) Discussion: CMV colitis is a rare diagnosis in immunocompetent patients with early, steroid naïve IBD. Serum PCR positive infection has been reported more commonly after 2-3 weeks of steroid therapy. CMV infection is a recognized complication and marker of poor prognosis in moderate to severe UC, especially those who present with steroid refractory disease. It is believed that the inflammatory mediators associated with UC play a synergistic role in CMV reactivation and subsequent disease. In addition, local corticosteroid induced immunosuppression may further facilitate CMV gene transcription, resulting in disease progression and poor steroid response. There remains no consensus for management of UC with concomitant CMV colitis however, in our patient the use of antiviral and biologic therapy (IFX) promoted disease regression and clinical improvement.Figure 1.: H&E Stain (20x) demonstrating active chronic colitis (left). Immunohistochemical staining (40x) showing CMV immunoreactivity (right).

Cytomegalovirus Infection in Ulcerative Colitis: An Ambispective Study from a Single Center

Abstract Background and Objectives Cytomegalovirus (CMV) is often detected in colonic tissue of patients with inflammatory bowel disease. Its role as a “bystander” or “culprit” in ulcerative colitis (UC) flares is unclear. The aim of the study is to detect the prevalence and outcomes of CMV infection in UC Materials and Methods All adult patients (both retrospective and prospective), diagnosed with UC in a tertiary care center, were included. Patients underwent colonic biopsies for histopathological examination for CMV. CMV immunoglobulin G (IgG) was also tested to ascertain seroprevalence in this population. CMV infection was defined as presence of CMV inclusions in histopathology. Treatment outcomes were defined as remission, clinical improvement, and partial response. The number of flares and outcomes of disease activity in terms of flare of disease, hospitalization, need of colectomy, and mortality was noted at follow-up. Results A total of 58 patients of UC were included (mean age was 37.3 years, males—66%). Serum CMV IgG was positive in all patients. Twelve patients (20.6%, 9 males) with active UC were found to have CMV infection in histopathology specimens with hematoxylin and eosin staining. Two-third of patients (8/12) had severe disease, while the remaining (4/12) had moderate disease activity. Nine patients (9/12) with CMV colitis achieved complete remission with standard treatment without antiviral therapy. Of the three patients who needed antiviral therapy, two underwent colectomy in follow-up. CMV-positive patients to be predominantly male (p = 0.58) had more frequent relapses (p = 0.08) and were hospitalized for their flares (p = 0.06) when compared with CMV-negative patients. None of these factors were found to be statistically significant. Conclusion CMV infection was found in one-fifth of patients of UC with flare. All patients with CMV infection had moderate-to-severe disease. Majority achieved remission without the need of antiviral therapy.

HIGH DOSE TOFACITINIB AS SALVAGE THERAPY IN STEROID REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS FOLLOWING NON-RESPONSE TO INFLIXIMAB

Abstract INTRODUCTION Acute Severe Ulcerative Colitis (ASUC) requiring hospitalization remains a serious concern in patients with Ulcerative colitis. In patients with steroid-refractory disease, Intravenous infliximab salvage therapy is used. Colectomy is reserved for patients refractory, even to salvage therapy. We present a young female with ASUC, who was successfully treated with high dose Tofacitinib after Steroids and Infliximab failure. CASE HISTORY A 23 years old female was diagnosed with pan-UC six months prior to the first presentation at our center. Since then, she has had a Steroid dependent disease. She was on the maximum 5-Aminosalicylic dose and could not tolerate azathioprine in the past. At the presentation, she had iron deficiency anemia (10.1 gm/dL), hypoalbuminemia (27 gm/L), C-reactive protein 4 mg/L and calprotectin of 670 mg/Kg. The colonoscopy showed pan-colitis Mayo score 3. Given her steroid dependency for the last six months, she was started on Infliximab induction followed by maintenance. After the second Induction dose of Infliximab, the patient was admitted with worsening of her clinical symptoms. Sigmoidoscopy was performed for the patient, which showed severe colitis. Biopsy showed cytomegalovirus inclusion by immunohistochemistry. The third dose of Infliximab was postponed, and the patient received IV ganciclovir followed by oral therapy for two weeks duration. She responded clinically but before her third dose again had worsening of the disease. At the time of admission, she had a hemoglobin of 7.1 gm/dL, albumin 21 gm/L, CRP 72 mg/L, and calprotectin of 1352 mg/Kg. She met Truelove and Witts criteria for ASUC with a Mayo score of 12. Sigmoidoscopy again showed pan-colitis but was negative for cytomegalovirus. The patient did not respond to 60 mg methylprednisolone daily for five days. She was re-inducted with High dose infliximab and was given two doses 10 mg/Kg one week apart. However, the Mayo score showed no improvement, and surgery was consulted for possible colectomy. After discussing with the patient, we started her on a high dose Tofacitinib of 10 mg three times a day as salvage therapy. She showed dramatic improvement within the next 72 hours, and by day five, was discharged home. Her hemoglobin improved, CRP normalized. At three months, calprotectin was less than 100 mg/Kg, and colonoscopy showed mucosal healing with a Mayo score of 1. DISCUSSION In Steroid refractory ASUC, with non-response to Infliximab, High-dose tofacitinib can be used as rescue therapy. Our patient showed clinical and biochemical remission within three days. At three months follow up, the patient remained colectomy-free and was in sustained remission.

A Rare Case of Cytomegalovirus and Herpes Simplex Virus Coinfection Gastritis and Colitis in a Person Living With HIV/AIDS

Abstract Herpes simplex virus (HSV) colitis and gastritis is a very rare gastrointestinal manifestation in immunocompromised patients. We report the case of a 46-year-old man with a medical history of poorly controlled HIV/AIDS who presented with 2 months of progressively worsening nonbloody diarrhea. Esophagogastroduodenoscopy showed gastritis and sigmoidoscopy revealed severe colitis. Biopsy immunostaining revealed cytomegalovirus and HSV viral inclusions in the stomach, appendix, and rectum. The patient's symptoms largely improved with ganciclovir. To our knowledge, this is the first case demonstrating cytomegalovirus and HSV coinfection gastritis and colitis in a patient with HIV/AIDS.

Bone marrow examination of HIV-infected children in HAART era reveals a spectrum of abnormalities: a study from single tertiary care center of North India

Pediatric HIV is a significant contributor to childhood morbidity and mortality. As HIV infects bone marrow CD34-positive progenitor cells, the hematological abnormalities are well-expected. The viral load is much higher in children predisposing them to opportunistic infections and hematopoietic malignancies. The present study aimed to determine the spectrum of hematological abnormalities that may yield clinically useful information in HIV-infected children. This was a retrospective study of 19 HIV-infected children who underwent bone marrow examination. Overall, 20 peripheral blood and bone marrow samples were analyzed for morphological changes in all hematopoietic lineages. Immunohistochemistry was performed on trephine biopsy sections for evaluation of B and T cells and cytomegalovirus inclusions. Anemia was the most common cytopenia (95%), followed by thrombocytopenia (45%) and leukopenia (40%). Myelodysplasia was noted in 70% of cases. Dysmegakaryopoiesis was predominant in 65% of cases, while dyserythropoiesis was noted in 25% of cases. Hemophagocytosis and reactive cellular changes were noted in 20% of cases each. Benign lymphoid aggregates and granulomatous inflammation were observed in 15% and 10% of cases, respectively. Significant myelofibrosis was found in 35% of cases. One case showed infiltration by Burkitt lymphoma. Parvoviral inclusions were identified in 1 case. An interstitial increase and aggregates of CD8 + T cells and reduced CD4 + T cells were noted. CD20 + B cells were normal to mildly increased in the bone marrow. Bone marrow examination provides clinically significant information in pediatric HIV revealing the underlying cause of hematopoietic abnormalities and allows the exclusion of major hematological neoplasms.

S3073 A Rare Cause of Repeat Hemorrhage: When Cytomegalovirus Hides in the Small Bowel

Introduction: Cytomegalovirus (CMV) is an opportunistic infection typically seen in immunocompromised patients, like those with Human Immunodeficiency Virus (HIV) or organ and stem cell transplant recipients. CMV infections are exceedingly uncommon in the immunocompetent duodenum. We describe such a case, confirmed with biopsy and complicated by severe repeated gastrointestinal hemorrhage. Case Description/Methods: A 74-year-old male with PMH of diabetes, bladder cancer (status-post resection and ureteral stent placement), presented to the ED with general malaise. Was found to meet sepsis criteria and was anemic with bright red blood on rectal exam. CT abdomen and pelvis revealed multiple pelvic abscesses and free air. Stool testing was positive for C. diff and oral vancomycin and IV zosyn were started. Patient was admitted to telemetry and required 3 separate units pRBC for persistent anemia. CTA abdomen performed on day 3 revealed a duodenal bleed. IR performed an embolization, however, patient remained unstable and required intubation and pressors. Anemia continued to worsen, and patient received an additional 2 units pRBC. GI performed a bedside EGD revealing a large clot and duodenal ulcer. Sepsis continued to worsen, and antibiotics were broadened to meropenem and vancomycin. Anemia continued to worsen, and an additional EGD was performed with source control reported. Patient was extubated, and shortly thereafter, had melena, so a final EGD was performed, identifying friable mucosa and a bleeding duodenal vessel. Hemospray and a clip were deployed to contain bleeding, and the patient received a seventh unit of blood. Biopsied duodenal tissue stain showed CMV (Figure 1A) and histology revealed inclusions (Figure 1B), so ganciclovir was started. Recurrent bleeding subsequently resolved, and patient was discharged to subacute rehabilitation to complete a course of IV ganciclovir. Discussion: Though rare in immunocompetent patients, CMV infections should be considered in severe or persistent gastrointestinal bleeds. CMV duodenitis, while very uncommon, has been documented in case reports and is associated with ischemia and massive hemorrhage. In this case, the patient ultimately required seven units of blood, intubation, and numerous endoscopic procedures as a result of CMV duodenitis. Clinical improvement was seen only once the underlying infection was treated and illustrates the need to consider CMV infection in the differential for recurrent gastrointestinal bleeding.Figure 1.: A: Immunohistochemical stain of tissue from duodenal biopsy identifying CMV. B: Histology of duodenal tissue biopsy under high power showing CMV inclusions.

Cutaneous Coinfection of Cytomegalovirus and Mycobacterium chelonae Accelerated by Immunosuppression

A mildly diabetic 58-year-old male had traumatic ulceration on the left popliteal fossa, and the lesion progressed to a painful 6 cm deep ulcer. After surgical debridement and skin grafting, ulceration recurred. Pyoderma gangrenosum was clinically diagnosed after the first biopsy, indicating a noninfective ulcer. Immunosuppressive therapy (prednisolone and cyclosporine A) induced complete epithelialization in three months. Four months later, subcutaneous nonulcerated nodules appeared on the anterior area of the left lower leg. Subcutaneous induration progressed and ulceration recurred, so that immunosuppressive therapy continued for one year. Cytomegalovirus (CMV) viremia was detected, and the second biopsy demonstrated CMV inclusions of endothelial and perivascular cells in fibrosing septolobular panniculitis. Cyclosporine A was cancelled, prednisolone was tapered, and ganciclovir started. Viremia soon disappeared, but the lesion progressed to large induration with multiple ulcers measuring up to 3 cm. The third biopsy disclosed infection of Gram-positive mycobacteria, accompanying fat droplet-centered suppurative granulomas without CMV infection. Microbial culture identified Mycobacterium chelonae. Clarithromycin with thermotherapy was effective. A review of the second biopsy confirmed coinfection of CMV and Gram-positive mycobacteria. Immunostaining using a panel of anti-bacterial antibodies visualized the mycobacteria in the lesion. Positive findings were obtained with antibodies to Bacillus Calmette-Guérin, Bacillus cereus, MPT64 (Mycobacterium tuberculosis-specific 24 kDa secretory antigen), LAM (Mycobacterium tuberculosis-related lipoarabinomannan), and PAB (Propionibacterium acnes-specific lipoteichoic acid).

Congenital pulmonary airway malformation – A histomorphological spectrum of 15 cases: A 5-year study from a tertiary care center

Objective:Congenital pulmonary airway malformation (CPAM) is a rare developmental lung disease. The aim of this study is to analyze the histomorphological spectrum of CPAM in a series of 15 cases.Materials and Methods:A retrospective descriptive study of 15 cases of CPAM was carried out from 2013 to 2018 in our hospital, and cases were classified based on the Stocker's classification.Results:The age ranged from 4 days to 9 years (66.6% were infants). The left lung was most commonly involved (66.6%). The most common lobe was the left upper lobe (60%), followed by right lower lobe (20%). Grossly, cysts measured 0.2–5 cm, filled with mainly serous fluid with few having hemorrhagic and brownish mucoid secretions. On microscopy, single to multiple noncommunicating cysts of size 0.2–5 cm were seen, lined by ciliated columnar epithelium (60%), pseudostratified ciliated columnar epithelium (26.7%), mucin-secreting columnar epithelium (6.7%), and flattened epithelium (6.7%). Few cases showed smooth muscle (20%) and cartilage (13.3%) in the cyst wall. Chronic inflammation (73.3%) with dense histiocytic infiltrate (13.3%) was also seen. Emphysematous changes were also observed (13.3%). Cytomegalovirus inclusions (6.7%), zygomycete fungus (6.7%), and red hepatization (6.7%) were observed. The most common type was type II (60%), followed by type I (33.3%) and type IV (6.7%).Conclusion:Type II was the most common variant in this study. A careful observation should be done to look for fungal hyphae or viral inclusions.

S2601 A Curious Case of Transient Autoimmune Hepatitis

INTRODUCTION: Autoimmune Hepatitis (AIH) is a rare disease among human immunodeficiency virus (HIV) infected individuals due to their impaired immune system. Opportunistic hepatotropic viruses such as cytomegalovirus (CMV) have been described to trigger AIH. We report a case of a young male with suspected AIH who was ultimately diagnosed with HIV and disseminated CMV. There have been reports of CMV infection triggering AIH and awareness of the association between CMV and AIH is important as the clinical presentation of these entities may overlap ultimately resulting in erroneous diagnoses and management in an already immunocompromised population. CASE DESCRIPTION/METHODS: A 34 year-old-male who presented for evaluation of chronically elevated liver enzymes. He referred no significant symptoms. Denied illicit drug and alcohol use. Liver workup with negative hepatitis panel, positive ASMA 1:160 with elevated IgG of 2174 md/dL. Also found with acute HIV. During follow-up visit patient reported chronic watery diarrheas. He underwent liver biopsy due to suspected AIH with findings of one hepatocyte with an inclusion body consistent with CMV. In addition, pericellular fibrosis with early bridging fibrosis with increase in plasma cells suggestive of AIH. Laboratories with positive CMV IgG and CMV DNA quantitative of 75944 IU/ml. Sigmoidoscopy with diffuse, friable, erythematous lesions from 40 cm to rectum. Biopsies consistent with CMV colitis. Later he developed CMV retinitis. He was started on ganciclovir and HAART therapy with normalization of liver enzymes. DISCUSSION: AIH is an uncommon disease with a global incidence that ranges from 0.7 to 2 per 100,000 population per year. The incidence of AIH in HIV patients is even lower and this diagnosis is often not suspected as it is counterintuitive in the setting of impaired immune system. Most AIH cases reported in HIV patients are associated with the immune reconstitution phase and rarely as a consequence of infection with opportunistic hepatotropic viruses as appeared to be in our case. The mechanism of AIH overlapping with CMV is believed to be molecular mimicry via cross reactivity between CMV exons and cytochrome CYP2D6. This case illustrates the importance of considering hepatotropic viruses when AIH is suspected given their potential for triggering AIH. The treatment strategies of these entities are vastly different highlighting the importance of ensuring a correct diagnosis at time of presentation.Figure 1.: Hepatocyte with inclusion consistent with Cytomegalovirus.Figure 2.: Diffuse friable erythematous lesions consistent with Cytomegalovirus colitis.Figure 3.: Focal acute colitis with areas of mucosal hemorrhage and Cytomegalovirus inclusions.

S2895 Cytomegalovirus Ileitis: A Rare Cause of Sub-Acute Diarrhea

INTRODUCTION: Cytomegalovirus (CMV) enteritis is a common infection in immunocompromised patients. In the gastrointestinal tract, CMV infections are often seen in the esophagus and colon; only rarely do they involve the small bowel. We present a case of acute CMV pan-ileitis confirmed on histopathology. CASE DESCRIPTION/METHODS: A 77-year-old man with previous history of high-grade muscle-invasive urothelial carcinoma treated with resection, biweekly chemotherapy, and radiation presented with sub-acute non-bloody watery diarrhea up to 10 times per day. Symptoms were not associated with fever, melena, hematochezia or abdominal pain. Initial laboratory values were notable for elevated inflammatory markers and an elevated fecal calprotectin without leukopenia (Table 1). A CT scan of the abdomen and pelvis revealed pan-ileitis. Initial clinical management focused on possible infectious ileitis versus undiagnosed Crohn’s disease. He was empirically treated for bacterial enteritis with ceftriaxone and metronidazole, without improvement after completing a one-week course. Colonoscopy then was performed and showed erythema, edema, and ulceration at the Terminal ileum (TI) (Figure 1). Pathology showed fibrin-inflammatory exudates and lymphoplasmocytic infiltrates in the lamina propria, with mild architectural distortion (Figure 2). Viral immunostains demonstrated CMV inclusion bodies. Due to these results, he then was started on oral valganciclovir and discharged home. Subsequent serum immunoglobulin test results confirmed elevated levels of both CMV IgM and IgG. DISCUSSION: The usual presentation of CMV enteritis includes abdominal pain, vomiting or diarrhea, with only rare reports of ileal perforation. Arriving at this diagnosis can be challenging, especially in the absence of immunosuppression or pathognomonic punched-out ulcerations. CMV enteritis also can mimic both infectious and ischemic colitis. Current guidelines recommend treating active CMV enteritis with antiviral therapy, regardless of whether the patient is immunocompromised. Previous reports have suggested there can be prolonged and persistent infection with lack of spontaneous resolution, even in young immunocompetent individuals. In addition, there is an increased mortality rate in immunosuppressed patients with CMV infection. Thus, patients undergoing biologic or chemotherapy who are diagnosed with CMV enteritis should receive appropriate treatment as soon as possible.Table 1.: WBC: white blood cell count; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; CRP: C-reactive protein; TB: tubercolosis; IBD: inflammatory bowel diseaseFigure 1.: A. Colonoscopy showing ulcerated mucosa and surrounding erythema in the Terminal Ileum. B. Inflammation characterized by erythema in the Terminal Ileum.Figure 2.: Low power Hematoxylin and eosin shows granulation tissue, inflammation; B,C. higher power hematoxylin and eosin shows and infected endothelial cell with nuclear and cytoplasmic inclusions D. shows positive immune-histochemical staining for CMV.

Different viral doses of cytomegalovirus infection in the left and right colons

Objective: To compare the differences in the detection rates of cytomegalovirus (CMV) infection between the left and right colons for guiding endoscopic biopsy-sites. Methods: The cases of colonic CMV infection confirmed by histology at the Peking Union Medical College Hospital from July 2015 to July 2018 were collected and analyzed. Splenic curvature was used as the dividing point between the left and right colons. The CMV inclusions were identified histologically, and the CMV infected cells were detected using immunohistochemistry (EnVision method). The numbers of infected cells in the left and right colons were compared by histological and immunohistochemical results. A total of 731 patients were identified. Ten of the 731 patients had histological specimens of both left and right colons and were confirmed with CMV EnVision immunohistochemical study. There were 25 biopsy or resection specimens. Seven patients were male and 3 were female, and their ages ranged from 29 to 66 years, with a median age of 55 years. All of the 10 patients were also diagnosed with ulcerative colitis. Results: The number of the cells infected with CMV in the left colon was 115 (1-41), while that in the right colon was 76 (0-51). In 8/10 cases, the number of CMV infected cells in the left colon was more than that in the right colon. Conclusions: The study on the biopsies and resection specimens suggests that CMV infection is mostly present in the left colon. The left colon thus might be an important endoscopic biopsy-site for the cases with suspicion of CMV infection.

Cytomegalovirus enteritis with intractable diarrhea in infants from a tertiary care center in China

Background: Cytomegalovirus (CMV) is rarely thought to be the cause of significant gastrointestinal infection in immunocompetent children. CMV colitis is seldom observed in young infants. This study aims to examine the clinical features of CMV colitis in Chinese children.Methods: Patients with infantile onset CMV colitis diagnosed in intestinal tissue at Children’s Hospital of Fudan University from 1st January 2017, to 31st January 2019 were enrolled. Clinical data were retrieved from medical records, and the literature on infant CMV colitis was also reviewed.Results: Ten patients were included with a median age of 2.5 months [interquartile range 2.0, 6.3 months]. All 10 patients had diarrhea, 10 patients had anemia, seven patients reported hematochezia, five patients had hypoalbuminemia, five patients had retinitis, two patients had hearing impairment, and one patient had perianal abscess and anal fistula. The patients had punched-out ulcerations, longitudinal ulcerations or irregular ulcerations on the rectum and/or colon. Typical histologic evaluation showed crypt distortion and inflammatory infiltration. CMV inclusion bodies were noted in four patients. Immunohistochemistry on intestinal tissue was performed to diagnose CMV, with all patients positive. After follow-up, all patients are clinically recovered or in remission; six patients received antiviral therapy, and five patients had healed ulcers on endoscopic examination.Conclusions: CMV colitis might be a rare cause of intractable diarrhea in immunocompetent children. Clinicians should be aware of the possibility of CMV colitis in patients with intractable diarrhea.