Refractory pharyngeal ulceration due to cytomegalovirus in a patient with HIV infection: a case report and literature review.

BACKGROUND: Cytomegalovirus (CMV) is an important pathogen among immunocompromised hosts. Typically, CMV in human immunodeficiency virus (HIV) infection causes diseases of the retina, digestive tract, lungs and liver, but there are few cases of CMV infection of the pharynx and larynx. CASE PRESENTATION: A 57-year-old man with HIV infection was admitted because of pharyngeal pain. Before and after admission, pharyngeal biopsies guided by laryngeal endoscopy were performed four times, but pathological examination showed nonspecific inflammation, and the cause of pharyngeal ulceration was unclear. Additionally, the ulceration deteriorated after initiation of retroviral therapy. Laryngomicrosurgery was conducted under general anesthesia to remove tissue, and pathological diagnosis confirmed CMV infection. Pathological features included enlargement of the cytoplasm and nucleus in infected cells, and intranuclear bodies called owl's eye inclusions. Ganciclovir dramatically improved the symptoms and laryngoscopic findings. CONCLUSIONS: This case was diagnosed as pharyngitis and pharyngeal ulceration caused by CMV infection, related to immune reconstitution inflammatory syndrome. In previous reports of CMV-induced pharyngeal or laryngeal ulceration in HIV infection, we found six cases similar to our present case. All cases were diagnosed by biopsy. The present case indicates the importance of biopsy for definitive diagnosis. CMV infection should be considered as a differential diagnosis of pharyngeal ulceration in patients with HIV infection.

Fatal Herpes Simplex Esophagitis of an Infant Case Report and Review of the Literature.

ABSTRACT: Herpes simplex virus esophagitis is a rare and not readily recognized condition which is often seen in immunocompromised individuals. This case highlights the rare complication of herpes simplex virus in an otherwise healthy male infant who presented with a possible seizure after listlessness, fever, and black stools for 1 day. The decedent died shortly after arrival to the hospital emergency department, and a complete autopsy was performed, which was remarkable for upper gastrointestinal bleeding due to esophageal ulcers secondary to viral infection (herpes simplex virus type 1). To our knowledge, this is the first reported case in which herpes simplex virus esophagitis resulted in ulcerations that extended through the esophagus and involved the adjacent wall of the aorta with subsequent upper gastrointestinal bleeding leading to the death of an infant.

A rare case of Epstein-Barr virus-positive mucocutaneous ulcer that developed into an intestinal obstruction: a case report.

BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is a new category of mature B-cell neoplasms. Ulcers occur in the oropharyngeal mucosa, skin, and gastrointestinal tract. The onset of EBV-MCU is suggested to be related to the decreased immunity of the patient, the causes of which include the use of immunosuppressive agents and aging. EBV-MCU may regress spontaneously and it often has a benign course after the dose reduction or discontinuation of immunosuppressive agents or during follow-up. Here, we report the case of a patient who required surgical resection for the intestinal obstruction arising from EBV-MCU. CASE PRESENTATION: A Japanese elderly male visited our hospital with chief complaints of a palpable mass and dull pain in the left upper quadrant, loss of appetite, and weight loss. Although abdominal computed tomography and total colonoscopy (TCS) revealed a tumor with circumferential ulcer in the transverse colon, histopathological analysis of a biopsy specimen of this lesion showed only nonspecific inflammation. Because the tumor spontaneously regressed during the time he underwent tests to obtain a second opinion from another hospital, TCS was reperformed on the patient. TCS revealed that the tumor decreased in size and the inflammatory changes in the surrounding mucosa tended to improve; however, tightening of the surrounding mucosa due to scarring was observed. Another histopathological analysis of a biopsy specimen showed widespread erosion of the mucosa and the formation of granulation tissue with marked infiltration of various inflammatory cells into the mucosal tissue of the large intestine. Moreover, some of the B-lymphocyte antigen CD20-positive B cells were also positive for EBV-encoded small RNA-1, suggesting the possibility of EBV-MCU. Later, the tumor developed into an intestinal obstruction; thus, the transverse colon was resected. Histopathological analysis of the resected specimen demonstrated scattered Hodgkin and Reed-Sternberg-like multinucleated large B cells in addition to EBER-1-positive cells. The patient was finally diagnosed as having EBV-MCU. CONCLUSIONS: This is the first report of a case of EBV-MCU that developed into an intestinal obstruction requiring surgical resection. It is necessary to consider the possibility of EBV-MCU when examining an ulcerative or tumorous lesion in the gastrointestinal tract.

Epigastric pain associated with herpes esophagitis: case report.

BACKGROUND: Herpes esophagitis is uncommon disease caused by Herpes simplex virus (HSV). While the disease most often occurs in immunocompromised patients, including post-chemotherapy, immunosuppression with organ transplants, and in AIDS, Herpes esophagitis can also occur in immunocompetent individuals. CASE PRESENTATION: We report a case of herpes esophagitis in a 72 year- old woman who was presumed to be immunocompromised following prolonged radiotherapy and chemotherapy for lymphoma. Her main symptom was epigastric pain. Upper endoscopy showed multiple rounded ulcers in lower esophagus. The diagnosis was confirmed histologically by multiple biopsies. The patient received Valacyclovir for 2 weeks and started to get better within 3 days of treatment. CONCLUSION: Although there are few published cases of Herpes esophagitis disease in the medical literature, we recommend that this disease should be considered as one of the differential diagnoses when assessing immuno-compromised patients presenting with non-specific abdominal symptoms.

Epstein-Barr virus-associated enteritis with multiple ulcers: The first autopsy case.

Epstein-Barr virus (EBV)-associated enteritis is extremely rare and has not been well characterized. Herein, we present the first autopsy case of EBV-associated enteritis with multiple ulcers in a 73-year-old Japanese male. The patient had abdominal pain and was clinically diagnosed with enteritis. An endoscopic examination revealed multiple ulcers at the terminal ileum. His condition worsened due to serosanguinous bowel discharge and the patient was then admitted to the hospital. Ileocecal and subtotal small intestinal resection was performed for repetitive hemorrhage from ulcers. However, the patient died due to uncontrolled hemorrhage. An autopsy was then performed in order to explore the cause of ulcers in the small intestine. Macroscopic findings revealed multiple ulcers with occasional cobblestone-like appearance of the ileum. Histological analysis revealed marked infiltration of lymphocytes and plasma cells around the ulcer. EBV-encoded RNA in situ hybridization (EBER-ISH) revealed positive inflammatory cells. Cytomegalovirus was immunohistochemically negative. Macroscopic and microscopic findings obtained from autopsy specimens showed no foci of inflammation and EBER-ISH-positive stromal cells in the esophagus, stomach, and colorectum. EBV-associated enteritis can cause uncontrolled repetitive hemorrhage from ulcers and result in critical condition of the patient, which can be used for differential diagnosis.

Epstein-Barr Virus-Positive Mucocutaneous Ulcer in a Pediatric Patient-Case Report.

The Epstein-Barr virus (EBV)-positive mucocutaneous ulcer is a rare entity in the spectrum of lymphoproliferative diseases associated with the EBV. It occurs typically in patients with immunosuppression associated with immunosenescence, as well as due to iatrogenic causes, posttransplant patients and primary immunodeficiency disorders. It is often a benign and self-limited disease that recedes by stopping or reducing the immunosuppressive agents in most of the cases. Histologically, it is characterized by a population of EBV-positive atypical lymphoid cells. Here, we present a rare case of a 5-month-old pediatric patient, born preterm at 24 weeks of gestational age, presenting a lump on the right shoulder, later evolving to EBV-positive mucocutaneous ulcer.

Atypical severe progressive perioral ulceration due to herpes simplex virus on the background of undiagnosed HIV/AIDS.

Perioral ulcerative plaques have a broad list of differential diagnoses. We describe an unusual presentation of chronic progressive perioral ulceration due to herpes simplex type (HSV)-1 on a background of undiagnosed human immunodeficiency virus infection with acquired immunodeficiency syndrome. Whilst chronic mucocutaneous HSV is an AIDS-defining condition with both HSV-1 and HSV-2 implicated, typical reported cases describe vesicular eruptions rather than perioral ulcerative plaques. This case highlights that common infections may present atypically in immunocompromised individuals and may be a clue to underlying systemic illness.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma arising in patient with a history of EBV-positive mucocutaneous ulcer and EBV-positive nodal polymorphous B-lymphoproliferative disorder.

Elderly patients with Epstein-Barr virus (EBV) infection are at increased risk for developing B-cell lymphoproliferative disorder (B-LPD) due to immunosenescence. Here, we describe a case of a 75-year-old man who developed an EBV-positive (EBV+) mucocutaneous ulcer (EBVMCU) in the gingiva with spontaneous regression. Eighteen months after regression, he had a cervical lymph node enlargement that was diagnosed as EBV+ nodal polymorphous B-LPD, Ann Arbor stage IA. Clinicians decided to observe his clinical course without any treatment. Fourteen months later, the patient developed EBV-positive diffuse large B-cell lymphoma (DLBCL), Ann Arbor stage IIA, and received six courses of age-adjusted dose chemotherapy and achieved a complete remission. No evidence of a clonal relationship was found among these three lesions by standard polymerase chain reaction (PCR) analysis for immunoglobulin heavy chain. However, they all had expression of PD-L1 in the EBV+ large B-cells and Hodgkin Reed-Sternberg-like cells. This is the first case report of a PD-L1-positive (PD-L1+) EBVMCU and the development of multiple EBV-driven B-LPDs in the setting of immunosenescence within a 32-month period.

EBV-positive mucocutaneous ulcer arising in rheumatoid arthritis patients treated with methotrexate: Single center series of nine cases.

Methotrexate (MTX) is currently used as first-line anchor drug for rheumatoid arthritis (RA). Therefore, the number of MTX-associated lymphoproliferative disorders, including Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU), has increased. Some aspects of MTX-associated EBVMCU (MTX-EBVMCU), particularly clinical behavior and treatment for RA after MTX cessation, have not been well described. Herein, we report nine cases of MTX-EBVMCU with clinical information regarding RA. Seven of nine patients showed spontaneous regression (SR) after immunosuppressive (IS) cessation. The other two required cytotoxic chemotherapy. Eventually, all achieved complete remission. No patients experienced EBVMCU relapse. Eight patients had RA flare after IS cessation. To control the RA activity, rituximab was administered to three patients. The remaining patients were treated by other agents. Regarding the RA activity, all were in the status of low disease activity or clinical remission. In conclusion, MTX-associated EBVMCU has an indolent clinical course and SR after IS cessation can be expected. After the withdrawal of MTX, the majority of patients experience RA flare and required treatment. In our series, RA was well controlled without reinitiating MTX. Therefore, to prevent the EBVMCU relapse, it might be advisable to avoid MTX reintroduction, and rituximab might be the more preferable agent for RA treatment.

Lipschütz genital ulcer revisited: is juvenile gangrenous vasculitis of the scrotum the male counterpart?

Since its first description as ulcus vulvae acutum by Benjamin Lipschütz in 1912, the etiopathogenesis of this peculiar genital ulcer remains incompletely understood. In his original description, two different types of genital ulcers were observed and proposed, which were not precisely defined and distinguished in most subsequent reports. The first type is characterized by acute excruciating genital ulcers of first-time onset with self-limited non-recurrent course in association with gravely symptomatic systemic infections, in which a primary Epstein-Barr virus (EBV) infection is later identified to be probably the most common aetiology. The second type of ulcer usually refers to little painful ulcers of unknown etiopathogenesis in the absence of fever or chills and with a slow torpid progression and recurrent nature. Differentiation from idiopathic aphthous ulcers is unclear. The changes of the cervicovaginal microbiota and microbiome in diseased state deserve further clarification. Acute genital ulcers associated with primary EBV infection in women have drawn attention since 1970s, while the corresponding penile ulcers in men were already known in 1950s. First presented in 1973, juvenile gangrenous vasculitis of the scrotum with an acute painful scrotal ulcer preceded by symptomatic pharyngeal infections can be considered as the male counterpart of ulcus vulvae acutum, and the future clinical survey should include primary EBV infection.

Comparison of Epstein-Barr virus-positive mucocutaneous ulcer associated with treated lymphoma or methotrexate in Japan.

AIMS: The aim of the present study was to compare treated lymphoma-associated Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) and methotrexate (MTX)-associated EBVMCU. METHODS AND RESULTS: Of a series of 15 Japanese patients (11 women, four men; median age 74 years, range 35-84 years), seven received MTX for the treatment of autoimmune disease and eight developed EBVMCU after treatment of malignant lymphoma [diffuse large B-cell lymphoma (n = 4) without EBV association, adult T-cell leukaemia/lymphoma (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), and follicular lymphoma (n = 1)]. Ulcers were observed in the oral cavity (n = 11), gastrointestinal tract (n = 2), and skin (n = 2). All were histologically characterised by a mixture of EBV-positive large B-cell proliferation and Hodgkin/Reed-Sternberg-like cells on a polymorphous background. A total of 46% (6/13) had monoclonal immunoglobulin heavy chain gene rearrangement, but none had clonal T-cell receptor gene rearrangement. Spontaneous regression occurred in 13 of 15 cases (87%); the other two cases (13%) achieved complete remission after treatment. Of two patients in the treated lymphoma-associated subgroup, one developed multiple new ulcerative lesions on previously unaffected skin, and the other had a relapse of EBVMCU in the oral cavity. No significant clinicopathological differences were found between the subgroups. Notably, none of the patients died from EBVMCU. However, the treated lymphoma-associated subgroup had lower overall survival (P = 0.004) and a shorter follow-up period (P = 0.003) than the MTX-associated subgroup, owing to death from non-associated causes. CONCLUSIONS: Treated lymphoma-associated EBVMCU, which is an indolent and self-limited condition, must be recognised to avoid misdiagnosing it as a relapse of malignant lymphoma during treatment.

Epstein-Barr virus positive diffuse large B-cell lymphoma presenting with vaginal sloughing and ulcerated skin nodule.

Malignant lymphomas presenting in the female genital tract are extremely rare. We report a case of Epstein-Barr virus associated diffuse large B-cell lymphoma of the genital tract and skin in a 60-year-old woman on long-term azathioprine.

Acute genital ulcers: keep Lipschütz ulcer in mind.

AIM: Lipschütz ulcers (LU) were first described as rare vulvar ulcerations that affect adolescents without previous history of sexual contact. However, more LU patients have been identified in acute genital ulcers (AGU) services in Europe. PURPOSE: To review cases of AGU and analyze the occurrence of LU in the Ob/Gyn Emergency Department of a Brazilian private hospital, using the currently used diagnostic criteria. METHODS: All female patients who sought our service with AGU complaints from January 2009 to July 2015 were selected and had their medical records reviewed, considering the clinical data and some diagnostic criteria, that included: < 20 years old, first AGU episode, sudden onset, absence of sexual contact 3 months before onset and the absence of immunodeficiency. RESULTS: 273 patients eligible for analysis were identified according to the criteria and 12 (4.39%) of them were identified with the possible diagnosis of LU. By applying less restrictive criteria that allowed the inclusion of patients of any age and sexual status, 98 were identified (35.89%). CONCLUSIONS: Despite being described as a rare pathology, ours and previous results indicate a considerable number of AGU cases, suggesting that LU should be better known and considered for differential diagnosis.

[The clinical characteristics of immunocompetent adults with chronic active Epstein-Barr virus associated enteritis].

Objective: To investigate the clinical and pathological characteristics of chronic active Epstein-Barr virus associated enteritis (CAEAE) . Methods: The clinical data of 6 CAEAE patients in Peking Union Medical College Hospital were retrospectively analyzed from January 2010 to November 2017, including clinical manifestations, endoscopic, pathological features, medications and clinical outcome. Results: The male∶female ratio was 4∶2 and the average age was 34 years old. All patients did not have personal and family history of immunodeficiency. The common symptoms consisted of fever (6/6), abdominal pain (6/6), hematochezia (6/6) and diarrhea (5/6). The most frequently affected sites were colorectum (5/6), followed by small intestine (3/6). Further serologic tests revealed a high load of serum Epstein-Barr virus(EBV) DNA. The main manifestations under endoscopy were multifocal or diffuse irregular ulcers. There was inflammation in the ulcer bases and surrounding areas, where EBV-encoded small RNA (EBER) was positive by in situ hybridization (6/6). The common complications were massive hemorrhage (3/6) and intestinal perforation (2/6). None of treatment agents including glucocorticoid, ganciclovir, foscarnet sodium and cytotoxic drugs was effective. All patients died within 0.5 to 13 months after diagnosis. Conclusions: CAEAE in immunocompetent individuals is a rare disorder with poor prognosis. It is difficult to differentiate CAEAE from inflammatory bowel disease due to similar clinical and endoscopic manifestations.

Epstein-Barr Virus Positive Mucocutaneous Ulcer: A Case Report.

Epstein-Barr virus (EBV) is known to be associated with B-cell lymphoproliferative disorders, and EBV-positive mucocutaneous ulcer (EBV-MCU) is a recently described entity observed in immunocompromised individuals. EBV-MCU is an aggressive appearing ulcerated lesion seen in the skin, oral cavity, and gastrointestinal tract. The process has Hodgkin-like features with a self-limited, indolent course, generally responding well to conservative management. We present a case of EBV-MCU recently encountered in a 54-year-old renal transplant recipient. She had persistent rectal pain and bleeding for over a year following hemorroidectomy. A large ulcer in the distal rectum with excoriation and granular margins was noted on examination, and an initial biopsy from the lesion was inconclusive. A repeat biopsy demonstrated ulcerated squamous and colonic mucosa with a polymorphic lymphoid infiltrate in the submucosa that contained large atypical cells. The large atypical cells were positive for PAX-5 and CD30 and demonstrated EBV RNA by in situ hybridization. EBV-MCU is a recently described occurrence in transplant patients, and awareness of this recently described entity is necessary for appropriate diagnosis and treatment.

Successful treatment with anti-programmed-death-1 antibody in a relapsed natural killer/T-cell lymphoma patient with multi-line resistance: a case report.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (NKTCL), nasal type, is an aggressive malignancy with poor prognosis. Currently, there is no recommended standard therapy for relapsed NKTCL. CASE PRESENTATION: A 37-year-old woman with lymphadenopathy was diagnosed with NKTCL by biopsy of an enlarged lymph node on the right side of her neck. Enhanced computed tomography revealed no metastasis. For this patient, we performed continuous chemotherapy followed by radiotherapy; however, nodule biopsy showed metastases in her lower limbs 3 months after radiotherapy, which confirmed disease progression. Unfortunately, the patient' s temperature was persistently high and her skin ulcers could not be controlled well using multi-line treatment. Therefore, we attempted treatment with the anti-programmed-death-1 (PD-1) antibody, pembrolizumab. Surprisingly, the patient achieved clinical complete remission (CR) after four cycles of pembrolizumab treatment, despite having persistent detectable Epstein-Barr virus (EBV) DNA. Other molecular monitoring techniques were unavailable for this patient owing to the retrospective nature of the study. The only adverse event was soreness of the upper limb joints and muscles. CONCLUSION: This relapsed NKTCL case treated with pembrolizumab showed that multimodal therapy including pembrolizumab would be partially or totally effective for relapsed NKTCL.

Genital Aphthous Ulcers and a Case of Suspected Chikungunya: A Short Clinical Case.

Genital aphthous ulcers can result from multiple conditions including febrile syndromes. Chikungunya infection manifests mainly as fever accompanied by polyarthralgia and pruritic rash. Nevertheless, healthcare providers should be alert to additional presentations. This is the case of a young woman presenting with painful genital ulcers after a three day prodome of fever and polyarthralgia. As a suspected case of Chikungunya infection and a clinical diagnosis of aphthae, treatment with oral prednisone for two weeks produced complete resolution of ulcers with no scarring. It is important to recognize that genital aphthous ulcers can develop in a febrile presentation such as that with Chikungunya. Although sexually transmitted diseases should be ruled out as a more common diagnosis in cases of genital lesions, knowledge about this unusual dermatological presentation would represent not only adequate prompt treatment but will minimize equivocal diagnosis as a sexually transmitted disease.

Etiology of Genital Ulcer Disease in Male Patients Attending a Sexually Transmitted Diseases Clinic: First Assessment in Cuba.

BACKGROUND: Sexually transmitted diseases (STDs) and in particular genital ulcer disease (GUD) have a major impact on morbidity and mortality in developing countries. The World Health Organization recommends the use of syndromic guidelines for the treatment of sexually transmitted infections (STIs) in resource-constrained countries. Surveillance of autochthonous etiologies provides epidemiological information contributing to the prevention and treatment of STIs. We investigated the etiology and factors associated with GUD among male patients attending a STD clinic in Havana, Cuba. METHODS: Swabs from genital ulcers of 113 male patients, collected from May 2012 to June 2015, were analyzed using PCR for herpes simplex virus types 1 and 2, Treponema pallidum, Haemophilus ducreyi, and Chlamydia trachomatis. We also investigated the clinical and epidemiological characteristics associated with the presence of these pathogens in GUD. RESULTS: At least one of the pathogens was detected in 70% of patients. The occurrence of the pathogens was herpes simplex virus type 2 (HSV-2) (51.3%), T. pallidum (29.2%), and C. trachomatis (1.8%). Co-infections occurred as follows: T. pallidum-HSV-2 (10.6%), C. trachomatis-HSV-2 (0.9%) and C. trachomatis-T. pallidum (0.9%). Herpes simplex virus type 1 and H. ducreyi were not detected. Ages 15 to 40 years, HIV-positive serostatus, and no condom use were significant risk factors for the presence of HSV-2 in genital ulcers. CONCLUSIONS: Our preliminary results highlight the predominance of HSV-2 and T. pallidum as the leading GUD etiologies in the study population and identified risk factors associated with HSV-2. This information should help to inform guidelines for better management of GUD in Havana, Cuba.