Disseminated Herpes Infection Research Articles

Interesting Case of Disseminated Herpes Infection in A Healthy Female Patient Resembling Monkeypox

Normally we find cases of disseminated cutaneous herpes-simplex in immunocompromised individuals. With the advent of monkeypox, many reports have been falsely purporting cases of this disease when the lesions were either herpes simplex or an unspecified skin infection. In this case report we document the finding of a healthy 31-year-old female with herpetic lesions on her arms, legs, and vulvar area.

Precision in Cardiovascular Care Using Targeted Neonatal Echocardiography in Lethal Neonatal Disseminated Herpes Infection: A Case Series.

Neonates with disseminated neonatal herpes simplex virus infection often present with cardiorespiratory failure. The pathophysiological contributors to the disease phenotype, biologic mechanisms underlying the hemodynamic instability and optimal approach to cardiovascular treatment have not been well described. We describe clinical and echocardiography features of cardiovascular dysfunction, in a case series of neonates with disseminated herpes simplex virus, and response to physiology-based hemodynamic management. The biologic phenotype includes low systemic vascular resistance state, hypovolemia secondary to third space losses, myocardial dysfunction and pulmonary hypertension. Early targeted neonatal echocardiography provided hemodynamic insights on blood flow, shunt characterization, vascular resistance and cardiac function, that were difficult to gauge clinically (eg, differentiating parenchymal from pulmonary vascular disease) thereby positively impacted clinical care. All patients were stabilized hemodynamically without utilizing extracorporeal membrane oxygenation, although all patients died of multiorgan failure.

Simultaneous VZV and HSV-1 Reactivation after Minor Head Injury.

An 81-year-old patient presented to the emergency department with a dark lesion on his forehead and swelling of his left eye, 3 days after a minor forehead injury and skin laceration. He also showed singular papules on his chin, upper chest, upper arms and back, later evolving into vesicles. Polymerase-chain reaction testing of vesicle content was positive for VZV and HSV-1, confirming a diagnosis of disseminated cutaneous herpes virus infection and concomitant HSV-1 reactivation. Antiviral and antibiotic treatment was initiated for 1 week with an immediate response. This case report highlights the association of head trauma and subsequent reactivation of VZV in patients at risk. Simultaneous reactivation of HSV-1 and VZV is rare in immunocompetent patients.LEARNING POINTSMinor trauma can cause VZV and HSV reactivation.Consider herpes virus reactivation in case of unclear rash; the appearance of vesicles can be delayed for a few days.Screen for immunodeficiency disorders in disseminated herpes virus infection; if non-apparent, close monitoring is recommended.

CARDIOVASCULAR DERANGEMENT IN NEONATAL HERPES INFECTION

Abstract BACKGROUND Disseminated Herpes Simplex infection is a severe neonatal illness with high mortality and morbidity. Despite acyclovir treatment, the fulminant disease may be rapidly progressive and treatment is largely supportive. A significant proportion of neonates with this illness require intensive care support for circulatory insufficiency and hypoxic respiratory failure. Extracorporeal membrane oxygenation may be used as rescue therapy, though mortality remains high. The pathophysiological contributors to the disease phenotype, the mechanisms underlying the hemodynamic instability and therapeutic strategies to treat such cardiovascular dysfunction have not been well described. OBJECTIVES To describe patterns of cardiovascular dysfunction using targeted neonatal echocardiography and response to therapy for neonates with disseminated herpes infection in a quaternary neonatal intensive care unit. DESIGN/METHODS A cohort of all neonates with confirmed disseminated herpes simplex virus (HSV) infection admitted over the period of November 2014- April 2017 were included in this study. All neonates were evaluated by comprehensive targeted neonatal echocardiography (TnECHO) assessment within the first 24h of admission. Demographic and clinical features were collected retrospectively from the electronic medical record. All TnECHO measurements were performed by a single expert operator. Ethical approval was obtained from the institutional ethics board. RESULTS Five neonates, 3 with HSV 1 and 2 with HSV 2, were identified during the study period. All had features of profound circulatory insufficiency such as hypotension, metabolic acidosis with high lactate, oliguria/anuria, poor capillary refill etc. Three neonates had severe oxygenation failure. On functional echocardiographic assessment, we found that all cases demonstrated underfilled cardiac chambers and low cardiac outputs suggesting severe vasodilatation and third space losses. These cases were managed by aggressive volume resuscitation and use of peripheral vasoconstrictors such as Vasopressin and Nor-Epinephrine. Primary ventricular dysfunction was identified in 3 neonates, who were treated with dobutamine and/or epinephrine. Significant pulmonary hypertension was detected in three infants which prompted the use of Inhaled Nitric Oxide. Acyclovir was initiated early on. Significant cardiovascular stabilization could be achieved by such targeted hemodynamic therapy. However, in view of extensive neurological and hepatic damage, life sustaining therapy was eventually withdrawn in all of them. CONCLUSION Cardiovascular dysfunction in neonates with disseminated HSV infection may be due to either primary ventricular dysfunction, vasodilatation and third space losses or due to pulmonary hypertension. Early targeted neonatal echocardiography may enhance physiologic definition and facilitate targeted therapy. Mortality from multisystem complications, however, remains universal, which raises the question of the role of ECMO in this population.

Fulminant Hepatic Failure Secondary to Herpes Hepatitis in a Patient With Myasthenia Crisis: An Elusive Diagnosis

Herpes hepatitis is a rare cause of fulminant hepatic failure contributing to less than 1% of all cases. It is most often seen in persons who are immunosuppressed and in pregnant women. The presentation is usually non-specific and rapidly progressive, thus making antemortem diagnosis of this condition rare. We present a patient who was on chronic immunosuppressive therapy for systemic lupus erythematosus and subsequently developed multi-organ failure with anicteric transaminitis as a result of disseminated herpes infection. The diagnosis was only made post-mortem. A confounding factor in this case was the fact that the patient underwent plasmapheresis, which skewed the interpretation of liver function tests in the setting of acute liver failure.

Hemophagocytic Lymphohistiocytosis Associated with NK Cell Dysfunction and Disseminated Herpesvirus Infection in GATA2 Deficiency/Monomac Syndrome

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive immune activation. Herpesvirus infection is a common trigger of HLH, and in some patients may indicate an underlying immunodeficiency. Primary immunodeficiencies associated with HLH are often characterized by impaired cytotoxic function of NK cells and/or cytotoxic T lymphocytes and include Chediak-Higashi, Hermansky-Pudlak, and Griscelli syndromes and the X-linked lymphoproliferative disorders, SAP and XIAP deficiency.GATA2 deficiency, also known as MonoMAC syndrome, is a primary immunodeficiency resulting from haploinsufficiency of the GATA2 transcription factor, a master regulator of hematopoiesis. Clinically, GATA2 deficiency is characterized by progressive cytopenias of monocytes, dendritic cells, and B and NK lymphocytes; susceptibility to infection with human papillomavirus, herpesviruses, nontuberculous mycobacteria, and invasive fungi; and bone marrow failure with risk for clonal evolution to myelodysplastic syndrome and acute myelogenous leukemia. Additional manifestations may include pulmonary alveolar proteinosis, congenital lymphedema, and sensorineural hearing loss. We report two patients with GATA2 deficiency/MonoMAC syndrome who developed aggressive HLH in the setting of marked NK cell dysfunction and disseminated herpesvirus infection.Case 1The patient was an African-American female with severe bilateral lymphedema since age 9 requiring multiple hospitalizations for lymphedema cellulitis. At age 12, she was hospitalized for severe pulmonary blastomycosis with necrotizing pneumonia. An immunologic workup revealed profound monocytopenia and B and NK lymphocytopenia, and NK functional testing revealed markedly reduced cytotoxicity and near absence of the CD56(bright) subset. Genetic testing for mutations in PRF1, UNC13D, and STX11 was negative. At age 18, she presented with septic shock and persistent fevers despite empiric antibiotics, and HSV-1 DNA was detected in the blood. The diagnosis of MonoMAC syndrome was strongly suspected in light of her congenital lymphedema and highly characteristic cytopenias and infections. Unfortunately, she rapidly decompensated and developed massive hyperferritinemia, hypofibrinogenemia, pancytopenia, and fulminant hepatitis concerning for HSV-1-driven HLH. An autopsy following her death revealed disseminated HSV-1 infection in the lungs, liver, and genitalia, and a hypocellular bone marrow with hemophagocytosis. The cause of death was HLH in the setting of NK cell deficiency and widespread HSV-1 infection. Genetic testing for GATA2 mutation was performed posthumously and is currently in progress.Case 2A Chinese female presented at age 20 with persistent fevers, cervical lymphadenopathy, and cutaneous ulcers. Mycobacterium avium complex was identified in the sputum and urine, and she was treated with clarithromycin, rifampin, and ethambutol. HIV testing was negative. Biopsy of her skin lesions revealed an EBV+ hydroa vaccineforme-like cutaneous T-cell lymphoma, and she was found to have significant EBV viremia with over 1 million copies/mL detected by quantitative PCR. An immunologic workup revealed profound B and NK lymphocytopenia. Monoallelic GATA2 mRNA expression was demonstrated leading to haploinsufficiency. She developed persistent fevers, worsening hyperferritinemia, hypofibrinogenemia, pancytopenia, and transaminitis. Bone marrow biopsy revealed a hypocellular marrow with EBV+ T cells and abundant hemophagocytosis. She was diagnosed with EBV-driven HLH and was treated with etoposide and dexamethasone followed by nonmyeloablative, haploidentical related donor stem cell transplant. She is currently 12-months post-transplant with an undetectable EBV viral load and complete resolution of her T cell lymphoma and HLH.ConclusionGATA2 deficiency is associated with NK cell dysfunction and disseminated herpesvirus infection, which can lead to aggressive HLH. Genetic testing for GATA2 mutation should be considered in patients with HLH and underlying NK cell deficiency and/or herpesvirus infection. NK functional testing typically shows markedly reduced cytotoxicity and near absence of the CD56(bright) subset. Allogeneic transplant represents a potentially curative approach in this setting. DisclosuresNo relevant conflicts of interest to declare.

Selective head cooling for the treatment of neurologic complications of acute liver failure in a newborn with disseminated herpes infection

BackgroundNeurologic complications of pediatric acute liver failure (ALF) are a major determinant of outcome. Management of these complications, including increased intracranial pressure (ICP) is largely supportive. Although hypothermia is an effective treatment for perinatal asphyxia and is used to reduce ICP following traumatic brain injury, it has not been evaluated for neurologic complications of ALF in the newborn.MethodsCase report.ResultsWe present a case of neonatal herpes simplex virus (HSV)-associated ALF with profound neurologic impairment and increased ICP. The patient was treated with selective head cooling, and monitored with transcranial doppler (TCD) studies of cerebral blood flow velocity, and electroencephalograms (EEG). The duration of head cooling was influenced by absent diastolic flow on TCDs, which subsequently improved during hypothermia. Continuous EEGs captured subclinical seizures, which improved with antiepileptic medications. Her death was attributed to a massive pulmonary hemorrhage and a hypoxemic cardiac arrest secondary to significant coagulopathy.ConclusionThis case demonstrates that selective head cooling may attenuate increased ICP in neonatal encephalopathy, and that TCDs may guide management in the absence of invasive monitoring.

L1. Imitators of severe preeclampsia

There are many obstetric, medical, and surgical disorders that share many of the clinical and laboratory findings of patients with severe preeclampsia–eclampsia. Imitators of severe preeclampsia–eclampsia are life-threatening emergencies that can develop during pregnancy or in the postpartum period. These conditions are associated with high maternal perinatal mortality and morbidities, and survivors may face long-term sequelae. The pathophysiologic abnormalities inmany of these disorders include vasospasm, platelet activation or destruction, microvascular thrombosis, endothelial cell dysfunction, and reduced tissue perfusion. Some of these disorders include acute fatty liver of pregnancy (AFLP), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), acute exacerbation of systemic lupus erythematosus (SLE), catastrophic antiphospholipid antibody syndrome, and disseminated herpes simplex. AFLP is associated with increased rate of maternal mortality (1.8–10%), and severe morbidities such as DIC (50–100%), hypoglycemia (50–70%), acute tubular necrosis (50–100%), encephalopathy, and sepsis. The perinatal mortality in recent case series is approximately 13% with 75% preterm delivery. In patients with TTP/HUS, the reported maternal mortality with the use of plasma pheresis in recent case series ranged from 0% to 10%, however, maternal morbidities such as central nervous system and renal injury remain high. The perinatal mortality rte in these pregnancies is 29%. In pregnancies complicated by SLE,maternal complications are substantially increased in those with antiphospholipid syndrome (APS), and maternal mortality is almost 50% in those who develop the catastrophic APS. Finally, disseminated herpes infection is associated with maternal and perinatal mortality if not

T cell lymphoma with disseminated herpes zoster on presentation and subsequent recurrence leading to blindness—a case report

Dear Editor, Lymphomas are known to be associated with immunologic defects [1, 2]. Immunosuppressive chemotherapy often aggravates the problem. Reactivation of varicella zoster virus may occur in immunocompromised patients. Depending on the level of immunodeficiency, this may either present as localized herpes zoster or disseminated herpes infection. Conventional chemotherapy for lymphomas, except for regimens containing fludarabine or alemtuzumab, is not considered profoundly immunosuppressive. Antiviral prophylaxis is not routinely recommended with these regimens [3]. We report a case of peripheral T cell lymphoma, who developed disseminated herpes zoster infection on initial presentation of lymphoma and subsequently developed recurrent infection after few weeks of salvage chemotherapy, which led on to bilateral choroidoretinitis, retinal detachment, and blindness. A 50-year-old diabetic lady presented with a 2-week history of fever, night sweats, generalized lymphadenopathy, and multiple papulovesicular skin lesions on the back, buttocks, and right. lower limb, proved to be due to disseminated herpes zoster infection. She had a history of chickenpox in childhood. Excision biopsy of the cervical node reported as peripheral T cell lymphoma—

Cortical Hyperostosis Secondary to Prostaglandin E 1 Therapy

Infants born with ductal-dependent congenital heart defects often require prolonged treatment with prostaglandin E1 (PGE1) while awaiting corrective surgery. An uncommon, and frequently overlooked, adverse effect of prolonged PGE1 infusion is cortical hyperostosis. A 4-day-old female infant sustained cardiogenic shock resulting from coarctation of the aorta necessitating intravenous PGE1 (0.1 mcg/kg/min). Because of confounding disseminated herpes infection, corrective surgery could not be immediately performed. PGE1 was continued until palliative stent placement at 38 days of life. Alkaline phosphatase levels were noted to be elevated during the infant’s hospital course. (Figure 1; available at www.jpeds.com). A 5’ nucleotidase level in the reference range ruled out hepatic origin of the elevated alkaline phosphatase level. Chest roentograms (Figure 2) showed normal cortical bone at 10-days of age (A), with gradual increase in hyperostosis at 30 days (B) and 50 days (C) of age, seen best in the right humerus and clavicle. With cessation of PGE1 infusion, the alkaline phosphatase level began to decrease and continued to do so until the time of discharge from the hospital. Follow-up at 9 months of age showed both the alkaline phosphatase level and the radiography abnormalities had normalized.Figure 2This series of chest roentograms shows the gradual increase in cortical bone during treatment with prostaglandin E1. The findings are best seen in the right humerus and clavicle. The patient’s age at the time of the radiographs is 10-days (A), 30-days (B) and 50-days (C).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Prostaglandins of the E series have been shown to promote osteogenesis.1Udea K. Saito A. Nakano H. Aoshima M. Yokota M. Muraoka R. et al.Cortical hyperostosis following long-term administration of prostaglandin E1 in infants with cyanotic congenital heart disease.J Pediatr. 1980; 97: 834-836Abstract Full Text PDF PubMed Scopus (242) Google Scholar Infants with cyanotic heart defects are at high risk for the development of elevated circulating levels of PGE1 because of decreased pulmonary inactivation caused by right to left shunting and the administration of pharmacological amounts to ensure ductus arteriosus patency. A large number of infants receiving PGE1 while awaiting cardiac transplantation have radiographic evidence of cortical hyperostosis.2Woo K. Emery J. Peabody J. Cortical hyperostosis: a complication of prolonged prostaglandin infusion in infants awaiting cardiac transplantation.Pediatrics. 1994; 93: 417-420PubMed Google Scholar Risk of cortical hyperostosis increases with duration of continuous PGE1 infusion from 42% at <30 days to 100% at >60 days; the severity of cortical hyperostosis correlates with both duration and total dose of PGE1 infused.2Woo K. Emery J. Peabody J. Cortical hyperostosis: a complication of prolonged prostaglandin infusion in infants awaiting cardiac transplantation.Pediatrics. 1994; 93: 417-420PubMed Google Scholar Although most cases are asymptomatic, cortical hyperostosis can mimic osteomyleitis,3Velaphi S. Cilliers A. Beckh-Arnold E. Mockhachane M. Mphahlel R. Pettifor J. Cortical hyperostosis in an infant on prolonged prostaglandin infusion: case report and literature review.J Perinatol. 2004; 24: 263-265Crossref PubMed Scopus (16) Google Scholar thus complicating the decision making process on proceeding with further cardiac surgery. PGE1-induced cortical hyperostosis is benign, reversible, and self-resolving on withdrawal of PGE1 treatment.

Phase I, Open-Label, Dose-Escalating Study of a Genetically Engineered Herpes Simplex Virus, NV1020, in Subjects with Metastatic Colorectal Carcinoma to the Liver

Current regimens of systemic chemotherapy result in only modest lengthening of survival in patients with advanced stage, liver-dominant, metastatic colorectal cancer who have failed first-line chemotherapy. The objective of this study was to investigate the safety and tolerability of NV1020, a replication-competent, attenuated, genetically engineered herpes simplex virus type 1 (HSV-1), in patients with hepatic colorectal metastases refractory to first-line chemotherapy. A phase I, open-label, dose-escalating study of a single 10-min hepatic arterial infusion of NV1020 in four cohorts. Three patients in each cohort received doses of 3 x 10(6), 1 x 10(7), 3 x 10(7), and 1 x 10(8) plaque-forming units. Adverse events were either mild or moderate in severity, and self-limiting. Only three serious adverse events (one transient rise in serum y-glutamyltransferase, one diarrhea, and one leukocytosis) experienced by three patients were considered to be possibly or probably related to NV1020. There were no deaths during the study, and there was no evidence of disseminated herpes infection. Viral presence was detected in only one saliva sample and two serum samples from one asymptomatic patient in the highest dose cohort. In the first week after viral administration only rare and minor increases were noted for tumor necrosis factor-alpha (six samples; three patients; peak, 40 pg/ml), interleukin (IL)-1 (two samples; two patients; peak, 28 pg/ml), and interferon-y (four samples; two subjects; peak, 54 pg/ml). No IL-2 was detected. Mild liver enzyme elevations were self-limiting and not associated with clinical symptoms. We conclude that NV1020, a genetically engineered but replication-competent HSV-1 oncolytic virus, can be safely administered into the hepatic artery without significant effects on normal liver function.

Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma

This Phase II study was undertaken to assess the efficacy and toxicity of chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone (EPOCH regimen) in patients with advanced, refractory cutaneous T-cell lymphoma (CTCL). Fifteen patients were treated with a 96-hour continuous infusion of etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone, followed by granulocyte-colony stimulating factor support and trimethoprim/sulfamethoxazole prophylaxis. The median age of the patients was 53 years (range, 17-82 years). Six patients had Sézary syndrome (SS), four patients had visceral involvement, and four patients had anaplastic large cell morphology, three with Ki-1 (CD30) positivity. All patients had disease that was refractory to prior chemotherapy or electron beam irradiation and eight of these patients had received cyclophosphamide, doxorubicin, vincristine, and prednisone. Seven patients had received prior interferon therapy and nine patients had received fludarabine and/or 2-CDA. After a median of 5 cycles (range, 1-9 cycles), 4 patients achieved a complete response (27%) and 8 patients achieved a partial response (53%) for an overall response rate of 80% (95% confidence interval, 52-96%). Three patients with visceral involvement, two of three patients with anaplastic large cell morphology, and one patient with human T-cell lymphoma virus leukemia/lymphoma did not respond. All 12 responders had improvement in skin disease; 2 of 6 patients with SS had complete disappearance of circulating Sézary cells. The median progression free survival was 8.0 months (range, 3-22 months). After a median follow-up of 11.4 months (range, 2-56+ months), the median patient survival was 13.5 months. Grade 3 or 4 hematologic toxicity occurred in 8 patients (61%); 5 of these 8 patients had febrile neutropenia. Six patients developed staphylococcal bacteremia, two patients had disseminated herpes infection, and one patient had Pneumocystis carinii pneumonia. Grade 3 neurotoxicity occurred in one patient. Two patients had a significant decrease in left ventricular ejection fraction and one patient had supraventricular tachycardia. EPOCH chemotherapy has a high response rate with acceptable toxicity in patients with advanced and refractory CTCL.

Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis

Several members of the herpesvirus family have been implicated in the pathogenesis of multiple sclerosis (MS). Recently, HHV-6 viral antigen has been demonstrated in association to MS plaques, as well as DNA from human herpesvirus 6 (HHV-6) in cerebrospinal fluid from a few MS patients by polymerase chain reaction (PCR). In the present study, CSF from patients with MS, optic neuritis and other neurological diseases, as well as consecutive CSF and serum samples from MS patients included in a clinical trial with acyclovir, were analysed by nested PCR for the presence of DNA from herpes simplex virus 1 and 2, Epstein-Barr virus, varicella zoster virus, cytomegalovirus, human herpesvirus 6 and 7. No virus DNA was found in any CSF (n = 115) or serum (n = 116) sample. These findings argue against a continuous disseminated herpesvirus infection in MS, but do not rule out a lesion-associated, low-grade herpesvirus infection within the MS brain.

Rethinking Life and Death. The Collapse of Our Traditional Ethics

With the advent of effective antiviral treatment for disseminated herpes infection it has become important to be able to make a firm clinical diagnosis of this condition. We undertook a retrospective analysis of 20 patients with disseminated herpes simplex infection diagnosed at necropsy to derive useful clinical pointers to this severe form of the disease. The most useful clinical criteria were malnutrition, post measles state, and local herpes infection in addition to encephalopathy, enlarging hepatomegaly, and deteriorating pneumonia. The liver showed characteristic histological changes in 18 of 19 patients. These clinical criteria combined with liver biopsy were applied in a prospective pilot study of five patients at risk for disseminated herpes infection and the results were encouraging.

Ogilvieʼs Syndrome from Disseminated Varicella-Zoster Infection and Infarcted Celiac Ganglia

We report a patient who had refractory Hodgkin's disease and who received an autologous bone marrow transplantation and 8 months later developed abdominal pain associated with acute colonic dilation. The course of the patient was rapidly fatal due to a lobar pneumonia. Autopsy revealed signs of disseminated herpesvirus infection with marked hemorrhagic infarction of celiac sympathetic ganglia. This finding supports the hypothesis that denervation caused by virus reactivation and secondary hemorrhage is a main mechanism of acute colonic pseudoobstruction.

Infections Complicating Mycosis Fungoides and Sézary Syndrome

To determine, in patients with mycosis fungoides and Sézary syndrome, the incidence of infections, the importance of nosocomial infections, and the epidemiologic factors associated with cutaneous and visceral infections. Retrospective inception cohort study at a university medical center referral clinic. Three hundred fifty-six patients with mycosis fungoides or Sézary syndrome. Incidence rates for specific infections, and multivariate risk ratios for demographic and clinical factors associated with infection. Cutaneous bacterial infection was most common (17.0 infections per 100 patient-years), followed by cutaneous herpes simplex virus and herpes zoster virus infection (3.8 infections per 100 patient-years), bacteremia (2.1 infections per 100 patient-years), bacterial pneumonia (1.7 infections per 100 patient-years), and urinary tract infection (1.4 infections per 100 patient-years). Twenty-seven percent of herpesvirus infections disseminated on the skin but none disseminated to internal organs. Pneumonia or bacteremia was present in 88% of patients who died of infection. Only three patients had invasive fungal or protozoal infection. Nosocomial infections accounted for 19% of cutaneous bacterial infections, 59% of bacteremias, 62% of pneumonias, and 88% of infections leading to death. By logistic and Cox regression, the presence of extracutaneous involvement with lymphoma was the most important independent risk factor for recurrent bacterial skin infection (risk ratio [RR], 12; 95% confidence interval [CI], 1.2 to 120), disseminated herpesvirus infection (RR, 28; 95% CI, 2.7 to 290), bloodstream infection (RR, 5.5; 95% CI, 1.7 to 18), and death from infection (RR, 15; 95% CI, 3.6 to 64). Community-acquired bacterial skin infections are a common cause of morbidity in patients with mycosis fungoides and Sézary syndrome but are usually treated without hospital admission. Bacteremia and pneumonia, which are usually nosocomial, are the major infectious causes of death. Advanced disease stage, independent of corticosteroids and other therapies, is the most important risk factor for both cutaneous and systemic infections.

Hemorrhagic cystitis due to herpes simplex virus as a marker of disseminated herpes infection

Herpetic cystitis has rarely been reported. Herein are described two immunocompromised female patients with genital or buttock herpetic lesions in whom hemorrhagic cystitis due to herpes simplex virus type 2 developed in the setting of disseminated herpetic infection. Both patients had indwelling Foley catheters. Urinary tract instrumentation may cause local or widespread dissemination of genital herpes in immunocompromised patients.

Usefulness of clinical features and liver biopsy in diagnosis of disseminated herpes simplex infection.

With the advent of effective antiviral treatment for disseminated herpes infection it has become important to be able to make a firm clinical diagnosis of this condition. We undertook a retrospective analysis of 20 patients with disseminated herpes simplex infection diagnosed at necropsy to derive useful clinical pointers to this severe form of the disease. The most useful clinical criteria were malnutrition, post measles state, and local herpes infection in addition to encephalopathy, enlarging hepatomegaly, and deteriorating pneumonia. The liver showed characteristic histological changes in 18 of 19 patients. These clinical criteria combined with liver biopsy were applied in a prospective pilot study of five patients at risk for disseminated herpes infection and the results were encouraging.

Visceral Herpesvirus Infections in Leukemic Patients Receiving Cytarabine

Autopsy evidence of herpesvirus infection was found in visceral organs of four leukemic patients who had received large doses of cytarabine (cytosine arabinoside; Ara-C) shortly before their death. In three of these patients the infection was clinically unsuspected; in the fourth, cutaneous herpes zoster developed after administration of 300 mg of cytarabine daily for the preceding five days. Although cytarabine exhibits pronounced in vitro virucidal activity against herpes viruses and has been successfully used in clinical treatment of severe herpesvirus infections, the present findings and a review of the recent literature cast doubt on the antiviral effectiveness of this drug, particularly in already immunosuppressed patients, and suggest instead that such patients actually have an increased risk for development of disseminated herpesvirus infection owing to further depression of host defenses by the drug.

720 THE EFFECT OF VIRAL INFECTION ON THE ABILITY OF HUMAN LYMPHOCYTES TO DEVELOP ANTIBODY PRODUCING CELLS AFTER MITOGEN STIMULATION in vitro

Using a plaque forming cell (PFC) assay system the effects of clinically and laboratory diagnosed viral illness were determined on the ability of human peripheral blood lymphocytes to be stimulated with the mitogens phytohemagglutinin (PHA), pokeweed (PWM), staphylococcal protein A (SpA), lipopolysaccharide (LPS) and the antigens candida (C) and tetanus-diphtheria toxoids (Td). In contrast with control subjects who had a geometric mean 7 PFC's/106 cells, children with viral infections had a mean of 1188 PFC/106 cells for unstimulated cultures. PWM was found to be the most effective PFC stimulant in control subjects (geometic mean 1995 PFC/106 cells); however concurrent viral infection resulted in a reduced number (geometric mean 267 PFC/106 cells) of PWM induced PFC's when compared with background. Control subjects produced no PFC's in response to PHA, Con A, LPS, Td, SpA or C; however, children with rubella and disseminated herpes infection had PFC's with these mitogens, although again the absolute numbers were less than the unstimulated control cultures. These results suggest that viral infection produces dramatic shifts of peripheral blood lymphocyte subpopulation composition and function, reducing the effect of the mitogens on cellular differentation. Alternatively, direct virus-B cell interaction may result in differentiation to immunoglobulin producing cells without a mitogen-T-B cell interaction.