Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

Association between intrathecal anti-HIV-1 immunoglobulin G synthesis and occurrence of HIV-1 in cerebrospinal fluid.

The levels of antibodies to HIV-1 and the occurrence of HIV-1 were determined in the cerebrospinal fluid (CSF) and the blood of 60 people in various stages of HIV-1 infection. Intrathecal synthesis of anti-HIV-1 immunoglobulin (Ig) G was detectable at a low frequency in individuals with normal immunological parameters, and in the majority of patients with various degrees of immunodeficiency. The intrathecal production of antibodies to HIV-1 was strongly associated with the recovery of the virus from CSF. A relationship between high anti-HIV-1 IgG levels and occurrence of HIV-1 was also found in blood. Patients without overt neurological symptoms exhibited intrathecal synthesis of anti-HIV-1 IgG as often as those with such symptoms. These findings suggest that intrathecal synthesis of antibodies to HIV-1 is related to a persistent HIV-1 antigenic stimulation in the central nervous system (CNS). HIV-1 often seems to elicit a humoral immune response in the CNS, without concomitant overt neurological symptoms.

Elevated neopterin and beta 2-microglobulin levels in blood and cerebrospinal fluid occur early in HIV-1 infection.

Neopterin and beta 2-microglobulin (beta 2-M) concentrations in cerebrospinal fluid (CSF) and blood were measured in 56 individuals in various stages of HIV-1 infection. Elevated levels of neopterin as well as beta 2-M were found in the CSF of three patients with primary HIV-1 infection and also in subjects in the early stages of chronic HIV-1 infection, with the highest levels in HIV-1 isolation-positive people. There was a clear correlation between the concentrations of the two substances and the levels seemed to increase in parallel with progress of infection. A similar pattern was found in blood. Higher concentrations of neopterin and beta 2-M in CSF than in blood were found in patients with advanced dementia in particular. These findings indicate that the cellular immune system in the central nervous system (CNS) may be activated during the early stages of HIV-1 infection without concomitant overt neurological symptoms. The pathological processes in CNS and blood seem to develop in parallel rather than being restricted to one compartment.

Relationship between cell-free viraemia, antigenaemia and antibody levels in HIV-1-infected Ethiopian patients.

OBJECTIVE: To determine the relationship and occurrence of cell-free viraemia, free or immune-complexed p24-antigen and p24-antibody levels in blood from HIV-1-infected patients in Ethiopia. METHODS: Peripheral blood was obtained from 66 Ethiopian and 137 Swedish HIV-1-seropositive patients. Blood samples were analysed for free or immune-complex bound p24 antigen by enzyme-linked immunosorbent assay before and after acid hydrolysis of immune complexes for infectious virus in plasma and peripheral blood mononuclear cells (PBMC), and for p24-antibody levels. We compared the kinetics of viral replication of Ethiopian with Swedish isolates in vitro. RESULTS: Infectious virus was isolated from PBMC in 95% and from plasma in 81% of Ethiopian AIDS patients. In contrast, p24 antigen was detected in only 5% of AIDS patients from Ethiopia, compared with 76% of those from Sweden. p24-antibody levels were much higher and more persistent in Ethiopian than in Swedish subjects. The ratio between reverse transcriptase activity and p24 antigen was significantly higher in Ethiopian isolate culture than in those of the Swedish isolates. CONCLUSIONS: Our results show that relationships between viraemia, p24 antigenaemia and p24-antibody levels in HIV-1-infected Ethiopian patients differ from those found in comparable Swedish patients. This pattern may partly explain the differences seen in the natural course of HIV-1 infection in Ethiopia and Sweden.

PIP: Researchers conducted hematologic tests on 66 HIV-1 positive adults from Ethiopia and compared the results with those of 137 HIV-1 patients in Stockholm, Sweden, to determine the incidence of cell-free viremia, free or complexed p24 antigen, and p24 antibody levels. They isolated HIV-1 from peripheral blood mononuclear cells in 95% and from plasma in 81% of the Ethiopian subjects. The corresponding percentages for the Swedish subjects were 95% and 92%. They found p24 antigen in only 5% of AIDS patients from Ethiopia (none for asymptomatic HIV-1 subjects) compared with 76% of Swedish patients (p .01). The Ethiopian subjects had significantly higher p24 antibody levels than did the Swedish subjects (85% vs. 52%; p = .008). The ratio between reverse transcriptase activity and p24 antigen concentration stood much higher in the Ethiopians than in the Swedes (7.5 vs. 3.6; p = .0019). These results suggested that the HIV-1 strains in the Ethiopian subjects resembled rapid high HIV-1 strains. In addition, the high degrees of cell-free viremia, relative lack of free or immune complexed p24 antigen, and a persistence of p24 antibody during the entire course of infection in Ethiopian HIV-1 infected subjects intimated that the interaction between HIV-1 and the Ethiopians may be different in Africa than it is in Europe and North America. The results of another study conducted by the researchers supported this conclusion. They included high levels of tumor necrosis factor-alpha and neopterin and low levels of interferon-alpha in HIV-1 positive Ethiopians.

Zidovudine in the management of primary HIV-1 infection.

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28-111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3-14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of immunoglobulin M antibody in primary human immunodeficiency virus infection.

Consecutive serum samples obtained from 20 homosexual men during symptomatic primary HIV infection were examined by a variety of IgG and IgM antibody assays. All sera obtained 2-5 weeks after onset of disease contained IgM anti-HIV as demonstrated by an IgM antibody capture assay. The IgM antibodies appeared during the 2 first weeks of illness, reached peak titres at 2-5 weeks and declined thereafter to undetectable levels at 2-3 months after the onset of disease. By contrast, IgG anti-HIV appeared later, during the second week after the onset of symptoms, and did not reach maximal levels until the IgM response had waned. The first IgM antibodies to appear were directed against gag proteins. IgM antibodies against env antigens were found less frequently and later in the course of the disease. These results suggest that IgM antibody determination may be helpful in the diagnosis of early HIV infection as a possible addition to the combined use of antigen detection and a second generation ELISA, which, in the present study, was found to be highly reliable for diagnostic purposes.

HIV isolation from cerebrospinal fluid in relation to immunological deficiency and neurological symptoms.

Human immunodeficiency virus (HIV) could be isolated from the cerebrospinal fluid (CSF) of the majority (62%) of 72 patients in various stages of HIV infection. This high rate of successful virus isolation was achieved only when the time from lumbar puncture to initiation of the cell cultures was short, i.e. not exceeding 5 h. The HIV isolation rates were equally high in patients with persistent generalized lymphadenopathy (PGL), AIDS-related complex (ARC) and AIDS. Although the HIV recovery rate was low in patients with normal immunological parameters it was not correlated with the degree of severity of the immunodeficiency in the other patients. Furthermore, the recovery rates were not significantly correlated to the duration of the infection. HIV was recovered as often from patients with neurological symptoms as from patients without such symptoms. These findings suggest that in the majority of patients there is central nervous system (CNS) involvement early in the course of HIV infection and that HIV replication in the CNS may occur in the absence of a pronounced systemic cellular immunodeficiency and frequently without causing overt neurological symptoms.

Differences in PCR reactivity between HIV proviruses from individuals in Ethiopia and Sweden.

The polymerase chain reaction (PCR), using primer pairs in the gag, pol, and env regions, was used in a comparative study of HIV-1 DNA in peripheral mononuclear blood cells from HIV-1-seropositive individuals in Ethiopia and Sweden. Although all Swedish samples were positive by PCR, the reactivity was more pronounced in samples from late stages than in those from early stages of infection. Six of nine Ethiopian samples from HIV-1-seropositive patients were positive by PCR, but the reactions were much weaker than those observed for Swedish samples, and in most cases seen with one primer pair only. These results suggest that the burden of HIV-1 DNA in peripheral mononuclear blood cells increases with advancing disease. PCR using primer pairs designed to detect HIV-1 infection in Europe and North America is not always suitable for the detection of HIV-1 infection in Ethiopia. The differences in PCR reactivity could possibly be a consequence of differences regarding host responses to the virus in the two countries, but more likely due to genomic differences between HIV-1 strains prevalent in Ethiopia and Sweden.

Indomethacin modulation of monocyte cytokine release following pelvic irradiation for cancer.

Pelvic irradiation for urogenital cancer reduced monocyte release of tumour necrosis factor alpha (TNF-alpha). Addition of indomethacin to monocyte cultures increased TNF-alpha production after but not before irradiation. E. coli lipopolysaccharide (LPS) increased TNF-alpha release before as well as after radiation therapy and addition of indomethacin to LPS-stimulated monocytes further increased TNF-alpha production following radiotherapy. Spontaneous interleukin-1 (IL-1) release was increased in the cancer patients and was not significantly affected by radiation therapy. LPS increased IL-1 release before as well as after irradiation, but indomethacin did not further change IL-1 secretion. These findings suggest that prostaglandins differentially regulate TNF-alpha and IL-1 release. Administration of cyclo-oxygenase inhibitors during radiation therapy might increase TNF-alpha release in vivo and thereby enhance the host defence against tumours.

Detection of HIV-1 DNA and infectious virus in cerebrospinal fluid.

The polymerase chain reaction (PCR) and a virus culture technique were used to detect human immunodeficiency virus type 1 (HIV-1) DNA in cerebrospinal fluid (CSF) cells and infectious virus in cell-free CSF, respectively, of 28 HIV-1 seropositive homosexual men. Provirus was detected in 24 patients of whom 15 were also culture positive. One subject was virus culture positive but not PCR positive. Two asymptomatic HIV-1 seropositive persons and one individual with persistent generalized lymphadenopathy were negative by both techniques. All of four patients with overt neurological symptoms, but also 20 of 24 patients without such symptoms were PCR positive. The data indicate that viral replication is common, and that the vast majority of HIV-1-infected individuals harbor the virus DNA in CSF, during all stages of infection.

Interferon-alpha and tumor necrosis factor-alpha in serum of patients in various stages of HIV-1 infection.

Serum samples of 120 patients in different stages of chronic human immunodeficiency virus type 1 (HIV-1) infection, 11 patients with primary HIV-1 infection (PHI), and 49 HIV-1 seronegative homosexual men were analyzed for tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), and HIV-1 p24 antigen. Increased levels of IFN-alpha and TNF-alpha were found in some, but not all, cases with PHI. During progressing disease IFN-alpha occurred in serum with increasing frequency and concentration. Raised levels of TNF-alpha were found in all stages of chronic infection, but were less common in patients with AIDS than were raised levels of IFN-alpha. The levels of the two substances were not correlated. There was a correlation between IFN-alpha, but not TNF-alpha, and the occurrence of HIV-1 p24 antigen in serum. These results suggest that IFN-alpha and TNF-alpha are induced by different agents during HIV-1 infection. The findings would be consistent with the hypothesis that IFN-alpha and TNF-alpha are counteracting forces that have important down- and upregulatory effects, respectively, on HIV-1 replication in vivo.

Rotavirus infections in young Nicaraguan children.

BACKGROUND: Rotavirus is an important cause of dehydrating diarrhea in young children throughout the world. Knowledge about frequency of reinfections, development of immunity to the virus and the possible protective effect of breast milk is important, in particular in relation to possible strategies for immunization. METHODS: A prospective study of rotavirus infections in a cohort of 235 infants followed from birth until 2 years of age was performed in León, Nicaragua. Fecal and serum specimens were collected at specified times, and stools were also obtained during episodes of diarrhea. Fecal specimens were screened by rotavirus antigen detection and serum and colostral specimens were analyzed by isotype-specific rotavirus antibody enzyme-linked immunosorbent assay. RESULTS: As judged by anti-rotavirus IgA antibody seroconversion and/or demonstration of rotavirus antigen in fecal specimens, > 50% of the babies had evidence of past rotavirus infection by the age of 2 months. The total incidence of rotavirus infections, including many reinfections, was 0.7 infection/child-year, of which only 17% were associated with diarrhea. The time from birth to the first demonstration of rotavirus in stool samples correlated significantly with the concentration of anti-rotavirus IgA antibodies in colostrum. There was also a tendency toward a relationship between long duration of breast-feeding and asymptomatic infection. CONCLUSIONS: Rotavirus infections are acquired very early in infants in León, Nicaragua, and reinfections are common. Most infections are asymptomatic. Breast milk appears to confer partial protection against rotavirus infection, probably mediated by specific IgA antibodies. To be effective rotavirus vaccination would probably have to be given at a very early age to infants in developing countries.

Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds.

Human immunodeficiency virus type 1 (HIV-1) isolates of 8 Ethiopian and 8 Swedish untreated AIDS-patients were examined for their sensitivity to 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) and leukocyte-derived interferon-alpha (IFN-alpha). No significant difference in drug sensitivity was found between Ethiopian and Swedish isolates, which all were sensitive to AZT, ddI and IFN-alpha except for one Swedish isolate. This isolate exhibited a mutation at amino acid position 215. These results suggest that it should be possible to perform clinical trials in Ethiopia using the same dose regimens as in Sweden.

PIP: Human immunodeficiency virus (HIV-1) isolates from 8 Ethiopian and 8 Swedish AIDS patients, none of them treated with antiviral drugs, were compared for sensitivity to azido-deoxy-thymidine (AZT), dideoxy-inosine (ddI) and interferon-alpha. HIV was isolated from peripheral blood mononuclear class, identified by Western blot and nucleotide sequencing, and passaged 1-3 times. Sensitivity to the 3 drugs, expressed as ED50s relative to positive controls, was determined by culturing HIV in the presence of drugs in a range of concentrations and assaying the supernatant for p24 antigen and the virus pellet for reverse transcriptase (RT). Dose-dependent anti-HIV activity for AZT was seen in the 8 Ethiopian isolates, and ED50s for p24 antigen and RT activity were correlated. 1 Ethiopian HIV isolate was sensitive to ddI, and another, to interferon-alpha. 1 Swedish HIV was resistant to AZT, and on analysis had a mutation from threonine to tyrosine at position 215. There were no significant differences between ED50s for interferon in the Swedish and Ethiopian HIVs. Combined data for each drug showed correlation between the p24 antigen and RT activities of the Ethiopian and Swedish HIVs. Since there was no resistance observed in the Ethiopian HIV to AZT or ddI, low-dose treatment would probably slow progression of HIV infection in Ethiopians, if these drugs could be made available for clinical trials.

Prevalence of antibodies to hepatitis A, B, C, and E viruses in a healthy population in Leon, Nicaragua.

A cross-sectional survey of the seroprevalence of hepatitis A virus (HAV), B (HBV), C (HCV), and E (HEV) antibodies in a healthy population in Leon, Nicaragua was conducted and associated with demographic data. The overall prevalence of antibodies to HAV was 94.6%, to HBV 6.5% and to HEV between 4.6% and 8.0%, whereas none of 399 tested subjects showed confirmed seropositivity to HCV. A high HAV seropositivity rate (72.7%) was observed even in the lowest age groups tested (2-4 years of age). In contrast, HBV and HEV seropositivity was observed mainly in adults, the seroprevalence in > 40-year-old individuals being 15.4% and 17.6%, respectively. The overall mean hepatitis B surface antigen carrier rate was estimated to be 0.9%, and in individuals more than 20 years of age, 2.0%. The prevalence of anti-HAV as well as anti-HEV was significantly higher in people having their water supply outside rather than inside the house. Furthermore anti-HAV seroprevalence correlated with lack of access to a flush toilet. Hepatitis B virus seropositivity was more frequent in people living in a crowded environment than in those living with few household members. These findings indicate that hepatitis A is a childhood infection in Nicaragua and that the spread of the infection is facilitated by poor socioeconomic conditions. In contrast, HBV infection is relatively infrequent in the country and HCV seems to be very uncommon. Hepatitis E virus infection may occur in all age groups and is apparently associated with water-borne transmission.

Respiratory syncytial virus infection in hospitalized patients and healthy children in El Salvador.

Nasopharyngeal specimens from 42 children less than one-year old hospitalized with bronchiolitis or pneumonia in El Salvador were analyzed for the presence of subgroup-specific respiratory syncytial virus (RSV) antigens by the indirect immunofluorescence technique. The antigen RSV-A was demonstrated in 28 children, RSV-B in three, and in one child subgroup, specificity could not be determined. The male:female ratio in the RSV-infected children was 1.9:1. The most severe disease, requiring intensive care, was observed in two infants with RSV-B infection. Determination of serum IgG, IgA, and IgM antibodies in acute and convalescent sera showed that none of the tests alone had sufficient sensitivity for routine diagnostic purposes, although, in combination, they provided a correct diagnosis in 86% of the RSV-infected children. A seroprevalence study of IgG, IgA, and IgM antibodies in 206 healthy children showed that a primary RSV infection is usually acquired during the first year of life in El Salvador. These results also indicated that reinfections with RSV frequently occur during the first 3-4 years of life and suggest that the occurrence of serum RSV IgA antibodies may be a marker of reinfection.

Human immunodeficiency virus infection of the brain. I. Virus isolation and detection of HIV specific antibodies in the cerebrospinal fluid of patients with varying clinical conditions.

Isolation of the human immunodeficiency virus (HIV) has been attempted from the cerebrospinal fluid (CSF) of 29 subjects with varying severity of HIV infection. Virus could be isolated from patients in all stages of disease including patients with primary HIV infection and asymptomatic carriers. In the early stages of infection free virus was infrequently present in the CSF but could be isolated from the cells present in CSF. This suggests that HIV may reach the brain at a very early stage of infection and that initially there is little production of virus from infected cells. In the late stages of HIV infection, associated with increasing severity of immunodeficiency, free virus could readily be isolated from the CSF. With one exception, all of these patients had neurological and/or psychiatric symptoms, as compared to only 2 (of 13) subjects in the early stages of infection. All patients with HIV-specific antibodies in serum had antibodies also in CSF. Examined by a radioimmunoprecipitation assay, CSF was more often found to contain antibodies to the precursor (p55) of viral core proteins than the corresponding serum of the patients. We propose that immune disturbances have an essential pathogenic role in the neurological/psychiatric symptoms associated with HIV infection, possibly through allowing increased viral expression in the central nervous system.

Cytokine release from mononuclear cells in patients irradiated for breast cancer.

Mononuclear cells from blood of 19 breast cancer patients were cultured in vitro before and following postoperative radiation treatment. Interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1) were determined in supernatants from stimulated and unstimulated cultures with or without addition of indomethacin. The release of all three cytokines was uninhibited in tumour patients. Spontaneous IL-1 secretion was increased in patients compared to controls. Indomethacin enhanced IFN-gamma release and spontaneous and induced TNF-alpha secretion in all groups but stimulated IL-1 only in irradiated patients. In patients with a low tumour burden, ability to produce cytokines seems to be unchanged although increased spontaneous IL-1 secretion indicates macrophage activation. Cyclooxygenase inhibition in conjunction with irradiation might be tried as a therapeutic modality in patients with cancer.

Monocyte release and plasma levels of interleukin-6 in patients irradiated for cancer.

Interleukin-6 (IL-6) release from purified blood monocytes was determined in patients with breast cancer or prostatic cancer before and after radiation treatment (Rx). Plasma levels of IL-6 and neopterin were also determined. Spontaneous IL-6 release in vitro was higher in breast than in prostatic cancer or in controls. Strong lipopolysaccharide (LPS)-induced cellular IL-6 release was detected in breast cancer and controls but was subnormal in prostatic cancer. Addition of indomethacin to cultures had no effect on IL-6 release. Rx generally increased levels of in vitro released IL-6 and raised LPS-stimulated IL-6 secretion in prostatic cancer to normal. Plasma levels of IL-6 were lower in breast than in prostatic cancer or controls. Rx resulted in a tendency towards raised levels in both patient groups suggestive of monocyte activation. In accordance with this, plasma levels of neopterin, which were normal before treatment, increased in prostatic cancer patients after Rx. Taken together, the results of this study indicate that monocyte release as well as plasma levels of IL-6 are affected by the malignant state as well as by radiation treatment. In view of the antiproliferative effects of IL-6, the findings may have bearing on the pathogenesis and treatment of malignant disease.

The T-cell deficiency in atopic disease and its relation to hyperproduction of IgE.

Recent studies have given ample evidence that atopy is associated with a T-cell deficiency. This deficiency appears to be primary and not merely a consequence of disease manifestations. Several studies have indicated that the T-cell defect displays a certain selectivity, resulting in imbalance between helper and suppressor T-cell in atopics. Suppressor cells, carrying Fc IgG marker (T gamma cells) or being inducible by concanavalin A, have been found to be deficient, and recent data suggest that there is an imbalance between T8+ (cytotoxic/suppressor) and T4+ (inducer/helper) T-cells in individuals with severe atopic disease. There appears to be a negative correlation between suppressor cell activity and serum IgE levels. These findings suggest that there is a causal relationship between the T-cell deficiency and hyperproduction of IgE in atopy. The immunological abnormalities in atopy cannot be easily explained by the beta-adrenergic blockade which is associated with the disease. Further immunopharmacological studies may help to elucidate the pathogenesis of atopic disease.

Viral infections in atopic dermatitis.

In a study of almost 1000 patients with past or present atopic dermatitis (AD) it was found that histories of recurrent (greater than 5 episodes/year) cold sores and upper respiratory infections, as well as histories of zoster were significantly more common in AD patients than in non-atopic controls. Serological studies revealed that AD patients have clearly elevated titers of antibodies against Epstein-Barr virus. These findings suggest that the increased susceptibility to viral infections in AD is due to immune dysfunction rather than to cutaneous alterations which are associated with the disease. The mechanisms underlying the increased susceptibility to infections may be related to immunological aberrations that are secondary to a basic abnormality in the fatty acid or cyclic AMP metabolism.