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Nonepisodic angioedema with eosinophilia (NEAE) is characterised by a single episode of angioedema localised to the extremities and peripheral eosinophilia. While NEAE can develop in response to infection or vaccination, NEAE associated with acute parvovirus B19 (B19V) infection is rare. We describe the case of a young woman with NEAE that developed during acute B19V infection. She presented with 1-week history of pruritus and polyarthralgia in the extremities, followed by the development of peripheral oedema, and was positive for anti-B19V IgM antibody. Her arthralgia improved within 2 weeks without any specific intervention; however, the oedema and pruritic erythema persisted and the peripheral eosinophil count increased. A short course of prednisolone therapy for suspected NEAE alleviated the symptoms, which have not recurred for more than 2 years. Thus, we believe that the patient was affected by NEAE and that NEAE can develop following acute B19 infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Human polyomaviruses (HPyVs) have been associated with several cutaneous inflammatory conditions. More investigation is needed to identify further presentations of cutaneous pathology associated with HPyVs. Our aim was to investigate the possible association of skin-tropic HPyVs with folliculitis, particularly eosinophilic pustular folliculitis (EPF)., Methods: This study included 55 Japanese patients, comprising 13 patients with EPF and 42 patients with suppurative folliculitis. HPyV DNAs were detected by quantitative polymerase chain reaction. Expression of viral antigen and geographically related viral genotypes were also assessed., Results: Human polyomavirus 6 (HPyV6) DNA was found in 9 of 13 (69%) patients with EPF, a rate significantly higher than that found in suppurative folliculitis (1/42; 2%). Of the 7 HPyV6 DNA-positive EPF specimens analyzed, 4 were positive for HPyV6 small tumor antigen. All the HPyV6 strains detected in this study were of the Asian/Japanese genotype., Conclusions: The predominant detection of HPyV6 DNA and the expression of viral antigen suggest a possible association between HPyV6 infection and EPF in a subset of patients. Worldwide studies are warranted to determine whether Asian/Japanese genotype HPyV6 is associated preferentially with the incidence and pathogenesis of this eosinophil-related skin disease that has an ethnic predilection for the East Asian population., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Rhinovirus C (RV-C) infection is associated with severe asthma exacerbations. Since type 2 inflammation is an important disease mechanism in asthma, we hypothesized that RV-C infection, in contrast to RV-A, preferentially stimulates type 2 inflammation, leading to exacerbated eosinophilic inflammation. To test this, we developed a mouse model of RV-C15 airways disease. RV-C15 was generated from the full-length cDNA clone and grown in HeLa-E8 cells expressing human CDHR3. BALB/c mice were inoculated intranasally with 5 x 10 6 ePFU RV-C15, RV-A1B or sham. Mice inoculated with RV-C15 showed lung viral titers of 1 x 10 5 TCID 50 units 24 h after infection, with levels declining thereafter. IFN-α, β, γ and λ2 mRNAs peaked 24-72 hrs post-infection. Immunofluorescence verified colocalization of RV-C15, CDHR3 and acetyl-α-tubulin in mouse ciliated airway epithelial cells. Compared to RV-A1B, mice infected with RV-C15 demonstrated higher bronchoalveolar eosinophils, mRNA expression of IL-5, IL-13, IL-25, Muc5ac and Gob5/Clca, protein production of IL-5, IL-13, IL-25, IL-33 and TSLP, and expansion of type 2 innate lymphoid cells. Analogous results were found in mice treated with house dust mite before infection, including increased airway responsiveness. In contrast to Rora fl/fl littermates, RV-C-infected Rora fl/fl Il7r cre mice deficient in ILC2s failed to show eosinophilic inflammation or mRNA expression of IL-13, Muc5ac and Muc5b. We conclude that, compared to RV-A1B, RV-C15 infection induces ILC2-dependent type 2 airway inflammation, providing insight into the mechanism of RV-C-induced asthma exacerbations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rajput, Han, Ishikawa, Lei, Goldsmith, Jazaeri, Stroupe, Bentley and Hershenson.)

Abstract: Patients with eosinophilic pustular folliculitis (EPF), a sterile eosinophilic infiltration of hair follicles, often present with papulopustules that tend to form annular plaques. Histopathologic examination revealed eosinophilic infiltration around the pilosebaceous units and eosinophilic microabscess formation. Although the pathogenesis of EPF is unknown, T-helper type 2 immune responses were suggested to be important based on their stimulating effect on the sebaceous glands. Here, we report the first case of EPF associated with herpes zoster, indicating that herpes zoster and EPF are correlated with T-helper type 2 immune responses., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Good's syndrome is a primary immunodeficiency phenocopy characterized for thymoma and immunodeficiency. The most frequent clinical presentation is recurrent or opportunistic infections, hematological alterations, and chronic diarrhea. We treated a 66-year-old man who consulted for 5 days of headache and diplopia with right sixth cranial nerve palsy at examination. Patient reported chronic diarrhea and prolonged febrile syndrome accompanied by weight loss of 23 kg in the last year. Exhaustive evaluation revealed Herpes simplex virus (HSV) type 2 meningitis, eosinophilic colitis, and type A thymoma. Severe antibody deficiency (hypogammaglobulinemia) associated with thymoma confirmed the diagnosis of Good's syndrome.

Asthma exacerbations are often caused by rhinovirus (RV). We and others have shown that Toll-like receptor 2 (TLR2), a membrane surface receptor that recognizes bacterial lipopeptides and lipoteichoic acid, is required and sufficient for RV-induced proinflammatory responses in vitro and in vivo. We hypothesized that viral protein-4 (VP4), an internal capsid protein that is myristoylated upon viral replication and externalized upon viral binding, is a ligand for TLR2. Recombinant VP4 and myristoylated VP4 (MyrVP4) were purified by Ni-affinity chromatography. MyrVP4 was also purified from RV-A1B-infected HeLa cells by urea solubilization and anti-VP4 affinity chromatography. Finally, synthetic MyrVP4 was produced by chemical peptide synthesis. MyrVP4-TLR2 interactions were assessed by confocal fluorescence microscopy, fluorescence resonance energy transfer (FRET), and monitoring VP4-induced cytokine mRNA expression in the presence of anti-TLR2 and anti-VP4. MyrVP4 and TLR2 colocalized in TLR2-expressing HEK-293 cells, mouse bone marrow-derived macrophages, human bronchoalveolar macrophages, and human airway epithelial cells. Colocalization was absent in TLR2-null HEK-293 cells and blocked by anti-TLR2 and anti-VP4. Cy3-labeled MyrVP4 and Cy5-labeled anti-TLR2 showed an average fractional FRET efficiency of 0.24 ± 0.05, and Cy5-labeled anti-TLR2 increased and unlabeled MyrVP4 decreased FRET efficiency. MyrVP4-induced chemokine mRNA expression was higher than that elicited by VP4 alone and was attenuated by anti-TLR2 and anti-VP4. Cytokine expression was similarly increased by MyrVP4 purified from RV-infected HeLa cells and synthetic MyrVP4. We conclude that, during RV infection, MyrVP4 and TLR2 interact to generate a proinflammatory response.

Background: As the expression of type III IFN receptor is restricted to the mucosal surfaces, its evaluation could be crucial to characterize the role of IFNλs during bronchiolitis., Objectives: This study was designed to investigate airway type III IFN receptor (IFNLR1/IL10RB) expression during respiratory syncytial virus (RSV) or human rhinovirus (HRV) bronchiolitis., Study Design: Seventy-one 1-6 month old infants hospitalized with their first episode of acute RSV or HRV bronchiolitis were selected for this study. Expression of IFNLR1, IL10RB and IFN-stimulated genes (ISGs) MxA and ISG56 in cells of nasopharyngeal washings taken within the first 48 h of admission were determined by a real-time hydrolysis probe RT-PCR assay. The ability of types I and III IFNs to induce the expression of both IFNLR1 and IL10RB in vitro was also evaluated., Results: Airway IFNLR1 transcript levels were significantly higher in HRV bronchiolitis infants compared to those with RSV bronchiolitis. No differences were recorded for IL10RB-mRNA between RSV or HRV infection. IFNLR1 mRNA levels increased significantly in infants infected with the C species of HRV and in those with a higher clinical score index and with an eosinophil count >3%. There were no correlations in vivo between type III IFN receptors and those of ISGs and neither IFNLR1 nor IL10RB were induced in vitro by IFNs., Conclusions: These results suggest that IFNLR1 are increased in HRV-infected infants with more severe bronchiolitis and blood eosinophilia and in those infected with the HRVC species., (Copyright © 2018. Published by Elsevier B.V.)

Background: In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown., Objective: To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation., Methods: Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection., Results: Sputum eosinophils and FeNO were similar between virus-positive (n = 44) and negative patients (n = 44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p = 0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p = 0.01) and higher FEV1 (p = 0.03). In virus-positive patients, %-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p = 0.02 and p = 0.05, respectively)., Conclusion: Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Respiratory syncytial virus (RSV) is an important human pathogen. Expression of virus structural proteins produces self-assembled virus-like nanoparticles (VLP). We investigated immune phenotypes after RSV challenge of immunized mice with VLP containing RSV F and G glycoproteins mixed with F-DNA (FdFG VLP). In contrast to formalin-inactivated RSV (FI-RSV) causing vaccination-associated eosinophilia, FdFG VLP immunization induced low bronchoalveolar cellularity, higher ratios of CD11c(+) versus CD11b(+) phenotypic cells and CD8(+) T versus CD4(+) T cells secreting interferon (IFN)-γ, T helper type-1 immune responses, and no sign of eosinophilia upon RSV challenge. Furthermore, RSV neutralizing activity, lung viral clearance, and histology results suggest that FdFG VLP can be comparable to live RSV in conferring protection against RSV and in preventing RSV disease. This study provides evidence that a combination of recombinant RSV VLP and plasmid DNA may have a potential anti-RSV prophylactic vaccine inducing balanced innate and adaptive immune responses., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To determine the prevalence of eosinophilia among antiretroviral therapy (ART)-naïve patients infected with human immunodeficiency virus (HIV) and to identify variables associated with eosinophilia., Methods: We included all ART-naïve HIV-infected patients entering into care at the Thomas Street Health Center (Houston, Texas) between February 2007 and January 2009. Eosinophilia was defined as absolute eosinophil count ≥ 400 cells per cubic millimeter. Patients with eosinophilia (cases) at baseline were matched to patients without baseline eosinophilia (controls). Clinical and laboratory data were collected for cases and controls. Variables associated with eosinophilia were evaluated by univariate and multivariate analyses., Results: Sixty-five (9.7%) of 671 ART-naïve patients had eosinophilia. There was no difference in age, sex, race, or baseline CD4 count between patients with and without eosinophilia; however, patients with eosinophilia were more likely to have higher HIV RNA viral loads (5.05 vs 4.82 log10 copies per milliliter; P = 0.019). A total of 52 (80%) of 65 patients with eosinophilia (cases) had at least two follow-up clinic visits. They were matched to 104 controls. Skin rash was the only variable associated with eosinophilia (odds ratio 2.16, 95% confidence interval 1.04-4.47) in our multivariate analysis. Of eight cases tested, only one, from Central America, had a parasitic infection (hookworm). Thirty-eight (73.1%) patients experienced resolution of their eosinophilia by the end of the study (mean follow-up 1019 days). Resolution of eosinophilia did not differ between patients with and without HIV viral suppression., Conclusions: Eosinophilia is not an infrequent occurrence among ART-naïve HIV-infected patients. Patients with eosinophilia are more likely than patients without eosinophilia to present with a skin rash. HIV RNA viral suppression did not necessarily result in the resolution of eosinophilia. Extensive workup for eosinophilia may not be necessary in most cases.

Eosinophilic dysplasia of the cervix is recently described unusual and somewhat obscure dysplastic lesion of squamous epithelium. We present histological features of a lesion in 41 years old woman. It was composed of cells with brightly eosinophilic cytoplasm contoured by a sharp and slightly broader cytoplasmic membrane, lacking maturation, with mild increase in nuclear-cytoplasmic ratio, slight chromatin clumping and uneven mild nuclear clearing. Electronmicroscopic study showed mild crevices of the nuclear membrane in some dysplastic cells. Tissue in situ hybridization study confirmed the presence of HPV 6 in the form of patchy dotted pattern of integrated type. Immunohistochemistry revealed diffuse positive expression of antigen p16, extraordinarily in this case focally sparing basal part of the epithelium. Underestimation of this lesion can be avoided by paying attention to strong eosinophilia of the cytoplasm and sharp cellular contouring of the examined epithelium in routine hematoxylin-eosin staining.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity syndrome that presents with diffuse cutaneous eruptions, fever, and multiorgan involvement. Here we present a pediatric case of DRESS complicated by human herpesvirus (HHV)-6 reactivation. After 1 week of sulfasalazine, our patient developed a diffuse morbilliform eruption. Sulfasalazine was discontinued. The patient presented to the emergency department soon thereafter with worsening eruption, fever, rigors, facial edema, and lymphadenopathy. Methylprednisolone was initiated. Peripheral smear did not demonstrate eosinophilia but showed toxic granulation with atypical lymphocytes. Transaminase levels and white blood cell count quickly became elevated, with increased eosinophils, suggesting DRESS. During the methylprednisolone taper, our patient experienced symptom exacerbation, acute hepatitis, and HHV-6 seroconversion, indicating HHV-6 reactivation as the cause. As demonstrated by our patient, a decelerated methylprednisone taper is important because of potential symptom flaring during taper. Additionally, in the care of individuals with DRESS, HHV-6 is often tested for upon admission and not repeated. Delay in the rise of titers necessitates repeat testing., (© 2013 Wiley Periodicals, Inc.)

Wells' syndrome, otherwise known as eosinophilic cellulitis, is a rare dermatosis seen more commonly in adults than in children. In this article, we present a 5-year-old Caucasian boy who initially presented with pruritic, erythematous macules and papules evolving to bullae formation. Subsequent histology confirmed diagnosis of Wells' syndrome, and additional blood work also demonstrated positive immunoglobulin (Ig)M and IgG for parvovirus. In many instances, the direct etiology of Wells' syndrome is unclear, but the link between parvoviral infection and development of Wells' syndrome could further support an additional cause., (© 2011 Wiley Periodicals, Inc.)

The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (drug-induced hypersensitivity syndrome), presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.

This study was conducted to determine the relationship between eosinophilia and parasitic infection in HIV-infected individuals. HIV-positive patients attending an HIV clinic in Birmingham were recruited and classified as either eosinophilic (>400 eosinophils/mm(3)) or non-eosinophilic. A demographic and parasitic risk history was taken and clinical examination was performed. Urine and stool were examined for parasites, and blood samples taken for parasite serology. A total of 266 patients (96 eosinophilic and 170 non-eosinophilic) were recruited. Of 64 eosinophilic patients who had a stool examination, one (1.6%) was positive for both Strongyloides larvae and schistosomal eggs. Urine microscopy was negative in the 245 patients (88 eosinophilic, 157 non-eosinophilic) from whom a sample was available. Two hundred and sixty-three patients underwent serological investigation (96 eosinophilic and 167 non-eosinophilic): 13 (4.9%) were positive for schistosomiasis and three (1.1%) positive for Strongyloides. A significant association between eosinophilia and positive schistosomal serology was found (P = 0.003): 11 (10.5%) were eosinophilic patients, while only four (2.3%) were non-eosinophilic patients. Eosinophilia was associated with a low nadir CD4 count (P = 0.021) and prior AIDS-defining illness (P = 0.041). In all, 7.8% of patients from a developing country and 5.3% of patients from a developed country with a travel history had positive parasitic serology. Eosinophilia in HIV-infected patients was significantly associated with positive serology for schistosomiasis, low nadir CD4 count and prior AIDS-defining illness. Geographical exposure is also an important determinant of positive parasitic serology.

Background: Among the papular-pruriginous dermatoses related to human immunodeficiency (HIV) infection, two entities remain poorly differentiated leading to confusion in their diagnosis: HIV-related pruritic papular eruption (HIV-PPE or prurigo) and eosinophilic folliculitis (HIV-EF)., Objective: To establish histopathological and immunohistochemical parameters to differentiate between two conditions associated with HIV infection, the pruritic papular eruption (HIV-PPE) and eosinophilic folliculitis (HIV-EF)., Methods: Clinically typical HIV-PPE (18 cases) and HIV-EF (10 cases) cases were compared with each other in terms of the following topics: clinical and laboratory features (gender, age, CD4+ cell and eosinophil count), histopathological features (hematoxylin-eosin and toluidine blue staining) and immunohistochemical features (anti-CD1a, anti-CD4, anti-CD7, anti-CD8, anti-CD15, anti-CD20, anti-CD30, anti-CD68/macrophage and anti-S-100 reactions)., Results: Among the HIV-EF patients, we found an intense perivascular and diffuse inflammatory infiltration compared with those patients with HIV-PPE. The tissue mast cell count by toluidine staining was higher in the HIV-EF patients, who also presented higher expression levels of CD15 (for eosinophils), CD4 (T helper), and CD7 (pan-T lymphocytes) than the HIV-PPE patients., Limitations: Only quantitative differences and not qualitative differences were found., Conclusions: These data indicate that HIV-related PPE and EF could possibly be differentiated by histopathological and immunohistochemical findings in addition to clinical characteristics. In fact, these two inflammatory manifestations could be within the spectrum of the same disease because only quantitative, and not qualitative, differences were found., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

We present a case of a 46-year-old Japanese woman with an eosinophilic ulcer of the oral mucosa (EUOM), located in the buccal mucosa, who was found by various examinations to be a human T-cell leukemia virus type I (HTLV-1) carrier with peripheral eosinophilia. Her peripheral eosinophilia and EUOM promptly improved in response to oral corticosteroid therapy. EUOM has been described to be possibly associated with trauma, but its etiology has not been fully elucidated to date. In the present case, the presence of peripheral eosinophilia in addition to the EUOM indicated possible influence of certain immune system abnormalities associated with HTLV-1 infection., (Crown Copyright © 2012. Published by Mosby, Inc. All rights reserved.)

Background: IL-33 through its receptor ST2 protects the heart from myocardial infarct and hypertrophy in animal models but, paradoxically, increases autoimmune disease. In this study, we examined the effect of IL-33 or ST2 administration on autoimmune heart disease., Methods and Results: We used pressure-volume relationships and isoproterenol challenge to assess the effect of recombinant (r) IL-33 or rST2 (eg, soluble ST2) administration on the development of autoimmune coxsackievirus B3 myocarditis and dilated cardiomyopathy in male BALB/c mice. The rIL-33 treatment significantly increased acute perimyocarditis (P=0.006) and eosinophilia (P=1.3×10(-5)), impaired cardiac function (maximum ventricular power, P=0.0002), and increased ventricular dilation (end-diastolic volume, P=0.01). The rST2 treatment prevented eosinophilia and improved heart function compared with rIL-33 treatment (ejection fraction, P=0.009). Neither treatment altered viral replication. The rIL-33 treatment increased IL-4, IL-33, IL-1β, and IL-6 levels in the heart during acute myocarditis. To determine whether IL-33 altered cardiac function on its own, we administered rIL-33 to undiseased mice and found that rIL-33 induced eosinophilic pericarditis and adversely affected heart function. We used cytokine knockout mice to determine that this effect was due to IL-33-mediated signaling but not to IL-1β or IL-6., Conclusions: We show for the first time to our knowledge that IL-33 induces eosinophilic pericarditis, whereas soluble ST2 prevents eosinophilia and improves systolic function, and that IL-33 independently adversely affects heart function through the IL-33 receptor.

Mouse models of allergic asthma are characterized by airway hyperreactivity (AHR), Th2-driven eosinophilic airway inflammation, high allergen-specific IgE (anti-OVA IgE) levels in serum, and airway remodeling. Because asthma susceptibility has a strong genetic component, we aimed to identify new asthma susceptibility genes in the mouse by analyzing the asthma phenotypes of the Leishmania major resistant (lmr) recombinant congenic (RC) strains. The lmr RC strains are derived from C57BL/6 and BALB/c intercrosses and carry congenic loci on chromosome 17 (lmr1) and 9 (lmr2) in both backgrounds. Whereas the lmr2 locus on chromosome 9 contributes to a small background-specific effect on anti-OVA IgE and AHR, the lmr1 locus on chromosome 17 mediates a strong effect on Th2-driven eosinophilic airway inflammation and background-specific effects on anti-OVA IgE and AHR. The lmr1 locus contains almost 600 polymorphic genes. To narrow down this number of candidate genes, we performed genome-wide transcriptional profiling on lung tissue from C.lmr1 RC mice and BALB/c control mice. We identified a small number of differentially expressed genes located within the congenic fragment, including a number of Mhc genes, polymorphic between BALB/c and C57Bl/6. The analysis of asthma phenotypes in the C.B10-H2b RC strain, carrying the C57Bl/6 haplotype of the Mhc locus in a BALB/c genetic background, reveals a strikingly similar asthma phenotype compared with C.lmr1, indicating that the differentially expressed genes located within the C.B10-H2b congenic fragment are the most likely candidate genes to contribute to the reduced asthma phenotypes associated with the C57Bl/6 allele of lmr1.

Eosinophilic ulcer of the oral mucosa is a benign lesion of unclear pathogenesis mostly affecting the tongue. It has been suggested to represent a reactive pattern to several stimuli. We report on a 12-year-old boy who presented with a painless infiltrating ulcer on the gingiva of the lower jaw, which was covered by necrotic yellowish slough. There were no pathologic features of the jawbones or regional lymph nodes. Histopathological, immunohistochemical and gene rearrangement studies were in agreement with eosinophilic ulcer with predominant oligoclonal CD3+ and CD30+ T lymphocytes expressing the Epstein-Barr virus membrane protein. The ulcer resolved within 4 weeks and follow-up for 3 years revealed no evidence of recurrence. Epstein-Barr virus may have played a role in triggering this reactive lymphoproliferative disorder., (Copyright © 2011 S. Karger AG, Basel.)

With the advent of highly sensitive and specific screening of respiratory specimens for viruses, new viruses are discovered, adding to the growing list of those associated with wheezing illness and asthma exacerbations. It is not known whether early childhood infections with these viruses cause asthma, and, if so, what exactly are the pathophysiologic mechanisms behind its development. The current consensus is that respiratory viral infection works together with allergy to produce the immune and physiologic conditions necessary for asthma diasthesis. One link between viruses and asthma may be the eosinophil, a cell that plays a prominent role in asthma and allergy, but can also be found in the body in response to viral infection. In turn, the eosinophil and its associated products may be novel therapeutic targets, or at the very least, used to elucidate the complex pathophysiologic pathways of asthma and other respiratory illnesses. Together or separately, they can be used for diagnosis, treatment and monitoring. Not only symptoms, but also the underlying disease mechanisms must be taken into consideration for the optimal care of a patient., (Copyright © 2010 S. Karger AG, Basel.)

Background: A 19-year-old white woman presented with a 6-month history of progressively worsening dysphagia., Investigations: Esophagogastroduodenoscopy, esophageal biopsies followed by histological evaluation of biopsy samples including immunohistochemical staining for herpes simplex virus., Diagnosis: Herpes esophagitis with concurrent eosinophilic esophagitis., Management: Valaciclovir and fluconazole.

The present study was conducted to determine whether lactate dehydrogenase-elevating virus (LDV) infection at the sensitization and challenge phases affect the development of delayed allergic eosinophilic rhinitis induced by ovalbumin (OVA) in BALB/c mice (DAR group). Compared to the DAR group, LDV infection at the priming (DAR/LDVs group) and immunizing (DAR/LDVc group) phases reduced the induction of eosinophils in the bone marrow (BM) and/or blood. However, the number of eosinophils in the BM was not affected in the DAR/LDVc group. In addition, total blood IgE values were reduced in the DAR/LDVs but not the DAR/LDVc groups. Compared to the production of cytokines from splenic cells and blood IgE values in the DAR group, OVA-specific IL-4 and IFN-gamma productions and IgE values were reduced in the DAR/LDVs, whereas OVA-specific IFN-gamma and IL-4 productions were increased and decreased, respectively in the DAR/LDVc,but not the DAR/LDVs groups. Both DAR/LDVs and DAR/LDVc groups reduced the development of eosinophilic rhinitis associated with reduced VCAM-1 expression on endothelium in blood vessels and ICAM-1 expression on nasal respiratory epithelium at inflamed areas. The present study suggests that LDV infection at the sensitization phase may reduce the development of T helper (Th) 1 and Th2 responses, whereas LDV infection at the challenge phase may inhibit the development of Th2 response by shifting to Th1 response. These may be responsible for the reduction of the development of DAR by LDV infection.

A 3-year-old boy developed transient protein-losing gastroenteropathy associated with cytomegalovirus (CMV) infection. Both IgG and IgM antibodies to CMV were positive in a serologic blood test. Upper gastrointestinal endoscopy showed multiple erosions throughout the body of the stomach, without enlarged gastric folds. Histological examination of the biopsy specimens indicated eosinophilic gastroenteritis and CMV infection. The patient had complete resolution without specific therapy for CMV in four weeks. An allergic reaction as well as CMV infection played important roles in the pathogenesis of this case.

The presence of asymptomatic eosinophilia in HIV patients has been demonstrated to have a wide variety of causes. Untreated parasitic infections in immunocompromised individuals can have potentially serious consequences. The utility of screening for parasitic infections in immigrant HIV-positive Africans with eosinophilia was investigated in a UK-based HIV clinic. HIV-positive African patients with eosinophilia were matched with HIV-positive African controls without eosinophilia. More than half of African HIV patients with eosinophilia had positive parasitic serology, and were significantly more likely to have positive serology compared with African HIV patients without eosinophilia. This study shows that asymptomatic eosinophilia in HIV-1-infected Africans is strongly suggestive of underlying parasitic infection. Individuals with eosinophilia should thus be screened for parasitic infections according to the infections prevalent in the countries they have lived in or visited for substantial periods of time.

Although eosinophilia in wheezing infants predicts subsequent wheezing, it is not known how long the association persists. Our aim was to evaluate the connection between blood eosinophilia in infancy and later wheezing/asthma until adulthood, with special attention paid to infection-induced changes in blood eosinophils. We have prospectively followed up 83 infants until adulthood after hospitalization for bronchiolitis in 1981-1982. Blood eosinophils were determined in a counting chamber on admission and on convalescence 4-6 weeks later. Data on recurrent wheezing and asthma were registered prospectively at five follow-ups until the age of 18-20 years. The median (25th-75th percentile) eosinophil count was 0.100 x 10E9/L (0.028-0.321) on admission and 0.231 x 10E9/L (0.119-0.368) on convalescence. Eosinophils during bronchiolitis or infection-induced changes in eosinophils were not associated with subsequent wheezing/asthma at any age during the follow-up. The result was similar in univariate and multivariate analyses. Respiratory syncytial virus (RSV) bronchiolitis patients had lower eosinophils on admission than non-RSV cases, but the changes induced by RSV or other infection did not differ significantly. In univariate analyses, elevated eosinophils on convalescence predicted later wheezing until 3-4 years of age. In multivariate analysis, adjusted for RSV etiology, age on admission, and histories of earlier wheezing and atopy, elevated eosinophils on convalescence predicted increased asthma risk at 2-3 years (OR, 2.26; 95% CI, 1.29-3.95), at 3-4 years (OR, 2.24; 95% CI, 1.27-3.95), and at 8.5-10 years (OR, 2.16; 95% CI, 1.01-4.64). Eosinophilia outside, but not during, infection predicted recurrent wheezing until preschool and early school years but not thereafter.

A relationship between viral infections and the simultaneous or subsequent development of allergic inflammation has often been observed in various clinical situations. Recent studies suggest an intimate relationship between reactivations of herpesviruses including human herpesvirus 6 (HHV-6) and the development of a severe systemic hypersensitivity reaction referred to as drug-induced hypersensitivity syndrome (DIHS). This syndrome has several important clinical features that cannot be solely explained by drug antigen-driven oligoclonal expansion of T cells: they include paradoxical worsening of clinical symptoms after discontinuation of the causative drug. In view of the similarity to GVHD or immune reconstitution syndrome (IRS) in clinical manifestations and emergence of viral infections, the clinical symptoms observed during the course of DIHS and GVHD are likely to be mediated by antiviral T cells that can cross-react with the drug and alloantigens, respectively. In considering common intrinsic properties of the causative drugs to potentially induce immunosuppression, reconstitution of a valid immune response to these viruses, which is typically observed in IRS, may be the most crucial process that takes place after withdrawal of the causative drug in patients with DIHS. Thus, this syndrome should be regarded as a reaction induced by a complex interplay among several herpesviruses (EB virus, HHV-6, HHV-7, and cytomegalovirus), antiviral immune responses, and drug-specific immune responses. This review includes discussion of the pathomechanism, the clinical symptoms, laboratory findings, pathological findings and therapy.

Respiratory syncytial virus (RSV) infection in early life is suspected to play a role in the development of post-bronchiolitis wheezing and asthma. Reinfection is common at all ages, but factors that determine the development of altered airway function after reinfection are not well understood. This study was conducted in a mouse model to define the role of age in determining the consequences on airway function after reinfection. Mice were infected shortly after birth or at weaning and were reinfected 5 wk later, followed by assessment of airway function, airway inflammation, and lung histopathology. Infection of mice at weaning elicited a protective airway response upon reinfection. In this age group, reinfection resulted in increased airway inflammation, but without development of airway hyperresponsiveness (AHR) or eosinophilia and decreased IL-13 levels. By contrast, neonatal infection failed to protect the airways and resulted in enhanced AHR after reinfection. This secondary response was associated with the development of airway eosinophilia, increased IL-13 levels, and mucus hyperproduction. Both CD4- and CD8-positive T cells were a source of IL-13 in the lung, and inhibition of IL-13 abolished AHR and mucus production in these mice. Inoculation of UV-inactivated virus failed to elicit these divergent responses to reinfection, emphasizing the requirement for active lung infection during initial exposure. Thus, neonatal RSV infection predisposes to the development of airway eosinophilia and enhanced AHR via an IL-13-dependent mechanism during reinfection, whereas infection at a later age protects against the development of these altered airway responses after reinfection.

The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

Interleukin-10-deficient mice develop a robust pulmonary inflammatory response but no airway hyperresponsiveness (AHR) to inhaled methacholine (MCh) following allergen sensitization and challenge. In the present study, we investigated the effect of respiratory syncytial virus (RSV) infection on AHR and pulmonary inflammation in allergic IL-10-/- mice. Unlike littermate control mice, RSV-infected or ovalbumin (OVA)-sensitized/challenged IL-10-/- mice failed to develop significant AHR. In contrast, sensitized/challenged IL-10-/- mice infected with RSV did develop AHR accompanied by increased eosinophil numbers, both in bronchoalveolar lavage (BAL) and pulmonary tissue, and mucin production in airway epithelium. The cytokine profile in OVA-sensitized/challenged IL-10-/- mice was skewed toward a Th1 response but after RSV infection, this response was more of a Th2 type, with increased IL-5 levels in the BAL. Studies with an RSV mutant that lacks the G and SH genes showed equal enhancement of the AHR response as the parental wild-type strain, indicating that G protein is not essential to this response. These data suggest that RSV infection can overcome the failure of development of AHR in allergic IL-10-/- mice.

Despite advances in the therapy of chronic hepatitis C for some hepatitis C virus (HCV) genotypes interferon and ribavirin combination therapy is effective in less than 50% of patients. Abnobaviscum Quercus (AQ) is a mistletoe preparation containing defined amounts of mistletoe lectins (ML). It has shown immunomodulatory properties in vitro and in vivo. In small clinical trials AQ resulted, within an anthroposophical treatment concept, in a biochemical or virological response in up to 40% of patients with chronic hepatitis C. In order to evaluate the effect of this preparation we conducted an individually controlled cohort study. 25 patients with chronic hepatitis C (mean duration 147 +/- 80 months) and elevated alanine aminotransferase (ALT) levels were included in the study. As control they were observed for 6 months pre-treatment. This pre-treatment period was followed by 6 months of active treatment in which the mistletoe preparation was subcutaneously injected three times a week. Main outcome parameters were normalization of ALT and viral load. Hepatitis C associated signs and symptoms like tiredness, fullness in the right upper abdomen and musculoskeletal pain were assessed monthly in a standardized questionnaire. All 25 patients completed the study and most of the patients wanted to continue treatment. Mean duration of treatment was 9.1 months. None of the patients had complete or partial normalization of ALT or HCV RNA levels during pre-treatment or treatment period. Mean ALT did not change during the study. Tiredness, fullness in the right upper abdomen and musculoskeletal pain were present in 18, 8 and 4 patients respectively. They significantly improved within two months of treatment. A significant eosinophilia (p=0.0001) occurred between month 2 and 6 during treatment. 9 month treatment with a ML containing mistletoe preparation has no effect on viral load or ALT as markers of activity in patients with chronic hepatitis C. However, frequency and intensity of clinical signs and symptoms in our patients decreased significantly, similar to reports of improved quality of life in tumour patients treated with such preparations. A significant eosinophilia suggests that ML containing mistletoe preparations induce a T-helper 2 immune response.

An apathogenic strain of duck enteritis virus was injected into the allantoic cavity of duck embryos at 17 or 18 days of incubation. Four to 6 days later, the embryos showed massive infiltration of eosinophilic granulocytes in the spleen. Peroxidase and immunohistochemical labelling showed that the granulocytes were peroxidase-positive and contained major basic protein, and were most likely eosinophils. UltraIstructural examination of the eosinophils demonstrated granules of various sizes and shapes, and granules within the granules. Electron microscopy also showed that splenic macrophages were capable of phagocytosis, indicating that duck embryos, even at 23-24 days of incubation, were capable of responding to infection.

Background: There is a current debate regarding the association of human herpesvirus 6 (HHV-6) infection and drug reaction with eosinophilia and systemic symptoms (DRESS)., Methods: Seven consecutive patients hospitalized with DRESS were enrolled in a prospective study to evaluate evidence of active HHV-6 infection., Observations: The imputable drugs were carbamazepine (5 patients), ibuprofen (1 patient), and sulfasalazine (1 patient). All patients were seropositive for anti-HHV-6 IgG antibodies. Anti-HHV-6 IgM antibodies were detected in 4 of the 7 patients with a seroconversion in 2 patients. Neither anti-cytomegalovirus nor anti-Epstein-Barr virus early antigen IgM antibody was detected. Human herpesvirus 6 genome was not detected by polymerase chain reaction in the first serum sample of all patients. It was weakly detected in skin lesions in the last patient tested by polymerase chain reaction but was not found in uninvolved skin., Conclusions: The results suggest an association between HHV-6 active infection (primo-infection or reactivation) and severe DRESS. Absence of anti-cytomegalovirus or anti-Epstein-Barr virus early antigen IgM antibodies argues against a nonspecific viral reactivation. Human herpesvirus 6 infection may play a role in the development of DRESS in susceptible patients. Some drugs with reactive metabolites could favor reactivation and propagation of HHV-6.

The effect of infection history is ignored in most animal models of infectious disease. The attachment protein of respiratory syncytial virus (RSV) induces T helper cell type 2-driven pulmonary eosinophilia in mice similar to that seen in the failed infant vaccinations in the 1960s. We show that previous influenza virus infection of mice: (a) protects against weight loss, illness, and lung eosinophilia; (b) attenuates recruitment of inflammatory cells; and (c) reduces cytokine secretion caused by RSV attachment protein without affecting RSV clearance. This protective effect can be transferred via influenza-immune splenocytes to naive mice and is long lived. Previous immunity to lung infection clearly plays an important and underestimated role in subsequent vaccination and infection. The data have important implications for the timing of vaccinations in certain patient groups, and may contribute to variability in disease susceptibility observed in humans.