Infections of the esophagus: an update on risk factors, diagnosis, and management.

Infectious esophagitis is a leading cause of esophagitis worldwide. While esophageal infections have traditionally been associated with immunocompromised patients, these disorders are becoming increasingly recognized in immunocompetent individuals. The three most common etiologies of infectious esophagitis are Candida, herpes simplex virus, and cytomegalovirus. Human papilloma virus infection can also involve the esophagus in the form of ulcerative lesions and papillomas. Less common etiologies include various other fungal, bacterial, and viral organisms. This review provides a comprehensive update on risk factors, diagnosis, and management of both common and less common infections of the esophagus.

[HPV infection in oral, pharyngeal and laryngeal papillomas]. / HPV-Infektion in oralen, pharyngealen und laryngealen Papillomen.

BACKGROUND: HPV infections play a major role in the pathogenesis of squamous cell carcinomas of the head and neck. Regarding benign papillomas, the role of HPV is still uncertain. MATERIALS AND METHODS: To clarify this issue, 100 exophytic papillomas of the oral cavity, pharynx and larynx were subjected to histopathological and molecular pathological examination. Excision biopsies were taken from 62 male and 38 female patients with an age range of 18 to 87 years. Biopsies were tested for p16 expression by immunohistochemistry and analyzed for HPV subtypes 6/11 (low-risk), 16/18 and 31/33/53 (high-risk) by chromogenic in situ hybridization. RESULTS: HPV infections were verified molecularly in 34 % of biopsies; in all cases with the low-risk HPV subtypes 6/11. Only one case showed infection with both 6/11 and 31/33/53 subtypes, but not subtype 16/18; whereas expression of p16 was found in 67 %. The rate of positive molecular verification of HPV infection (in situ hybridization) was highest in the laryngeal lesions with 61.1 %, followed by the oral cavity with 52.9 %, and lowest in pharyngeal lesions (21.5 %). Recurrent papillomas were seen in 18 cases (18 %), of which 14 were molecularly positive for HPV (in situ hybridization). A correlation between inflammatory infiltration and HPV infection could be verified in 82 %. CONCLUSION: Our data demonstrate an important role of HPV infection for the development of benign papillomas of the head and neck region. Furthermore, there is a positive correlation between HPV infection and recurrent papillomas. Therefore, a molecular morphological HPV analysis of papillomas could provide important prognostic data.

Consideraciones prácticas de la anoscopia de alta resolución en pacientes infectados por el virus de la inmunodeficiencia humana / Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus

El cáncer de ano, una enfermedad infrecuente en la población general, presenta una incidencia elevada y progresiva en ciertos grupos de riesgo, fundamentalmente en hombres que tienen sexo con hombres, y particularmente en aquellos con infección por el virus de la inmunodeficiencia humana. La anoscopia de alta resolución se considera actualmente la técnica estándar en el diagnóstico de la neoplasia intraepitelial anal, pero su uso protocolizado aún está por consensuar en los sistemas sanitarios. Aunque no está exenta de dificultades, es una técnica asequible que puede llegar a ser fundamental en el cribado del cáncer de ano y sus lesiones precursoras. Actualmente estamos estudiando la estrategia más efectiva para el manejo de las lesiones premalignas anales, y con esta publicación intentamos animar a otros grupos interesados en la reducción de una neoplasia epidemiológicamente en progresión

Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia

[Laryngeal papillomatosis: problem update].

The objective of the present overview was to analyse the available data on etiology, pathogenesis, diagnostics, and treatment of laryngeal papillomatosis. It is shown that the pathogenetic mechanism underlying the development of this pathology is related to cell proliferation mechanisms. The human papilloma virus is most effectively identified by the polymerase chain reaction technique in combination with in situ hybridization. It is expected that new and more informative criteria for diagnostics, treatment,and prognosis of laryngeal papillomatosis will be proposed based on recent progress in molecular biology, morphology,and immunology. Different variants of the therapeutic strategy for the treatment of laryngeal papillomatosis are described.Modern practice of the management of laryngeal papillomatosis takes advantage of the three main approaches and/or their combination. First, further improvement of surgical techniques, such as the application of endoscopic devices and surgical lasers.Second, the search for new pharmaceutical agents (indole-3-carbinol, cidofovir, antiviral medicines, etc.) most frequently used for adjuvant therapy. Third, the development of new vaccination methods. Besides these three approaches, photodynamic therapy and the use of ionizing radiation are currently being studied as the tools for the treatment of extensive and recurrent laryngeal papillomatosis as well as the methods of laser-induced interstitial thermotherapy.

Estudio comparativo de conizaciones realizadas en la provincia de Segovia antes y después del uso del test del virus del papiloma humano (2007-2010) / Comparative study of conizations performed in the province of Segovia before and after the use of the human papilloma virus test (2007-2010)

Objetivo. Este estudio pretende evaluar los cambios epidemiológicos, diagnósticos y terapéuticos en la provincia de Segovia desde la introducción de técnicas de detección de ADN del virus del papiloma humano (VPH) en el cribado de cáncer de cerviz, en mujeres mayores de 30 años en atención primaria en enero de 2009. Material y métodos. Estudio observacional, descriptivo, transversal, retrospectivo, de conizaciones realizadas desde enero de 2007 hasta diciembre de 2010. Se incluye a 86 pacientes: 40 mujeres conizadas en el período 2007-2008 y 46 en el período 2009-2010. Resultados. No se ha incrementado significativamente el número de conizaciones pero sí ha aumentado el número de lesiones de alto grado en citología (p=0,017) y en el estudio histológico posquirúrgico (p=0,047). Observamos un incremento del valor predictivo positivo (VPP) del cribado para lesiones de alto grado, aunque sin significación estadística (p=0,059). Conclusiones. El VPP del cribado de cáncer de cérvix ha aumentado en nuestra provincia con el test de VPH sin aumentar el número de conizaciones (AU)

Objective. To assess epidemiological, diagnostic and therapeutic changes in the province of Segovia since the introduction of techniques for the detection of human papillomavirus (HPV) DNA in cervical cancer screening in women aged more than 30 years in primary care in January 2009. Material and methods. We carried out an observational retrospective study of conization procedures undertaken from January 2007 to December 2010. Eighty-six patients were included: 40 women who underwent conization from 2007-2008 and 46 who underwent the procedure from 2009-2010. Results. The number of conization procedures showed no significant change but the number of high-grade lesions found in cytology (P = .017) and postsurgical histological analysis (P=.047) increased. The positive predictive value (PPV) of screening for high-grade lesions showed a nonsignificant increase (P=.059). Conclusions. The PPV of cervical cancer screening increased in our province with the HPV test, without increasing the number of conization procedures (AU)

Polar invasion and translocation of Neisseria meningitidis and Streptococcus suis in a novel human model of the blood-cerebrospinal fluid barrier.

Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.

Antimicrobial susceptibility of Treponema phagedenis-like spirochetes isolated from dairy cattle with papillomatous digital dermatitis lesions in Japan.

The minimal inhibitory concentrations (MICs) of 23 Treponema phagedenis-like spirochetes isolated from dairy cattle with papillomatous digital dermatitis (PDD) lesions in Japan were investigated by a broth microdilution method using 15 antimicrobial agents. Although all MIC values showed a monomodal distribution, the MICs of the antimicrobial agents for 90% (MIC(90)) of the isolates tested varied among the agents examined. The MIC(90) values for penicillin G, ampicillin, and erythromycin were <0.06 microg/ml. In contrast, the MIC(90) values for kanamycin, streptomycin, rifampicin, sulfamethoxazole, trimethoprim, and colistin were >128 microg/ml. Oxytetracycline, lincomycin, enrofloxacin, chloramphenicol, ceftiofur, and gentamicin showed intermediate values, i.e., 0.5~32 microg/ml. The present study suggested that no isolate had acquired resistance to the antimicrobial agents examined, although they may have natural resistance to some agents. Furthermore, the in vitro antimicrobial susceptibility data would provide helpful information for PDD treatment and the development of a selective medium for isolating the organism effectively.

Dietzia papillomatosis sp. nov., a novel actinomycete isolated from the skin of an immunocompetent patient with confluent and reticulated papillomatosis.

An actinomycete isolated from an immunocompetent patient suffering from confluent and reticulated papillomatosis was characterized using a polyphasic taxonomic approach. The organism had chemotaxonomic and morphological properties that were consistent with its assignment to the genus Dietzia and it formed a distinct phyletic line within the Dietzia 16S rRNA gene tree. It shared a 16S rRNA gene sequence similarity of 98.3% with its nearest neighbour, the type strain of Dietzia cinnamea, and could be distinguished from the type strains of all Dietzia species using a combination of phenotypic properties. It is apparent from genotypic and phenotypic data that the organism represents a novel species in the genus Dietzia. The name proposed for this taxon is Dietzia papillomatosis; the type strain is N 1280(T) (=DSM 44961(T)=NCIMB 14145(T)).

Lesion formation and antibody response induced by papillomatous digital dermatitis-associated spirochetes in a murine abscess model.

Papillomatous digital dermatitis (PDD), also known as hairy heel wart, is a growing cause of lameness of cows in the U.S. dairy industry. Farms with PDD-afflicted cows experience economic loss due to treatment costs, decreased milk production, lower reproductive efficiency, and premature culling. While the exact cause of PDD is unknown, lesion development is associated with the presence of anaerobic spirochetes. This study was undertaken to investigate the virulence and antigenic relatedness of four previously isolated Treponema phagedenis-like spirochetes (1A, 3A, 4A, and 5B) by using a mouse abscess model with subcutaneous inoculation of 10(9), 10(10), and 10(11) spirochetes. Each of the PDD isolates induced abscess formation, with strain 3A causing cutaneous ulceration. Lesion development and antibody responses were dose dependent and differed significantly from those seen with the nonpathogenic human T. phagedenis strain. Strains 3A, 4A, and 5B showed two-way cross-reactivity with each other and a one-way cross-reaction with T. phagedenis. Strain 5B showed one-way cross-reactivity with 1A. None of the isolates showed cross-reactivity with T. denticola. In addition, distinct differences in immunoglobulin G subclass elicitation occurred between the PDD strains and T. phagedenis. From these data, we conclude that spirochetes isolated from PDD lesions have differential virulence and antigenic traits in vivo. Continuing investigation of these properties is important for the elucidation of virulence mechanisms and antigenic targets for vaccine development.

Bartonella-related pseudomembranous angiomatous papillomatosis of the oral cavity associated with allogeneic bone marrow transplantation and oral graft-versus-host disease.

Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Human infections due to Bartonella spp. are viewed as emerging diseases typical in, although not exclusive to, immunosuppressed patients, in particular those with AIDS, organ transplants and haematological malignancies. We describe four patients, three children and one adult, who developed vegetating papillomatous lesions exclusively on the oral mucosae. They shared a history of haematological malignancy and allogeneic bone marrow/stem cell transplantation, and later developed chronic graft-versus-host disease, also involving the oral mucosae. Histopathologically, the vegetating lesions were characterized by a diffuse neoangiogenesis, granulation-like tissue, and a mixed cell infiltrate predominantly composed of neutrophils. Gram-negative bacteria were found in the endothelial cells of the vessels in the deeper portion of the corium by electron microscopy. In three cases, DNA of B. henselae was detected by polymerase chain reaction (PCR), and confirmed by sequencing of the PCR products. All the lesions healed after systemic antibiotic therapy, although some recurred after months, and regressed again after systemic antibiotic treatment associated with conservative surgical excision.

Confluent and reticulate papillomatosis (Gougerot-Carteaud syndrome): a minocycline-responsive dermatosis without evidence for yeast in pathogenesis. A study of 39 patients and a proposal of diagnostic criteria.

BACKGROUND: Confluent and reticulate papillomatosis (CRP) (Gougerot-Carteaud syndrome) is a disorder that has been characterized in only small cohorts of patients. OBJECTIVES: Better to characterize the clinical and pathological findings of the disorder. METHODS: We retrospectively reviewed the clinical presentation, response to treatment and histological findings of patients presenting to Mayo Clinic (Rochester, MN, U.S.A.) with CRP. RESULTS: The disorder was diagnosed in 39 patients between 1972 and 2003. Mean age at onset of the skin eruption was 15 years (range 8-32); 21 patients (54%) were male; most were white; most (33) presented for reasons of cosmesis; and eight described the rash as mildly pruritic. At presentation, the skin eruption had been present for a mean of 3.1 years (range 3 months-20 years) and had been recalcitrant to treatment, including antifungal treatment. Typical objective findings were scaling brown macules and patches and velvety papules and plaques, reticulated and papillomatous at least in part, involving the upper trunk, axillae and neck. The most frequent initial diagnostic impressions were tinea versicolor, acanthosis nigricans and CRP. Scales in 32 cases were examined with potassium hydroxide: eight (25%) showed hyphae, and 24 (75%) did not. Skin biopsy specimens from 21 patients showed variable degrees of hyperkeratosis, acanthosis and papillomatosis. Minocycline was prescribed for 22 patients, of whom 14 of 18 (78%) had complete clearing of the skin eruption and four (22%) a partial response. The skin eruptions recurred after stopping treatment in six patients. CONCLUSIONS: CRP occurs predominantly in young adults and teenagers, with cosmetically displeasing brown scaling patches and plaques affecting the neck, upper trunk and axillae. Frequently, the diagnosis is delayed and the disorder not recognized by physicians, including dermatologists. Clinically, the eruption is most often confused with tinea versicolor. Potassium hydroxide staining of the scale is negative in the majority of cases, implying that fungi are not involved in the pathogenesis of this condition, as has been previously proposed. It is important to recognize this disorder, because minocycline therapy is highly effective in most patients. Criteria for the diagnosis are proposed.

Dietzia strain X: a newly described Actinomycete isolated from confluent and reticulated papillomatosis.

Confluent and reticulated papillomatosis (CRP) is a rare skin disorder. To date its aetiology remains uncertain. The possibility of an infectious aetiology has been supported by case reports of therapeutic response to antibiotic therapy. We have isolated and identified a previously unknown Dietzia strain, an Actinomycete, from skin scrapings of a 17-year-old boy with CRP. We propose that this organism may be the aetiological agent of CRP. Further investigations are necessary to determine the potential role of this Actinomycete in the pathogenesis of CRP.

Use of interferon-alpha in recurrent respiratory papillomatosis: 20-year follow-up.

OBJECTIVES: The aim of this study was analysis of the results of use of interferon-alpha (IFN-alpha) in patients with recurrent respiratory papillomatosis (RRP) and correlation of the results with human papillomavirus (HPV) type. METHODS: A multicenter prospective series (42 patients from 22 hospitals) yielded 20 years of follow-up of patients with RRP and HPV typing who were treated with IFN-alpha in doses of 3 MU/m2 3 times per week. RESULTS: During long-term follow-up (mean +/- SD, 172 +/- 36.8 months), the rate of event-free survival evaluated by Kaplan-Meier analysis was 42.8%, and the overall survival rate was 82.6%. The HPV typing revealed an association of HPV 11 with a more aggressive disease course (64% of HPV 11 patients versus 24% of HPV 6 patients), a lower incidence of long-term response to IFN-alpha therapy (14% of HPV 11 patients versus 64% of HPV 6 patients), and a higher incidence of malignant transformation and mortality during follow-up (36% and 24%, respectively, of HPV 11 patients versus 0% of HPV 6 patients). CONCLUSIONS: The obtained results revealed maximal effectiveness of IFN-alpha therapy in RRP patients with HPV 6 as compared with HPV 11. The association of HPV 11 with a worse long-term response to IFN-alpha therapy and a higher incidence of malignant transformation and mortality is clinically important and indicates the necessity of HPV typing in RRP patients after the first biopsy.

[Laryngeal papillomatosis - first recognition in Germany as an occupational disease in an operating room nurse]. / Larynxpapillomatose - erstmalige Anerkennung als Berufskrankheit bei einer OP-Schwester.

BACKGROUND: The CO (2)-Laser is an established and well-proven tool in the excision and vaporisation of laryngeal papillomatosis. Actually there exists only one report of an iatrogenous infection with the Human Papillomavirs (HPV) in a gynecological laser surgeon. CASE REPORT: A 28-year-old gynecological operating room nurse, who assisted repeatedly in electrosurgical and lasersurgical excisions of anogenital condylomas, developed a recurrent and histologically proven laryngeal papillomatosis. The expert opinion of a virological institute confirmed a high probability of correlation between the occupational exposition and the laryngeal papillomatosis so that it was accepted as occupational disease. INFECTIVITY OF LASER PLUME: HPV-DNA has been repeatedly detected in laser-plume after excision of papillomas and condylomas. As of the present an exact proof that these particles are infectious has not been brought forward. CONCLUSION: When following the recommended protective measures the potential risk of infection is estimated as very low for surgeons and nurses. The risk of exposition seems to be higher in gynecological interventions than in ENT because of the much larger tissue masses and because laser plume escapes easier into the room air when applying an open approach.

Characterization of Treponema phagedenis-like spirochetes isolated from papillomatous digital dermatitis lesions in dairy cattle.

Four spirochete strains were isolated from papillomatous digital dermatitis (PDD) lesions in Iowa dairy cattle and compared with two previously described spirochete strains isolated from dairy cattle in California. These six strains shared an identical 16S ribosomal DNA sequence that was 98% similar to Treponema phagedenis and 99% similar to the uncultivated PDD spirochete sequence DDLK-4. The whole-cell protein profiles resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of these six strains were similar. However, these strains showed differences in the antigenic diversity of lipopolysaccharide (LPS). Genetic diversity was also detected by pulsed-field gel electrophoresis of genomic DNA digests, revealing differences among five of the six strains. Serum immunoglobulin G antibodies from dairy cattle with active PDD lesions reacted with the LPS of all but one PDD spirochete strain. Likewise, peripheral blood mononuclear cells from cattle with active PDD lesions produced blastogenic responses to one of the two California isolates. Both antibody and lymphocyte blastogenic responses were reduced in convalescent dairy cattle, suggesting the immune response to these spirochetes has short duration. These results demonstrate genetic and antigenic diversity among T. phagedenis-like treponemes and provide further evidence for the involvement of these spirochetes in the pathogenesis of PDD.

Malassezia species in skin diseases.

Since the taxonomic revision carried out in 1996, enlarging the genus Malassezia to comprise seven different species, a number of studies have investigated from different points of view -- mycological, molecular and immunological -- the relationships of these species with the pathologies associated with lipophilic yeasts, as well as its presence in healthy skin. From these studies, it now appears clear that Malassezia globosa is the main species associated with pityriasis versicolor, which is the only cutaneous disease in which the involvement of Malassezia is undisputed. Nevertheless, this species can also be found in normal skin, in which the predominant species is Malassezia sympodialis. In the remaining dermatological disorders related to Malassezia, the role of these yeasts is controversial. In seborrhoeic dermatitis, atopic dermatitis and folliculitis, several studies have focused on the immunological aspects that could explain the pathogenic mechanism. In other diseases, such as confluent and reticulate papillomatosis, neonatal pustulosis, otitis and onychomycosis, the presence or significance of Malassezia is still a matter of dispute.

Association between milk production, somatic cell count and bacterial dermatoses in three dairy cattle herds.

OBJECTIVE: To determine the correlations between three bacterial dermatoses in cattle, milk production and bulk-milk somatic cell count (BMSCC). DESIGN: Field observations in three dairy cattle herds. METHODS: Milk production, BMSCC, fertility and all herd diseases were recorded by computerised dairy management systems. Each herd was visited twice weekly and the clinical signs, course of diseases and morbidity and culling rates were noted. Bulk-tank milk was sampled twice monthly and analysed for somatic cell count. Bacteriological and histological examinations were carried out from samples collected from affected animals in the respective herds. RESULTS: The acute exudative form of dermatophilosis was diagnosed only in first-calving cows. The morbidity rate was 53% and the culling rate was 16% of the affected animals. The BMSCC increased by a factor of 2.4 times, and there was an average loss of milk production of 30%/cow/day in affected animals. Ulcerative lymphangitis was diagnosed in first-calving cows (22%) and older cows (15%). The culling rate was 28%. The BMSCC increased by a factor of 17.3 times, and the average loss of milk production was 5.5%/affected animal/day. Papillomatous digital dermatitis (PDD) was diagnosed in first-calving cows (25%) and in older cows (18%). The culling rate was 8%. The BMSCC increased by a factor of two times, and the average loss of milk production was 1.7%/affected animal/day. CONCLUSIONS: The correlations between three skin diseases (ulcerative lymphangitis, dermatophilosis, papillomatous digital dermatitis), milk production and BMSCC have been found to be unfavourable.

Efficacy of two modified nonantibiotic formulations (Victory) for treatment of papillomatous digital dermatitis in dairy cows.

A field trial was conducted to compare the efficacy of the original and two modified formulations of Victory and oxytetracycline among dairy cows affected with papillomatous digital dermatitis. Seventy-eight cows with papillomatous digital dermatitis lesions were randomly allocated to one of four treatment groups (A, B, C, D). Cows in group A (n = 19) were treated with an oxytetracycline solution; cows in group B (n = 22) were treated with the original formulation of Victory containing soluble copper, peroxide compound, and a cationic agent; cows in group C (n = 17) were treated with a modified formulation of Victory containing reduced soluble copper and peroxide compound but increased levels of cationic agent; and cows in group D (n = 20) were treated with a modified formulation of Victory containing levels of soluble copper and cationic agent equivalent to the original formulation but with reduced concentrations of peroxide compound. Cows were examined 7, 14 and 28 d after initial treatment; during each examination, pain and lesion scores were recorded. The modified nonantibiotic formulation used in cows in group C appeared to be the most effective for treatment of papillomatous digital dermatitis. Proportions of cows with signs of pain were significantly lower among cows in group C, compared with cows in group A. Similarly, pain scores were significantly lower among cows in treatment group C, compared to cows in group A. The 2 low efficacy of oxytetracycline was an unexpected result b and may have clinical implications associated with possible antibiotic resistance in dairy cows affected with papillomatous digital dermatitis.

Papillomatous pastern dermatitis with spirochetes and Pelodera strongyloides in a Tennessee Walking Horse.

Papillomatous digital dermatitis is a common disease in cattle. The pastern dermatitis observed in a horse shared many of the gross characteristics of papillomatous digital dermatitis in cattle. Lesions included a mixture of proliferative and erosive changes, with a verrucose appearance in some areas. Microscopic similarities included pseudoepitheliomatous and papillomatous epidermal hyperplasia with hyperkeratosis, spongiosis of the epidermis, and intraepidermal spirochetes. The horse was also concurrently infected with Pelodera strongyloides. Papillomatous digital dermatitis in cattle is associated with poor husbandry practices. The environment of the affected horse was heavily contaminated with urine, manure, and other organic debris. Verrucous pododermatitis of horses may be the same as or similar to bovine papillomatous digital dermatitis, and these conditions have similar etiologies.