[Topical antiseptic agents]. / Antiseptische Wirkstoffe in Topika.

Topical therapy is an important domain in the treatment of dermatological diseases in the 21st century. Because multiresistant bacteria are becoming an increasing issue in medical care of chronic diseases, it is important to develop appropriate therapeutic management for acute and chronic dermatoses. The current discussion about the skin microbiota shows the importance of preserving the resident skin flora. There is a need for alternatives to topical antibiotics, e. g. topical antiseptics, which should be safe, fast, and effective but not allergenic or toxic. Even with frequent and prolonged application it is important that they do not develop a resistance. This article focusses on the use of antiseptics for medical indications. Mechanisms of action, tolerability, maximum concentrations, and possible contraindications are discussed and examples of extemporaneous antiseptic preparations are provided.

Cutaneous manifestations of systemic viral diseases in neonates: an update.

PURPOSE OF REVIEW: Dermatologic findings may be the first signs of a neonatal viral infection. This review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus, enterovirus, and Zika virus] that present with cutaneous manifestations in the neonate. RECENT FINDINGS: HSV DNA polymerase chain reaction of plasma and cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have expanded utility in assessing prognosis and acyclovir therapeutic efficacy. Maternal antiviral suppressive therapy may alter the clinical appearance of congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella zoster immune globulin, is a US Food and Drug Administration approved form of prophylaxis for varicella. The Centers for Disease Control and Prevention has expanded the period of VariZIG eligibility for preterm infants, a group particularly susceptible to severe varicella infection. For severe neonatal enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an effective therapy. Human Parechovirus type 3, a strain within a newly formed viral genus, has a similar, and potentially underestimated, clinical presentation to enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in the neonate may present with a nonspecific macular and papular rash. As this rash is not specific, obtaining a maternal travel history and, if appropriate, requesting additional diagnostic testing are critical for early diagnosis. SUMMARY: Neonatal rashes may be harmless and transient, whereas others may reflect the presence of a severe systemic illness. Recognizing key cutaneous features of viral-associated rashes may aid in the prompt and accurate diagnosis and treatment of neonatal viral illnesses.

Bacterial and viral skin diseases.

At least two populations of microorganisms are found in skin microbiota: a resident flora and a transient flora. Colonization and invasion by pathogenous microorganisms is counteracted both by the host defenses and by the resident flora. Most skin infections are therefore self-limiting in healthy subjects and are defined as primary infections. Secondary infections develop on preexisting skin lesions and are usually polymicrobial and caused by microorganisms that in themselves have little pathogenic power. When immune defenses are low, secondary infections arise readily and develop rapidly. This article describes the main bacterial and viral skin diseases.

Topical immunomodulators for the treatment of external genital warts, cutaneous warts and molluscum contagiosum.

Topical immunomodulators (TIMs) include both immunostimulatory and immunosuppressive agents. Newer immunostimulatory compounds such as imidazoquinolines (e.g. imiquimod) act by cytokine secretion from monocytes/macrophages (interferon-alpha, interleukin-12, tumour-necrosis factor-alpha), leading to a Th1-dominance and cell-mediated immunity. This immune milieu has been clinically used to treat viral infections such as human papillomavirus (condyloma and common warts), herpes simplex virus and mollusca in immunocompetent and immunosuppressed patients.

[Fever and skin hemorrhages in children--is it meningococcal disease?]. / Feber og hudblødninger hos børn--er det meningokoksygdom?

INTRODUCTION: Our main aims were to establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes of haemorrhagic rashes accompanied by fever. MATERIALS AND METHODS: This prospective study comprised 264 infants and children hospitalised with fever and skin haemorrhages. RESULTS: We identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables discriminated meningococcal disease from other conditions on admission: skin haemorrhages of (1) characteristic appearance; (2) universal distribution and (3) a maximum diameter of > 2 mm; (4) poor general condition; and (5) nuchal rigidity. DISCUSSION: If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false-positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.

Viral skin infections: diagnosis and treatment considerations.

Skin lesions are prominent features of many viral diseases. In some instances, characteristic skin lesions suggest a specific viral illness, the diagnosis of which can be quickly established by appropriate procedures. In addition to clinical manifestations, laboratory methods including virus isolation are used to diagnose viral infections. In viral diseases, prophylaxis has proved more successful than the specific treatment of established infection. However, recent progress in molecular biology has facilitated the development of new vaccines and new drugs to treat viral infections.

Tests for detecting herpes simplex virus and varicella-zoster virus infections.

Several laboratory diagnostic methods are available for the diagnosis, differentiation, and subtyping of HSV and VZV infections. In the office or at the bedside of a hospitalized patient, a positive Tzanck smear preparation is an inexpensive, rapid, and morphologic technique for confirming a suspected diagnosis of a herpesvirus infection. An expedient, slightly more expensive, reliable technique for establishing a HSV infection, yet not able to differentiate the subtype of that infection, is a recently marketed monoclonal antibody-based filtration type enzyme immunoassay (Kodak SureCell Herpes Test Kit). Serologic tests traditionally do not have a major role in the diagnosis of HSV infection; yet, new type-specific methods using Western blot assays may be useful for confirming the presence of unrecognized, subclinical HSV2 infections that are presently being underdiagnosed by current procedures. The gold standard for establishing the diagnosis of HSV infection has been the viral tissue culture. The fluorescent antibody to membrane antigen test and viral tissue culture have been the principal methods for diagnosing VZV infection. Immunomorphologic techniques have been useful adjuvant methods for both the diagnosis and the differentiation of HSV and VZV infections. Molecular virology techniques (particularly those using PCR) are likely to become the diagnostic methods of choice for both HSV infection and VZV infection once these tests become commercially available.

Laboratory testing in patients with morbilliform viral eruptions.

The explosion of immunologic testing capabilities over the past 20 years has enabled clinicians to accurately diagnose many conditions that previously were very difficult to identify solely on a clinical basis. Among these disorders are the viral exanthems. Infections with some of these viruses are of relatively little import (erythema infectiosum), whereas others have more significant consequences (HIV, cytomegalovirus). Clinical suspicions may be pursued more fully now, sometimes even in an office setting.

An epidemic of infantile papular acrodermatitis (Gianotti-Crosti syndrome) due to Epstein-Barr virus.

Five out of twelve 13- to 15-month-old children, attending the same class of a crèche in Forlì (Italy), presented infantile papular acrodermatitis (Gianotti-Crosti syndrome), associated with lymphocytosis and evidence for a recent Epstein-Barr virus infection. This cluster may be due to two facts: (1) the long and close contacts among the patients and (2) the concurrent immunization with a combined diphtheria-tetanus-pertussis-poliomyelitis vaccine from 2 to 6 weeks previously.

Papular-purpuric 'gloves and socks' syndrome: not only parvovirus B19.

We previously described an acute dermatosis characterized by pruritic erythematous and slightly papular lesions on the hands and feet in a 'gloves and socks' distribution associated with oral aphthoid lesions and fever (papular-purpuric 'gloves and socks' syndrome = PPGSS). We strongly suspected a viral origin, but serologic tests for a large panel of viruses remained negative. Subsequently, 2 cases of PPGSS with serologic evidence of a parvovirus B19 infection have been reported in the literature. Since then we observed 5 additional patients with a PPGSS. Parvovirus B19 infection could be confirmed in only 2 cases. Our findings suggest that the PPGSS can be another, yet undescribed manifestation of parvovirus infection. However, this cannot be shown in all the cases. As the papular acrodermatitis of childhood, this syndrome may be caused by various viral agents.

Herpes zoster: daily marking of new vesicles in therapeutic studies. A clinical method for objective assessment of the end of the eruptive phase.

BACKGROUND: The efficacy of a therapeutic agent must be evaluated by objective criteria. However, in herpes zoster (HZ) studies there has been no generally accepted objective clinical criterion. OBJECTIVE: Our purpose was to establish a clinical method for determining objectively the point in time at which the eruptive phase of HZ is completed (no new vesicle formation). This point is said to be a clinical criterion for the end of viral replication in the skin and thus for measuring the efficacy of a virustatic agent. METHODS: Newly formed vesicles were marked with differently colored permanent marker pens each day. This method was evaluated by comparing the results of acyclovir therapy in two groups of patients with HZ. (Group A, no underlying malignancy; n = 9. Group B, underlying malignancy; 64% of these patients were undergoing cytostatic polychemotherapy or had immunodeficiency; n = 22). RESULTS: In both groups, acyclovir stopped the eruption of new vesicles within 1.8 and 2.8 days, respectively (not statistically significant). Group B showed a tendency toward more protracted hematogenous dissemination and a longer duration of therapy. The total duration of the eruptive phase depended solely on the length of the interval between the onset of the HZ and the beginning of therapy. CONCLUSION: The method of marking new vesicles is independent of laboratory facilities, simple, and cost effective; in addition, this method is suitable for statistical evaluation. It is thus superior to other clinical methods for objective assessment of the progression of HZ.

Ultrastructural findings in mucocutaneous infections of patients seropositive to HIV.

Tissue samples from 19 HIV-seropositive immunocompromised patients suffering from oral hairy leukoplakia, chronic vesicular or ulcerative herpes simplex, chronic nonmetameric herpes zoster, secondary syphilis, condylomata acuminata, molluscum contagiosum, or disseminated cutaneous mycobacteriosis were examined ultrastructurally in order to better define the fine structure of the causative organisms in parasitic conditions and to clarify the host-parasite relationships. Taking into account the few data in the literature regarding the same disorders in immunocompetent subjects, no striking differences in the morphology of the infectious agents or in the types of parasitism were found. Nevertheless, isolated herpesvirus and papillomavirus virions were found outside the infected cells, and this observation, if confirmed in a larger series of cases, could suggest a persistent infectivity of the lesions in immunocompromised patients. Moreover, electron microscopy proved to be useful for diagnostic purposes; in one case of disseminated cutaneous mycobacteriosis, repeated cultures failed to grow the organism.

Human papillomavirus DNA in the urogenital tracts of men with gonorrhoea, penile warts or genital dermatoses.

OBJECTIVE: To assess the presence of human papillomavirus (HPV) DNA in urethral and urine specimens from men with and without sexually transmitted diseases. DESIGN: Prospective study. SETTING: Two London departments of genitourinary medicine PATIENTS: 100 men with urethral gonorrhoea, 31 men with penile warts and 37 men with genital dermatoses. METHODS: Urethral and urine specimens were taken, HPV DNA extracted and then amplified using the polymerase chain reaction. HPV types 6, 11, 16, 18, 31 and 33 were identified using Southern blotting followed by hybridisation. RESULTS: HPV DNA was detected in 18-31% of urethral swab specimens and in 0-14% of urine specimens. Men with penile warts had HPV detected in urethral swabs more often than did men in the other two clinical groups. "High risk" HPV types were found in 71-83% of swab specimens and in 73-80% of urine specimens containing HPV DNA. CONCLUSIONS: HPV is present in the urogenital tracts of men with gonorrhoea, penile warts and with genital dermatoses. In men with urethral gonorrhoea, detection of HPV in urethral specimens is not related to the number of sexual partners, condom usage, racial origin or past history of genital warts. HPV DNA in the urethral swab and urine specimens may represent different aspects of the epidemiology of HPV in the male genital tract. The preponderance of HPV types 16 and 18 in all three groups of men may be relevant to the concept of the "high risk male".

Human papillomavirus DNA in the urogenital tracts of men with genital dermatoses: evidence for multifocal infection.

In an attempt to assess the multifocal nature of anogenital HPV infection in men, skin biopsies, urethral swabs and urine specimens were obtained from 100 men with genital dermatoses. The specimens were examined for the presence of human papillomavirus (HPV) types 6, 11, 16, 18, 31 and 33 using the polymerase chain reaction and Southern blotting techniques. HPV DNA was detected in one or more specimens from 39 patients, that is 29 of 100 biopsy specimens, 21 (25%) of 85 urethral swab specimens and 6 (10%) of 59 urine specimens. HPV DNA was more common in men with at least 20 lifetime sexual partners and in those who gave a history of anogenital warts. Twelve (18%) of 66 biopsy specimens with no histological evidence of warty change or neoplasia had detectable HPV DNA. HPV DNA was detected no more frequently in the urethral and urine specimens from men with histological evidence of warts or neoplasia than from men without such changes. HPV types 6 and 11 were most common in biopsy specimens with histological changes of typical HPV infection. HPV type 16 was commonest in biopsy specimens with neoplasia and type 18 with other changes. Furthermore, 'high-risk' HPV types were found proportionately more often in urethral swab and urine specimens than in biopsy specimens. There was generally a poor correlation between the detection of HPV DNA at the different sites. A greater understanding of the role of HPV in the production of genital abnormalities is required in order to develop a rational approach to the management of these patients.

Comparative immunohistochemical study of herpes simplex and varicella-zoster infections.

Herpes simplex (HSV) and varicella-zoster (VZV) skin infections share so many histological similarities that distinguishing between them may prove to be impossible. We developed and characterized a new monoclonal antibody, VL8, IgG kappa isotype, directed to the VZV envelope glycoprotein gpI. Immunohistochemistry with VL8 appeared highly sensitive and specific on formalin-fixed paraffin-embedded biopsies and a clear-cut distinction between HSV and VZV infections was possible. The pattern of VL8 immunolabelling in VZV infections was strikingly different from that found in HSV infections studied with polyclonal antibodies to HSV I and II. Double immunolabelling revealed the VL8 positivity of sebaceous cells, endothelial cells, Mac 387- and CD68-positive monocyte-macrophages, and factor XIIIa-positive perivascular, perineural and interstitial dendrocytes. Intracytoplasmic VL8 labelling of endothelial cells and perivascular dendrocytes was found at the site of leukocytoclastic vasculitis.

Capsaicin-sensitive peptidergic neurons are involved in the zosteriform spread of herpes simplex virus infection.

The intraneuronal transport of herpes simplex virus (HSV) is an essential component in disease pathogenesis. Capsaicin, a neuropharmacologic agent lacking direct antiviral activity, has been shown to protect animals against HSV-induced disease. It has been hypothesized that capsaicin acts by interfering with the intraneuronal transport of virus. Since animal models have been useful in studying the spread of virus, we used two guinea pig models of zosteriform herpes to examine the effect of capsaicin on HSV spread. Capsaicin was subcutaneously administered to Hartley guinea pigs prior to intravaginal or cutaneous HSV-2 inoculation. Treatment did not prevent the development of herpetic vesicles at the site of inoculation but significantly reduced the zosteriform spread of lesions in male and female animals. Further, after recovery from primary infection, capsaicin-treated male guinea pigs were observed to have fewer days with recurrent herpetic lesions. These results suggest that capsaicin-sensitive nerve fibers play a role in the pathogenesis of primary and recurrent HSV infections. Capsaicin appears to reduce the severity of cutaneous HSV infections by interfering with the spread of virus.