Varicella-zoster virus DNA in granulomatous skin lesions following herpes zoster

Granulomatous reactions at sites of previous cutaneous herpes zosier lesions occur, but their etiology is not known. Three tissue specimens from 5 cases identified clinically and hislologically as post-zosteric granulomatous reactions were studied for the presence of varicella-zoster virus (VZV) deoxyribonucleic acid (DNA) by the polymerase chain reaction using specific primers For VZV. VZV DNA was detected in 1 of 3 cases where the granulomatous reaction occurred immediately in the wake of resolving vesicular herpes zoster lesions. Finding viral DNA in earlier reactions probably represents residue from the active herpetic process. VZV DNA was not identified in granulomatous reactions arising between 1 month and up to 4 years after resolved herpes zoster. The negative result in these cases supports the hypothesis that there is no association between persistence of VZV DNA and granuloma formation. How long VZV DNA is detectable at sites of resolved herpes zoster lesions could be the subject of further studies.     

Virus replication and induction of interferon in human epidermal keratinocytes following infection with herpes simplex virus

Keratinocyte cultures derived from surgical skin specimens of healthy newborns and adults were infected with herpes simplex virus (HSV) type 1 or 2. Typical HSV cytopathic effects involved all cell layers in stratified colonies, and paralleled the production of infectious virus. Virus growth curves and production of virus were comparable in newborn and adult keratinocytes. Interferon (IF) production by keratinocytes paralleled the yield of virus over at least 72 h, and was greater in cultures of adult cells than cultures from newborns. UV irradiation of HSV resulted in progressive virus inactivation and a parallel reduction in induced IF. This suggests that IF production was related to virus replication, and that irradiated (noninfectious) HSV DNA did not contribute significantly to the generation of IF in this system. These results establish that human epidermal keratinocytes can serve as a model system for quantitative assessment of herpes simplex virus infection.     

Chronic verrucous varicella zoster virus skin lesions: clinical, histological, molecular and therapeutic aspects

The outbreak of HIV infection introduced a new phenomenon in varicella zoster virus (VZV) pathology, namely the long-standing wart-like skin lesions that are frequently associated with resistance to thymidine kinase (TK)-dependent antiviral agents. This paper reviews the clinical, histological, and molecular aspects and the therapeutic management of these verrucous lesions. The majority of lesions are characterized by chronically evolving, unique or multiple wart-like cutaneous lesions. The main histopathological features include hyperkeratosis, verruciform acanthosis and VZV-induced cytopathic changes with scant or absent cytolysis of infected keratinocytes. The mechanism that establishes the chronic nature of the lesions appears to be associated with a particular pattern of VZV gene expression exhibiting reduced or nondetectable gE and gB synthesis. Drug resistance to TK-dependent antiviral agents is a result of nonfunctional or deficient viral TK. This necessitates alternative therapeutic management using antiviral agents that target the viral DNA polymerase.     

Freeze-fracture replication technique of human skin

The freeze-fracture replication technique represents one of the most advanced methods for studying the ultrastructure of biological tissues and has given a new dimension to the ultrastructure research. This technique makes it possible to obtain a cast of a fracture surface of frozen preparations. Apart from allowing samples to be examined without being dehydrated, i.e. under conditions very close to those of living state, it has proved especially useful for the analysis of many tissue functions concerned with membrane activity and exchanges between cells and their disturbance in specific disease conditions. Even through good quality replicas had already been obtained back in 1961 (Moor et al. 1961), only after 1970, mainly thanks to the contribution made by Breathnach and his collaborators (Breathnach et al. 1972, Breathnach 1973, Breathnach et al. 1973) was the freeze-fracture replication technique successfully used in the study of the skin, since this tissue had proved especially difficult to process. In this review paper, technical principles will be summarized and the most important findings so far obtained in the study of normal and pathologic skin will be illustrated.     

Vitronectin in normal human skin and in skin lesions]

Vitronectin (S-protein of complement, serum spreading factor) is a multifunctional glycoprotein present in human plasma and in the elastic tissue of various organs. It belongs to the group of adhesion proteins and is of importance in the terminal stages of both the coagulation and complement system and in fibrinolysis. In human skin it is localized on dermal elastic fibers and on pathologically altered elastic material (solar elastosis, pseudoxanthoma elasticum) as well as on keratin filament material such as keratin bodies in lichen planus or amyloid deposits in localized cutaneous amyloid. It is also found in the abnormally thickened cutaneous blood vessels in erythropoietic protoporphyria and porphyria cutanea tarda. Late-stage inhibition of the complement cascade in bullous disorders in which activation of the complement system is of pathogenetic significance may be an additional important function of vitronectin in skin diseases.     

Prolonged herpes zoster in a patient infected with the human immunodeficiency virus.

In 1983, varicella zoster virus (VZV) disease was first recognized in the context of infection with the human immunodeficiency virus (HIV). Since that time, there have been many reports discussing the occurrence and clinical manifestations of hepes zoster in HIV-infected patients. We describe the development of prolonged herpes zoster in a patient with acquired immunodeficiency syndrome (AIDS) over the course of 104 days. Viral isolates at the three different clinical stages of the skin lesions were sensitive in vitro to acyclovir, and supposed to be a same strain by polymerase chain reaction (PCR) analysis. We also discuss an effective treatment for prolonged cases of zoster.     

Detection of varicella zoster virus infections using polymerase chain reaction]

The polymerase chain reaction (PCR) was used to detect varicella zoster virus (VZV) DNA in vesicle samples from patients with varicella and zoster. Primers and the oligonucleotide probe were chosen from the region of the immediate early gene 63. Procedures for preparing the DNA from the specimens were omitted, and the amplified DNA was directly detected in ethidium bromide-stained polyacrylamide or agarose gels, thus providing a rapid and less laborious assay. A total of 66 vesicle specimens including 3 crusts (collected on days 1-14 after the onset of exanthem) were tested by the simplified VZV-PCR, and 64 (97%) were positive. When the direct visualization of the amplified DNA was confirmed by DNA hybridization, a non-radioactive hybridization assay involving a digoxigenin-labelled oligonucleotide probe and detection by chemiluminescence proved as adequate as a radioactive hybridization assay. Thus, the VZV PCR described appears to be a useful diagnostic test for detecting and identifying varicella zoster virus.     

In vivo Zika virus detection in human skin

A number of recent studies suggest that tanning has the potential to be addictive. Tanned skin is often viewed as more attractive than untanned skin, and being tanned has been associated with increased energy and self‐confidence. Additionally, sunbathing has been shown to provide pleasant feelings of warmth and relaxation to most individuals. However, sunbathing and tanning to excess are associated with an increased risk of a variety of health problems, such as skin cancers and specific eye diseases. Excessive tanning can be linked to a number of mental health disorders, such as obsessive‐compulsive behaviours, body dysmorphic disorder and impulsive control disorders. Still, much evidence suggests that excessive tanning should be regarded as a behavioural addiction, and this study describes a new, brief screening tool for assessing tanning addiction. In this study, a web‐based survey was published in the online edition of five nationwide Norwegian newspapers during March to May 2014. Questions addressed criteria that are used to diagnose addiction, and included preoccupation with tanning, tanning improving mood, more tanning being required in order to be satisfied, and restlessness or negative feelings when not tanning. People were asked about the past month and the response format adhered to a 5‐point Likert scale (from 0=never to 4=always). The new system, called the Bergen Tanning Addiction Scale, requires further testing but performed well. Tanning addiction was associated with being female, not being in a relationship, extroversion, neuroticism, anxiety and obsessive‐compulsiveness.     

Response of varicella zoster virus and herpes zoster to silver sulfadiazine

The addition of silver sulfadiazine to cultures of varicella zoster virus resulted in inactivation of the viral infectivity. At a concentration of 10 micrograms/ml or higher the virus was inactivated after thirty minutes exposure at 37 degrees C. Forty-two patients with herpes zoster were treated topically with 1 percent silver sulfadiazine cream applied four times a day. All patients experienced complete drying of vesicles, marked reduction erythema and edema, and striking elimination of pain and burning sensation within twenty-four to seventy-two hours. The sooner the treatment began after the onset of symptoms, the more dramatic was the response. Postherpetic neuralgia was either mild or did not occur. Signs of local, systemic, or laboratory-documented toxicity were not observed.     

Isolation of human immunodeficiency virus type 1 from human epidermis: virus replication and transmission studies.

For a better understanding of the pathogenetic events operative in the cutaneous manifestations of human immunodeficiency virus type 1 (HIV-1) disease, we investigated whether epidermal cells (EC) from HIV-1-seronegative persons can be infected with HIV-1 and, vice versa, whether HIV-1 can be rescued from the epidermis of HIV-1-infected individuals. In a series of three experiments, we consistently found that exposure of EC from HIV-1-seronegative donors to HIV-1 led to viral replication in these cells as evidenced by the detection of HIV-1 p24 in culture fluids. Because EC had been substantially enriched for Langerhans cells (LC) before being exposed to HIV-1, it is reasonable to assume that these CD1a+/CD4+/MHC class II+ antigen-presenting cells of the epidermis represented the actual targets of infection. This assumption is further strengthened by the observation that T cell-depleted cell suspensions from Langerhans cell histiocytosis (LCH) lesions could be productively infected with HIV-1. Conversely, co-culture of epidermal sheets from HIV-1-seropositive individuals with mononuclear phagocytes (MNP) from HIV-1-seronegative donors resulted, after 3 to 5 weeks, in the detection of HIV-1 p24 in 12 of 23 cases. Immunocytochemical analysis, using a monoclonal antibody specific for p24, revealed the presence of HIV-1 in adherent MNP in three cocultures tested. In addition, cellular DNA from these cultures showed strong signals when hybridized to a HIV-1-specific DNA probe. The further finding that two isolates examined exhibited different restriction enzyme patterns indicates that they are separate entities rather than contaminants. Transmission of these isolates to MNP, B- or T-cell lines resulted in cultures strongly positive for p24 and, in the case of H9 cells, for viral particles as detected by electron microscopy. Our results therefore strongly suggest that EC not only can serve as targets for HIV-1, but also can allow efficient virus replication and transmit HIV-1 to various cell types of the hematopoietic lineage.     

Paralytic abdominal hernia in zoster]

In a 56 year old patient with zoster in the thoracic segments 10 and 11 an abdominal hernia developed. The hernia was caused by peripheral motorial paresis.     

Nonmelanoma skin cancers and infection with the human immunodeficiency virus.

BACKGROUND AND DESIGN--Forty-eight human immunodeficiency virus-infected patients with nonmelanoma skin cancers seen during a four-year period were evaluated in a retrospective, case-control study. Patients were followed up after therapy and recurrence rates were determined. RESULTS--One hundred and sixteen nonmelanoma skin cancers were identified, 101 of which were basal cell carcinomas (87%), mostly superficial multicentric (67%) of the trunk (62%). There were 15 low-grade squamous cell carcinomas, most commonly of the head and neck. Half of the patients had multiple cancers. Compared with age-matched controls, the patients with skin cancer more commonly had blue/hazel eyes (89% vs 66%; odds ratio [OR] 4.1; confidence interval [CI], 1.25 to 13.44; P = .033), blond hair (42% vs 13%; OR = 4.53; CI, 1.40 to 13.74, P = .003), a family history of skin cancer (45% vs 5%; OR = 11.88; CI, 2.85 to 49.57; P = .00), and a history of regular sunbathing (92% vs 48%; OR = 11.24; CI, 3.17 to 39.83; P = .00). The number of cancers or the presence of squamous cell carcinoma did not correlate with the degree of immunosuppression. The recurrence rate for basal cell carcinomas following standard treatment methods (mostly curettage and electrodesiccation and excision) was 5.4% for those tumors followed up for longer than 12 months. Three of the 15 squamous cell carcinomas recurred, all following curettage and electrodesiccation. CONCLUSION--Nonmelanoma skin cancers are a not uncommon cutaneous finding in human immunodeficiency virus-infected patients. The major risk factors for developing skin cancer in association with human immunodeficiency virus disease seem to be the same as in the normal population--fair skin, a positive family history, and sun exposure. Standard treatment methods seem to be associated with acceptable cure rates, except for squamous cell carcinomas, which had a high (20%) recurrence rate following curettage and electrodesiccation.     

Chronic mucocutaneous herpes simplex virus and varicella zoster virus infections

Chronic herpes simplex virus (CHSV) and chronic varicella zoster virus (CVZV) are defined as atypical mucocutaneous wart-like and/or ulcerative HSV or VZV infections, persisting for at least 1 month. Both are commonly associated with HIV infection and may occasionally present with other types of immunosuppression. CHSV and CVZV occur despite the immune restoration effect of highly active antiretroviral therapy for HIV. The clinical polymorphism of CHSV and CVZV makes recognition difficult. Histology, immunohistology, PCR and viral culture all help to confirm the diagnosis. Treatment is frequently complicated by resistance to thymidine kinase (TK)-dependent antivirals, including acyclovir, valacyclovir and famciclovir. Viral culture remains an essential tool for antiviral drug susceptibility testing. Therapeutic alternatives include non-TK-dependent antivirals, such as foscarnet or cidofovir, which directly target viral DNA polymerase. With few exceptions, CHSV and CVZV infections do not constitute significant risk factors for disseminated cutaneous or systemic infection. This review compares the similarities of and differences between CHSV and CVZV infections.     

Absence of Epstein-Barr virus, human papillomavirus, and simian virus 40 in patients of central european origin with lymphoepithelioma-like carcinoma of the skin

The authors report 10 cases of lymphoepithelioma-like carcinoma (LELC) of the skin and the results of a molecular biological study for HPV, EBV, and SV40 in lesional tissues. All patients originated from Central Europe. There were seven men and three women, ranging in age from 57 to 86 years. Locations included the face (n = 4), scalp (n = 2), penis (n = 2), and retroauricular area (n = 1); location was unknown for one subject. All but two patients presented with a tumor confined to the skin; in both patients with the penile carcinoma, the tumors had metastasized to an inguinal lymph node. Six patients with available follow-up included four individuals with no evidence of tumor metastasis or recurrences at 2, 3, 4, and 5 years, one patient who died with metastatic disease 7 years after diagnosis, and one patient who died of an unrelated course. Microscopically, all cases showed distinctive features of LELC characterized by variably sized and shaped nodules or syncytial sheets of epithelial cells that contained vesicular chromatic and prominent nucleoli and that were permeated and surrounded by small, well-differentiated lymphocytes and plasma cells. Because all 10 cases studied proved negative for EBV, HPV, and SV40, these viruses seem to play no causal role in LELC of the skin in patients from Central Europe.