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[Studies on the novel association of human herpesvirus-7 with skin diseases].

INTRODUCTION AND AIM: Human herpesvirus 7 in pityriasis rosea, this and other viruses in papular-purpuric gloves-and-socks syndrome have been implicated, but their primary or recurrent infections are still in question. PATIENT AND METHODS: In one available blood sample, therefore, IgM, IgG and its high avidity fraction characteristic for recurrent infections were quantitated by indirect immunofluorescence. Peripheral lymphocytes were subjected to nested polymerase chain reaction to detect viral DNA, or cocultivated with several cell cultures. RESULTS: One third of 33 pityriasis rosea patients had elevated IgM, another third had elevated IgG without high avidity molecules to human herpesvirus 7 suggesting primary infection. Thirty percent of controls, more than half of the patients had virtual DNA in their lymphocytes, but only one in 5 skin biopsy specimens were PCR positive. All three co-cultivation attempts yielded viruses extremely rapidly, verified by electron microscopy, polymerase chain reaction and monoclonal antibodies as human herpesvirus 7. These are the first isolates in the geographical regions of Hungary. These data suggest that pityriasis rosea is the consequence of a primary human herpesvirus 7 infection in seronegative adults, and only occasionally is due to virus reactivation. One patient with gloves-and-socks syndrome had an acute, another patient had a persistent coinfection with human herpesvirus 7 and parvovirus B19, two others had a primary herpesvirus 7 infection. Interestingly, this disease might be elicited by both viruses individually or in synergism. CONCLUSION: Neither human herpesvirus 7 nor parvovirus B19 infect skin cells, but both can be detected in the infiltrating lymphocytes of skin eruptions, in which they induce an altered mediator production, that might be responsible for the general and local symptoms.

Adult↗

[Pink pityriasis in primary care. Review of 46 cases].

OBJECTIVE: We pretend to improve the knowledge and management of pityriasis rosea by family practitioners. DESIGN: A retrospective qualitative study by the review of the registry in a outpatient Dermatology clinic. SETTING: This work is made in the Dermatology clinic attending to San Sebastián de los Reyes population (Madrid) that's situated in the V Centenario Center. MEASUREMENTS AND MAIN RESULTS: 46 patients (28 females) were diagnosticated (mean age 25 +/- 13). Incidence was 85/100,000 hab; 12 patients were derivated urgently; 38 cases showed herald patch (82.6%). Lesions had characteristical distribution in 36 patients (78.3%); 43 cases had a clinic diagnosis (93.5%). Treatment wasn't necessary in 20 patients (43.5%). Most usual General Practitioner's presumption diagnosis was pityriasis rosea (21.7%); there was no diagnosis in 36.9%. CONCLUSIONS: We find inexperience in general practitioners about pityriasis rosea. It's necessary a correct knowledge and management of this pathology in Primary Care.

Adolescent↗

Immune-mediated pathology following hepatitis B vaccination. Two cases of polyarteritis nodosa and one case of pityriasis rosea-like drug eruption.

The association of hepatitis B virus infection and vasculitis or other immune-mediated manifestations is well documented. Reports on such manifestations in relation to hepatitis B vaccination are scarce, however. We report 2 patients who developed polyarteritis nodosa following vaccination against hepatitis B. In one patient this resulted in an ischemic and necrotic digital ulcus, necessitating surgical amputation. The other patient presented with typical cutaneous polyarteritis nodosa which responded well to corticosteroid treatment. A third patient developed a severe pityrias rosea-like eruption. He was treated with topical steroids with healing of the lesions, leaving only post-inflammatory hyperpigmentation. The literature on these associations is reviewed.

Adrenal Cortex Hormones↗

Different in situ distribution patterns of dendritic cells having Langerhans (T6+) and interdigitating (RFD1+) cell immunophenotype in psoriasis, atopic dermatitis, and other inflammatory dermatoses.

Dendritic cells bearing Langerhans cell (OKT6+) or interdigitating cell (RFD1+) immunophenotype may be regularly detected within the dermis of chronic skin diseases characterized by a lymphohistiocytic (lymphoreticular) infiltrate. These 2 subsets of antigen-presenting cells within the dermis of lesions of exacerbating chronic plaque psoriasis, exacerbating nummular dermatitis (discoid eczema), atopic dermatitis, allergic contact dermatitis, pityriasis rosea, lichen ruber planus, and cutaneous lupus erythematosus were quantified using computer-assisted morphometry. The mean dendrite length per dermal dendritic cell was significantly higher for RFD1 than for OKT6 (74.4 +/- 0.98 microns vs 70.0 +/- 1.26 microns: p = 0.0023). The mean dendrite length per dermal dendritic cell was remarkably constant for each marker in the various diagnostic categories studied. Disease-specific patterns of total dendrite length and number (expressed per 100 infiltrating mononuclear cells) of these 2 dendritic cell types within the subepidermal infiltrates were obtained. Pityriasis rosea was characterized by its unique high percentage of OKT6+ Langerhans cells. Atopic dermatitis and psoriasis had relatively high percentages of both RFD1+ interdigitating cells and OKT6+ Langerhans cells. Nummular dermatitis had an intermediate number and total dendrite length for OKT6, but was relatively low in RFD1+ cells. Allergic contact dermatitis, lichen planus, and lupus erythematosus had low numbers and dendrite lengths for both dendritic cell subsets. It is suggested that pityriasis rosea is characterized by an abnormal migration pattern of Langerhans cells. Psoriasis and atopic dermatitis may be examples of diseases in which skin-localized antigen-presenting and T-cell-inducing events are continuously taking place. The other diseases may reflect inflammatory processes in which local antigen presentation is less relevant to the tissue reaction.

Antigen-Presenting Cells↗

Group A streptococcal antigen-specific T lymphocytes in guttate psoriatic lesions.

A strong association exists between guttate psoriasis and group A, beta-haemolytic streptococcal infections. To demonstrate the presence of streptococcal-specific T cells in psoriatic skin, T-cell lines (TLs) were established from biopsies of lesions from five patients with guttate psoriasis, and compared with TLs from five patients with eczema, five with lichen planus, two with pityriasis rosea and three with nickel contact dermatitis. TLs from purified protein derivative (PPD)-induced delayed hypersensitivity sites in three normal individuals were also studied. All five of the psoriatic TLs responded in a proliferation assay to heat-killed isolates of group A streptococci, compared with only one eczema, two lichen planus and one pityriasis rosea. The response of one nickel contact dermatitis and two PPD TLs to group A streptococci was markedly less than to nickel and PPD, respectively. One of the psoriatic TLs was cloned in the presence of type 5 streptococcal M protein. The nine clones obtained were all CD3+, CD4+, CD45RO+, TCR alpha, beta+, gamma, delta-. However, they were all unreactive with antibodies to TCR V beta 5, 6, 8 or 12. Eight of the nine clones reacted, to a varying extent, to one or two of three preparations of group A streptococci expressing different M proteins. The streptococcal response of four consistently reactive clones from this patient was HLA-DR-restricted and inhibited by anti-HLA-DR antibody in a dose-dependent manner. On stimulation these four clones secreted high levels of gamma-interferon and detectable levels of IL-2, IL-10 and granulocyte/macrophage colony stimulating factor (GM-CSF) depending upon the nature of the stimulus, but no IL-4 or TNF-alpha production was detected. This study has demonstrated, for the first time, that T lymphocytes specific for group A streptococcal antigens can be consistently isolated from guttate psoriatic lesions. The role of streptococcal-specific T cells in the pathogenesis of psoriasis remains to be determined.

Antigens, Bacterial↗

Epidermal DR+T6- dendritic cells in inflammatory skin diseases.

T lymphocyte and dendritic cell subpopulations were counted in three biopsies each of endogenous eczema and pityriasis rosea and two of lichen planus and compared with previous findings in psoriatic lesions. In common with psoriasis, proportionately more CD4 T cells than CD8 T cells were DR+ in both epidermis and dermis of all lesions. In addition, total numbers of epidermal dendritic cells were significantly increased in endogenous eczema and pityriasis rosea, and variably in lichen planus lesions. Interestingly, a DR+T6- subpopulation of dendritic cells was present in varying proportions in all three skin lesion types. Electron microscopy of DR+T6- dendritic cells from psoriatic lesions, using an immunogold staining technique, showed the cells to be of the Langerhans' cell lineage. DR+T6- dendritic cells are a subpopulation of Langerhans' cells which are not specific to psoriasis, but present in the lesions of other benign, inflammatory skin conditions in which CD4 T cells are preferentially activated.

Antigens, Differentiation, T-Lymphocyte↗

Corneocytes in scaly parakeratotic diseases.

BACKGROUND AND OBJECTIVES: The stratum corneum of some of the scaly (parakeratotic) diseases was examined with light and scanning electron microscopy (SEM) with the purpose to reveal the importance of this layer in the diagnosis of some of the diseases associated with the formation of scales. MATERIALS AND METHODS: Two biopsies of the skin surface were taken: one, obtained from 80 patients with various parakeratotic scaly diseases and from 25 control subjects, was processed for light microscopy; the other biopsy for SEM was taken from 10 control subjects and 25 patients. The diagnoses of these patients were: psoriasis (5 patients), erythrodermic psoriasis (2 subjects), parapsoriasis (5 patients), pityriasis rubra pilaris (5 subjects), pityriasis rosea (3 subjects), and seborrheic dermatitis (5 subjects). RESULTS: The light microscopic studies showed that normal corneocytes are of polygonal shape with their largest diameter measuring 42 microns; these cells lacked nuclei. All parakeratotic cells appeared bizarre in shape, smaller than normal, and the cells contained a nucleus. With SEM, normal cells appeared relatively regular in size and shape, trabeculated, and had a flat surface. Cells examined in all the diseases revealed various sizes, outlines, and trabeculae. Specific surface patterns (print) of diseased cells were: "fish-scale" in psoriasis; "marbled" in parapsoriasis, "rocky stone" in pityriasis rubra pilaris; "heart-shaped" in seborrheic dermatitis, and semicrystalloid in pityriasis rosea. CONCLUSIONS: Parakeratosis is characterized not only by the retention of the nucleus in keratinocytes, but is also characterized by a cell of smaller size. The specific print of a disease helps in the diagnosis. The print will change with different stages of a disease.

Biopsy↗

Improving diagnostic accuracy using a hierarchical neural network to model decision subtasks.

A number of quantitative models including linear discriminant analysis, logistic regression, k nearest neighbor, kernel density, recursive partitioning, and neural networks are being used in medical diagnostic support systems to assist human decision-makers in disease diagnosis. This research investigates the decision accuracy of neural network models for the differential diagnosis of six erythematous-squamous diseases. Conditions where a hierarchical neural network model can increase diagnostic accuracy by partitioning the decision domain into subtasks that are easier to learn are specifically addressed. Self-organizing maps (SOM) are used to portray the 34 feature variables in a two dimensional plot that maintains topological ordering. The SOM identifies five inconsistent cases that are likely sources of error for the quantitative decision models; the lower bound for the diagnostic decision error based on five errors is 0.0140. The traditional application of the quantitative models cited above results in diagnostic error levels substantially greater than this target level. A two-stage hierarchical neural network is designed by combining a multilayer perceptron first stage and a mixture-of-experts second stage. The second stage mixture-of-experts neural network learns a subtask of the diagnostic decision, the discrimination between seborrheic dermatitis and pityriasis rosea. The diagnostic accuracy of the two stage neural network approaches the target performance established from the SOM with an error rate of 0.0159.

Chronic Disease↗

Predominance of "memory" T cells (CD4+, CDw29+) over "naive" T cells (CD4+, CD45R+) in both normal and diseased human skin.

Absolute numbers of CD3+ T lymphocytes and their subpopulations were determined and statistically evaluated in the lesional skin of psoriasis, atopic dermatitis, nummular dermatitis, pityriasis rosea, and lichen planus. Skin sections were divided into horizontal layers and the numbers of CD3+ T cells as well as CD4+ inducer and CD8+ suppressor-cytotoxic T-cell subsets were counted. In addition, absolute numbers of the two subpopulations of inducer T cells, i.e., "memory" (4B4+ 2H4-) and "naive" (4B4- 2H4+) were evaluated. Unexpectedly, epidermal infiltration by T cells was highest in psoriasis and lowest in atopic dermatitis. In most cases, this exocytosis was dominated by CD8+ suppressor/cytotoxic T lymphocytes, with a minimal epidermal mean CD4/mean CD8 ratio of 0.04 in pityriasis rosea and a maximum of 0.48 in psoriasis. Inducer T cells within the epidermis were almost exclusively of the 4B4+ 2H4- "memory" T-cell subpopulation, whereas 4B4- 2H4+ "naive" T cells were extremely uncommon in lesional epidermis. Similar results were obtained for dermal T cells in all diseases studied, i.e., 4B4- 2H4+ "naive" T cells were relatively rare. Papillary dermis infiltration by T cells was highest in lichen planus where a mean CD4/mean CD8 ratio of 1.10, the minimum in this comparative study, was obtained. The mean CD4/mean CD8 ratio of the papillary infiltrate was highest in atopic dermatitis (4.12). Our results indicate disease-specific and significantly different infiltration patterns of T-lymphocyte subsets in the chronic inflammatory dermatoses investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Asymmetric periflexural exanthem of childhood: a clinical, pathologic, and epidemiologic prospective study.

OBJECTIVE: To assess the clinical, pathologic, and epidemiologic features of asymmetric periflexural exanthem of childhood (APEC), a clinically distinctive eruption, especially its link with pityriasis rosea and pattern of transmission. DESIGN: A prospective case series, including an analysis of epidemiologic triggering factors and mode of transmission. Pathologic study, including immunohistochemistry of the inflammatory infiltrate. SETTING: A mixed, community-based referral center. PATIENTS: A total of 37 girls and 30 boys with typical APEC referred from April 1994 to December 1996 were included in the study; 82% came from the greater Bordeaux area in France. INTERVENTION: None. MAIN OUTCOME MEASURE: Possible interhuman transmission of APEC. RESULTS: [corrected] No triggering factor was identified; no interhuman transmission occurred; and no demonstrable link with pityriasis rosea was apparent. Several new clinical variants were recognized or confirmed (high fever, facial and peripheral involvement, prolonged course). Distinctive perisudoral interface CD8+ infiltrate was suggestive of diagnosis. CONCLUSIONS: Interhuman transmission was doubtful, but inoculation disorder was still possible. Histopathologic findings seem more specific than previously thought.

Child, Preschool↗

Update on selected viral exanthems.

Viral exanthems are common in childhood and account for a large number of patient visits to pediatric or family medicine clinics. Most exanthems are virtually harmless to the healthy child, but others can be signs of more significant systemic disease. Some exanthems that are benign or self-limited in the healthy child may propose significant risk to pregnant or immunocompromised individuals. Therefore, recognition of exanthems, which may be associated with certain viral illnesses, is important for the primary care provider. For example, prompt recognition of a viral exanthem caused by parvovirus may allow a pregnant female from exposing her fetus to a potentially fatal infection, or, if the exposure has already occurred, may indicate the need for appropriate fetal monitoring. In this manuscript, we review the recent literature pertaining to four characteristic exanthems that are thought to be viral in nature: papular purpuric gloves and socks syndrome; pityriasis rosea; unilateral lateral thoracic exanthem; and Gianotti-Crosti syndrome.

Acrodermatitis↗

Cutaneous adverse effects associated with terbinafine therapy: 10 case reports and a review of the literature.

Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions associated with terbinafine therapy which required discontinuation of the antifungal agent: erythema multiforme (five patients), erythroderma (one), severe urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis (two patients). The spectrum of cutaneous adverse effects associated with terbinafine therapy is reviewed. Patients should be counselled about discontinuing terbinafine at the onset of a cutaneous eruption and about seeking medical advice about further management.

Adult↗

[Recently discovered herpes viruses explain the etiology of well-known diseases].

Three new members of the family of human herpesviruses (HHVs) have been identified in less than a decade, HHV 6 7 and 8. HHV-6 and HHV-7, both infecting T-lymphocytes and phylogenetically related to cytomegalovirus, were identified as causative agents of exanthema subitum. In addition, HHV-6 has been reported to manifest central nervous system tropism and to be frequently detected in normal brain tissue, but has also been associated with febrile seizures. HHV-7 has been suggested to be involved in the development of pityriasis rosea, but has also been found to occur in normal dermal tissue. HHV-8, related to Epstein-Barr virus and infecting B-lymphocytes, was the first herpesvirus to be identified with molecular techniques. Recent research has been focused on the involvement of proteins expressed by HHV-8 in the pathogenesis of two rare tumours, Kaposi's sarcoma and body-cavity B-cell lymphomas.

Exanthema Subitum↗

[HHV 6,7 and 8. Recently discovered herpesviruses explain the etiology of well-known diseases].

Three new members of the family of human herpesviruses (HHVs) have been identified in less than a decade, HHV 67 and 8. HHV-6 and HHV-7, both infecting T-lymphocytes and phylogenetically related to cytomegalovirus, were identified as causative agents of exanthema subitum. In addition, HHV-6 has been reported to manifest central nervous system tropism and to be frequently detected in normal brain tissue, but has also been associated with febrile seizures. HHV-7 has been suggested to be involved in the development of pityriasis rosea, but has also been found to occur in normal dermal tissue. HHV-8, related to Epstein-Barr virus and infecting B-lymphocytes, was the first herpesvirus to be identified with molecular techniques. Recent research has been focused on the involvement of proteins expressed by HHV-8 in the pathogenesis of two rare tumours, Kaposi's sarcoma and body-cavity B-cell lymphomas.

Adult↗