Pityriasis rotunda: a survey of 42 cases observed in Sardinia, Italy.

BACKGROUND: Pityriasis rotunda (PR) is an uncommon dermatosis characterized by multiple, round or oval, sharply demarcated scaling patches that are dyschromic and asymptomatic. It has been described in Japanese and in blacks, usually in association with certain infective or malignant systemic diseases. OBJECTIVE: The aim of this study is to further clarify this rare entity which in Italy seems to be confined to the island of Sardinia. METHODS: We studied 42 Sardinian patients, 22 males and 20 females, in an age range of 3-32 years. In 29 cases, the disease involved more than one family member. The patients were observed in Cagliari, the capital city of Sardinia. RESULTS: Bacterial, viral and fungal investigation yielded negative results. Haematochemical and immunological examination and thyroid, hypophyseal and adrenal hormones did not reveal any alterations. No systemic pathologies were found associated with the disease. CONCLUSIONS: The cases studied by us and those previously reported seem to indicate the presence of two distinct types of PR with significant prognostic differences.

CD7-negative helper T cells accumulate in inflammatory skin lesions.

Recently, we identified a particular T-cell subset in the peripheral blood of normal individuals that lack CD7 expression. In this study we determined the portion of CD7- T cells in the peripheral blood and skin of patients with various inflammatory skin diseases. We found that skin-infiltrating lymphocytes isolated from different benign and malignant skin lesions (n = 20) contain a high portion of CD7- helper T cells, whereas the number of CD7- T cells in the peripheral blood was not altered compared to healthy controls. Cell activation in vitro did not induce CD7 expression in negative T cells but increased CD7 expression in CD7-positive cells. Thus, lack of CD7 expression seems to be a stable characteristic in a major subset of skin-infiltrating lymphocytes. During long-term culture of CD7- helper T-cell clones derived from a psoriasis skin lesion, no phenotypic change in the CD7 phenotype could be monitored by sequential flow-cytometric analyses. No CD7 mRNA could be detected by Northern blot analysis, indicating transcriptional regulation of CD7 expression. The results show that CD7- T cells accumulate in certain inflammatory skin lesions without alteration of the circulating CD7- population. These cells may be identical to or derived from CD7- T cells of the peripheral blood.

Lymphomatoid papulosis: clinicopathological comparative study with pityriasis lichenoides et varioliformis acuta.

We have compared the clinical and histopathological features of 6 patients with lymphomatoid papulosis (LP) and 14 patients with pityriasis lichenoides et varioliformis acuta (PLEVA). There were some differences between the clinical features in the two diseases, including the size and appearance of skin lesions and the duration of the course of disease. Ki-1 Ag positive, large, atypical, lymphoid cells were always seen in lymphomatoid papulosis; none of lymphoid cells of pityriasis lichenoides et varioliformis acuta demonstrated this antigen. We conclude that lymphomatoid papulosis and PLEVA, although sharing some common features, should be considered to be different clinical and immunopathological entities.

HLA-DR antigen expression on peripheral T cell subsets in pityriasis rosea and herpes zoster.

Using 2-color fluorescein-activated cytometric analysis, HLA-DR antigen expression on peripheral blood T cell subsets was studied in patients with herpes zoster (HZ), pityriasis rosea (PR) and psoriasis. In HZ and PR, HLA-DR was found to be significantly expressed on T cell surfaces (CD3+ cells), when compared to that of the normal control (HZ: p less than 0.001, PR: p less than 0.05). Among T cell subsets, such HLA-DR antigen was predominantly expressed on suppressor/cytotoxic cells (CD8+) in HZ (vs. normal control, p less than 0.01). However, in the case of PR, it was predominantly expressed on helper cells (CD4+; vs. control, p less than 0.05). On the other hand, activated T cell antigen (CD25+) was not significantly expressed on T cells (CD3+) in either HZ or PR. In the T cell subsets, HLA-DR antigen expression returned to normal levels during the recovery phases of HZ and PR.

Koebnerization as a cutaneous manifestation of immune complex-mediated vasculitis.

Two unusual examples of the cutaneous manifestations of vasculitis are presented. In both cases lesions occurred on previously traumatized skin and on normal skin of the dependent areas. Lesional skin biopsy specimens obtained from the koebnerized sites and from the other dependent sites revealed evidence of vascular injury in both patients. A diagnosis of leukocytoclastic vasculitis was made in one patient and pityriasis lichenoides et varioliformis acuta in the other. Direct immunofluorescence microscopy of lesional skin specimens from both patients demonstrated dermal vascular immune deposits. Raji cell assay detected a significant elevation of circulating immune complexes in the serum of both patients. Neither koebnerizing leukocytoclastic vasculitis nor koebnerizing pityriasis lichenoides et varioliformis acuta has been reported previously.

Immunohistochemical distinction of lymphomatoid papulosis and pityriasis lichenoides et varioliformis acuta.

Lymphomatoid papulosis (LyP) and pityriasis lichenoides et varioliformis acuta (PLEVA) are benign self-healing cutaneous eruptions that may be clinically and histologically similar. However LyP has a 5% to 20% risk of associated lymphoid malignancy, whereas PLEVA does not. To determine whether the immunophenotype of lymphoid cells is useful in the distinction of these two disorders, the pattern of expression of lymphoid cell lineage and activation antigens in nine cases of LyP and seven cases of PLEVA were compared. In all cases of LyP most larger cells expressed the activation antigen Ki-1 (CD30) and lacked expression of the T-cell antigen CD7 and at least one other T-cell antigen (CD2, CD3, CD5). In contrast, CD30-antigen expression was rare or absent in PLEVA, CD3- and CD7-antigen expression was found in all cases, and diminished expression of T-cell antigens (CD2 and CD5) was seen in only one case. Diffuse expression of HLA-DR antigen by epidermal keratinocytes was found in a greater proportion of PLEVA cases (6 of 7) than LyP cases (3 of 6). In addition, CD8+ cells predominated at the dermal/epidermal junction in 3 of 6 cases of PLEVA but in only 1 of 7 cases of LyP. We conclude that LyP and PLEVA can be distinguished immunohistochemically in most, if not all, cases. Furthermore these results suggest that LyP and PLEVA are separate disorders, thus accounting for their variable prognoses.

[HLA-DR antigen expression on peripheral T cell subsets in pityriasis rosea Gibert, herpes zoster, and psoriasis].

Using 2 color fluorescein activated cytometric analysis, HLA-DR antigen expression in T cell subsets was studied in pityriasis rosea (PR) and compared to the results from herpes zoster (HZ) of viral origin and psoriasis (Ps). In HZ and PR, HLA-DR was significantly expressed on the T cell surface (Leu-4+ cells). Among the T cell subsets, HLA-DR antigen was predominantly expressed on suppressor/cytotoxic cells (Leu-2a+) in HZ. In contrast, it was predominantly expressed on helper cells (Leu-3a+) in PR. However, activated T cell antigen (Tac) was not significantly expressed on T cells (Leu-4+) in either HZ or in PR. This HLA-DR antigen expression of T cell subsets was depressed to the normal level in the recovery phases of HZ and PR.

Evolutionary changes of immunohistological characteristics of secondary lesions in pityriasis rosea.

In 15 patients with pityriasis rosea, we studied the evolutionary changes of the immunohistological characteristics of the secondary lesions. Many CD1a+ cells were seen in the epidermis and dermis of early lesions. In the well-developed lesions, the number of CD1a+ cells greatly increased in the dermis. In the late lesions, CD1a+ cells in the dermis significantly decreased as compared with the well-developed lesions. Early lesions showed a moderate T-cell infiltrate. In the well-developed lesions, the dermal T-cell infiltrate was dense, and the CD4 CD8 ratio was 2.9. The late lesions had a moderate T-cell infiltrate, in which the CD4 CD8 ratio significantly decreased as compared with the well-developed lesions. Thus, the relative decrease in CD4+ helper inducer cells during lesion regression, concomitant with a decrease in number of CD1a+ Langerhans cells, is in accordance with a broader concept of increased suppressor mechanisms during healing.

[Lichenoid pityriasis. Immunologic study of 10 children]. / Pitiriasis liquenoide. Estudio inmunológico de diez niños.

Ten children clinically and histologically diagnosed as having pityriasis lichenoides (PL), have been studied by direct immunofluorescence (DIF). Circulating immune complexes (CI) have also been studied in four children. Granular deposits of IgM, located in the walls of the dermal vessels have been observed in two cases, but they have never been found at the dermo-epidermal junction. Granular deposits of C3 have been observed in three children, both in the walls of the dermal vessels and at the dermo-epidermal junction. The search for immune complexes gave negative results in all cases. The hypothesis of some authors that PL is an immune complex disease cannot be confirmed by our findings.

Immunopathologic studies in pityriasis lichenoides.

Skin biopsy specimens from five patients with pityriasis lichenoides et varioliformis acuta and from six patients with pityriasis lichenoides chronica were studied by direct immunofluorescence and by an immunoperoxidase technique using a panel of monoclonal antibodies. The dermal inflammatory infiltrate was composed of T cells, macrophages, and a small proportion of CD1a+ cells, mostly perivascular. CD8+ cells (cytotoxic/suppressor phenotype) predominated in the epidermis according to the degree of epidermal necroses, whereas CD4+ cells (helper/inducer phenotype) were superior in number among dermal T cells. A few B cells and Leu7+ cells were detected in only a small proportion of lesions. The results obtained confirm that the two conditions are variants of a single disease process and suggest that cell-mediated immune mechanisms may be important in the pathogenesis of the epidermal and vascular damage. Endothelial cells (HLA-DR+ and HLA-DQ+) and CD1a+ cells (epidermal and possibly dermal) could be primarily involved, acting as antigen-presenting cells.

Pityriasis rosea. An immunologic study.

Some immunologic studies were carried out for 31 patients with pityriasis rosea. Normal levels of serum IgG and IgA but higher levels of IgM were obtained. Serum C3 values were decreased while C4 values were normal. B lymphocytes showed no difference from the controls, whereas T-cell counts were significantly lower in the patients. The migration inhibition indices were higher in the patients than the controls. Direct immunofluorescence tests were negative in the studied three cases. The possible implication of a viral infection in the production of the reported changes was discussed.

Clonal T-cell populations in pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease).

Patients with the skin disorder pityriasis lichenoides et varioliformis acuta (PLEVA) develop recurrent, self-healing papulonecrotic lesions that contain infiltrates of cytologically and antigenically normal T lymphocytes. DNA extracted from the lesions of 3 patients with PLEVA was analyzed for rearrangement of beta-T-cell receptor genes for the purpose of assessing the clonality of T lymphocytes within the tissues of this disease. Lesions from all 3 cases showed clonal gene rearrangements. In each of 2 cases from which two separate lesions were biopsied, identical rearrangements were found in specimens from both sites. DNA from a variety of inflammatory lesions obtained from patients with other types of skin diseases failed to show detectable rearrangements of beta-T-cell receptor genes. These results suggest that PLEVA represents a T-cell lymphoproliferative process, rather than an inflammatory disorder, as had been previously thought.

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.

Immunohistologic studies in pityriasis rosea. Evidence for cellular immune reaction in the lesional epidermis.

Biopsy specimens of the skin lesions of pityriasis rosea obtained from 15 patients were studied. Characteristic histologic changes were composed of focal intercellular edema, epidermotropism of mononuclear cells often associated with the formation of focal intraepidermal collections of mononuclear cells, and of a perivascular lymphohistiocytic cell infiltration in the superficial dermis. Immunologic analysis using monoclonal antibodies showed that large numbers of lymphoid cells in the perivascular infiltrate reacted with anti-pan-T-cell, anti-helper-inducer subset, and anti-HLA-DR monoclonal antibodies, while the epidermotropic mononuclear cells consisted of helper-inducer cells or suppressor-cytotoxic cells without any predominance pattern. In addition to epidermal Langerhans' cells, some of the dermal infiltrating cells were reactive with monoclonal antibody OKT6. Moreover, there was localized expression of HLA-DR antigen on the keratinocytes. We think that cellular immune reactions are taking place in the lesional epidermis of pityriasis rosea.

Pityriasis rosea (Gibert): abnormal distribution pattern of antigen presenting cells in situ.

Pityriasis rosea is a skin disease which is obscure in its etiology and pathogenesis. We studied its immunopathology by immunophenotyping the inflammatory cells in situ using monoclonal antibodies that define leukocyte subsets. Findings as to T-cells and their major subsets did not reveal disease-specific data. Monocytes stained only rarely. Neither natural killer cells, B-cells nor plasma cells were ever found. An unexpected finding was the presence within the infiltrates and rarely within the epidermis of cells having the immunophenotype of interdigitating cells (RFD1+). Intense and dendritic staining with anti-T6 and anti-HLA-DR indicated Langerhans cells to be present in the dermal infiltrates, in between these infiltrates in the papillary dermis, and focally within the parakeratotic horny layer. This Langerhans' cell pattern provides evidence for dermal Langerhans cell compartmentalization and transepidermal Langerhans' cell elimination. Such a distribution indicates a change in Langerhans' cell migration processes in pityriasis rosea pathogenesis.

HLA-DR antigen expression on the keratinocyte surface in dermatoses characterized by lymphocytic exocytosis (e.g. pityriasis rosea).

We have investigated the immunoperoxidase staining pattern of the epidermis in several dermatoses characterized by exocytosis of mononuclear cells into the epidermis. We found that HLA-DR antigens showed an intercellular distribution in localized areas of the epidermis in nine of ten cases of pityriasis rosea, and in all four cases of spontaneously regressing flat warts, two cases of pityriasis lichenoides chronica, two of Schamberg's disease, and one case of lichen striatus. Lichen planus and mycosis fungoides cases were used as positive controls. OKT6 antigen was recognized only on the dendritic cells of the epidermis in all these cases. Judging from the distribution of Langerhans cells, the epidermal intercellular HLA-DR antigen seems to be expressed on the keratinocytes in such diseases, and this feature was confirmed by immunoelectron microscopy. These findings support the hypothesis that the expression of HLA-DR antigen on keratinocytes in these dermatoses is linked to cellular immune reactions involving the epidermis.

Immunopathology of pityriasis lichenoides acuta.

Eleven biopsy specimens (five papules and six dusky or crusted lesions) from four patients with pityriasis lichenoides et varioliformis acuta ( PLEVA ) were studied by direct immunofluorescence and immunoperoxidase technics. Slight vascular deposits of IgM and C3 were present in most lesions. Slight perivascular deposits of fibrin were observed in early lesions; more extensive perivascular and interstitial deposits of fibrin were detected in advanced lesions. Most of the infiltrating cells were T lymphocytes; cells with cytotoxic/suppressor phenotype (T8-positive) were generally more numerous than cells with helper/inducer phenotype (Leu-3a-positive, T4-positive). A marked increase in epidermal T8-positive cells over epidermal Leu-3a/T4-positive cells was found in late lesions. Moreover, a reduction of the ratio of circulating T4-positive to T8-positive cells was observed in most cases. The number of epidermal T6-positive (Langerhans/indeterminate) cells was decreased in the lower as compared with the upper stratum spinosum. About 5% of perivascular infiltrating cells were T6-positive. These results suggest that cell-mediated immune mechanisms are probably important in the pathogenesis of PLEVA .

Naturally occurring T lymphocytotoxic antibody in viral and related skin diseases.

The naturally occurring T lymphocytotoxic antibodies in patients with viral and related skin diseases were investigated and compared with those of systemic lupus erythematosus (SLE). The incidences of T lymphocytotoxic antibodies in exanthema suspected of viral infection, infectious mononucleosis, rubella and pityriasis rosea were 28%, 44%, 8% and 28% respectively. Sera from patients with herpes zoster and erythema infectiosum did not show positivity. Incidence in SLE sera as positive control was 82%. The T lymphocytotoxic antibodies detected in skin diseases were similar in nature to those of SLE patients, but were transient and lower in titer than those of SLE.