The spectrum of dermatological symptoms of pachydermoperiostosis (primary hypertrophic osteoarthropathy): a genetic, cytogenetic and ultrastructural study.

Pachydermoperiostosis (PDP) is characterized by finger clubbing, periostosis and peculiar skin involvement (pachydermia, seborrhea and folliculitis). The aim of our work was to determine the occurrence of dermatological symptoms in patients with PDP and their relatives, and to study ultrastructural skin changes in the complete and incomplete forms of the disease. A genetic and cytogenetic study was performed in order to identify the mechanism of transmission, to discover possible links to other genetic and non-genetic diseases and to determine the chromosomal complement and eventual chromosomal anomalies. Pachydermia was the most frequent skin alteration together with seborrhea; folliculitis was present in five patients. In the relatives mild pachydermia was detected in 2 out of 26, while seborrhea was present in 6 subjects. Light microscopic observation showed acanthotic epidermis and endothelial hyperplasia in the dermis with partial occlusion of the lumen, lymphohistiocytic infiltrate, and thickening and packing of collagen fibers. Electron microscopy showed fibroblast activation with increased fibrillogenic activity as shown by hypertrophic Golgi complexes and rough endoplasmatic reticulum with cisternae filled with microfibrils. Endothelial cells partially or completely occluded the capillary lumen and presented an increased amount of Weibel Palade bodies. These data show that skin involvement in PDP is a prominent feature, that sometimes these symptoms may also be present in their relatives, and that endothelial and fibroblast activation is present in the skin. Unfortunately the cytogenetic study did not provide any information about possible karyotype abnormalities.

Treatment pearls from Europe.

Discussing the need for psychological treatment of a dermatological condition with children and families can be a daunting task. Families must be given accurate information about the role of psychological or behavioral factors in the exacerbation or maintenance of their child's condition; however, this information must be presented in a way that families and children do not feel criticized or judged. This article discusses nondrug treatments of skin diseases.

Cutaneous necrotizing vasculitis. Relation to systemic disease.

Cutaneous necrotizing vasculitis (CNV) is a complex multisystem disease generally involving the skin and mucous membranes, often accompanied by renal, gastrointestinal, pericardial, neurological, and articular signs and symptoms. CNV may be idiopatical or occur in association with a drug, infection, or underlying disease. CNV has been shown in patients with chronic infections (viral, bacterial, protozoa, helminthic), serum sickness, a variety of collagen vascular diseases (systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, Behçet's disease) hyperglobulinemic states, cryoglobulinemia, bowel bypass syndrome, ulcerative colitis, cystic fibrosis, primary biliary cirrhosis and HIV infection. Association with malignancies is not frequent. Lymphoproliferative disorders (Hodgkin's disease, mycosis fungoides, lymphosarcoma, adult T-cell leukemia, multiple mieloma) and solid tumors (lung cancer, colon carcinoma, renal, prostate, head and neck cancer and breast cancer) may be associated with CNV. Whenever possible, treatment is directed at the elimination of the cause. In other cases after adequate laboratory screening local and systemic therapy are recommended.

Cellular steps in the pathogenesis of cutaneous necrotizing vasculitis.

Cutaneous necrotizing vasculitis (CNV) have been traditionally divided into "leukocytoclastic" and "lymphomonocytic" forms. The etiology and the pathogenesis of the two forms are not clear. We studied by immunohistochemistry and electronmicroscopy the infiltrate of 5 cases of leukocytoclastic form and 5 cases of lymphomonocytic form of CNV in two phases (early and late). Aim of the study was to evaluate: 1. the immunophenotypical characteristics of the infiltrate; 2. the expression of some adhesion molecules receptors; 3. the ultrastructural characteristic of the infiltrate; 4. the possible sequence of the events. Our results showed, by immunohistochemistry, a rich infiltrate of CD3+, CD4+, CD1a+ cells in both phases of lympho-monocytic vasculitis and a poor infiltrate of CD4+, CD1a+ and CD36+ cells in the early phase of leukocytoclastic vasculitis, while the perivascular infiltrate was rich of these cells in the late phase of this latter form. ICAM-1 and LFA-1 were strongly expressed in lympho-monocytic vasculitis. By electronmicroscopy, most infiltrating cells showing the ultrastructural markers of immature cells of dendritic lineage were in contact with each other and with lymphocytes and perivascular dendritic macrophages in lymphocytic form and in the late phase of leukocytoclastic form. Our results suggest that lymphocytic vasculitis might be related to a cell-mediated immune reaction and that the leukocytoclastic form of CNV, formerly considered a typical neutrophilic disease, is also maintained by a cell-mediated immune response to not yet identified endogenous antigens released in the lesional area.

Langerhans cells and vasculitis.

Langerhans cells are members of the dendritic cell system, which reside in the skin. These cells have many immunohistochemical and ultrastructural markers (for example, they are CD1a+ and possess Birbeck granules), which consent to identify them in an infiltrate. Langerhans cells have the specific role to present the antigens to T lymphocytes and to induce the cell-mediated immune reaction. Cutaneous necrotizing vasculitis (CNV) can be divided in two major forms: a leukocytoclastic type and a lymphocytic type. The pathogenesis of the first one is presumably immune complex-mediated, while for the second one a cell-mediated immunity has been proposed. Our group investigated on the cell infiltrate of some cases of CNV, both leukocytoclastic and lymphocytic type; and for leukocytoclastic CNV two phases were studied: an early one (at the onset of the lesion) and a later one (more than 24 hours). Special attention was paid to the presence of dendritic cells in the infiltrate and to their relationship to lymphocytes, if present. By immunohistochemistry and electron microscopy we could find many Langerhans cells and T lymphocytes in lymphocytic and in the late phase of leukocytoclastic CNV. The observed pattern of the cell infiltrate suggests that a cell mediated immune response play a major role in the pathogenesis of lymphocytic vasculitis and that dendritic cells and lymphocytes contribute to self-perpetuate leukocytoclastic vasculitis, which cannot be anymore considered as simply due to infiltration of neutrophils.

Working classification of vasculitis.

Vasculitis is defined as angiocentric segmental inflammation of the blood vessels and fibrinoid necrosis of the vessel wall. Classification of vasculitis is a controversial problem, because of the difficulty in incorporating globally different criteria such as histologic features, size of affected blood vessels, etiology, pathogenesis and other factors in a single classification schema. In this paper we review the principal classifications and make a novel attempt to classify vasculitis on the basis of the size of affected vessels. We hope that a new generation of basic and clinical investigators can achieve a better understanding of the pathogenesis of various vasculitis-related syndromes and that this understanding will facilitate future classification schemas.

Gamma/delta T lymphocytes in cutaneous necrotizing vasculitis.

Sections of lesional skin of 5 patients with leukocytoclastic cutaneous necrotizing vasculitis (CNV) (3 with documented infective etiology and 2 with unknow etiology) and of 5 patients with lymphocytic CNV with unknow etiology were investigated with immunoperoxidase technique. In lymphocytic CNV the dermal infiltrate was mainly constituted of CD3+, CD4+, CD1a+ and CD36+ cells. ICAM-1 and LFA-1 were strongly expressed. In leukocytoclastic CNV the infiltrate was poor of these cells in the early phase of disease, but they increased in the late phase. ICAM-1 and LFA-1 were strongly expressed in the late phase, while gamma/delta T cells and the expression of 72 kD heat shock protein were significantly present only in leukocytoclastic CNV with documented infective etiology. These results seem to suggest the role of a secondary cell-mediated immune response in the late phase of leukocytoclastic CNV, indicating gamma/delta T cells as a possible clue to the infective etiology of CNV.

Treatment of psoriasis vulgaris with topical calcipotriol: is the clinical improvement of lesional skin related to a down-regulation of some cell adhesion molecules?

Calcipotriol is demonstrably efficacious for the treatment of psoriasis by virtue of its effects on the skin's immune system and on epidermal growth. We performed this study to emphasize the difference in the expression of certain cell adhesion molecules (CAMs) (ICAM-1, ELAM-1, LFA-1, VLA-3, VLA-6) in lesional and perilesional skin of 10 patients with psoriasis, before and after treatment with topical Calcipotriol. We took two biopsies of lesional and perilesional skin from each patient before and after treatment and then performed an immunohistochemical study to observe the expression of these CAMs, utilizing monoclonal antibodies against these adhesion molecules. We noticed reduced levels of infiltrating cells along with the expression of ICAM-1, LFA-1, ELAM-1 and of CAMs VLA-3, VLA-6 in basal and suprabasal keratinocytes. On the basis of these data we hypothesize that, besides epidermal keratinocytes, another target for Calcipotriol may be the skin's own immune system, suggesting that Calcipotriol can modify T lymphocyte activity (IL-1 dependent) through a down-regulation of CAMs.

[Pityriasis rosea-like skin eruptions caused by captopril]. / Eruzione cutanea da captopril "pitiriasi rosea-like".

Captopril is an antihypertensive drug that works by inhibiting the angiotensin-converting enzyme and provokes increased levels of plasma quinine. In the case here reported a picture of pityriasis rosea-like reaction is described. The frequency of the observed and reported reactions by captopril suggests a particular caution in the use of this drug.