[Diagnostic image (143). A neonate with a skin disorder. Congenital cutaneous candidiasis]. / Diagnose in beeld (143). Een neonatus met een huidafwijking. Congenitale cutane candidiasis.

A premature neonate was born with a generalized eruption of vesicles, within a day developing into an erythrodermia, with bullae and widespread desquamation, due to congenital cutaneous candidiasis.

[From gene to disease; epidermolysis bullosa due to mutations in proteins in or around the hemidesmosome]. / Van gen naar ziekte; epidermolysis bullosa door mutaties in eiwitten in of rond het hemidesmosoom.

Epidermolysis bullosa is a group of hereditary mechanobullous dermatoses in which detachment of the skin and mucosa in or around the epidermal basement membrane takes place from birth on. The clinical manifestations vary from abnormalities in the nails to painful mutilation of the skin, eyes, mouth, throat, oesophagus and locomotor apparatus. Ten genes have been identified that can cause a form of epidermolysis bullosa. These genes code for proteins in or around the hemidesmosome, the site of anchorage of the basal cell to the basement membrane. The prevalence of epidermolysis bullosa is about 1 in 22,000. The diagnosis is on the basis of the medical history, clinical findings, immunofluorescence microscopy, electron microscopy and DNA studies. The current treatment is still primarily symptomatic and prophylactic.

[Diagnostic image (105). A woman with painful nodules. Infection with O. volvulus]. / Diagnose in beeld (105). Een vrouw met pijnlijke noduli. Infectie met O. volvulus.

A 17-year-old woman from the Democratic Republic of Congo presented with painful nodules on the legs and malaise. An infection with Onchocerca volvulus was diagnosed.

Expression of endoglin in the transition between psoriatic uninvolved and involved skin.

Endoglin is a glycoprotein which is predominantly expressed on endothelial cells. It is upregulated under inflammatory conditions as well as in skin lesions where endothelial cell proliferation occurs. Endoglin has the capacity to bind transforming growth factor beta (TGF-beta) and can reduce the bioavailability of TGF-beta. TGF-beta has a growth-inhibiting effect on keratinocytes and a restraining influence on the extravasation of peripheral white blood cells. In order to find out how endoglin is expressed in the margin zone of psoriatic plaques and how it correlates with the appearance of an inflammatory infiltrate, punch biopsies were taken from the margin zone of actively spreading psoriatic plaques in 8 patients. Indirect immunoperoxidase staining was performed using PAL-E (vascular endothelium), PN-E2 (anti-endoglin) and T11 (T-lymphocytes). In all patients it was found that the appearance of parakeratosis correlated with a clear increase of PN-E2 expression. PAL-E and PN-E2 expression was assessed, using a 5-point scale. Thus a tendency to decreased PN-E2 expression in uninvolved skin compared to PAL-E expression was found within the margin zone (1.6 +/- 0.4 and 2.2 +/- 0.4, respectively), whereas in involved skin PN-E2 expression and PAL-E expression were in agreement (2.6 +/- 0.5 and 2.6 +/- 0.5 respectively), suggesting that in the overt plaque all endothelium is in a so-called activated state. Also correlating with PN-E2 expression was the appearance of a huge dermal lymphocytic infiltrate and epidermal T-lymphocytic expression. The present study lends further support for a permissive role of endoglin expression in the development of the psoriatic lesion.

Extremely low levels of epidermal skin-derived antileucoproteinase/elafin in a patient with impetigo herpetiformis.

Impetigo herpetiformis (IH) is a rare pustular dermatosis with unknown aetiology, typically occurring during pregnancy. Based upon a similar clinical and histological presentation, i.e. spongiform accumulation of polymorphonuclear leucocytes in the stratum corneum, several authors consider IH as a variant of generalized pustular psoriasis (GPP), while others state that IH is a separate entity. Skin-derived antileucoproteinase (SKALP) is a strong and specific inhibitor of human leucocyte elastase (HLE) and proteinase 3, two neutral proteinases that have been implicated in leucocyte migration and tissue destruction. Previously, we reported decreased SKALP activity in pustular forms of psoriasis compared with plaque psoriasis. In this study we present a case study of a patient with IH, where SKALP activity was measured using biochemical and immunochemical techniques. Epidermal scales and sera were collected during the course of the disease. Comparison was made with three patients with GPP and six patients with plaque psoriasis. Initially, anti-HLE activity in epidermal scales of the patient with IH was comparable with values in patients with GPP, i.e. decreased compared with plaque psoriasis. During the course of the disease, anti-elastase activity dropped to undetectable levels, concomitant with the appearance of free elastase activity. This finding suggests a total saturation of epidermal anti-HLE activity. Low levels of SKALP, presumably complexed with HLE, could be measured immunochemically in scale extracts. Serum levels of total SKALP correlated with the disease activity. We suggest that a reduced amount of epidermal SKALP contributes to an imbalance between elastase and its inhibitor, resulting in the formation of epidermal pustules. This mechanism of pustule formation could apply both to GPP and IH, suggesting a final common pathway in the pathogenic mechanisms of IH and GPP.

Expression of endoglin in psoriatic involved and uninvolved skin.

Endoglin is a glycoprotein with TGF-beta binding capacity and is predominantly expressed on endothelial cells. In psoriasis, TGF-beta has appeared to play a role in the extravasation of peripheral blood mononuclear cells via the endothelium. In order to find out more about the role of endoglin in psoriasis, immunohistochemical staining with PN-E2, a novel anti-endoglin, and of PAL-E, recognizing vascular endothelium, was carried out in psoriatic involved, psoriatic uninvolved and normal skin. The expression of the antigens was assessed semi-quantitatively using a five-point scale. In psoriatic involved skin, a high endoglin expression was found. In psoriatic uninvolved skin, however, we found that endoglin expression was significantly decreased compared with normal skin. The relevance of these findings to the pathogenesis of psoriasis is discussed.

Response of the clinically uninvolved skin of psoriatic patients to repeated tape stripping during cyclosporin A treatment.

It is well established that cyclosporin A (CyA), a widely used immunosuppressant in human organ transplantation, is an effective drug in the treatment of psoriasis. Although it has been postulated that the effect of CyA in psoriasis is mediated through antilymphocyte activity, there is also evidence suggesting that CyA exerts a direct cytostatic effect on epidermal keratinocytes, but results of studies relating to the latter have been contradictory. Using immunohistochemical methods we investigated the influence of systemic CyA on proliferation and differentiation in the tape-stripped uninvolved skin of psoriatic patients, a model which provides the opportunity of studying epidermal regeneration in the absence of a significant accumulation of T lymphocytes. We addressed the question of whether CyA (3-5 mg/kg/day) modulates epidermal proliferation and differentiation following standardized injury in uninvolved skin of psoriatic patients. Ten patients with severe psoriasis participated in this study. The dosages of CyA were sufficient to induce a marked and statistically significant improvement (PASI, week 0, 20.5 +/- 4.4; PASI, week 16, 4.3 +/- 0.6). Before CyA treatment, and during week 16 of treatment, Sellotape stripping was carried out on a 2-cm2 area of the uninvolved skin of psoriatic patients. After 48 h punch biopsies were taken. Immunohistochemical assessment of recruitment of cycling cells (Ki-67), filaggrin, involucrin, T lymphocytes and tenascin, was carried out. We did not find any significant alteration during the treatment period in the tape-stripped uninvolved skin of psoriatic patients. We conclude that epidermal hyperproliferation and abnormal keratinization are not modulated directly by CyA at therapeutic doses in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Topical treatment of psoriatic plaques with 1,25-dihydroxyvitamin D3: a cell biological study.

Calcitriol, 1 alpha,25 dihydroxycholecalciferol (1 alpha,25 (OH)2 D3) is a natural active vitamin D3 metabolite, which has been shown to have antipsoriatic efficacy. In vitro studies have demonstrated that calcitriol influences various aspects of inflammation, epidermal proliferation and keratinization. The aim of the present study was to determine to what extent calcitriol (3 micrograms/g in white petrolatum) affects these parameters in vivo. Using an immunohistochemical assessment of recruitment of cycling epidermal cells, filaggrin and involucrin expression, T-cell accumulation, polymorphonuclear neutrophil (PMN) accumulation, amount of endothelium and ICAM-1 expression, we demonstrated that: (i) modulation of all these parameters occurred during calcitriol treatment; (ii) there was early reduction of epidermal proliferation and PMN accumulation; (iii) the order of changes was comparable with the response to treatment with calcipotriol. In conclusion, at the cell biological level, calcitriol (3 micrograms/g in white petrolatum) has a substantial effect on various elements of the psoriatic lesion.

Normal human skin demonstrates marked site-variation of tenascin expression, not correlated to epidermal proliferation (Ki-67 binding).

In disorders of the skin characterized by epidermal hyperproliferation, it has been demonstrated that the expression of tenascin in the dermis is markedly increased. In normal dermis, however, tenascin is slightly expressed in the upper dermis beneath the basal membrane. Using an immunohistochemical approach, tenascin expression (T2H5 binding) and recruitment of cycling epidermal cells (nuclear binding to Ki-67) were studied in normal skin at various localizations of the body surface. Whereas recruitment of cycling epidermal cells did not show a significant body-site variation, tenascin expression was most pronounced at the extensor surface of the lower arm. In normal skin, no significant correlation was observed between both phenomena in striking contrast to the well-established correlation in hyperproliferative skin conditions.

Topical application of 13-cis-retinoic acid in the treatment of chronic plaque psoriasis.

Topical retinoids are of potential value in the treatment of psoriasis. The aim of the present study was to find out whether topical application of 13-cis-retinoic acid (13-cis-RA) has an antipsoriatic effect. Nine patients participated in the investigation. In each patient, two comparable psoriatic lesions (5 x 5 cm or more) were selected for treatment with either 13-cis-RA in a 0.1% cream base or with the vehicle only (placebo), using a double-blind approach. The investigation was a left-right within-subject comparison. The lesions were recorded for clinical scores 4 weeks before and after the investigation. Punch biopsies were taken from eight patients before and after treatment and examined using immunohistochemical methods to assess epidermal proliferation and keratinization, and to assess inflammation. Thirteen-cis-RA treatment resulted in a mild decrease of scaling and induration. Erythema however increased. No statistically significant difference in biological effects was achieved between 13-cis-RA and placebo treated lesions and no changes in expression of the immunohistochemical markers were seen.

Treatment of inflammatory linear verrucous epidermal nevus.

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare and chronic skin disorder, which may trouble the patient considerably. The condition is generally believed to be resistant to therapy, although some authors have reported success with several treatments. including dithranol and etretinate. The present case, a classical presentation of ILVEN, again illustrates the refractoriness to various treatments, including an experimental treatment with topical 13-cis-retinoic acid. A review of the literature on therapeutic possibilities of ILVEN is presented. Based on our own observations and literature data, it is attractive to hypothesize that a positive result with treatments such as dithranol and retinoids should be interpreted as an antipsoriatic effect in ILVEN with superimposed psoriasis.

Inflammatory linear verrucous epidermal naevus (ILVEN) versus linear psoriasis. A clinical, histological and immunohistochemical study.

Inflammatory Linear Verrucous Epidermal Nevus (ILVEN) has been suggested to be a separate disease entity. However, the distinction from linear psoriasis has been discussed in the literature over recent decades. The aim of the present study was to investigate, in addition to the clinical and histological criteria, the immunohistochemical aspects of inflammation, epidermal proliferation and keratinization. From a clinical and histological point of view, ILVEN and psoriasis, according to the established criteria, have been proved to overlap. The immunohistochemical study suggests that the following procedures have an additional diagnostic impact: assessment of elastase-positive cells, assessment of keratin 16 and of keratin 10.