Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole.

Liarozole, a novel imidazole derivative, inhibits the cytochrome P450-dependent 4-hydroxylation of retinoic acid, resulting in increased tissue levels of retinoic acid. Twelve male patients with ichthyosis were given oral liarozole, 150 mg twice daily, in an open study for 12 weeks. Immunohistochemical parameters of inflammation, epidermal proliferation and differentiation were assessed before and after treatment. Extent and severity of the skin lesions was markedly reduced in all patients. Clinical side-effects were reminiscent of those with synthetic retinoids. No relevant changes were found in the haematological, urinary and biochemical parameters. Immunohistochemical assessment showed a statistically significant induction of keratin 4 after liarozole treatment in 10 of 12 patients. In two of these patients keratin 13 was induced. This open study showed that oral liarozole treatment was efficacious and well tolerated in the treatment of different types of ichthyosis. The immunohistochemical results suggest a retinoid mechanism as the mode of action.

Acquired ichthyosiform erythroderma and sarcoidosis.

We describe a patient with ichthyosiform erythroderma as a manifestation of sarcoidosis. This is the first report of the simultaneous occurrence of erythroderma and ichthyosis in sarcoidosis.

[Keratosis palmoplantaris varians et punctata. Clinical variability of an single genetic defect?]. / Keratosis palmoplantaris varians et punctata. Klinische Variabilität eines einzigen genetischen Defektes?

Palmoplantar keratodermia (PPK) varians and PPK punctata are considered different entities within the group of hereditary palmoplantar keratodermas. Keratosis punctata of the palmar creases constitutes a localized form of keratodermia palmoplantaris punctata. We describe a 31-year-old man exhibiting both nummular and papular keratoses on the soles, as well as small punctate keratoses confined to the palmar creases. In view of the co-occurrence of these two types of PPK, the question arises whether keratosis palmoplantaris of the varians and the punctate type represent distinct entities or represent variable manifestations of the same gene defect.

Flow-cytometric investigation of epidermal cell characteristics in monogenic disorders of keratinization and their modulation by topical calcipotriol treatment.

A flow-cytometric study was performed in monogenic disorders of keratinization, to assess DNA distribution as well as the expression of keratins and involucrin. In addition, the changes in expression of these markers under influence of calcipotriol treatment were investigated. Proliferation, measured by the percentage of epidermal cells in SG2M-phase of the cell cycle, was increased in Darier's disease, lamellar ichthyosis, congenital bullous ichthyotic erythroderma of Brocq and the Comel-Netherton syndrome, whereas normal proliferation was found in autosomal dominant ichthyosis vulgaris, X-linked recessive ichthyosis, keratosis pilaris, ichthyosis bullosa of Siemens and the Sjögren-Larsson syndrome. Keratin 6 was enhanced in erythrodermic lamellar ichthyosis, congenital bullous ichthyotic erythroderma of Brocq and the Comel-Netherton syndrome, showing also reduction of keratin 10. Involucrin was only slightly reduced in erythrodermic lamellar ichthyosis, congenital bullous ichthyotic erythroderma of Brocq and the Comel-Netherton syndrome, compared to the pronounced reduction in all other skin disorders studied. Calcipotriol was found to enhance differentiation in Darier's disease, erythrodermic lamellar ichthyosis, and congenital bullous ichthyotic erythroderma of Brocq. Only Darier's disease did not show clinical improvement. In conclusion, flow cytometry provides a useful method for quantification of epidermal cell characteristics in monogenic disorders of keratinization. Further studies need to be performed to establish its usefulness as a diagnostic and prognostic tool.

Topical R-85355, a potent and selective 5-lipoxygenase inhibitor, fails to improve psoriasis.

Inhibitors of 5-lipoxygenase have been studied with respect to antipsoriatic efficacy. Of these compounds, R-68151 is of particular interest as it proved to inhibit 5-lipoxygenase without inhibiting 12-lipoxygenase, cyclooxygenase and thromboxane-A2 synthetase. R-68151 has been shown to have a mild-to-moderate therapeutic effect in psoriasis. In the present study a new 5-lipoxygenase, R-85355, was investigated with respect to its efficacy in psoriasis. R-85355 is 3 times more potent compared to R-68151 with respect to inhibition of in vitro A-23187-stimulated leukotriene-B4 production by polymorphonuclear leukocytes. In a left-right double-blind comparative study, the compound was studied at saturation with respect to its antipsoriatic efficacy in 11 patients with chronic stable plaque psoriasis. In addition, various markers for epidermal proliferation, keratinization and inflammation were assessed. In no single patient was a left-right difference observed in favour of R-85355 compared to placebo with respect to clinical severity scores or the cell-biological markers. The present study indicates that a selective and highly potent 5-lipoxygenase inhibitor was not effective in the topical treatment of chronic plaque psoriasis.

Acrokeratosis paraneoplastica (Bazex syndrome) occurring with acquired ichthyosis in Hodgkin's disease.

We report a patient who exhibited two paraneoplastic skin disorders, acrokeratosis paraneoplastica and acquired ichthyosis, in association with Hodgkin disease. Treatment of the Hodgkin's disease resulted in rapid improvement of both skin disorders, confirming a causal relationship. The simultaneous presence of two paraneoplastic skin disorders suggests a common pathogenetic factor. Transforming growth factor alpha, produced by tumour cells, may play a part in the aetiopathogenesis of hyperproliferative paraneoplastic skin conditions.

Pachyonychia congenita tarda.

Pachyonychia congenita is a distinct hereditary disorder of keratinization, in which dystrophy of all nails is associated with palmoplantar keratoderma and other hyperkeratoses. Recently a late-onset type has been reported. We report a second family with late-onset pachyonychia congenita, showing a remarkable clinical heterogeneity. Furthermore, one patient demonstrated a number of associated hyperkeratoses not previously recognized. Acitretin proved useful in the treatment of this late-onset form of pachyonychia congenita.

Topical treatment of Sjögren-Larsson syndrome with calcipotriol.

Two patients with Sjögren-Larsson syndrome were treated with calcipotriol in ointment and the ointment base only for 12 weeks, using a double-blind bilaterally paired comparative study. Unilateral improvement was observed in both patients in favour of the calcipotriol-treated side. The present case is the first demonstration of a substantial clinical effect of calcipotriol in the Sjögren-Larsson syndrome.

Effect of topical calcipotriol on congenital ichthyoses.

We investigated the clinical efficacy of topically applied calcipotriol in six patients with congenital ichthyosis, using a double-blind, bilaterally paired, comparative approach. Unilateral improvement, in favour of the calcipotriol-treated side, was observed in three patients with lamellar ichthyosis. A beneficial response was also observed in a patient with bullous ichthyotic erythroderma of Brocq. No clinical side-effects or laboratory anomalies were observed. This study indicates that calcipotriol constitutes a new and promising approach in alleviating disorders of keratinization characterized by hyperproliferation, other than psoriasis.

Widespread leucokeratosis in Noonan's syndrome.

A case of Noonan's syndrome is presented. In addition to the typical manifestations of the disease, widespread leucokeratosis of the lips and gingiva appeared to be a prominent feature.

The hereditary palmoplantar keratoses: an updated review and classification.

The palmoplantar keratoses (PPKs) comprise a heterogeneous group of disorders of keratinization, which can be subdivided into hereditary and acquired forms. Many authors have attempted to classify the hereditary forms, and most classifications have been based on the morphology, distribution, associated symptoms and mode of inheritance. Subsequently, many new forms have been recognized, and what were previously considered to be distinct types have been shown to be variants of a single type, both of which limit the usefulness of previous classifications. Hence, we propose a new, updated classification, which enables accurate diagnosis of these disorders.

The coexistence of linear and giant porokeratosis associated with Bowen's disease.

Linear and giant porokeratosis are both rare variants of this disorder of keratinization. We present a case exhibiting the clinical features of both variants coexisting in one patient, which to our knowledge has not been described previously. Furthermore, Bowen's disease was found to be present in the giant lesion, reflecting the enhanced risk of malignant transformation of this rare subtype of porokeratosis.

Evaluation of the frequency of contact allergic reactions to Kathon CG in the Maastricht area--1987-1990.

In the period 1987-1990, 999 patients suspected of a contact allergy were patch-tested with Kathon CG 100 ppm active ingredients aq. Of these patients, 84 (8.4%) showed a positive reaction (70% females). In 62% of these cases clinical relevance was established. Most of them suffered from contact dermatitis of the face, the hands or the perianal region.