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M J Gerritsen

Publications and source records attributed to M J Gerritsen.

At least 19 recordsLinked to original sources
PubMed2000

Cutis marmorata telangiectatica congenita: report of 18 cases.

We report 18 patients with cutis marmorata telangiectatica congenita (CMTC) who visited the University Hospital Nijmegen between 1982 and 1999. In 11 patients (61%), associated abnormalities of varying severity were observed. Three of these patients had a previously described distinct syndrome comprising CMTC, a naevus flammeus at the upper lip/philtrum, macrocephaly and syndactyly, among other abnormalities. Findings in the other eight patients with associated abnormalities included hydrocephalus, hyperplasia/hypoplasia (body asymmetry), anal atresia, hearing loss, cardiovascular abnormalities, strabismus hypothyroidism, haemangioma, naevus anaemicus, café-au-lait spot, lipoma and an elevation of the right diaphragm. All cases were sporadic.

Abnormalities, Multiple↗
PubMed2000

Efficacy of calcipotriol ointment applied under hydrocolloid occlusion in psoriasis.

BACKGROUND: Hydrocolloid (HCD) dressings enhance the efficacy of topical corticosteroids. OBJECTIVE: We wanted to evaluate the effect of calcipotriol ointment under an HCD dressing in the treatment of psoriatic plaques. METHODS: In 9 psoriatic patients, we cleared one plaque using this approach and took biopsies at start, clearance and relapse. Clinical and immunohistochemical validation was assessed. RESULTS: After an average treatment of 3.6 weeks, each lesion had cleared (apart from some residual erythema). The average remission period was 8 weeks. During this treatment, the number of cycling epidermal cells (Ki-67-positive nuclei) and the expression of keratin 14 and keratin 16 had decreased substantially. In biopsies taken from the skin immediately adjacent to the relapsing lesion, these markers remained reduced which indicated the prolonged effect of calcipotriol on epidermal differentiation. CONCLUSION: It is speculated that combination therapy of calcipotriol with treatments with a different mode of action such as photo(chemo)therapy, corticosteroids and cyclosporine might be worthwhile.

Adult↗
PubMed2000

Cell-kinetic evidence for increased recruitment of cycling epidermal cells in psoriasis: the ratio of histone and Ki-67 antigen expression is constant.

BACKGROUND: One of the hallmarks of the psoriatic plaque is increased epidermal proliferation. Whether this is the result of an increased recruitment of cycling epidermal cells or a decrease in cell cycle time has been a matter of debate for years. OBJECTIVE: Calculating cell-kinetic information from the number of S phase cells in psoriasis by in situ hybridisation using a histone probe and the number of cycling epidermal cells by immunohistochemistry using the MIB-1 antibody. METHODS: Immunohistochemistry and non-isotopic in situ hybridisation were performed on serial sections of 33 untreated psoriatic samples and 14 tacalcitol-treated samples. RESULTS: The labelling index (number of cells in S phase/number cycling cells per millimetre length of section) in psoriatic untreated as well as in treated plaques is 16%. The amount of S phase cells in our experiment is equal compared with the number of cells in S phase as determined by BrdU incorporation. CONCLUSION: Using this direct approach to study cell-kinetic behaviour of psoriatic skin, we reconfirm that the psoriatic abnormality is due to a defect in the G(0)-G(1) recruitment mechanism (by increased recruitment of G(0) cells), a decrease in apoptosis or an increase in the number of cell divisions in the transit-amplifying compartment, rather than a reduction in the cell cycle time.

Cell Cycle↗
PubMed1999

The epidermal phenotype during initiation of the psoriatic lesion in the symptomless margin of relapsing psoriasis.

BACKGROUND: The mature psoriatic lesion does not necessarily demonstrate changes relevant to early phases of the lesion. OBJECTIVE: In a model for relapsing psoriasis we examined the epidermal phenotype by means of a panel of immunohistochemical parameters: keratins 14 and 16, epidermal growth factor receptor (EGFR), Ki-67 antigen, and Tdt-mediated Unscheduled Nick End Labeling to detect apoptosis. METHODS: In 9 patients, we cleared psoriatic plaques by topical treatment with clobetasol-17-propionate under hydrocolloid occlusion. Relapse (defined as a clinical sum score > or = 6) was awaited. Biopsy specimens of the psoriatic lesion, the cleared skin, the relapsed plaque, and its clinically normal margin were assessed. RESULTS: Psoriasis recurred after 19+/-6 weeks (mean +/- SEM). During treatment all parameters improved considerably; however, the number of apoptotic cells was not affected. Ki-67 values decreased well below the normal range. At initial relapse, the symptomless skin adjacent to the relapsing lesion (margin) showed a marked expression of keratin 16 and EGFR. Ki-67 expression was increasing in the margin but was below values of the mature lesion. The localization of cycling cells in the first suprabasal layers was a remarkable feature. Keratin 14 expression was increased in the recurrent lesion itself, but not in the symptomless margin. CONCLUSION: Keratin 16 and EGFR expression are early phenomena in the evolution of the lesion, and they anticipate epidermal proliferation. The expression of keratin 14 follows overt epidermal hyperproliferation. The present observation in incipient psoriasis lends support to the hypothesis that the basal cell compartment does not have a primary involvement in the initiation of epidermal abnormalities in psoriasis, but that a coordinated sequence of events involving proliferation and differentiation markers in the first suprabasal layers of the epidermis could be the key to the pathogenesis of this puzzling disease.

Administration, Topical↗
PubMed1999

Proliferation is the main epidermal target in the treatment of psoriatic plaques with once daily application of tacalcitol ointment.

We studied the effect of tacalcitol (1 alpha, 24 dihydroxy vitamin D3) ointment on clinical and immunohistochemical efficacy in psoriatic patients during 2 months of treatment. The psoriasis area and severity index decreased significantly after only 1 month and the total body surface index decreased 55% after 2 months. To characterize the epidermal compartment keratin 14, keratin 16, epidermal growth factor receptor, apoptotic and Ki-67 positive cells were examined. After 1 week of treatment no significant changes were found in any of these parameters. After 2 months, keratin 16 reached the levels observed in normal skin and Ki-67 and keratin 14 expression also reduced significantly. Epidermal growth factor receptor staining and the number of apoptotic cells did not alter during treatment. We conclude that tacalcitol is effective in the treatment of plaque psoriasis. Because the main epidermal effect observed immunohistochemically is a reduction in proliferation, a combination therapy using either corticosteroids, vitamin A derivatives or dithranol seems rational.

Administration, Cutaneous↗
PubMed1998

Epidermal cell kinetics by combining in situ hybridization and immunohistochemistry.

Double labelling can serve as a useful tool for providing information about cell kinetics in normal and hyperproliferative tissues in general, and skin in particular. We have developed a double-labelling method that combines immunohistochemistry using the monoclonal antibody MIB1 and non-isotopic in situ hybridization using either a digoxigenin-labelled RNA probe specific for histone 3 mRNA sequences or a Fluorescein-labelled oligonucleotide probe specific for histone 2b, 3, 4 mRNA sequences. Double labelling was performed on normal, tape-stripped normal skin and psoriatic skin. The three proliferation markers were also examined by single labelling. The ratio of cells in the S-phase (Ns) and the growth fraction (Ncy) was determined. In normal skin, psoriatic skin and tape-stripped normal skin after 24 h and after 48 h, we calculated that 15%, 16%, 3% and 12% of growth fraction consisted of cells in the S-phase respectively. The S-phase lasts approximately 10 h, so the cell cycle time in normal and psoriatic skin is approximately 62.5 h. At present, the MIB1/H3 digoxigenin or MIB1/H2b-H3-H4 Fluorescein double-labelling technique cannot be used routinely. Therefore, in order to understand the cell kinetic processes better, experiments are recommended to optimize these methods. From a practical point of view and for reasons of specificity and sensitivity, we prefer the Fluorescein-labelled oligonucleotide probe method.

Cell Division↗
PubMed1997

Recruitment of cycling epidermal cells and expression of filaggrin, involucrin and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin of psoriatic patients and in the normal healthy skin.

The peripheral changes in the uninvolved skin adjacent to the extending psoriatic lesions may represent early events. The sequence of these events remains controversial. In the present study we evaluated epidermal and dermal aspects of the margin of the progressive psoriatic plaque, the distant uninvolved skin and normal healthy skin, using immunohistochemistry with markers for keratinization, proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin. The results showed that: (i) processes in distant uninvolved skin were comparable with the observations in normal skin; (ii) in the margin zone of the spreading psoriatic lesion, following the increased appearance of tenascin, the transition into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment of cycling epidermal cells, happened simultaneously. The simultaneous normalization of these epidermal processes might be a consequence of a signal which is simultaneously transduced to the basal and suprabasal cell layers of the epidermis. Based on the present results and earlier findings, we would like to propose a triple stage model for the development of the psoriatic lesion: Stage 1, involvement of the stroma; stage II, inflammatory infiltrate formation and penetration into the upper layers of the epidermis, with suprabasal expression of keratin 16; stage III, recruitment of cycling epidermal cells and abnormal terminal differentiation. Further studies are required on the regulation of tenascin expression, focusing on factors derived from the stroma affecting both recruitment of cycling epidermal cells, involucrin and filaggrin expression. An intermediate step in the dermo-epithelial interrelation is the inflammatory infiltrate, penetrating into the most superficial zone of the epidermis, and the suprabasal expression of keratin 16.

Adult↗
PubMed1996

A novel dithranol formulation (Micanol): the effects of monotherapy and UVB combination therapy on epidermal differentiation, proliferation and cutaneous inflammation in psoriasis vulgaris.

Micanol, in which dithranol is micro-encapsulated in crystalline monoglycerides, is easy to wash off and staining and irritation are inconspicuous. These features make it appropriate to use in an out-patient setting. In this study the immunohistochemical effects of this new dithranol formulation were studied and compared with UVB and the combination of these therapies in skin biopsies of 8 patients with psoriasis. Markers for epidermal differentiation, proliferation and cutaneous inflammation were assessed. The present study suggests that Micanol predominantly had diminishing effects on inflammation markers, hardly affecting the epidermis. UVB had a broad spectrum of reductions. It is feasible that the combination resulted in various synergistic effects. Previous studies, however, revealed a relative persistence of the inflammatory infiltrate with more effects on epidermal processes following dithranol treatment. Based on the present study and on previous studies, it is hypothesised that Micanol delivers the active substance more directly in the dermal infiltrate, leaving the epidermis relatively unaffected. This might explain the low irritancy of Micanol treatment.

Adult↗
PubMed1996

A therapeutic approach to erythrodermic psoriasis: report of a case and a discussion of therapeutic options.

In this case report a patient with therapeutically recalcitrant erythrodermic psoriasis is presented. After various attempts with several major therapies in this patient, the first substantial improvement was achieved using the combination of cyclosporine and calcipotriol, followed by the combination of UVB and calcipotriol. The therapeutic options for severe psoriasis are discussed, and since combined approaches seem to be an attractive alternative for severe psoriasis, mechanisms of synergy of combined therapeutic approaches are hypothesised.

Aged↗
PubMed1996

Response of the clinically uninvolved skin of psoriatic patients to tape stripping during acitretin treatment.

The aromatic retinoids etretinate and acitretin are widely used in the systemic treatment of severe psoriasis. The purpose of the present investigation was to further elucidate the mode of action of acitretin on abnormal keratinization and epidermal hyperproliferation in an in vivo model. Studies on the interference of acitretin with epidermal hyperproliferation and abnormal keratinization in psoriatic plaques are difficult to interpret, as acitretin-induced changes might be due to direct effects of acitretin or be the indirect effect of retinoid-induced modulation of cutaneous inflammation. Using an immunohistochemical assessment, we examined the in vivo effect of systemic acitretin ( > 35 mg daily) on the expression of filaggrin, involucrin, and on the recruitment of cycling epidermal cells, in the tape-stripped uninvolved skin of psoriatic patients, a model which provides the opportunity to study epidermal regeneration in the absence of significant accumulation of T-lymphocytes. During acitretin therapy and 3 weeks after withdrawal of acitretin, we took biopsies from uninvolved skin following tape-stripping in 6 patients with psoriasis. Six patients with psoriasis who had never used acitretin served as controls. We did not observe a Koebner response in our patients after tape stripping. Filaggrin expression was decreased, while the recruitment of cycling epidermal cells and the involucrin expression were increased in the biopsies taken from patients who did not use acitretin. During acitretin treatment, however, the filaggrin expression was similar, whereas the Ki-67 positive nuclei and the involucrin expression showed a statistically significant decrease compared to those parameters in the patients who did not use acitretin. Our findings indicate that epidermal hyperproliferation and abnormal keratinization are modulated directly by acitretin.

Acitretin↗
PubMed1996

Transition from symptomless to lesional psoriatic skin.

Numerous investigations have been carried out to describe the cellular biological changes in lesional and symptomless psoriatic skin. Although these studies have increased our knowledge of the pathogenesis of psoriasis, our insight into the relevance of the individual changes in the whole pathogenic process is still limited. Studies on the transition between symptomless and lesional skin are of importance in assessing the pathogenic relevance of the individual aspects. In this paper, the literature is reviewed with respect to the transitional changes; in particular, studies on changes at the margin of the psoriatic lesion and the response of the symptomless skin to standardized injury are reviewed. From the available studies it may be concluded that changes in the stroma (i.e. increased expression of tenascin and increased endothelial alkaline phosphatase activity) are early pathogenic features. The appearance of a predominantly lymphocytic infiltrate, in particular the extravasation of CD4+ T lymphocytes, and the suprabasal expression of keratin 16 are intermediary stages. Relatively late in the pathogenesis are increased recruitment of cycling epidermal nuclei, parakeratosis, decreased expression of filaggrin and premature expression of involucrin. In order to discover the pathogenic relevance of molecules which might have an impact on the development of psoriasis, sequential studies during transition from symptomless to lesional skin are worthwhile.

Animals↗