Marcel C. Pasch

High discordance between punch biopsy and excision in establishing basal cell carcinoma subtype: analysis of 500 cases

Background  Basal cell carcinoma (BCC) is the most frequently occurring cancer in humans. Worldwide incidences rise about 10% each year, increasing the burden on dermatologists, general practitioners and pathologists as well as increasing costs for the health care system. Increasingly non‐surgical treatment options are used in the treatment of BCC, without histological confirmation of BCC subtype, potentially resulting in under‐treatment.

Nail psoriasis: a questionnaire-based survey.

Skin manifestations are the most characteristic finding of psoriasis. However, nail involvement is also a clinical feature of disease although it is often overlooked. The documented prevalence of nail psoriasis varies between 10·0% and 81·1%.

Therapeutic effects of a 12-week course of alefacept on nail psoriasis.

Background and objectives  Nail psoriasis is a common finding in psoriatic patients and it affects the quality of life in a great proportion of patients. Topical or systemic treatments have limited effectiveness or have a serious toxicity potential. Biologicals such as alefacept are the most recent treatment modalities for psoriasis. In the present study we evaluated changes in nail pathology in patients with plaque psoriasis and nail involvement during treatment with alefacept.

The prevalence of onychomycosis in psoriatic patients: a systematic review

We systematically reviewed all available literature concerning the prevalence of onychomycosis in patients with nail psoriasis and the distribution of pathogens causing onychomycosis in this specific group of patients. Databases searched were Pubmed, EMBASE and the Cochrane Controlled Clinical Trial Register. All studies reporting on the prevalence of onychomycosis in nail psoriasis were obtained, and quality assessment was determined by the STrengthening the Reporting of OBservational studies in Epidemiology checklist. Literature search revealed 720 studies, of which 10 studies met the inclusion criteria. The major limitation of the review was the heterogeneity of the included studies, which prevented the possibility to conduct a meta analysis. However, the average prevalence of 18.0% of onychomycosis in psoriatic patients seems to be increased when compared with control groups and literature on healthy population, even though the ultimate evidence remains lacking. As in the literature hypothesized shift in causative agents from dermatophytes to yeasts and/or moulds could not be confirmed. The clinical consequence of the relatively high prevalence of onychomycosis in psoriasis may be a general advice to rule out onychomycosis or concomitant onychomycosis in these patients with (suspected) nail psoriasis. This advice is stressed by the relative simplicity of treating the contribution of onychomycosis in the nail dystrophy but also the fact that nail psoriasis mostly is treated by immunosuppressive drugs, like steroids, methotrexate or biologics which may aggravate mycotic nail infections.

Assessment of epidermal subpopulations and proliferation in healthy skin, symptomless and lesional skin of spreading psoriasis

Background  The margin zone in spreading psoriatic lesions has frequently been used as a model to study the changes in epidermal proliferation, keratinization and inflammation during the transition from symptomless to lesional skin. However, the dynamics of the changes in the epidermal subpopulations—basal cells, transit amplifying cells and differentiated cells—have not been studied in the transition between symptomless and lesional skin.

Treatment of plaque psoriasis with the two-compound product calcipotriol/betamethasone dipropionate versus both monotherapies: An immunohistochemical study

The combination of calcipotriol (Cp) and topical corticosteroids increases efficacy and reduces side effects as compared to monotherapies. Previous studies suggest that such combinations may have an added value with respect to reduction of T-cell subsets. A two-compound product consisting of Cp and betamethasone dipropionate (BD) has become available for the treatment of psoriasis and is clinically superior to both monotherapies. No immunohistochemical data are available on the in vivo effects of the two-compound formulation versus monotherapy with respect to the three key processes in psoriasis pathogenesis: epidermal proliferation, epidermal differentiation and inflammation. Therefore, 18 patients were treated with the two-compound product, Cp monotherapy or BD monotherapy for 6 weeks and biopsies were taken before and after 4 and 6 weeks of treatment. These biopsies were stained immunohistochemically and analysed (semi)quantitatively. All treatments decreased the number of Ki-67+ cells and increased the keratin 15+ staining. A more pronounced reduction of epidermal and dermal T-cell markers and human beta defensin-2 was seen following combination treatment, compared with both monotherapies. In conclusion, the investigated markers of the skin immune system and epidermal proliferation indicated an added value of the two-compound product over both monotherapies.

Colocalization of cystatin M/E and its target proteases suggests a role in terminal differentiation of human hair follicle and nail.

The cysteine protease inhibitor cystatin M/E is a key regulator of a biochemical pathway that leads to epidermal terminal differentiation by inhibition of its target proteases cathepsin L, cathepsin V, and legumain. Inhibition of cathepsin L is important in the cornification process of the skin, as we have recently demonstrated that cathepsin L is the elusive processing and activating protease for transglutaminase 3, an enzyme that is responsible for crosslinking of structural proteins in cornified envelope formation. Here, we study the localization of all players of this pathway in the human hair follicle and nail unit in order to elucidate their possible role in the biology of these epidermal appendages. We found that cathepsin L and transglutaminase 3 specifically colocalize in the hair bulb and the nail matrix, the regions that provide cells that terminally differentiate to the hair fiber and the nail plate, respectively. Furthermore, transglutaminase 3 also colocalizes with the structural proteins loricrin and involucrin, which are established transglutaminase substrates. These findings suggest that cathepsin L and transglutaminase 3 could be involved in the pathway that leads to terminal differentiation, not only in the epidermis but also in the human hair follicle and nail unit.

A double-blind, randomized quantitative comparison of calcitriol ointment and calcipotriol ointment on epidermal cell populations, proliferation and differentiation.

Background  Calcitriol and calcipotriol are widely used in the topical treatment of psoriasis. However, studies comparing both treatment modalities are scarce. Especially, there are almost no studies comparing the effects on epidermal cell populations in a quantitative manner.

The combination of the Zenon labeling technique and microscopic image analysis to study cell populations in normal and psoriatic epidermis.

Background:  In order to better characterize epidermal cell populations in psoriatic vs. normal skin, fluorescent immunohistochemical techniques were extended with a new labeling technique. The Zenon technique conjugates primary antibodies rapidly and quantitatively after which they are used in the same manner as covalently labeled primary antibodies. Digital microscopic images of epidermal expression of keratin 10 and keratin 6 (differentiation), Ki‐67 antigen (proliferation), and keratin 15 and β‐1 integrin (basal layer) were analyzed in a standardized way. Co‐expression of different proteins was demonstrated.

Novel quantitative immunofluorescent technique reveals improvements in epidermal cell populations after mild treatment of psoriasis.

A novel antibody labelling technique, the Zenon technique, was used in fluorescent immunohistochemistry for a better characterization of epidermal cell populations in a quantitative approach. With this technique, differences in proliferation and differentiation characteristics were shown between psoriatic and normal epidermis. The sensitivity of the method was investigated by assessing the effect of a mild topical treatment versus an emollient. Frozen sections of non-treated psoriatic epidermis and psoriatic epidermis treated once daily with either an emollient or betamethasone-17-valerate for only 2 weeks were compared immunohistochemically. Antibodies against keratin 6, 10 and 15 were labelled with the Zenon technique, whereas antibodies against the Ki-67 antigen and beta-1 integrin were covalently FITC-labelled. Using image analysis, these markers were measured in the epidermis in a standardized manner. Treatment of psoriasis with short-term topical steroid resulted towards normalization of Ki-67 antigen, beta-1 integrin, keratin 10 and keratin 6 expression, which are parameters for proliferation and differentiation. Although treatment with an emollient showed hardly any clinical response, changes towards a more normal phenotype could already be detected in several epidermal markers using this method.