C.J.M. van der Vleuten

Gait and calf muscle endurance in patients with chronic venous insufficiency

Objective: To gain insight in gait and calf muscle endurance in patients with severe chronic venous insufficiency. Methods: Fifteen patients with severe chronic venous insufficiency (healed or active ulcers) and 19 healthy controls were selected for this study. Subjects had to perform eight trials at preferred walking speed and eight trials at instructed walking speed (1.25 m/s) during which the gait parameters were recorded. The calf muscle endurance was tested by use of the heel-rise test. Results: Patients had a significantly lower preferred walking speed (1.25 m/s9 /± 0.31) compared with healthy controls (1.44 m/s± 0.0.15) (p=0.039). During preferred walking speed patients had a wider base of support (p=0.003), a bigger step time (p=0.005), and a bigger stride time (p=0.004) compared with healthy controls. At instructed walking speed only base of support was different between the two groups (p=0.016). Patients had a significantly (p=0.003) smaller number of heel rises (14.69 ± 7.34), indicating decreased calf muscle endurance compared with controls (23.59 ±6.54). Conclusion: This study indicates a disturbed gait and decreased calf muscle endurance in patients with severe chronic venous insufficiency.

Propranolol in a case series of 174 patients with complicated infantile haemangioma: indications, safety and future directions

Summary Background  Infantile haemangioma (IH) is a benign, common and self‐limiting tumour of infancy; only a minority of cases need active treatment. Currently, propranolol appears superior to classic treatments.

Kaposiform hemangioendothelioma with Kasabach-Merritt syndrome: a new indication for propranolol treatment.

Kaposiform hemangioendothelioma is a rare vascular tumor in children. Especially, in association with the Kasabach-Merritt Phenomenon it can be life threatening. The management of these patients is very difficult and an aggressive treatment regime is required. Several multimodality and chemotherapeutic regimens have been described but with variable success and many side effects. We present a 6-week-old boy with Kaposiform hemangioendothelioma and Kasabach-Merritt Phenomenon. Ongoing propranolol treatment with only 4 initial courses of vincristine resulted in a remission that lasted at least 1 year.

Epidermal differentiation characteristics of the psoriatic plaque during treatment with calcipotriol

Treatment of psoriasis with vitamin D3 analogues is well established in present dermatological practice. One of the clinical sings of the psoriatic plaque that reduces early and markedly during treatment with the vitamin D3 analogue calcipotriol is scaling. Since scaling is the clinical manifestation of disordered epidermal differentiation, early changes in immunohistochemical markers for differentiation (transglutaminase, involucrin and filaggrin) were studied in patients who had been treated with calcipotriol for 4 weeks. Markers for proliferation (Ki-67 antigen) and inflammation (polymorphomuclear leucocytes and T lymphocytes) were also studied and correlated with the differentiation characteristics. Clinically, a major improvement was seen in all patients. A significant decrease in the percentage of transglutaminase-positive cell layers was observed during the first week of treatment. In contrast, an increase in transglutaminase activity in epidermal cell cultures following incubation with calcipotriol has been reported. Involucrin expression was only slightly modulated in vivo. However, a major restoration of the filaggrin-positive cell layer and significant reduction in the recruitment of cycling epidermal cells characterized the epidermal response to calcipotriol treatment. Markers for inflammation (T11-positive cells and elastase-positive cells) were also reduced substantially during the first week of treatment with calcipotriol. From this study it may be concluded that inhibition of epidermal growth and recovery of the filaggrin-positive cell layer are among the in vivo effects of calcipotriol.

The immunohistochemical effects of a single challenge with an intermediate dose of ultraviolet B on normal human skin.

Ultraviolet B (UVB) irradiation has extensively been advocated for use in the investigation of cutaneous inflammation in vivo. Mostly doses above the threshold of skin damage have been used. Therefore it is not clear whether the changes observed are specific effects of UVB or to a certain extent represent wound healing. In this study the dose-dependent effects of UVB on normal human skin were assessed using histology and immunohistochemistry. The dose of 1 MED was chosen as a dose unducing tissue changes with adequate morphology: no toxicity but evident immunohistochemical changes. The sequential effects of this 1 MED of UVB were studied for up to 14 days after irradiation, using immunohistochemistry with a panel of monoclonal antibodies. Substantial effects were observed, mainly on proliferation and differentiation; the markers for inflammation did not reveal major changes. This model might be a promising approach to evaluate the effect of drugs on epidermal proliferation and differentiation in vivo.

Clobetasol-17-propionate lotion under hydrocolloid dressing (Duoderm ET) once weekly versus unoccluded clobetasol-17-propionate ointment twice daily in psoriasis: an immunohistochemical study on remission and relapse

Abstract It is well established that the efficacy of corticosteroids under occlusion with hydrocolloids (HCD) is superior compared to monotherapy with topical corticosteroids. However, following treatment with more potent corticosteroids, increased side effects and a more pronounced rebound might be expected. In the present clinical study, the efficacy of relapse after and the safety characteristics of two treatment modalities were compared: clobetasol-17-propionate lotion under an HCD dressing once weekly versus clobetasol-17-propionate ointment without an HCD twice daily. Clinical assessments were recorded and skin biopsies were taken before therapy, at clearance and 6 weeks after clearance. A panel of monoclonal antibodies to characterize epidermal proliferation, differentiation and inflammation were selected. In addition, clinical and histological assessments for skin atrophy were made. Both therapies had a major therapeutic effect, which was reflected in the clinical and immunohistochemical parameters. The only difference between the two therapies was a faster remission induction time in patients treated with corticosteroids combined with HCD. Six weeks after discontinuation of treatment, similar clinical and histological signs of relapse were observed for both therapies. Clinically, there were no signs of skin atrophy but histologically, epidermal thinning occurred to the same extent with both therapies but proved to be reversible within 6 weeks of discontinuation of treatment. From this study it can be concluded that the combination of HCD and corticosteroids is able to induce relatively fast remission compared to corticosteroid monotherapy but relapse and safety characteristics are comparable to the unoccluded corticosteroid therapy.It is well established that the efficacy of cor- ticosteroids under occlusion with hydrocolloids (HCD) is superior compared to monotherapy with topical cor- ticosteroids. However, following treatment with more potent corticosteroids, increased side effects and a more pronounced rebound might be expected. In the present clinical study, the efficacy of relapse after and the safety characteristics of two treatment modalities were compared: clobetasol-17-propionate lotion under an HCD dressing once weekly versus clobetasol-17-pro- pionate ointment without an HCD twice daily. Clinical assessments were recorded and skin biopsies were taken before therapy, at clearance and 6 weeks after clearance. A panel of monoclonal antibodies to charac- terize epidermal proliferation, differentiation and in- flammation were selected. In addition, clinical and his- tological assessments for skin atrophy were made. Both therapies had a major therapeutic effect, which was reflected in the clinical and immunohistochemical parameters. The only difference between the two ther- apies was a faster remission induction time in patients treated with corticosteroids combined with HCD. Six weeks after discontinuation of treatment, similar clini- cal and histological signs of relapse were observed for both therapies. Clinically, there were no signs of skin atrophy but histologically, epidermal thinning oc- curred to the same extent with both therapies but proved to be reversible within 6 weeks of discontinua- tion of treatment. From this study it can be concluded that the combination of HCD and corticosteroids is able to induce relatively fast remission compared to corticosteroid monotherapy but relapse and safety characteristics are comparable to the unoccluded cor- ticosteroid therapy.

The psychosocial impact of an infantile haemangioma on children and their parents

Infantile haemangiomas (IHs) are common, benign vascular tumours in children that appear soon after birth and regress before the age of 12 years. Physicians have always been concerned about the considerable psychosocial impact these lesions might have on children and their parents. This is the first critical review of studies on the psychosocial impact of IHs on children and their families. Future directions for research are suggested. As propranolol is becoming the most common first choice treatment for IHs, this article discusses its use in the light of this review.

Effects of calcipotriol and clobetasol-17-propionate on UVB-irradiated human skin:an immunohistochemical study

Corticosteroids and vitamin D3 analogues inhibit proliferation, enhance normal keratinisation and interfere with cutaneous inflammation in in vitro systems. Both treatments are effective in psoriasis, although several reports suggest that vitamin D3 is less effective in reducing the inflammatory changes compared to its potent effect on keratinocyte growth and differentiation. The aim of the present study was to compare and contrast the effects of the vitamin D3 analogue calcipotriol, clobetasol-17-propionate and a placebo on immunohistochemical markers for epidermal growth, keratinisation and inflammation induced by a standardised single challenge with ultraviolet B (UVB) radiation in normal human skin. Clobetasol proved to inhibit UVB-induced proliferation of epidermal cells, tenascin induction, keratin 16 induction and the accumulation of T lymphocytes and CD1a-positive cells. Epidermal thinning due to clobetasol was also observed. No effect of clobetasol was shown on the enhanced terminal differentiation following UVB challenge. In contrast, calcipotriol reduced the member of transglutaminase-positive cells following UVB challenge but increased the thickness of the epidermis without a significant effect on other markers for keratinisation, epidermal proliferation and inflammation. The present study reconfirms the potent effect of topical corticosteroids on various aspects of UVB-challenged skin. In contrast, calcipotriol interfered especially with one differentiation pathway (transglutaminase) without modulation of other UVB-induced changes.

Dapsone versus topical immunotherapy in alopecia areata

Twenty‐seven patients with severe alopecia areata were treated with dapsone. The results of a mean treatment duration of 10±0.5 months are reported, and compared with the results of long‐term topical immunotherapy obtained previously at the same institute. The efficacy of dapsone proved to be markedly inferior to that of topical immunotherapy. The percentage of patients showing regrowth of hair during treatment with dapsone was comparable with the occurrence of spontaneous regrowth of hair reported in the literature.

Shared Decision-Making in the Management of Congenital Vascular Malformations

Background: In shared decision-making, clinicians and patients arrive at a joint treatment decision, by incorporating best available evidence and the patients’ personal values and preferences. Little is known about the role of shared decision-making in managing patients with congenital vascular malformations, for which preference-sensitive decision-making seems obvious. The authors investigated preferences regarding decision-making and current shared decision-making behavior during physician-patient encounters. Methods: In two Dutch university hospitals, adults and children with congenital vascular malformations facing a treatment-related decision were enrolled. Before the consultation, patients (or parents of children) expressed their preference regarding decision-making (Control Preferences Scale). Afterward, participants completed shared decision-making–specific questionnaires (nine-item Shared Decision-Making Questionnaire, CollaboRATE, and satisfaction), and physicians completed the Shared Decision-Making Questionnaire–Physician questionnaire. Consultations were audiotaped and patient involvement was scored by two independent researchers using the five-item Observing Patient Involvement instrument. All questionnaire results were expressed on a scale of 0 to 100 (optimum shared decision-making). Results: Fifty-five participants (24 parents and 31 adult patients) were included. Two-thirds preferred the shared decision-making approach (Control Preferences Scale). Objective five-item Observing Patient Involvement scores were low (mean ± SD, 31 ± 15), whereas patient and physician Shared Decision-Making Questionnaire scores were high, with means of 68 ± 18 and 68 ± 19, respectively. The median CollaboRATE score was 93. There was no clear relationship between shared decision-making and satisfaction scores. Conclusions: Although adults and parents of children with vascular malformations express a strong desire for shared decision-making, objective shared decision-making behavior is still lacking, most likely because of poor awareness of the shared decision-making concept among patients, parents, and physicians. To improve shared decision-making practice, targeted interventions (e.g., decision aids, staff training) are essential.