Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly painless in treating actinic keratoses: a randomised, investigator-blinded, controlled, phase III study throughout Europe.

BACKGROUND: Unmet needs exist in actinic keratosis (AK) treatment. Daylight photodynamic therapy (DL-PDT) has shown good efficacy and safety results compared to conventional PDT (c-PDT) in a recent Phase III multi-centre randomised controlled trial in Australia among 100 subjects with AKs. OBJECTIVES: Demonstrate non-inferior efficacy and superior safety of DL-PDT compared to c-PDT in treating multiple mild and/or moderate facial/scalp AKs. METHODS: Phase III, 12 week, multi-centre, randomised, investigator-blinded, controlled, intra-individual study conducted at different latitudes in Europe. AKs of adult subjects were treated once with methyl aminolevulinate (MAL) DL-PDT on one side of the face and MAL c-PDT contralaterally. Endpoints for DL-PDT concerned efficacy (non-inferiority regarding complete lesion response at week 12) and safety (superiority regarding subject's assessment of pain after treatment, on an 11-point numeric rating scale). Safety evaluation also included incidence of adverse events. Subject satisfaction was described using a questionnaire at baseline and last visit. RESULTS: At week 12, the total lesion complete response rate with DL-PDT was similar (non-inferior) to c-PDT (70% vs. 74%, respectively; 95% CI [-9.5; 2.4] in PP analysis, confirmed in ITT analysis). In addition, efficacy of DL-PDT was demonstrated regardless of weather conditions (sunny or cloudy). DL-PDT was nearly painless compared to c-PDT (0.7 vs. 4.4, respectively; P < 0.001), better tolerated and resulted in higher subject satisfaction. CONCLUSION: DL-PDT in comparison with c-PDT was as effective, better tolerated and nearly painless with high patient satisfaction, and may be considered a treatment of choice to meet needs of patients with mild or moderate facial/scalp AKs.

[Alopecia areata]. / Alopecia areata.

The epidemiology of alopecia areata as well as murine models of this disease and genome-wide association studies support the concept of alopecia areata as an autoimmune disease. In addition, the genome-wide association studies have led to the identification of new potential therapeutic targets such as CTLA4; these results have already led to the initiation of clinical studies, for example, with abatacept. Currently topical and intralesional corticosteroids as well as immunotherapy with diphenylcyclopropenone are most common therapeutic approaches.

Porokeratosis: present concepts.

Porokeratosis represents a group of disorders of epidermal keratinization which are characterized by the histopathological feature of the cornoid lamella, a column of tightly fitted parakeratotic cells. The aetiology of porokeratosis is still unclear. This review summarizes the currently available data on the pathophysiology of this condition and discusses the clinical variants and the currently available therapies.

Irradiation with water-filtered infrared A plus visible light improves cutaneous scleroderma lesions in a series of cases.

BACKGROUND: Cutaneous scleroderma is a chronic inflammatory disease of the dermal and subcutaneous connective tissue leading to sclerosis. Sclerosis of the skin can lead to dysmorphism, contractures and restrictions of movement. OBJECTIVE: The purpose of the study was to evaluate sclerosis in cutaneous scleroderma patients and to determine the efficacy of water-filtered infrared A plus visible light treatment, wIRA(+VIS), in 10 patients. METHODS: Hardness of the normal and diseased skin was measured by durometry in 10 controls and 8 patients. Moreover, circumscribed scleroderma (CS) was treated with wIRA(+VIS) irradiations in 10 patients who had not responded to conventional therapies. RESULTS: wIRA(+VIS) therapy led to a marked improvement, persistent even during long-term follow-up, in 7 out of 10 patients with CS. Of the other patients, 1 showed decreased sclerosis and disease activity and developed a worsening after cessation of therapy. In 2 further patients, where previous UVA1 treatment had failed to reduce disease activity, wIRA(+VIS) produced a slight decrease in sclerosis, but disease activity was still present. CONCLUSION: wIRA(+VIS) appears to be effective in the treatment of CS. Durometry proved to be helpful in assessing the degree of sclerosis and in documenting the response to therapy in these patients.

[Acrodermatitis enteropathica-like skin lesions due to Crohn's disease-associated zinc deficiency]. / Acrodermatitis-enteropathica-ähnliche Hautveränderungen bei Morbus-Crohn-bedingtem Zinkmangel.

We report a case of acrodermatitis enteropathica-like skin eruptions presenting with alopecia, perlèche, glossitis, and genital erosions as well as multifocal eczematoid, psoriasiform, and bullous skin lesions due to zinc deficiency in Crohn's disease.

Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodes.

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side-effect. OBJECTIVES: To compare pain intensity, efficacy, safety and cosmetic outcome of MAL PDT with two different light sources in an investigator-initiated, randomized, double-blind study. METHODS: Eighty patients with multiple AKs grade I-II were assigned to two groups: group 1, MAL PDT with visible light and water-filtered infrared A (VIS+wIRA); group 2, MAL PDT with light from light-emitting diodes (LEDs), with a further division into two subgroups: A, no spray cooling; B, spray cooling on demand. MAL was applied 3 h before light treatment. Pain was assessed before, during and after PDT. Efficacy, side-effects, cosmetic outcome and patient satisfaction were documented after 2 weeks and 3, 6 and 12 months. Where necessary, treatment was repeated after 3 months. RESULTS: Seventy-six of the 80 patients receiving MAL PDT completed the study. Patient assessment showed high efficacy, very good cosmetic outcome and high patient satisfaction. The efficacy of treatment was better in the group of patients without spray cooling (P=0·00022 at 3 months, P=0·0068 at 6 months) and showed no significant differences between VIS+wIRA and LED. VIS+wIRA was significantly less painful than LED: the median of maximum pain was lower in the VIS+wIRA group than in the LED group for PDT without spray cooling. Pain duration and severity assessed retrospectively were less with VIS+wIRA than with LED, irrespective of cooling. CONCLUSIONS: All treatments showed high efficacy with good cosmetic outcome and high patient satisfaction. Efficacy of treatment was better without spray cooling. VIS+wIRA PDT was less painful than LED PDT for PDT without spray cooling.

[Imaging of actinic porokeratosis by optical coherence tomography (OCT)]. / Bildgebende Diagnostik der aktinischen Porokeratose mittels optischer Kohärenztomographie (OCT).

Disseminated superficial actinic porokeratosis (DSAP) is a rare, genetically heterogeneous skin disorder. We report a case of a 73-year-old female patient who was diagnosed with DSAP by optical coherence tomography (OCT) and histology. During the last 4 years prior to diagnosis, she had developed numerous (pre)malignant lesions of the skin of the lower legs including actinic keratoses, squamous cell carcinomas and Bowen's disease. DSAP lesions and actinic keratoses were resistant to topical treatment with imiquimod and retinoids, but improved with photodynamic therapy (PDT).

[Pemphigoid nodularis triggered by hypereosinophilic syndrome?]. / Pemphigoid nodularis ausgehend von einem Hypereosinophilie-Syndrom?

Pemphigoid nodularis (PN) is a rare clinical variant of pemphigoid characterized by prurigo-like skin lesions and antibodies against BP180 and BP230 characteristic for bullous pemphigoid. Interestingly, most PN patients never develop blisters. This condition is often resistant to treatment. We describe a female patient who was initially diagnosed with hypereosinophilic dermatitis. Later on, in the presence of eosinophilic infiltrations in the gastrointestinal tract, obstructive ventilation disorder, pericardial and pleural effusions, the diagnosis of idiopathic hypereosinophilic syndrome was made. During the following 3 years she developed recalcitrant PN.

5-aminolaevulinic acid photodynamic therapy in a transgenic mouse model of skin melanoma.

Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non-melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5-aminolaevulinic acid (5-ALA)-based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein-I/ret (MT-ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5-ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT-ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5-ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5-ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT-ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT-ret melanoma cells are vulnerable to 5-ALA PDT in vitro, malignant MT-ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.

Does botulinum type-A toxin affect motor activity after proctocolectomy and ileal pouch-anal anastomosis? An experimental study in dogs.

AIM OF THE STUDY: The use of anticholinergic drugs has provided a useful therapeutic approach to reduce stool frequency in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA). Botulinum type-A (BTA) toxin has been shown to specifically block acetylcholine release in the intestinal wall. Therefore this study investigated the effect of BTA on small intestinal and J-pouch motility after IPAA. MATERIAL AND METHODS: Proctocolectomy and IPAA were performed in 4 dogs. The motility of the small intestine and the ileal pouch was recorded by serosal electrodes and strain gauge transducers. The intestinal transit time was determined radiologically and pouch compliance was determined manometrically. Multiple measurements were performed before and after endoscopic injection of BTA into the pouch wall. RESULTS: This treatment did not significantly influence stool frequency, intestinal transit time or pouch compliance. Intrinsic pouch motility was characterized by irregular contractions, the amplitudes and frequencies of which remained unchanged after BTA administration. With the exception of lower contraction amplitudes directly proximal to the pouch, there were no significant differences in the characteristics of the migrating myoelectric complex or in the fed pattern of the small intestine and ileal pouch. CONCLUSIONS: BTA does not significantly affect ileal pouch motility. The beneficial effects of anticholinergic drugs therefore seem to be due to their multifactorial mode of action and not to the inhibition of cholinergic neurons in the pouch.

Progressive respiratory failure in paraneoplastic pemphigus associated with chronic lymphocytic leukemia.

A 70-year-old Caucasian man with chronic lymphocytic leukemia suffered from widespread, histologically proven cutaneous lichen planus responding to topical corticosteroids. 2 years later, he presented with painful erosive stomatitis and increasing dyspnea. Histology, direct and indirect immunofluorescence were diagnostic for paraneoplastic pemphigus. A full diagnostic workup could not disclose the cause of the progressive respiratory insufficiency. Despite aggressive treatment of the lymphocytic leukemia and the paraneoplastic pemphigus, the patient died 3 months after diagnosis. Paraneoplastic pemphigus may lead to pulmonary failure which is refractory to treatment and has a fatal outcome.

Defecation mechanisms after proctocolectomy and ileal pouch--anal anastomosis in dogs.

BACKGROUND AND AIMS: The role of intrinsic pouch motility after ileal pouch-anal anastomosis (IPAA) during defecation is still speculative. MATERIALS AND METHODS: IPAA was performed in 12 dogs. Defecation mechanisms were evaluated by motility recordings during spontaneous defecation and during expulsion of an endoluminal balloon and by radiography with sequential sector-related gray scale analysis. RESULTS: Spontaneous defecations appeared without significant changes in electrical or mechanical activity of the pouch. Sequential filling of the pouch led to defecation in only seven dogs while the others did not succeed in emptying their pouch even with maximal balloon inflation. Neither strain gauge measurements nor electromyography demonstrated peristaltic contractions of the pouch during defecation while sector-related gray scale analysis revealed strong contractions of the abdominal wall during pouch emptying. CONCLUSION: Pouch emptying is independent of intrinsic pouch motility. The ileoanal pouch acts as a functionally passive reservoir, and its evacuation is initiated by a rise of the intra-abdominal pressure.

Does loperamide affect motor activity after proctocolectomy and ileal pouch-anal anastomosis? An experimental study in dogs.

This study investigated the effect of loperamide on the motor function of small intestine and J-pouch. Proctocolectomy and ileal pouch-anal anastomosis were performed in four dogs. Motility was recorded by serosal electrodes and strain gauge transducers. The intestinal transit time was determined radiologically. Multiple measurements were performed before and during chronic administration of loperamide. This treatment led to a significant decrease in median stool frequency from 11 (10-13) to 9 stools/day (8-12) and a tendential increase in intestinal transit time from 60 (50-105) to 70 min (60-90). This was not accompanied by significant changes in fasted or postprandial motility. There were no significant differences in the characteristics of the migrating myoelectric complex or in the fed pattern, either in the small intestine or in the pouch. Loperamide thus does not significantly affect intestinal motility after ileal pouch-anal anastomosis. The reduction in stool frequency seems to be due to antisecretory effects in the first line.