Chronic or episodic severe itch is recurrent in atopic dermatitis (AD). Nonhistaminergic itch pathways are suggested to dominate in AD itch, contributing to an "itch-scratch-itch cycle" that prolongs and worsens itch, pain, and skin lesions. We hypothesized that nonhistaminergic neuronal sensitization contributes to itch in AD. Hence, we compared sensitivity with thermal, mechanical, and chemical pruritic stimuli in patients with AD and controls. The study comprised 25 patients with AD with chronic itch and 25 healthy controls. Questionnaires on itch characteristics were administered, and sensory tests were conducted intralesionally, extralesionally, and in homologous areas of controls. Thermal and mechanical quantitative sensory testing (QST) as well as histamine and cowhage provocations were performed. Subsequently, hyperknesis and vasomotor reactivity were assessed. Average itch and associated pain among patients with AD were 60.7 ± 4.3 and 39.7 ± 5.2 (VAS0-100), respectively. Patients experienced significantly higher itch from cowhage both intralesionally and extralesionally compared with controls, whereas histamine-evoked itch intensity was not significantly different between groups. No group differences were found for thermal quantitative sensory testings or pain evoked by itch provocations. Patients had decreased mechanical detection thresholds intralesionally and increased mechanical pain sensitivity intralesionally and extralesionally. Lastly, patients exhibited intralesional and extralesional hyperknesis before chemical itch provocations and augmented hyperknesis after itch provocations. Increased itch in response to cowhage (but not histamine) suggests nonhistaminergic pathway-specific itch sensitization in AD, whereas increased susceptibility to mechanically evoked itch and pain, particularly intralesionally suggests sensitization of mechanosensitive circuitry not normally associated with itch. Drugs targeting the nonhistaminergic (PAR2/TRPA1) itch pathway and itch sensitization are promising for treating AD itch.

Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.

The aim of this study was to evaluate the effect of photodynamic therapy with topical methylaminolevulinate for the treatment of basal cell carcinomas in a single dermatological department. Ninety patients (34.4% men and 65.6% women) with a total of 157 basal cell carcinomas (111 superficial, 40 nodular, 6 unknown) were treated. Primary endpoint was clinically observed recurrence verified by biopsy 3, 6 and 12 months after treatment, then once a year. Estimated patient recurrence rates were 7% at 3 months, 19% at 6 months, 27% at 12 months and 31% at 24 months. Patients aged over 60 years had significantly higher estimated recurrence rates compared with patients aged 60 years or under (at 12 months, 35% vs. 19%, p?=?0.01). Estimated recurrence rates for tumours was 4% at 3 months, 11% at 6 months, 16% at 12 months and 19% at 24 months. There were significantly higher estimated recurrence rates for nodular basal cell carcinomas compared with superficial basal cell carcinomas (at 12 months, 28% vs. 13%, p?=?0.008). In conclusion, photodynamic therapy is only appropriate for treatment of superficial basal cell carcinoma, and, age above 60 years and histology showing nodular basal cell carcinoma are independent risk factors for developing a recurrent basal cell carcinoma.

This report describes 9 patients who developed allergic contact dermatitis to methyl aminolevulinate used for photodynamic therapy (PDT). The risk of developing contact allergy to methyl aminolevulinate in PDT treated patients was calculated to 1% after an average of 7 treatments (range 2-21).

The natural biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), possesses antiproliferative, prodifferentiating and immunomodulatory properties. The actions of 1,25(OH)2D3 are mediated through the intracellular vitamin D receptor (VDR), and the level of VDR is believed to determine the cellular responsiveness to vitamin D3. In the present study we examined the effects of 1,25(OH)2D3 on the expression of VDR and its message in cultured human keratinocytes. Western analysis showed the mean VDR content to be higher in undifferentiated cultures (175 pg/microgram protein) than in differentiated cultures (90 pg/microgram protein). Incubation with 1,25(OH)2D3 induced an increase in the VDR in both undifferentiated and differentiated keratinocytes. The VDR increase was detectable after 2 h and maximal (approximately two-fold stimulation) after 8 h. The 1,25(OH)2D3-induced stimulation of VDR levels was dose dependent with a maximum at 10(-7) M. The VDR mRNA levels as determined by the ribonuclease protection assay showed a peak (50% stimulation) after approximately 2 h. Although this increase in VDR mRNA was not statistically significant, the results indicate that the ligand-induced upregulation of VDR involves increased transcription. The upregulation of VDR levels may increase the responsiveness to 1,25(OH)2D3 and may, therefore, be an important mechanism for regulating the effects of 1,25(OH)2D3 on keratinocyte proliferation and differentiation.

This study demonstrates a considerable risk of sensitization after Metvix-PDT. We suggest that the patients are interviewed to detect late or persistent local reactions after PDT. These reactions are often considered to be local infections but may represent allergic contact dermatitis, and therefore, patients should be offered patch testing with Metvix cream.

No abstract

Keratinocytes express receptors for 1,25-dihydroxy vitamin D₃ [1,25(OH)₂D₃], all-trans-retinoic acid (all-trans-RA), 9-cis-retinoic acid (9-cis-RA) and triiodothyronine (T₃). The vitamin-D receptor (VDR) can act as a transcription factor by forming homodimers or heterodimers with the retinoic-acid receptor (RAR), the retinoid X receptor (RXR) or the triiodothyronine receptor (TR). This study investigated whether the antiproli-ferative and prodifferentiating effects of 1,25(OH)₂D₃ on normal human keratinocyte cultures is modified by all-trans-RA, a ligand for RAR, by CD2809, a ligand for RXR, by 9-cis-RA, a ligand for the RAR and RXR, and T₃, a ligand for the TR. Submerged, second-passage normal human keratinocytes were grown to approximately 30% confluency before incubation for 4 days with ligands in keratinocyte growth medium supplemented with 3% charcoal-stripped fetal calf serum and 0.3 mM Ca²⁺. Proliferation was measured by the dimethylthiazolyl-diphenyl-tetrazolium-bromide assay. Then differentiation was determined in the same culture, performing a cell ELISA for transglutaminase type 1. All-trans-RA, 9-cis-RA and CD2809 had a slight stimulatory effect on proliferation. In combination with 1,25(OH)₂D₃, all retinoids partially counteracted the antiprol-iferative effect of 1,25(OH)₂D₃. The differentiation was dose-dependently inhibited by all-trans-RA, 9-cis-RA and CD2809 alone. In combination with 1,25(OH)₂D₃, all retinoids reversed the prodifferentiating effect of 1,25(OH)₂D₃, resulting in a net inhibition of differentiation. T₃ had no effect on proliferation of differentiation, either alone or in combination with 1,25(OH)₂D₃. In conclusion, retinoids with different receptor selec-tivities had similar effects on keratinocyte proliferation and differentiation. The effects of 1,25(OH)₂D₃ on proliferation and differentiation were reversed by all retinoids. Therefore, ligand-dependent heterodimer formation between the VDR and retinoid receptors may not be important for the combined effects of 1,25(OH)₂D₃ and retinoids on keratinocyte proliferation and differentiation in vitro.