Medium-dose ultraviolet (UV) A1 vs. narrowband UVB phototherapy in atopic eczema: a randomized crossover study.

BACKGROUND: Ultraviolet (UV) A1 and narrowband (NB)-UVB have been reported to be effective treatments for atopic eczema (AE). OBJECTIVES: We aimed to compare the efficacy of medium-dose UVA1 and NB-UVB mono-phototherapy in patients with AE. METHODS: A randomized double-blind controlled crossover trial (ClinicalTrials.gov Identifier: NCT00419406) was conducted in which patients with AE received a 6-week course of both medium-dose UVA1 and NB-UVB. Clinical efficacy was assessed using the Six Area, Six Sign, Atopic Dermatitis (SASSAD) score and a visual analogue scale for pruritus. Assessment of health-related quality of life was performed using the Skindex-29. Total immunoglobulin E (IgE) and eosinophilic cationic protein (ECP) were evaluated at baseline and after each phototherapy course. RESULTS: Twenty-eight patients who completed both UVA1 and NB-UVB phototherapy courses on an intention-to-treat basis were analysed according to the crossover design. Both interventions were associated with significant clinical improvement but there was no significant difference between treatments with respect to the mean +/- SD relative reduction (RR) of the clinical scores (SASSAD, 43.7 +/- 31.4% vs. 39.4 +/- 24.1%, P = 0.5; pruritus score, 16 +/- 61.8% vs. 25.2 +/- 30.5%, P = 0.5, respectively). There was no significant difference in the mean +/- SD RR of the Skindex-29 after UVA1 and NB-UVB phototherapy (12.7 +/- 18.8% vs. 16.5 +/- 17.6%, P = 0.1). Changes in the total IgE and ECP levels following UVA1 and NB-UVB did not differ significantly (P = 0.3 and P = 0.9, respectively). CONCLUSIONS: A 6-week course of NB-UVB and UVA1 phototherapy of AE resulted in significant clinical improvement. With regard to efficacy and tolerability, both phototherapeutic modalities may be considered comparably good.

Gene expression of cytokines in atopic eczema before and after ultraviolet A1 phototherapy.

BACKGROUND: Atopic eczema (AE) is a common pruritic and chronically relapsing inflammatory skin disease in which cytokines seem to represent important factors in the pathogenesis. OBJECTIVES: We aimed to investigate cytokine mRNA expression in the skin of patients with AE who underwent a course of ultraviolet A1 (UVA1) phototherapy. METHODS: We studied 21 patients diagnosed with extrinsic AE who were treated with a 6-week course of UVA1 phototherapy. Skin biopsies were taken from healthy controls (n=18) and patients with AE at baseline and after the last UVA1 exposure. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed for interleukin (IL)-4, IL-5, IL-10, IL-13 and IL-31. RESULTS: A significant reduction of the clinical scores was observed after treatment with UVA1. Except for IL-4, cytokine mRNA expression was significantly increased prior to phototherapy when compared with controls. mRNA levels of IL-4 and IL-10 before UVA1 did not significantly differ from levels observed after UVA1. However, a significant decrease of IL-5, IL-13 and IL-31 mRNA expression was observed following UVA1 treatment. IL-31 mRNA levels were even adjusted to the levels of healthy controls. CONCLUSIONS: We have shown that the resolution of extrinsic AE lesions following phototherapy is accompanied by significant reduction of mRNA expression of IL-5, IL-13 and IL-31, supporting current concepts that these cytokines play a crucial role in the pathogenesis of extrinsic AE and possibly represent targets for phototherapy.

Increased expression of TGF-beta/Smad proteins in basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in humans placing a significant burden on healthcare services worldwide. There is an increasing evidence that the development of cutaneous epithelial tumours is pathogenetically linked to dysregulations of the transforming growth factor beta (TGF-beta) and its signalling molecules, the Smads. OBJECTIVE: In the present study we aimed to investigate the mRNA as well as protein expression of TGF-beta/ Smad signalling proteins in patients with BCC and healthy controls. METHODS: In this prospective pilot study, 24 patients with BCC were recruited. Punch biopsies were harvested from the centre of the tumour (lesional) as well as an adjacent healthy skin site (non-lesional controls). In addition to the specimens of BCC patients, skin samples (healthy controls) were obtained from subjects who had no history of skin cancer (n = 25). Real-time RT-PCR as well as immunohistochemistry was performed. - RESULTS: The mRNA levels of TGF-b/Smad transducers observed in healthy controls did not significantly differ from TGF-beta/Smad levels observed in non-lesional skin of BCCs patients (P > 0.05). RT-PCR revealed significant mRNA overexpression of TGF-beta1, Smad3, and Smad7 in BCCs as compared to non-lesional skin (P < 0.05). TGF-beta1 mRNA expression significantly correlated with Smad3 (r = 0.60; P < 0.05) and Smad7 (r = 0.76; P < 0.05) levels. Immunohistochemistry demonstrated marked protein overexpression of Smad3 in tumour tissue as compared to non-lesional skin. CONCLUSIONS: Our data suggest a possible role of TGF-beta/Smad signalling in the pathogenesis of BCC.

Quantification of ultraviolet protective effects of pityriacitrin in humans.

Pityriacitrin (PIT), produced by Malassezia yeasts, is an UV absorbing substance that might cause hypopigmentation in pityriasis versicolor alba. We aimed to investigate the UV protective effect of PIT in humans using in vitro and in vivo test methods. Spectrophotometry of PIT cream and the vehicle was performed in the wavelength range from 290 to 400 nm. UV transmission and the sun protection factor (SPF) were assessed for different cream formulations. Using colorimetry we evaluated erythema and pigmentation following irradiation of cream-protected and non-protected skin of healthy subjects. UVB as well as UVA transmission decreased with increasing PIT concentrations. An increase of PIT concentration of 1.25, 2.5, and 5% was associated with slightly increasing SPFs of 1.4, 1.5, and 1.7, respectively. Our in vivo tests confirmed the validity of the SPF of PIT 5% cream determined in vitro. In conclusion, the UV protective effect of PIT is all in all very weak suggesting that PIT is likely only an inferior cofactor in the development of hypopigmentation in pityriasis versicolor alba lesions following sun exposure.

Repeat liposuction-curettage treatment of axillary hyperhidrosis is safe and effective.

BACKGROUND: Liposuction-curettage (LC) is an effective surgical therapy option for axillary hyperhidrosis, with less scarring compared with radical excision of axillary skin. Although this method has proven to be effective, the treatment of nonresponders to minimally invasive surgery has not been previously defined. Whether these patients benefit from a second surgical procedure has not been evaluated so far. OBJECTIVES: To investigate efficacy and side-effects of a second LC with an aggressive rasping cannula in patients with insufficient prior surgery. METHODS: Nineteen nonresponders to prior LC (13 female and six male) underwent a second LC with a rasping cannula. Gravimetry was performed before and 8 months after surgery. Side-effects, patient satisfaction, the surgeons' intraoperative evaluation and the Vancouver Scar Scale (VSS) before and after surgery were documented. RESULTS: Sweat rates showed a reduction of 69% in 17 (89%) patients. Two patients (11%) did not respond to surgery. Eighty-four per cent of all patients were completely satisfied or satisfied with postoperative results. No severe side-effects were observed. The surgeon reported slightly increased difficulties during dissection of dermis from subcutaneous fat in three patients. Assessment of scars showed an excellent aesthetic outcome (mean VSS 0.79 before vs. 1.1 after surgery). CONCLUSIONS: LC using an aggressive cannula is an effective therapy option for patients with insufficient response to prior LC surgery, with a low risk of side-effects.

Mycophenolate sodium for subacute cutaneous lupus erythematosus resistant to standard therapy.

BACKGROUND: Approximately 75-95% of patients with cutaneous lupus erythematosus respond to antimalarial therapy and/or topical glucocorticosteroids. Immunosuppressive agents are usually considered a second-line approach in patients with resistant disease. OBJECTIVES: This was a prospective, nonrandomized, open pilot study to evaluate the efficacy of mycophenolate sodium monotherapy in patients with recalcitrant subacute cutaneous lupus erythematosus (SCLE). METHODS: Monotherapy with oral enteric-coated mycophenolate sodium 1440 mg daily was given for a total of 3 months. Treatment outcome was evaluated by means of a validated clinical score for cutaneous lupus erythematosus, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), as well as 20-MHz ultrasound measurements and colorimetry. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. RESULTS: Ten patients with active SCLE resistant to at least one standard therapy were included in the trial. Mycophenolate sodium led to a remarkable improvement of skin lesions, resulting in a significant decrease of the mean +/- SD CLASI from 10.8 +/- 6.0 at the beginning to 2.9 +/- 2.6 at the end of therapy. Clinical improvement was confirmed by ultrasonographic assessments and colorimetry. No serious side-effects were noted. CONCLUSIONS: Mycophenolate sodium is beneficial and safe in the treatment of patients with SCLE that failed standard therapy. However, these preliminary data must be confirmed by randomized controlled trials including a larger sample size.

Expression of human beta-defensins in patients with mycosis fungoides.

The human beta-defensins (hBDs) are peptides with a strong antimicrobial activity. Patients with atopic dermatitis (AD) and mycosis fungoides (MF) are prone to skin infections. We aimed to investigate the mRNA expression of hBDs in lesional and non-lesional skin of MF patients, and to compare the data with hBD levels found in AD patients and healthy controls. In this prospective pilot study, 13 patients with MF were recruited. Punch biopsies were harvested from the centre of the tumour (lesional) as well as a healthy skin site (non-lesional controls). In addition to the specimens of MF patients, skin samples (healthy controls) were obtained from healthy subjects (n = 15) and patients with acute AD (n = 14). In order to detect mRNA of hBDs, we performed quantitative real-time reverse transcriptase polymerase chain reaction. As compared to healthy controls, skin of patients with MF (non-lesional and lesional) and AD patients showed significantly lower hBD-1 mRNA expression and significantly higher hBD-2 and hBD-3 mRNA expression. HBD-1 mRNA levels of lesional skin were significantly lower than those of non-lesional skin. By contrast, significantly increased hBD-2 and hBD-3 mRNA expression was found in lesional skin of MF patients when compared to non-lesional skin. HBD mRNA expression in lesional skin of MF patients did not significantly differ from hBD expression that was observed in AD lesions. We observed an identical pattern of hBD expression in MD and AD suggesting a common regulatory mechanism that might mainly be driven by T helper 2 lymphocytes.

Significant downregulation of transforming growth factor-beta signal transducers in human skin following ultraviolet-A1 irradiation.

BACKGROUND: Despite the significant role of the transforming growth factor (TGF)-beta/Smad pathway in cell growth and extracellular matrix regulation, relatively little is known regarding the effect of ultraviolet (UV) radiation on the TGF-beta/Smad signalling in human skin. OBJECTIVES: We aimed to investigate the impact of UVA1 and UVB on the mRNA and protein expression of TGF-beta/Smad signal transducers in human skin in vivo. METHODS: Fifteen subjects were exposed to 1.5 minimal erythema doses (MED) (4.5 MED cumulative) of UVA1 and UVB over a 3-day period. Skin biopsies were obtained at 24 and 72 h after the last UV exposure. Real-time reverse transcription-polymerase chain reaction and immunohistology were performed. RESULTS: In the UVA1-exposed sites (24 h, 72 h), mRNA expression of TGF-beta1 and Smad3/4/7 was significantly downregulated as compared with nonirradiated skin sites (P < 0.05). At 24 h, immunohistology revealed significantly reduced TGF-beta1 protein levels in fibroblasts (P < 0.05). However, mRNA and protein expression of TGF-beta/Smad proteins observed in UVB-irradiated sites did not differ significantly from control sites (P > 0.05). CONCLUSIONS: In contrast to UVB, UVA1 significantly downregulates the expression of TGF-beta/Smad proteins in human skin in vivo. The extent to which the acute effects of TGF-beta/Smad signalling reported in the present paper are related to the beneficial effect of UVA1-based phototherapy of fibrotic skin conditions and/or to the chronic effects of UV that result in photoaging and cancer remains to be established.

Optical coherence tomography of cutaneous lupus erythematosus correlates with histopathology.

Diagnosis of cutaneous forms of lupus erythematosus (LE), including chronic discoid LE (CDLE) and subacute cutaneous LE (SCLE), is usually based on characteristic clinical and histopathological findings. We aimed to visualize morphological changes in lesions of cutaneous LE using optical coherence tomography (OCT), and to correlate the OCT findings with histopathology. Six patients with CDLE and five patients with SCLE were investigated. Prior to skin biopsy, OCT assessment was performed on previously marked lesions. The images of OCT and corresponding histology were evaluated side-by-side on the PC screen. The thickening and disruption of the entrance signal in OCT images correlated with the hyperkeratosis which was observed in the histological sections. Atrophy of the epidermis, which was demonstrated by histology, could also be detected in the OCT pictures showing a thinned layer below the entrance signals. On OCT, a patchy reduction of reflectivity was observed in the upper dermis corresponding to dense patchy, partly lichenoid, lymphocytic infiltrates and oedema of the upper dermis. Furthermore, OCT images displayed increased signal-free cavities which histopathologically corresponded to dilated vessels in the upper dermis. All OCT parameters studied significantly (P < 0.05) correlated with histopathological features as indicated by coefficients of correlation ranging from 0.55 to 0.94. OCT enables to demonstrate micromorphological changes in cutaneous LE which correlate with histopathological findings. Nevertheless, the current technique does not allow one to visualize definite diagnostic features of cutaneous LE. However, OCT may be a promising method for objective monitoring of LE activity and treatment effects over time in vivo.

Changes of antimicrobial peptide mRNA expression in atopic eczema following phototherapy.

BACKGROUND: The epidermal expression of antimicrobial peptides (AMPs) such as human beta-defensin (hBD)-2 and cathelicidin LL-37 is downregulated in atopic eczema (AE) as compared with psoriasis. Hence, AMPs may represent important cofactors in the pathogenesis of AE. OBJECTIVES: In the present pilot study we aimed to investigate whether the cutaneous mRNA expression of AMPs is altered in patients with AE following narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: We studied 12 patients diagnosed with extrinsic AE who underwent a 6-week course of NB-UVB. Skin biopsies were taken from healthy controls (n = 12) and patients with AE at baseline and after the last NB-UVB irradiation. Quantitative real-time reverse transcription-polymerase chain reaction was performed for hBD-1, hBD-2, hBD-3 and LL-37. RESULTS: A significant (P < 0.05) reduction in the clinical score was observed after treatment with NB-UVB. As compared with controls, patients with AE showed a significantly lower hBD-1 mRNA expression and significantly higher hBD-2 levels (P < 0.05). Following NB-UVB treatment of patients with AE we observed a significant increase of hBD-1 expression as well a significant decrease of hBD-2 (P < 0.05). Levels of hBD-3 and LL-37 did not significantly differ between the groups (P > 0.05). CONCLUSIONS: The pattern of mRNA expression of constitutive (hBD-1) as well as inducible (hBD-2) AMPs seems to be altered in AE as compared with healthy controls. The resolution of AE lesions following phototherapy is accompanied by significant changes in mRNA expression of hBDs, indicating that AMPs may play a role in the pathogenesis of AE.

Cytokine mRNA expression in basal cell carcinoma.

There is evidence that cytokines (CKs) play a significant role in the development and/or progression of skin cancer. The aim of the present study was to investigate the mRNA expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 in biopsy specimens of basal cell carcinoma (BCC), and to compare the results with the mRNA levels of non-lesional skin of BCC patients and healthy subjects. Skin samples were obtained from 22 patients with BCC (lesional, non-lesional) and 25 healthy subjects (controls). Routine histology and real-time RT-PCR was performed. Histological examination revealed 12 nodular BCCs and 10 superficial BCCs. The mRNA levels of CKs observed in healthy controls did not significantly (P > 0.05) differ from non-lesional CK levels of BCCs patients. However, IL-6 and IL-8 levels of lesional skin were significantly (P < 0.05) higher than the CK levels observed in non-lesional skin and controls, respectively. mRNA expression of IL-6 and IL-8 showed a significant positive correlation (r = 0.51; P < 0.05). There was no significant (P > 0.05) difference between lesional mRNA levels of TNF-alpha and those levels observed in non-lesional skin and controls. The mRNA expression of CKs found in nodular and superficial BCCs did not significantly differ (P > 0.05). BCC is associated with a significant increase of IL-6 and IL-8 expression. We have shown for the first time that upregulation of IL-6 mRNA significantly correlates with IL-8 overexpresssion. In accordance with previous studies our data suggest a role for IL-6 and IL-8 in the development and/or progression of BCC, since mRNA expression of both CKs are significantly increased in tumour tissue.

Reference limits for erythema-effective UV doses.

Diagnostic phototesting, including the determination of the minimal erythema dose (MED), is a useful procedure to detect abnormal sensitivity to UV radiation. We aimed to estimate the reference limits (RLs) of the MED in a reasonably large reference sample of white individuals. Skin phototypes and MED values for broadband UVB and for UVA were determined in 461 white subjects. When appropriate, the 95% reference intervals, including the 0.025 fractile and 0.975 fractile, were computed for the MED-UVB reference values (by means of parametric methods) and the MED-UVA reference values (by means of nonparametric methods). MED data were also converted to standard erythema doses (SEDs). As described elsewhere we observed a considerable overlap of MED values for all skin phototypes and confirmed that age and sex do not substantially influence the MED. The lower RLs observed for MED-UVB were 33 mJ cm(-2) (0.5 SEDs) and for MED-UVA 12.6 mJ cm(-2) (1.2 SEDs). The MED and SED findings from this investigation may serve as reference data for white individuals and give support to the clinician in differentiating between normal and pathologically abnormal photosensitivity. Although the MED data given here are limited to the phototest device used in the present study, the SED results establish comparability between our data and phototest results obtained from laboratories using different UV sources.