Dory N. H. Enomoto

Quantification of cutaneous sclerosis with a skin elasticity meter in patients with generalized scleroderma

BACKGROUND The skin score, a subjective assessment of skin elasticity, is widely used in patients with systemic sclerosis. Although this scoring method is regarded as a validated and accepted tool, the interobserver and intraobserver reproducibility is relatively poor. OBJECTIVE Our purpose was to investigate whether the recently developed SEM 474 cutometer, which exerts a controlled vacuum force to the skin, can measure skin elasticity more objectively than the skin score. METHODS Skin elasticity was measured in 74 different body areas in patients with systemic sclerosis and compared with the skin score obtained from the same areas. RESULTS The cutometer produced quantitative and reproducible data. A large-diameter (8 mm) measuring probe was superior to a small probe. The interobserver intraclass correlation coefficient (ICC) was 0.92; the intraobserver ICC was 0.94. A linear correlation was found with the clinical skin score; the Spearman rank correlation test was 0.69. CONCLUSION The correlation with the skin score was reasonable, despite the observation that regional differences in skin elasticity were detected by the cutometer but not by the human observer, who automatically compensates for these factors and integrates them into the skin score. The high interobserver and intraobserver ICC makes the cutometer more suitable for quantifying changes in skin thickness than the subjective skin score.

Evaluation of Medium-Dose UVA1 Phototherapy in Localized Scleroderma with the Cutometer and Fast Fourier Transform Method

Purpose: To evaluate the efficacy of medium-dose UVA1 phototherapy in patients with localized scleroderma. Method: A controlled pilot study with medium-dose UVA1 (48 J/cm2) was performed. The results were evaluated by means of a skin score and two objective methods for quantifying sclerosis (cutometer and fast Fourier transform method). Patients were treated 4 times a week for 5 weeks. The follow-up period was 12 weeks. Results: All patients responded to therapy. Skin score and cutometer results showed improvement of skin elasticity of treated skin compared to control skin. Fast Fourier transform measurements showed no change in bundle orientation ratio and spacing. Conclusion: We concluded that treatment for 12 weeks 4 times a week with medium-dose UVA1 may be a beneficial therapy and a well-tolerated treatment modality for localized scleroderma (morphea). After 12 weeks, improvement of skin sclerosis can be detected by skin score and cutometer measurements but not by the fast Fourier transform method.

Extracorporeal photochemotherapy (photopheresis) induces apoptosis in lymphocytes : a possible mechanism of action of PUVA therapy

Abstract— The mechanism of action of psoralen plus UVA (PUVA) and photopheresis is not entirely understood. These therapies are assumed to be immunomodulating partly by gradually decreasing leukocyte viability. We investigated whether this delayed form of cell death was due to apoptosis. Untreated and treated (PUVA exposed) leukocytes obtained from six patients with systemic sclerosis and (untreated) leukocytes from healthy control individuals were studied. Qualitative gel electrophoresis and quantitative in situ nick translation analysis of DNA fragmentation was performed. Apoptosis of the treated cells did occur (gel electrophoresis) after 24 h. At t = 0 h, immediately after exposure to PUVA, there was no evidence of DNA fragmentation in the treated cells. The percentage of treated cells undergoing apoptosis was 20–55% at t = 24 h (in situ nick translation). The untreated leukocytes of the patients and the healthy individuals showed no distinctive rise in apoptotic cells. Apoptosis of the leukocytes after PUVA or photopheresis treatment might be a mechanism of action and might explain the therapeutic response.

Dermal organization in scleroderma: the fast Fourier transform and the laser scatter method objectify fibrosis in nonlesional as well as lesional skin

Scleroderma, a chronic, progressive disorder, is characterized by dermal fibrosis with collagen bundles orientated parallel to the epidermis. Simple objective parameters to evaluate disease progression and therapies are needed. We describe two methods, the laser scatter method and the fast Fourier transform (FFT), to measure collagen bundle orientation and spacing. Lesional sclerodermic skin (LS), nonlesional sclerodermic skin (nonLS), and control skin (CS) sections were evaluated for orientation ratio using the laser scatter method. The FFT was used to calculate orientation ratio, variation, and spacing of collagen bundles. Parameters were correlated with local and mean skin score measurements, on a scale of 0 (normal) to 3 (severely sclerotic). With both the laser scatter method and the FFT, orientation ratios of LS (respectively, 2.16 ± 0.33 and 1.83 ± 0.62) were significantly higher than CS (respectively, 1.70 ± 0.35 and 1.38 ± 0.15). NonLS orientation ratios (respectively, 1.92 ± 0.15 and 1.48 ± 0.44) were between LS and CS ratios. Orientation variation and bundle spacing of LS (respectively, 57.3 ± 19.4 and 15.7 ± 5.6 μm) were significantly reduced compared to CS (respectively, 73.8 ± 15.0 and 18.9 ± 1.9 μm). NonLS orientation ratios (respectively, 57.2 ± 29.0 and 15.6 ± 6.1 μm) were similar to LS. Bundles in LS are more parallel, show less variation in orientation, and are more densely packed than in CS. There was a linear correlation between mean skin score and orientation ratio. Local skin score was not linearly correlated to orientation ratio. Our findings suggest that nonLS dermis without clinical sclerosis already shows fibrotic characteristics. Both techniques were easy to use and suitable for objectifying dermal fibrosis in scleroderma lesions. FFT is more accurate and reproducible than the laser scatter method and allows simultaneous pathological evaluation of the location of the analyzed tissue sections. Future studies will need to focus on the correlation between clinical disease severity and collagen bundle characteristics.