Successful ultraviolet A1 phototherapy in the treatment of localized scleroderma: a retrospective and prospective study

Background Ultraviolet (UV) A1 phototherapy is an effective anti‐inflammatory treatment modality that influences fibroblast functions. Objectives To document the effects of UVA1 treatment in patients with localized scleroderma (LS) in a retrospective study (at least 6 months after UVA1 treatment) and in a prospective study before and immediately after medium‐dose UVA1 irradiation. Methods In total, 30 patients (retrospective study n = 17, prospective study n = 13) with LS receiving UVA1 phototherapy five times weekly (for 3–6 weeks) were investigated. Improvement was documented using standardized questionnaires and clinical evaluation (using modified Rodnan skin score, Cutometer and 7·5‐MHz ultrasound measurements). Levels of collagen I and collagen III metabolites were measured in serum and urine. Results In the retrospective study, medium‐dose UVA1 phototherapy had been performed 6 months–3 years earlier (cumulative dose 750–1400 J cm^?2; mean ± SD number of irradiations 19·3 ± 3·8). Fourteen of 17 patients (82%) reported an improvement in symptoms following UVA1 therapy. In the prospective study, skin elasticity increased in 77% of the patients following medium‐dose UVA1 phototherapy (cumulative dose 750–1250 J cm^?2; mean ± SD number of irradiations 20·8 ± 4·0). 7·5‐MHz ultrasound measurements showed a mean reduction of lesional skin thickness of 13% compared with skin thickness before UVA1 phototherapy. The ratio of deoxypyridinoline to creatinine was significantly elevated in about two‐thirds of the patients. Conclusions This open study showed a positive short‐ and long‐term efficacy of UVA1 phototherapy in patients with LS, with a reduction in sclerotic plaques, an increase in skin elasticity and a reduction of lesional skin thickness. UVA1 phototherapy had a significant effect on collagen metabolism. UVA1 phototherapy can be regarded as a safe treatment modality for patients with LS.     

Altered decorin expression of systemic sclerosis by UVA1 (340–400 nm) phototherapy: Immunohistochemical analysis of 3 cases

Background

Ultraviolet A1 (340–400 nm, UVA1) phototherapy is highly effective in sclerotic lesions of systemic sclerosis (SSc). Histological evaluation of skin specimens obtained before and after UVA1 phototherapy revealed loosening of collagen bundles and the appearance of small collagen fibers. We have previously shown that UVA1 irradiation induced collagenase in vitro study by using SSc fibroblasts. The increased levels of mRNA and protein of decorin in SSc fibroblasts were reported. In this study, we focus on the lesional expression of small dermatan sulfate proteoglycan, decorin that has a role of binding to collagen and fibrillogenesis.

Case presentation

We employed immunohistochemical analysis of decorin before and after UVA1 phototherapy. The skin specimens from three patients who were effectively treated with UVA1 phototherapy were analysed. Monoclonal antibody 6B6 as the specific reactivity to decorin was used. The increased decorin was focally accumulated in the newly synthesized collagen fibers in the sclerotic lesion of SSc. After UVA1 phototherapy, decorin was decreased in upper to middle dermis, although decorin was slightly increased in papillary dermis.

Conclusions

These results suggest that decreased and normalized levels of accumulated decorin may relate to the efficacy of sclerotic lesions in UVA1 phototherapy.

     

In situ expression of messenger RNA of interleukin-1 and interleukin-6 in psoriasis: interleukin-6 involved in formation of psoriatic lesions

Summary Psoriasis is a disease of abnormal proliferation and differentiation of epidermal cells. Several cytokines released by keratinocytes are implicated as factors responsible for this pathological condition of the epidermis. In order to elucidate the role of these cytokines in psoriasis, messenger RNA (mRNA) expression of interleukin-1 (IL-1) and IL-6 in psoriatic epidermis was investigated using biotin-labelled complementary DNA (cDNA) of the cytokines. Messenger RNA of IL-1 was weakly detected in some normal healthy epidermis specimens and more strongly in all the perilesional uninvolved psoriatic epidermis specimens. It was also expressed in the transitional zone between uninvolved and fully developed psoriatic skin, but was not expressed in lesional skin. In contrast, IL-6 mRNA was rarely expressed in normal healthy epidermis, but was expressed in perilesional uninvolved psoriatic epidermis, in the transitional zone and in the fully developed lesional epidermis, with the maximum intensity in the transitional zone. Expression of mRNA of IL-6 receptor showed a similar tendency to that of IL-6. It was expressed in psoriatic epidermis, most strongly in the transitional zone, but not in normal healthy epidermis. IL-6 was demonstrated immunohistochemically in psoriatic epidermis, but IL-6 receptor was demonstrated only in the transitional zone. Thus IL-6 and its receptor expression correlated well with the formation of psoriatic lesions where IL-1 may initiate their expression. IL-6 may play an important role in the pathogenesis of psoriasis.     

Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: results of a preliminary study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease in which numerous therapies have been used, with only limited success. Because low-dose UVA1 phototherapy has been shown to be an effective treatment option for localized scleroderma, which shares several similar clinical and histologic features with LS, we initiated a clinical trial with this phototherapeutic modality in patients with LS. METHODS: Ten patients suffering from extragenital LS were treated with low-dose UVA1 phototherapy 4 times weekly with single UVA1 doses of 20 J/cm(2). Forty treatment sessions were performed within 10 weeks, resulting in a cumulative UVA1 dose of 800 J/cm(2). RESULTS: Low-dose UVA1 phototherapy resulted in a marked reduction of the clinical score and a significant (P <.05) decrease of ultrasonographically measured skin thickness as well as a highly significant (P <.001) increase of dermal density. The patients reported a remarkable softening and repigmentation of the affected skin. CONCLUSION: Analogous to the treatment results in localized scleroderma, low-dose UVA1 phototherapy seems to be an effective and well-tolerated treatment option for extragenital LS.     

Interleukin-6 in the epidermis of patients with psoriasis before and during PUVA treatment

Biopsies from lesional and unaffected skin of 6 patients with psoriasis, taken before and during treatment with psoralen plus UVA (PUVA) were examined immunohistologically, using partially purified polyclonal antibodies to crude supernatants of activated human blood monocytes. By absorption with recombinant derived human monokines, we were able to demonstrate that interleukin-6 (IL-6) (but not IL-1 alpha or IL-1 beta) was located in a laminar and granular pattern in stratum corneum, and on epidermal cell membranes in the viable cellular epidermis. Before PUVA treatment, the intensity and the extension of staining for IL-6 were both markedly increased in lesional skin compared with uninvolved skin. A weaker staining for IL-6 was observed in lesional skin, simultaneous with the clinical improvement of psoriasis. The staining patterns for IL-6 in biopsies from cleared lesional skin and uninvolved psoriatic skin were identical at the conclusion of therapy.     

Interleukin-4 and the interleukin-4 receptor in allergic contact dermatitis

Cutaneous immune responses involving T helper (TH) type 1 (TH1) and type 2 (TH2) T cells, characterised by secretion of interferon-γ (Ifn-γ) and interleukin-4 (IL-4), respectively, have both been reported in allergic contact dermatitis (ACD). We used immunohistochemistry to localize expression of IL-4 in ACD lesions and unaffected skin. Atopic dermatitis (AD) and psoriasis biopsies provided positive and negative IL-4 immunoreactivity controls. To investigate the rôle of IL-4 in ACD, we investigated expression of IL-4 receptors in ACD, AD and psoriatic skin. IL-4 immunoreactivity was found in cells in the dermal infiltrate in 3 out of 7 ACD lesions, but not in unaffected skin from these patients. IL-4 immunoreactivity was found in the dermal infiltrate of all lesional and unaffected AD biopsies, but in none of the psoriatic biopsies. IL-4 receptor α chain immunoreactivity, associated with dermal mast cells, was found in all patients. Local expression of IL-4 in ACD indicates either TH2 or TH0 immunoregulation in some allergic contact dermatitis lesions. Our findings do not support exclusive TH1 or TH2 cutaneous immune responses in ACD. Expression of IL-4 receptors by cutaneous mast cells provides a route through which local effects of IL-4 might be mediated.     

T cells and mast cells as a major source of interleukin-13 in atopic dermatitis

BACKGROUND: Interleukin (IL)-13 is a T-cell-derived cytokine that shares several functions with IL-4, including the induction of immunoglobulin E synthesis. Recent studies suggest that cytokines expressed locally in the skin play several critical roles in atopic dermatitis (AD), however, little is known about the role of IL-13 in AD lesions. OBJECTIVES: The present study was designed to characterize the involvement of IL-13 in AD in the skin and peripheral blood mononuclear cells (PBMC). METHODS: Using lesional and nonlesional skin from adult AD patients and normal skin from healthy volunteers, we performed RT-PCR, in situ RT and immunostaining to determine the IL-13 expression at the mRNA and protein levels. The actual numbers of IL-13 expressing cells in biopsy specimens were counted under the microscope. IL-13 mRNA expression in PBMC from AD patients and healthy volunteers was examined by RT-PCR analysis. RESULTS: IL-13 mRNA expression was detected by RT-PCR in lesional and nonlesional skin and in PBMC from AD patients, but not in normal skin or PBMC from healthy volunteers. In AD lesional skin, numerous IL-13 mRNA-positive cells were demonstrated by in situ RT, and similar numbers of IL-13-positive cells were also detected immunohistochemically. Smaller numbers of IL-13-positive cells were observed in AD nonlesional skin and in normal skin. The differences in the numbers of IL-13-expressing cells between lesional and nonlesional skin were statistically significant. Double immunostaining revealed that IL-13 was produced in approximately 40% of T cells and 20% of mast cells in AD lesional skin, suggesting that T cells and mast cells are major sources of IL-13 in AD lesions. CONCLUSION: IL-13 may play a local as well as a systemic role in the development of AD lesions.     

Interleukin-11 production is increased in organ cultures of lesional skin of patients with active plaque-type psoriasis as compared with nonlesional and normal skin. Similarity to interleukin-1β, interleukin-6 and interleukin-8

Increased levels of several cytokines, mainly proinflammatory mediators, have been reported in psoriatic lesions. Little information, if any, is available concerning other cytokines, especially those initially studied as marrow differentiation agents. Using the experimental approach of measuring cytokines released by skin organ cultures. IL-11 and three other proinflammatory cytokines (IL-1β, IL-6 and IL-8) were determined using commercially available ELISA kits in supernatants of ten biopsies from lesional and nonlesional psoriatic skin areas and in supernatants of biopsies from ten normal volunteers. The results obtained showed that the amounts of IL-11 and the other three modulators were significantly increased in the material from the lesional areas ( P < 0.01). The amounts of IL-11, which is known to have functional activity similar to the proinflammatory cytokines and to share a receptor component with IL-6, were also correlated with the disease severity index ( R = 0.69, P = 0.04). In addition, a nearly significant correlation was noted between the amounts of IL-11 released by the lesional and the nonlesional skin biopsies ( R = 0.66, P = 0.05). More detailed studies are needed to clarify whether IL-11 plays a specific functional role in psoriasis, but this study emphasizes the complexity of the pathogenesis of psoriasis and the cytokine network, including activation of proinflammatory and haemopoietic biological response modifiers, in this disease. Received: 14 October 1996     

Serum interleukin-8 level is a more sensitive marker than serum interleukin-6 level in monitoring the disease activity of oral lichen planus

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease. Interleukin (IL)-8 is a pro-inflammatory cytokine of host response to injury and inflammation. OBJECTIVES: To investigate whether serum IL-8 level was a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP and to assess whether IL-8 was a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 and IL-8 in 158 patients with OLP, nine patients with traumatic ulcers (TU) and 54 normal control subjects. Some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration were treated with levamisole for 0.5-6.0 months and their serum IL-6 and IL-8 levels were measured after treatment. RESULTS: We found that 28% (44 of 158) OLP, 28% (40 of 142) erosive OLP (EOLP), and 25% (four of 16) nonerosive OLP (NEOLP) patients had a serum IL-6 level greater than the upper normal limit of 4.7 pg mL(-1). In contrast, 63% (99 of 158) OLP, 63% (90 of 142) EOLP and 56% (nine of 16) NEOLP patients had a serum IL-8 level greater than the upper normal limit of 8.7 pg mL(-1). In some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration, treatment with levamisole for a period of 0.5-6.0 months could significantly reduce the mean serum IL-6 level from 14.3 +/- 1.9 pg mL(-1) to 3.2 +/- 0.6 pg mL(-1) (P < 0.001) and could significantly reduce the mean serum IL-8 level from 95.8 +/- 17.1 pg mL(-1) to 14.8 +/- 5.8 pg mL(-1) (P < 0.001). CONCLUSIONS: Because measurement of the serum IL-8 level can detect more OLP patients with an abnormal serum level than measurement of the serum IL-6 level (63% vs. 28%), we conclude that serum IL-8 level is a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP. Levamisole can modulate both the serum IL-6 and IL-8 levels in OLP patients. IL-8, like IL-6, is also a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients.     

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-α (TNF-α), 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-α 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.