G. von Kobyletzki

Medium-dose UVA1 cold-light phototherapy in the treatment of severe atopic dermatitis

BACKGROUND Recently, conventional high-dose UVA1 phototherapy (340-400 nm) has been shown to be more effective than combined UVA-UVB therapy in the treatment of severe atopic dermatitis (AD). However, there are limitations of this treatment, such as intense sweating caused by the immense heat load during therapy and the high cumulative UVA1 doses that are required. For this reason, lavish UVA1 equipment was developed containing an advanced filtering and cooling system resulting in almost complete absence of heat load and sweating during therapy. OBJECTIVE In this study we compared the monotherapeutic efficacy of conventional medium-dose UVA1, medium-dose UVA1 cold-light, and combined UVA-UVB phototherapy in the treatment of severe AD. METHOD The study involved 120 patients with severe AD. Fifty patients each received conventional UVA1 or UVA1 cold-light phototherapy (15 days, 50 J/cm(2)/day), and 20 patients were treated with combined UVA-UVB (15 days, minimal erythema dose dependent). Severity of AD was scored by means of the SCORAD score, and clinical improvement was additionally monitored by serologic cytokine markers. RESULTS Six (12%) of 50 patients treated with UVA1, 2 (4%) of 50 patients treated with UVA1 cold-light therapy, and 4 (20%) of 20 patients treated with combined UVA-UVB therapy discontinued treatment prematurely because of an unsatisfactory clinical outcome or adverse reactions. Skin status improved or even cleared completely in 77.3% of the patients treated for 3 weeks with conventional UVA1 therapy and in 85.4% of the patients treated for 3 weeks with UVA1 cold-light therapy, resulting in a significant decrease in the SCORAD score in both UVA1 groups (P <.05 each). In the group treated with combined UVA-UVB, the SCORAD score also decreased but significantly less than in both groups treated with UVA1 photo-therapy (P <.05 each). At follow-up after 4 weeks, the patients treated with UVA1 displayed a more prolonged therapeutic benefit than the patients treated with UVA-UVB therapy. Plasma levels of soluble interleukin 2 receptors and soluble interleukin 4 receptors significantly decreased under both UVA1 and UVA1 cold-light phototherapy but not under combined UVA-UVB phototherapy. CONCLUSION Our study demonstrates that medium-dose UVA1 cold-light phototherapy displays advantages compared with conventional UVA1 phototherapy caused by the almost complete absence of heat load and intense sweating and is more effective than UVA-UVB phototherapy in the treatment of severe AD.

Low-dose ultraviolet-A1 phototherapy for lichen sclerosus et atrophicus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin disease characterized by white porcelain‐like sclerotic skin lesions. It is most commonly seen in adult females and usually affects the genitoanal area. Extragenital LSA appears in 15–20% of cases. We report a 9‐year‐old Caucasian girl suffering from extragenital LSA that was resistant to conventional treatment. After 40 treatment sessions with low‐dose UVA1 phototherapy, all skin lesions were resolved completely. Moreover, the improvement of skin status has been sustained during 6‐months of follow‐up. Long‐wave UVA irradiation has been shown to induce intensively collagenase activity in human dermal fibroblasts. We suggest that UVA1 irradiation could be an effective treatment in patients suffering from extragenital LSA.

Treatment of idiopathic mucinosis follicularis with UVA1 cold light phototherapy.

Mucinosis follicularis, first described in the thirties as a follicular skin disease with intraand perifollicular deposits of mucin [1, 2], is a chronic type of inflammatory dermatosis involving the sebaceous glands and outer root sheaths. Even though it is characterised clinically by a variety of unspecific skin affections, mucinosis follicularis reveals distinct characteristic histological features [3–5]. The age of onset, distribution, number and morphology of lesions are important prognostic signs. Two common clinical forms of mucinosis follicularis have been described, namely the infiltrated plaque form, which is characterised by prominent follicular openings and usually results in hair loss, and an idiopathic form with grouped follicular papules, which may resemble prurigo and which occurs on the trunk and proximal parts of the limbs as well as on the face and scalp [6, 7]. The association of malignant lymphoma such as Sézary syndrome, mycosis fungoides and nonHodgkin lymphoma with mucinosis follicularis lesions is the reason for determining this skin disease as a potential paraneoplasia or even as a precursor of cutaneous T cell lymphoma [8]. However, one common histopathological feature of mucinosis follicularis and mycosis fungoides is the predominantly lymphocytic infiltration of the skin [6]. Long-wave UVA1 (340–400 nm) phototherapy has been reported to be successful in the treatment of severe atopic dermatitis, cutaneous T cell lymphoma and other inflammatory skin diseases [9, 10]. Recent observations indicate that the T helper cells, present in the dermal layers of lesional skin, are important targets for UVA1 phototherapy [11, 12]. Accordingly, successful UVA1 phototherapy of atopic dermatitis is associated with down-regulation of the in situ expression of T-helper-cell-derived cytokines as well as a significant reduction in the number of intradermal CD4+ T cells caused by the induction of apoptosis in epidermal and dermal T helper cells, as a consequence of singlet oxygen generation and lipid peroxidation [12, 13]. We therefore hypothesised that UVA1 irradiation might have a strong anti-inflammatory and antiproliferative effect on the skin lesions seen in a patient with mucinosis follicularis. We report on a 26-year-old Caucasian woman with idiopathic mucinosis follicularis. The disease, diagnosed 7 months previously, was continually progressive. On examination, the patient revealed an eruption of pruritic follicular papules, partly excoriated, mainly on the trunk, extremities and in the submammary region (fig. 1). Histopathological examination of a 4-mm punch biopsy revealed an inflammatory infiltration around a pilosebaceous gland, accompanied by the intrafollicular deposit of moderate amounts of Alcian-blue-positive mucinous material (fig. 2). The dermal infiltrate predominantly consisted of lymphocytes (CD3+), histiocytes and numerous eosinophils. Initially, the patient was treated with a potent external corticosteroid (fluocortolone), with only temporary success. Also a combined UVA/UVB phototherapy carried out over a period of 6 weeks did not lead to a significant clinical improvement. After consideration of further treatment options, UVA1 phototherapy was given 5 times a week for 3 weeks, resulting in a total of 15 treatment sessions. At each treatment session, 60 J/cm2 UVA1 were applied, resulting in a cumulative dose of 900 J/cm2. As an irradiation source, we used a so-called UVA1 cold light (UVA1-cl) source emitting wavelengths of 340–530 nm only, with a peak between 370 and 380 nm (Photomed® CL 300.000, Wennigsen, Germany) [9, 10]. During therapy, no side effects were observed. Within 1 week after beginning UVA1-cl phototherapy, the number of pruritic papules had markedly decreased and, after 3 weeks, the skin lesions were completely cleared (fig. 3). Moreover, the improvement of skin status has been sustained during a follow-up period of 3 months. These first observations indicate that medium-dose UVA1-cl phototherapy may be highly effective in the treatment of therapyresistant mucinosis follicularis, even in patients with progressive disease. In contrast to other treatments like external corticosteroid therapy leading only to a temporary improvement of skin condition, in this case UVA1-cl phototherapy led to a complete healing of the pruritic papules and plaques. Although further clinical trials are required to confirm our treatment results, UVA1-cl phototherapy seems to be a promising new therapy modality for patients with idiopathic mucinosis follicularis.

Mechanisms of apoptosis: UVA1‐induced immediate and UVB‐induced delayed apoptosis in human T cells in vitro†

Objective The decreased number of lymphocytes combined with the induction of apoptosis and necrosis seems to be the key mechanism of many phototherapeutic agents. The purpose of our study was to determine the regulating pathway, time course and dose dependence of UVA1‐ vs. UVB‐induced cell death in human T lymphocytes.

Efficacy of ultraviolet A1 phototherapy on the expression of bcl-2 in atopic dermatitis and cutaneous T-cell lymphoma in vivo: a comparison study

Background/Purpose: Atopic dermatitis (AD) is characterized immunohistochemically by a high number of skin infiltrating T‐helper cells (CD4 + ). In most cases cutaneous T‐cell lymphoma (CTCL) is characterized by a malignant proliferation of CD4 +  T‐helper lymphocytes. The purpose of our study was to evaluate the extent of anti‐apoptotic effects in patients suffering from AD or CTCL, respectively, which may contribute to the prolonged inflammation. Furthermore, we investigated whether medium‐dose ultraviolet A1 (UVA1) phototherapy is able to modulate the expression of bcl‐2 within the dermal inflammatory infiltrate.

Opposing effects of UVA1 phototherapy on the expression of bcl-2 and p53 in atopic dermatitis

Abstract Recently, medium-dose UVA1 phototherapy (50 J/cm 2 ) has been introduced as an effective treatment for severe atopic dermatitis (AD). In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement in skin status in patients with AD, biopsy specimens from ten patients before and after treatment were analysed immunohistochemically for features of apoptosis. We sought to determine the extent to which UVA1 irradiation was able to modulate the balance between p53 and bcl-2 expression in vivo using monoclonal antibodies labelling these proteins. As compared with lesional skin of patients with AD before UVA1 irradiation, the number of dermal cells, apparently lymphocytes, that were positive for p53 had significantly increased after treatment and, in addition, some basal keratinocytes showed slight positive staining for p53. An increased expression of the bcl-2 gene before treatment in predominately dermal lymphocytes was significantly downregulated by UVA1 therapy. The increase in p53 + cells and the decrease in bcl-2 + cells were closely linked to a significant reduction in dermal T cells (CD3 + ) and a substantial clinical improvement in skin condition. In summary, medium-dose UVA1 irradiation led to a marked modulation of the expression of p53 and bcl-2, and this plays a key role in regulating UVA1-induced apoptosis.

Localized vitiligo successfully treated with cream-psoralen + ultraviolet A

To the Editor Oral psoralen plus ultraviolet A photochemotherapy (PUVA) is one of the most effective treatment modalities available for vitiligo. However, in a significant number of subjects adverse events occur and, therefore, this treatment is not considered appropriate for localized forms of the disease. 1,2 Recently, cream preparations containing 8-methoxypsoralen (cream PUVA) were found to be effective in treating a variety of skin diseases, including palmoplantar dermatoses 3 and granuloma anulare. 4

Akute generalisierte Katzenkratzkrankheit bei myelodysplastischem Syndrom

ZusammenfassungBei der Katzenkratzkrankheit treten bei Personen mit nicht gestörter Immunantwort außer einer häufig an der Eintrittspforte der Erreger vorhandenen Papel in der Regel keine weiteren Hautveränderungen auf. Wir stellen den Fall eines 73-jährigen Patienten mit einem myelodysplastischen Syndrom vor, bei dem sich im Rahmen einer Bartonelleninfektion generalisierte petechiale und teils papulöse, an eine Vasculitis allergica superficialis erinnernde Hautveränderungen entwickelten. Nach Diagnosestellung durch Erregernachweis in Lymphknoten heilte die Erkrankung unter 3-wöchiger antibiotischer Therapie mit Erythromycin vollständig ab. Außer dem löslichen Interleukin-2-Rezeptor waren alle anderen serologischen Entzündungsparameter normwertig. Die IgG-Antikörper gegen die Erreger Bartonella henselae und Bartonella quintana waren während der floriden Erkrankung nur leicht erhöht und stiegen erst nach mehreren Monaten deutlich an, erhöhte IgM-Antikörper waren nicht aufgefallen. Richtungsweisend für die Diagnose der Katzenkratzkrankheit war letztlich der in der Warthin-Starry-Färbung sichtbare Erreger in der Lymphknotenbiopsie.AbstractIn patients with normal immunity, cat scratch disease typically develop a papule at the portal of entry and no other cutaneous features. A 73 year old male patient with a myelodysplastic syndrome developed generalized petechial, papular and, vasculitic skin lesions in association with cat scratch disease. After the diagnosis was established by identifying the causative organism in a lymph node biopsy, the patient was treated with erythromycin for three weeks resulting in progressive clearance of the skin lesions. Apart from the soluble IL-2 receptor, no other serologic inflammatory parameters were elevated. IgG antibodies against Bartonella henselae and Bartonella quintana increased only slightly during acute exacerbation of the disease, but significantly increased some months later. The diagnosis was established by the positive staining of the lymph node biopsy using the Warthin-Starry stain.