A pragmatic randomized controlled trial on the effectiveness of low concentrated saline spa water baths followed by ultraviolet B (UVB) compared to UVB only in moderate to severe psoriasis.

OBJECTIVE: To evaluate whether low concentrated saline spa water baths followed by ultraviolet B (LC-SSW-UVB) are superior to UVB alone in moderate to severe psoriasis. BACKGROUND: There is a lack of sufficiently large randomized controlled clinical trial evaluating the additional benefit of saltwater baths followed by UVB compared to UVB only in psoriasis. STUDY DESIGN: Partly evaluator blind, multicentre, pragmatic, randomized controlled trial. SETTING: Five German spa centres. SUBJECTS: One hundred and forty-three adults with stable psoriasis during the last month and a Psoriasis Area and Severity Index (PASI) of > 10 and/or an affected body surface area of > 15%. INTERVENTIONS: LC-SSW-UVB or UVB thrice a week until remission (PASI < 5) or for a maximum of 6 weeks. Sodium chloride concentrations of natural springs varied between 4.5% and 12%. Conventional UVB (broadband UVB or selective UVB phototherapy) was used as irradiation source. MAIN OUTCOME: Reduction of PASI and/or affected body surface area of 50% at the end of the intervention period (PASI-50). Only participants receiving at least one intervention were included in the primary analysis. RESULTS: Patients allocated to LC-SSP-UVB attained a statistically significantly higher rate of PASI-50 at the end of the intervention period than patients allocated to UVB [58/79 (73%) vs. 32/64 (50%); P = 0.01; NNT, 4.3, 95% CI, 2.4-18.1]. Benefit persisted until 3 months only for one of two secondary outcomes considered. CONCLUSIONS: In routine clinical practice balneophototherapy using conventional UVB is superior to conventional UVB only at the end of a 6-week treatment course.

Chronic cutaneous sclerodermoid graft-versus-host disease: evaluation by 20-MHz sonography.

BACKGROUND: Chronic graft-versus-host disease (GVHD) is an immunological disorder frequently occurring as a late consequence of allogeneic bone marrow transplantation. Two variants, cutaneous lichenoid and sclerodermoid, have been described, based on clinical and histopathological examinations. It is, however, difficult to determine non-invasively the degree of cutaneous GVHD in vivo. Ultrasonographic methods have recently provided us with the means for objective and non-invasive monitoring of the dynamics of many chronic skin diseases. AIM, PATIENTS AND METHODS: In five patients with chronic cutaneous sclerodermoid GVHD skin thickness was measured with a 20-MHz B-mode ultrasound scanner (DUB 20S, taberna pro medicum, Lüneburg, Germany) in a clinically well-defined target skin lesion. Additionally cutaneous GVHD was assessed histologically before and after treatment. RESULTS: In all patients before treatment the corium of sclerotic skin was thicker than the corresponding areas of healthy skin. The skin thickness was increased from 45% to 83%. In the subcutaneous tissue proper echo-rich reflexes were prominent, representing the correlate of subcutaneous fibrotic trabeculae. In all patients ultrasonographic evidence of regression was shown (decrease of skin thickness by 18-83%). Moreover, it was demonstrated that quantitative assessment of skin thickness is feasible. CONCLUSIONS: In this paper we describe the detailed sonographic features of cutaneous sclerodermoid GVHD for the first time. As the method is simple and non-invasive, repeated examinations are possible. This provides the basis for monitoring treatment effects and efficient follow-up in these chronically progressive clinical conditions after bone marrow transplantation.

[Phototherapy and photochemotherapy of inflammatory dermatoses]. / Phototherapie bringt selbst hartnäckige Dermatosen zum Abklingen. Heilsames Bad im Licht.

Stubborn and extensive dermatoses, such as psoriasis vulgaris or atopic dermatitis (eczema), are indications for phototherapeutic methods. These include UVB phototherapy, UVA photochemotherapy (PUVA), UVA irradiation following prior photosensitization, UVA, treatment and combination treatments. Phototherapy is contraindicated in the case of light-induced dermatoses. Caution must also be exercised in patients receiving photosensitizing medications. When establishing the indication, consideration must be given to the treatment-related increased risk of developing skin cancer. The patient must also be informed of such undesired potential side effects as burns and premature aging of the skin.

The PUVA-turban as a new option of applying a dilute psoralen solution selectively to the scalp of patients with alopecia areata.

BACKGROUND: Alopecia areata is a burden for many patients and often resistant, even to extensive therapy. Orally administered PUVA therapy has been shown among numerous systemic and topical treatment modalities to be a therapeutic alternative. However, the clinical use of oral PUVA is often limited by systemic side effects. Bath-PUVA therapy offers an alternative solution because of the negligible systemic absorption of psoralen with this technique. Through use of a "PUVA-turban" it is now possible to administer a dilute bathwater solution containing 8-methoxypsoralen (8-MOP) to the scalp. OBJECTIVE: The purpose of this study was to determine whether PUVA turban therapy is effective in treating alopecia areata in different clinical stages. METHODS: We treated 9 patients with severe, rapidly progressing, treatment-resistant alopecia areata with PUVA-turban treatment as a modification of bath-PUVA therapy. At each treatment session a cotton towel was soaked with a 0.0001% 8-MOP solution (1 mg/L) at 37 degrees C, wrung gently to remove excess water, and wrapped around the patient's head in a turban fashion for 20 minutes. This was directly followed by UVA radiation. Treatment sessions were initially performed 3 to 4 times per week. RESULTS: The cumulative UVA doses given over treatment periods of up to 24 weeks were 60.9 to 178.2 J/cm(2), with single doses ranging from 0.3 to 8.0 J/cm(2). After up to 10 weeks of treatment, hair regrowth could be noticed in 6 of 9 patients. Two patients did not respond to the treatment, and one patient showed only vellus hair regrowth. CONCLUSION: PUVA-turban therapy can be considered a useful method of administering a dilute psoralen solution selectively to the scalp of patients. It has been shown to be a well-tolerated and, in some patients, efficient therapeutic alternative in the treatment of alopecia areata.

Calcipotriol vs. tazarotene as combination therapy with narrowband ultraviolet B (311 nm): efficacy in patients with severe psoriasis.

BACKGROUND: Phototherapy has been shown to be one of the most effective treatment modalities for patients with psoriasis. Nevertheless, photocombination therapies capable both of reducing cumulative ultraviolet (UV) doses and of accelerating clearance of skin lesions are important and of high interest. There have been no published studies comparing the effect of narrowband UVB irradiation in combination with topical application of tazarotene vs. calcipotriol. OBJECTIVES: To determine, in a half-side manner, whether a combination of UVB (311 nm) and tazarotene is superior to UVB (311 nm) plus calcipotriol or vice versa. METHODS: Ten patients suffering from widespread symmetrical psoriasis were treated for at least 4 weeks with topical calcipotriol and tazarotene in a half-side distribution. Additionally, the whole body was irradiated with narrowband UVB (311 nm) four times a week. Before treatment and once weekly during therapy a modified Psoriasis Area and Severity Index was estimated for each body half. The total treatment time, number of treatment sessions and cumulative UVB dose necessary for clearance of skin lesions were determined in an observer-blind fashion for each patient. Furthermore, all patients completed a quality of life questionnaire. RESULTS: Clearance of psoriasis was observed after a median of 19 treatment sessions (range 14-28) and a median cumulative UVB dose of 22.98 J cm-2 (range 9.24-58.22) simultaneously for both body halves. On the side treated with topical tazarotene gel, four patients complained of itching and dryness of the skin, and skin irritation was observed in three of them. Six patients preferred the application of tazarotene gel, while four preferred calcipotriol. CONCLUSIONS: Our clinical comparison of narrowband UVB with either topical calcipotriol or topical tazarotene revealed no significant therapeutic difference between both regimens. Although these results need to be confirmed in larger patient groups, we feel that both photocombination therapies can broaden the therapeutic options for moderate to severe psoriasis vulgaris and may reduce the cumulative UVB dose during therapy.

Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy.

Eosinophilic fasciitis is a rare disorder which can markedly affect the quality of life in individual patients. So far, no generally accepted and effective treatment modality has been available. Although the precise nature of eosinophilic fasciitis is still unknown, it is often regarded as a variant of localized scleroderma (morphoea). Phototherapy and photochemotherapy have been shown to be effective in the treatment of sclerodermatous skin lesions. We report a patient with eosinophilic fasciitis which was successfully treated with psoralen plus ultraviolet A bath photochemotherapy within 6 months.

Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel.

BACKGROUND: Narrow-band UVB (311 nm) phototherapy offering an emission spectrum closely conforming to the peak of the action spectrum for clearing psoriasis has significantly improved phototherapy for psoriasis. Because the majority of the commonly used topical therapies in treatment of psoriasis have limitations, a need for new topical agents remains. Tazarotene has been shown to be efficacious in plaque-type psoriasis. Combination of narrow-band UVB with topical agents has been shown to enhance efficacy of both treatment modalities. OBJECTIVE: We attempted to evaluate the efficacy of narrow-band UVB phototherapy in combination with topical tazarotene. METHODS: Ten patients with stable plaque psoriasis were treated with narrow-band UVB. In addition, topical tazarotene 0.05% was applied once daily to one side of the body. The follow-up period was 4 weeks. Efficacy was assessed separately for both body halves by means of a modified Psoriasis Area and Severity Index (PASI). RESULTS: Both treatment modalities notably reduced the PASI scores with values being significantly lower in skin areas treated with narrow-band UVB phototherapy in combination with topical tazarotene. CONCLUSION: The addition of tazarotene to narrow-band UVB phototherapy promotes more effective, faster clearing of psoriasis compared with UVB (311 nm) monotherapy.

Assessment of minimal phototoxic dose following 8-methoxypsoralen bath: maximal reaction on average after 5 days.

An essential procedure before starting bath psoralen ultraviolet (UV) A (PUVA) photochemotherapy is the evaluation of the minimal phototoxic dose (MPD), which is traditionally assessed 3 days after irradiation. However, there are no controlled studies supporting the 72 h peak of bath-PUVA erythema. The aim of this study was therefore to determine the exact time course of the erythematous reaction in human skin following bath-PUVA. For this purpose, the skin of 10 volunteers was exposed to 0.5-3.0 J/cm2 UVA directly after a 20-min 8-methoxypsoralen bath (0.5 mg/L, 37 degrees C). At 24, 48, 72, 96, 120 and 144 h (1-6 days) after irradiation, the MPD and the erythema sum score (ESS) were determined in each subject. The results showed a maximal erythematous reaction on average 5 days after irradiation. The mean MPD gradually decreased from day 2 (> 3.0 J/cm2) to day 5 (mean +/- SD 1.15 +/- 0.63 J/cm2) and started to increase at day 6 (mean +/- SD 1.6 +/- 0.52 J/cm2). The mean +/- SD ESS correspondingly increased from day 2 (0 +/- 0) to day 5 (10.5 +/- 3. 7) with a decrease at day 6 (7.5 +/- 3.1) (difference between day 3 and beyond statistically significant at P < 0.05). As our study indicates a maximal erythematous reaction to the bath-PUVA up to 5 days after irradiation, the traditional MPD assessment at 3 days generates a risk of phototoxic side-effects within the phototherapy course by underestimating the phototoxic effect in some patients. These findings contribute towards a more defined understanding of the kinetics of the phototoxic reaction in bath-PUVA therapy.

Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy.

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA(1) therapy (single dose, 20 J/cm(2), 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease.

Anaphylactic shock reaction to dibutyl-phthalate-containing capsules.

We report on a patient who was taking a Gelomyrtol forte capsule, a mucosecretolytic herbal product, to treat an infection of the upper respiratory tract. Itching, urticaria and respiratory distress occurred after 20 min which culminated in anaphylactic shock. Prick tests were carried out with the individual substances from Gelomyrtol forte capsules. Dibutyl phthalate produced a strong positive result. It is used as a plasticizer in films covering tablets, dragées and capsules. As a triggering agent of anaphylactic reactions to drugs, the auxiliary materials, e.g. dibutyl phthalate, should also be taken into consideration.

Phototherapy for atopic eczema with narrow-band UVB.

Management of atopic dermatitis has been less than satisfactory. Conventional therapy has not been particularly successful, and prolonged use of topical corticosteroids and systemic immunosuppressant drugs (eg, corticosteroids, cyclosporine, azathioprine) can result in severe cutaneous and systemic effects. We decided to evaluate the effect of UVB at 311 nm to treat 5 patients with moderate to severe atopic dermatitis. In each patient a mean cumulative dose of 9.2 J/cm2 was applied over a mean of 19 irradiations. Narrow-band UVB notably reduced atopic dermatitis after 3 weeks in all patients.

Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy.

PUVA-bath therapy developed into a first line topical PUVA therapy, and gel and cream preparations have been described as alternative modes of topical 8-MOP application. Because bath-PUVA can be difficult to manage, topical PUVA therapy using 8-MOP gel or cream preparations may become an important alternative when treating localised skin diseases. However, controlled comparisons of efficacy with this alternative topical PUVA therapy are lacking. We therefore compared the efficacy of PUVA-cream therapy with PUVA-bath therapy in 12 patients with recalcitrant dermatoses of the palms and soles using a left/right trial design. These patients responded well to both treatment modalities, meaning that both could be used successfully to treat recalcitrant dermatoses of the palms and soles.

Nitric oxide inhibits tissue factor synthesis, expression and activity in human monocytes by prior formation of peroxynitrite.

OBJECTIVE: Nitric oxide (NO) has antithrombotic properties by regulating platelet function, whereas direct effects on plasmatic coagulation are rarely described. In sepsis and inflammation, when synthesis of NO, oxygen radicals and toxic metabolites is crucial, the expression of tissue factor (TF) on monocytes stimulated by lipopolysaccharides (LPS) induces intravascular coagulation. This study was performed to examine the influence of NO and the NO-dependent metabolite peroxynitrite on LPS-induced TF expression and activity in human monocytes. DESIGN: Experimental study. SETTING: Laboratory for cell biology. METHODS: Human peripheral blood mononuclear cells were isolated from buffy coats by gradient centrifugation. The NO-releasing compounds SIN1 and NOC18 were used under different conditions. TF antigen was assayed by flow cytometry, and its activity by a clotting assay. TF-mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR-ELISA). MEASUREMENTS AND RESULTS: Whereas NOC18, a pure NO donor, had no effect, SIN1, releasing both NO and superoxide (O2-), reduced TF expression and activity in a dose- and time-dependent manner; superoxide dismutase (SOD) reversed the SIN1-mediated effect. Adding the O2(-)-deliberating system hypoxanthin/xanthin oxidase (which had no significant effect per se) to NOC18, or using the NO and O2- reaction product peroxynitrite resulted in a reduction of TF expression. RT-PCR-ELISA indicated upregulation of TF-mRNA by SIN1 with a peak at 500 microM; higher doses had less effect. CONCLUSION: These data demonstrate an influence of NO on LPS-induced TF expression in monocytes by prior formation of peroxynitrite; furthermore, the balance between NO and O2- seems to play a crucial role.