Resilience in patients and spouses faced with malignant melanoma. A qualitative longitudinal study.

Life-threatening diseases like malignant tumours are associated with considerable existential distress. Little is known about the factors that promote resilience within these individuals. This longitudinal qualitative partner study aimed to analyse resilience as per Antonovsky's sense of coherence. Eight patients with malignant melanoma and their partners were interviewed. They were asked about their coping strategies, attitudes towards the meaning of life and their cancer, and comprehension of what is happening to them. The questions were asked shortly after their diagnosis was made and 6 months later. All interviews were audio-taped and later transcribed and analysed according to the method of qualitative content analysis described by P. Mayring. At baseline, the majority of statements made (261; patients = 141/spouses = 120) related to coping/manageability of disease, with only 26 statements (patients = 15/spouses = 11) related to meaning and 127 (patients = 64/spouses = 63) to comprehension. There were no significant differences between the responses of patients and their partners and no significant changes in the number of statements during the 6-month interview. The most significant theme that emerged was manageability of disease, with distraction the most commonly utilised coping skill. The comprehension and meaning themes were far less prevalent. Hence, support should focus on disease and situational manageability.

Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial (NCT00056056).

BACKGROUND: Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. OBJECTIVE: To assess disease response and to compare the response rates of patients treated with PUVA alone or PUVA and bexarotene. METHODS: EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin(®) ) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. RESULTS: The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA + bexarotene. Total UVA doses received were 107 J cm(-2) (range 1·4-489·9) in the PUVA arm vs. 101·7 J cm(-2) (0·2-529·9) in the combination arm. The safety profile was acceptable with few grade 3-4 toxicities observed in either arm. More drop-outs due to toxicity were observed in the combination arm compared with the PUVA-alone arm. The best overall response (CCR + PR) rate was 71% for PUVA alone and 77% for the combination arm (P = 0·57). The median duration of response was 9·7 months for PUVA vs. 5·8 months for the combination arm (P = 0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P = 0·45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27·5) (P = 0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8 J cm(-2) ) compared with the PUVA arm alone (median 117·5 J cm(-2) ) (P = 0·5) was observed. CONCLUSIONS: No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA + bexarotene) but this did not achieve statistical significance due to insufficient power.

Split-face study of melasma patients treated with non-ablative fractionated photothermolysis (1540 nm).

BACKGROUND: Melasma treatment remains challenging despite various laser systems available, because of potential side-effects and high recurrence rates. OBJECTIVE: Non-ablative fractionated photothermolysis (FP) is a promising therapeutic method, long-time results comparing treated vs. non-treated site are lacking. METHODS: A total of 14 patients were treated with FP in a split-face mode with standardized adjustments in three sessions (weeks 0, 3-4, 6-8, follow-up: 26-28). At each consultation, improvement was evaluated by patients and physicians. Objective assessment was performed using digital photographs and the pigment imaging tool SIAscope(®). RESULTS: Melasma improvement was registered in 83% and 75% of the cases 26-28 weeks after the first treatment based on two evaluations: by patient and by physician, respectively. Digital photography and SIAscope(®) revealed improvement in 54% and 85% after the first, 61% and 85% after the second, 41% and 58% after the third treatment, accordingly, mostly due to reduction of the outline sharpness. Patients with lighter skin complexions revealed significant improvement ranged from slight to moderate (P=0.03). Postinflammatory hyperpigmentation occurred in two cases with skin types III and IV. CONCLUSION: Non-ablative FP can be considered as a valuable treatment option with short-term improvement in terms of mild reduction and softening the edges of melasma in patients with skin types I/II, if prior topical therapies failed. Treatment of patients with skin types III+ should be critically questioned.

[Vitamin D, ultraviolet rays and skin cancer]. / Vitamine D, ultraviolets et cancer de la peau.

Vitamin D, ultraviolets and skin cancer The vitamin D supply is fundamental for the prevention of falls and fractures in aged people, among other effects. UVB triggers vitamin D synthesis in the skin. This relationship has recently gained attention both with the general public and with health care professionals. Some authors suggest a relaxation of UV protection measures, while others even advocate regular sunlight exposure in order to increase cutaneous vitamin D synthesis. However, the UV irradiation responsible for vitamin D synthesis also is a known carcinogen. UV exposure is an insufficient and harmful method to increase vitamin D synthesis. Oral supplementation is the recommended way to prevent and cure vitamin D deficiency.

The optimal use of bexarotene in cutaneous T-cell lymphoma.

The management goal in cutaneous T-cell lymphomas (CTCLs) is to improve symptoms and induce remission. Early-stage disease is generally treated with skin-directed therapies. However, if these do not control the disease, systemic therapy becomes necessary. Bexarotene, a novel rexinoid, is an oral, noncytotoxic drug that has been approved in Europe for the treatment of refractory advanced-stage CTCL and in the U.S.A. for refractory CTCL. We provide guidance on the use of bexarotene in the management of CTCL, based on data from phase II/III clinical trials and the authors' clinical experience, and suggest how the potential of the drug can be maximized. The clinical trial results with bexarotene are reviewed, especially in comparison with interferon-alpha, which is the other commonly used noncytotoxic systemic therapy for CTCL. A treatment algorithm for bexarotene in refractory CTCL is suggested. As bexarotene may take time to achieve a maximum response, this algorithm recommends that therapy should be continued for a sufficient period to allow for a delayed onset of action. In addition, possible combination therapies with bexarotene are discussed. We conclude that bexarotene is effective in the management of CTCL, and has the advantage of oral administration. An on-going randomized clinical trial comparing psoralen plus ultraviolet A (PUVA) with PUVA plus bexarotene will provide valuable information about this combination regimen in early-stage disease, but further data are needed on the relative efficacies of other combination therapies with bexarotene in CTCL.

Combination of 308-nm xenon chloride excimer laser and topical calcipotriol in vitiligo.

BACKGROUND: A large variety of therapeutic agents are being used for the treatment of vitiligo, but treatment remains a challenge. Recently, monochromatic phototherapies such as 311-nm narrowband ultraviolet B therapy and 308-nm xenon chloride excimer laser have been reported to be an effective and safe therapeutic option in children and adult patients with vitiligo. Single reports stipulate that the addition of topically applied calcipotriol to phototherapy increases its effectiveness. OBJECTIVE: The purpose of the present pilot study was to determine if the addition of topical calcipotriol increases the efficacy of the 308-nm xenon chloride excimer in the treatment of vitiligo. METHODS: Ten patients with vitiligo with essentially bilateral symmetrical lesions were enrolled in this prospective right/left comparative, single-blinded trial conducted over a 15-month period. All patients received 308-nm XeCl excimer laser therapy three times weekly. Calcipotriol ointment (Daivonex) was applied to lesions on one side of the body twice daily. RESULTS: After 24 treatments (8 weeks), nine patients were evaluated. Eight patients showed evidence of repigmentation on both body sides, with no significant difference between the body side treated with calcipotriol and excimer laser and the side treated with excimer laser alone. The mean repigmentation rate was 22.4% (1-37%). CONCLUSION: The addition of calcipotriol ointment to 308-nm xenon chloride excimer laser phototherapy does not significantly enhance its efficacy. Small additive effects must be investigated in a larger trial.

[Pruritus in frequent skin diseases and therapeutic options]. / Juckreiz bei häufigen Hauterkrankungen und therapeutische Optionen.

Pruritus is a common symptom in many inflammatory skin conditions. In these cases, itch is typically pruritoceptive and is induced by cutaneous inflammation. The most common skin diseases associated with itch are eczemas, including atopic dermatitis, dry skin or contact dermatitis. Scabies has to be excluded. Psoriasis and lichen planus are other common skin disorders associated with itching. Therapy includes local treatment options including hydration with lotions or creams, topical application of Polidocanol, capsaicin or menthol, phototherapy is an option in many inflammatory skin diseases. Systemic approaches include antihistamines, antidepressants, gabapentin or opiate antagonists.

[Standard and experimental therapy of cutaneous T-cell lymphoma]. / Standard- und experimentelle Therapie kutaner T-Zell-Lymphome.

Cutaneous T-cell lymphoma represent a heterogeneous group of diseases characterized by skin invasion of monoclonal T-lymphocytes. These cutaneous T-cell lymphomas are divided into 3 groups based on clinical, histological and immunohistological characteristics: Indolent with a survival time of over 10 years, aggressive with a survival time less than 10 years and provisional (EORTC classification). Standard treatments such as PUVA, total skin electron beam, methotrexate, polychemotherapy regimens, retinoids and photopheresis have been used for years. Bexarotene is a newly registered drug. To achieve better response rates, several new drugs are being evaluated in clinical trails, including imiquimod, denileukon-diftitox, liposomal doxorubicin, adeno-interferon-gamma and various combination approaches.

[Cutaneous neoplasms]. / Neoplasien der Haut.

The skin is the organ most commonly affected by malignancies. Various cancers of the skin show a dramatic increase in incidence over the last decades. Epithelial skin tumors are most frequently, e.g., basal cell carcinoma and the squamous cell carcinoma with its precursors, the actinic keratoses. Melanoma, which is extremely difficult to treat in advanced tumor stages, is dreaded. Besides that, there are other epithelial malignant diseases, e.g. Morbus Bowen and adnexal tumors originating from the skin appendices. Mesenchymal malignant neoplasias such as Morbus Kaposi, angiosarcomas and other dermal sarcomas, are rare. Since the majority of malignant neoplasms is removable and curable by a simple surgical intervention, the knowledge of the different skin tumors is essential for non-dermatologist.

[Granulomatous slack skin: partial remission following intralesional administration of interferon-alpha and PUVA]. / Granulomatous slack skin. Partielle Remission unter intraläsionärer Gabe von Interferon-alpha und PUVA.

Granulomatous slack skin (GSS) is a rare cutaneous T-cell lymphoma which typically runs a protracted and indolent course. On histopathological assessment lymphoid infiltrates with multinucleated giant cells in the dermis and subcutis with elastophagocytosis can be observed. Skin lesions are characterized by pendulous folds. We report on the successful response of the lesions to intralesional interferon alpha combined with PUVA.

Comparison of 8-MOP aqueous bath and 8-MOP ethanolic lotion (Meladinine) in local PUVA therapy.

BACKGROUND AND OBJECTIVE: Local PUVA (psoralen plus UVA light) is an effective outpatient treatment for patients with palmoplantar eczema or psoriasis. In this study, the efficacy, applicability and patient acceptance of two local forms of 8-methoxypsoralen (8-MOP) PUVA therapy were compared. METHODS: The study design was a left-right comparison (n = 37): the left hand or foot was treated with (aqueous) 8-MOP bath PUVA whereas the right received (ethanolic) 8-MOP lotion PUVA. After 1 month, the more successful treatment was continued on both sides until lesions cleared. RESULTS: Both therapies were effective and both useful for particular clinical applications: patients with erosive lesions and rhagades appreciated the gentleness of bath PUVA. Those with pustules or hyperkeratotic lesions appreciated the greater effectiveness of 8-MOP lotion PUVA. The total UVA dose and number of sessions to clearance were smaller with 8-MOP lotion. There was no difference in the length of the relapse-free period. Therapy nonresponders usually became apparent within the first 12 sessions. CONCLUSIONS: The difference between bath PUVA and lotion PUVA can be described as 'gentle' versus 'strong' therapy. The better therapy depends on clinical indication.

Incidence and in-vivo relevance of anti-interferon antibodies during treatment of low-grade cutaneous T-cell lymphomas with interferon alpha-2a combined with acitretin or PUVA.

Interferon-alpha combined with retinoid or PUVA is used for the treatment of cutaneous T-cell lymphoma. Anti-IFN-alpha antibodies (IFN ab) occur regularly during IFN-alpha treatment. We investigated the incidence of neutralizing and binding IFN ab and analysed their relationship with clinical and immunological parameters. A group of 17 CTCL patients were treated with IFN alpha-2a three times weekly subcutaneously at a dose of 3 Mill. I.U. combined either with retinoid (acitretin, Neotigason; 0.5 mg/kg bodyweight) daily or with 5-methoxypsoralen (1.2 mg/kg bodyweight) plus UVA radiation three times weekly. Prior to and during treatment we monitored stage, skin involvement by a tumour burden index, serum levels of beta 2-microglobulin, neopterin, binding and neutralizing IFN ab, Interleukin-6 (IL-6), soluble IL-2 receptors (sIL-2r) and the CD4/CD8 ratio of peripheral blood mononuclear cells. We observed two complete, two partial and six minor responses, four patients with stable disease and three patients with progressive disease. Of the 17 patients, 7 developed binding IFN ab, but only 2 had neutralizing IFN ab which were associated with high titres of binding IFN ab. IFN ab formation was more frequent in patients with normal CD4/CD8 ratios and a high tumour burden index and showed a trend to be more frequent in PUVA-cotreated patients than in retinoid-cotreated patients. Responses were more frequently seen in IFN ab-negative patients. IFN ab developed in patients treated with PUVA or retinoid combined with IFN. Binding as well as neutralizing IFN ab may have an impact on the treatment success in CTCL patients.