Factors Influencing [F‐18] 2‐Fluoro‐2‐Deoxy‐d‐Glucose (F‐18 FDG) Accumulation in Melanoma Cells: Is FDG a Substrate of Multidrug Resistance (MDR)?

In order to specify the influence of multidrug-resistance (MDR) on the accumulation of the PET tracer, F-18 FDG ([Fluorine-18] 2-fluoro-2-deoxy-D-glucose, in melanoma cells, both the MDR function and expression of two human melanoma cell lines SK-MEL 23 and 24, were evaluated. The effects of MDR modulators on FDG accumulation and efflux were also investigated. A functional analysis using representative MDR fluorescent substrates and inhibitors clarified the following characteristics: 1) SK-MEL 23 possesses a highly active function of MRP, but not P-gp. 2) SK-MEL 24 possesses weak functions of both MRP and P-gp. Western blot analysis using monoclonal antibodies for MDR expression demonstrated an exceedingly high MRP expression of SK-MEL 23 and only slight P-gp and MRP expression of SK-MEL 24, corresponding to the functional data. The efflux inhibition assay using F-18 FDG revealed a considerable retention of FDG in SK-MEL 23 in the presence of the MRP inhibitor probenecid. It was also found that the P-gp inhibitor verapamil depressed the FDG efflux of SK-MEL 24. Our present in vitro study suggests that FDG may be a substrate of MDR in some melanoma cells and further MDR may be one of the important factors affecting FDG-PET melanoma imaging.     

Sind die klassischen Methoden zur mykologischen Diagnostik noch „State‐of‐the‐Art“?

The diagnostic workup of cutaneous fungal infections is traditionally based on microscopic KOH preparations as well as culturing of the causative organism from sample material. Another possible option is the detection of fungal elements by dermatohistology. If performed correctly, these methods are generally suitable for the diagnosis of mycoses. However, the advent of personalized medicine and the tasks arising therefrom require new procedures marked by simplicity, specificity, and swiftness. The additional use of DNA‐based molecular techniques further enhances sensitivity and diagnostic specificity, and reduces the diagnostic interval to 24–48 hours, compared to weeks required for conventional mycological methods. Given the steady evolution in the field of personalized medicine, simple analytical PCR‐based systems are conceivable, which allow for instant diagnosis of dermatophytes in the dermatology office (point‐of‐care tests).     

Short‐term isotretinoin treatment decreases insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 levels: does isotretinoin affect growth hormone physiology?

Summary Background Isotretinoin is an effective treatment for acne vulgaris. However, it has numerous side‐effects. It was previously reported that serum growth hormone (GH) levels decreased with isotretinoin treament. Objectives To analyse whether isotretinoin has any effects on insulin‐like growth factor‐1 (IGF‐1), insulin‐like growth factor binding protein‐3 (IGFBP3) and GH levels. Methods Forty‐seven patients aged 21·5 ± 5·1 years (mean ± SD) with acne vulgaris were included in this study. Isotretinoin therapy was initiated at a dose of 0·5–0·75 mg kg^?1 daily and then adjusted to 0·88 mg kg^?1 daily as maintenance dosage after 1 month. Screening for biochemical and hormonal parameters was performed just before initiation and after 3 months of isotretinoin treatment. Results IGF‐1 and IGFBP3 levels decreased significantly after treatment (P < 0·01), while GH levels did not change. Post‐treatment, significant increases were seen in aspartate aminotransferase, total cholesterol, low‐density lipoprotein cholesterol, triglycerides and low‐density lipoprotein cholesterol/high‐density lipoprotein cholesterol ratio (P < 0·0001) while high‐density lipoprotein cholesterol levels were significantly decreased (P < 0·0001). Conclusions Isotretinoin therapy may have an effect on GH physiology, and further studies are needed to understand this association.     

Hepatosplenisches T‐Zell‐Lymphom unter Therapie mit TNF‐α‐inhibierenden Biologics: (k)ein Risiko für Patienten mit Psoriasis?

Tumor necrosis factor (TNF)‐α antagonists have considerably improved the therapeutic approach to chronic inflammatory disorders including psoriasis vulgaris. Recently, some cases of highly aggressive hepatosplenic T‐cell lymphoma (HSTCL) have developed in patients with inflammatory bowel diseases (IBD) being treated with infliximab or adalimumab. Analysis of the published data suggests that the emergence of HSTCL is favored by the combination of purine analogues and infliximab or adalimumab in the therapy of a granulomatous inflammation involving Vδ1⁺γδ T cells. Because psoriasis vulgaris is different from IBD in regard to the type of inflammation, the concomitant therapies used and the tissue‐specific subsets of γδ T cells, the use of infliximab or adali‐mumab in psoriasis may not necessarily be associated with an increase in the risk of HSTCL.     

Druckurtikaria – Dapson auf dem Weg zur First‐Line‐Therapie?

Background: Pressure urticaria as a subform of physical urticaria is rare and treatment is often difficult. Established therapeutic regimes include antihistamines (generally exceeding approved dosages in order to achieve a therapeutic benefit) or antihistamines combined with montelukast. Complete relief of symptoms is difficult. Patients and methods: We used dapsone as an early therapeutic alternative in the event of treatment failure and established a standardized therapeutic regime at our clinic. We surveyed 31 patients retrospectively who had received dapsone between 2003–2009. Results: In 74 % of patients in whom symptoms persisted despite established therapies, the results of treatment with dapsone were good or very good. Longer‐term pressure urticaria and the co‐existence of a chronic spontaneous urticaria were associated with a smaller benefit (p<0.05). No significant effects were found related to age, gender, duration of therapy, side‐effects, or Met‐Hb elevation (a tendency toward a decreased benefit was associated with middle‐age, male sex, shorter duration of therapy, observed side‐effects, and Met‐Hb elevation). Conclusions: Therapy is well tolerated and results in a good therapeutic benefit which lasts after termination of therapy. With adequate monitoring, the use of dapsone in patients with pressure urticaria has such a good risk‐benefit ratio that we support early treatment initiation.     

Primär kutane CD4+ klein‐ bis mittelgroßzellige pleomorphe T‐Zell‐Lymphoproliferation: Wo stehen wir? Eine systematische Übersicht

Primary cutaneous CD4+ small/medium pleomorphic T‐cell lymphoproliferative disorder (PCSMP‐TLPD) is a provisional entity with uncertain malignant potential according to the latest revision of the WHO classification for lymphoid neoplasms. We conducted a systematic literature review of all previously reported cases of PCSMP‐TLPD to highlight their typical and atypical features. The main features of PCSMP‐TLPD and its possible clinicopathologic overlap with similar disorders are also discussed. It is hoped that this review will provide a useful outline of this condition and the most important differential diagnoses. Finally, we recommend a rigorous consensus among cutaneous lymphoma experts in drafting diagnostic criteria and the best case definition.     

Is Mcl‐1L the new anti‐apoptotic effector of B‐RAFV600E in melanoma?

A recent report has unveiled a novel mechanism by which oncogenic BRAF signalling might trigger apoptotic resistance in melanoma by selectively affecting the expression of Bcl‐2 family member Mcl‐1L (Exp Dermatol 2013: 22 : 767). Correlation of Mcl‐1 splice variants and B‐RAF mutational status was determined in a panel of melanoma cell lines. In vivo validation of this mechanism, which is supported by recent literature, might provide novel therapeutic approaches such as the use of targeted Mcl‐1 inhibitors to improve outcome in melanoma.     

Does ad hoc quality‐of‐life discussion in inflammatory skin disease consultations reflect standardized patient‐reported outcomes?

BACKGROUND: There is little information concerning how much health-related quality-of-life (HRQoL) information is elicited in dermatology outpatient consultations. OBJECTIVES: To observe and record ad hoc HRQoL discussion in inflammatory skin disease consultations, to systematically measure the patient's HRQoL and to measure patient satisfaction with dermatology care. METHODS: Clinic consultations of patients with inflammatory skin conditions attending a secondary care clinic were observed by a single researcher (CP). Data were collected on the 10 subject areas of the Dermatology Life Quality Index (DLQI) and on sleep, burden, frustration and depression. Patients were sent the DLQI and Medical Interview Satisfaction Scale (MISS)-21 questionnaires after the consultation. RESULTS: In total, 100 consultations were observed (psoriasis n = 50, eczema n = 17, acne n = 13 and others n = 20). In 26% (n = 26), there was no mention of HRQoL issues. In 59% (n = 44), HRQoL discussions were initiated by the clinician. In only 26% (n = 19) of consultations were > or = 3 items on the observer's checklist raised. In all, 57 evaluable DLQI and MISS-21 questionnaires were returned. The mean +/- SD DLQI score was 7.2 +/- 7.0 (n = 18) for patients with whom there was no HRQoL discussion and 10.8 +/- 6.7 (n = 39, P = 0.038) for those with whom HRQoL was discussed. The mean +/- SD MISS-21 score was 108.8 +/- 16.5 (n = 18) for the patients with whom there was no HRQoL discussion and 111.3 +/- 13.6 (n = 39, P = 0.42) for those with whom HRQoL was discussed. The mean +/- SD patient expectation score was 5.5 +/- 1.0 (median 5, range 3-7). There was a positive correlation between the patient expectation and MISS-21 scores (r(s) = 0.815, P < 0.0001). CONCLUSIONS: Despite little extent or depth to HRQoL discussion, HRQoL issues were raised in the majority of inflammatory skin disease consultations. The consultations usually met the patients' expectations and most patients were satisfied.     

Hydroxyurea‐induced dermatomyositis: true amyopathic dermatomyositis or dermatomyositis‐like eruption?

Background Hydroxyurea‐induced dermatomyositis is a rare adverse reaction of long‐term hydroxyurea therapy. It has been reported under different names; however, the exact classification and nomenclature of this eruption have been the subject of much debate, and a more precise term is still awaiting. Herein, we review the different aspects of this reaction and suggest a new term that might help to minimize the confusion about its nomenclature. Materials and methods We describe a 68‐year‐old woman who had been on long‐term hydroxyurea therapy for the treatment of chronic myeloid leukemia for nine years. She presented with typical dermatomyositis‐like lesions and many of the other mucocutaneous adverse effects of hydroxyurea. Results Skin examination revealed typical Gottron’s papules on the dorsa of the hands, atrophy, xerosis, acquired ichthyosis, photosensitivity, cutaneous, oral and nail hyperpigmentation, acral erythema, palmoplantar keratoderma, actinic keratoses, and leg ulcers. There was no clinical or laboratory evidence of proximal muscle weakness. Cessation of hydroxyurea was associated with remarkable improvement of the skin lesions. Conclusion Hydroxyurea‐induced dermatomyositis is a rare drug‐induced dermatomyositis characterized by skin lesions identical to classic dermatomyositis without clinical or laboratory evidence of myositis. We propose that the term hydroxyurea‐induced amyopathic dermatomyositis that adequately describes the findings reported in this subset of patients would be more precise and specific.