Deutliche Einschränkung der Lebensqualität bei Patienten mit Pemphigus vulgaris: Ergebnisse der deutschen Bullous Skin Disease (BSD)‐Studiengruppe

Background: Pemphigus vulgaris is a potentially life‐threatening autoimmune disorder of the skin and mucous membranes characterized by antibodies against epidermal adhesion molecules. Clinically characteristic are painful chronic blisters or erosions of mucous membranes and skin. There are no published studies on the impact o this disease on quality of life. Patients and methods: This registration was performed within the scope of the German BSD (Bullous Skin Disease) study group, from November 1997 until January 2002. A total of 36 patients with the first diagnosis of pemphigus vulgaris were registered at the university hospitals of Dresden, Erlangen, Kiel, Mannheim, München and Würzburg. Thirty of the 36 (83 %) patients participated in the quality of life questionnaire utilizing the German version of ‘Dermatology Life Quality Index’ (DLQI) provided by A. Y. Finlay. The DLQI varies from 0 to 30 with an increased DLQI score indicating a decrease in quality of quality. Results: The overall DLQI total score of 10 ± 6,7 in the investigated pemphigus patients was significantly increased in comparison to other skin diseases. Conclusions: These results suggest that the DLQI can be a very useful additional outcome criteria for clinical studies with pemphigus vulgaris and in the treatment of these patients.     

Mutations in mevalonate pathway genes in patients with familial or sporadic porokeratosis

Porokeratosis comprises heterogeneous keratinization disorders that are characterized by one or more atrophic patches surrounded by a ridge‐like cornoid lamella. In this study, we evaluated seven families affected by porokeratosis and five sporadic patients of the disease in a Chinese population. We performed Sanger sequencing of exons and flanking intron–exon boundaries of mevalonate pathway genes (MVD, MVK, PMVK and FDPS) and of SLC17A9. In five familial and three sporadic patients, we detected six variations, including four novel mutations (MVD c.1A>G; p.Met1?, c.916G>A; p.Ala306Thr, c.1013+1G>A, and PMVK c.65A>G; p.Lys22Arg) and two recurrent mutations (MVD c.746T>C; p.Phe249Ser, and MVK c.1028T>C; p.Leu343Pro). We then applied I‐TASSER and iGEMDOCK to assess these variants for probable functional impacts. The findings of this study extend the mutation spectrum of porokeratosis and provide further evidence for the genetic basis of this disease.     

[Translated article] Pruritus in Dermatology: Part 1—General Concepts and Pruritogens

Pruritus is the most common symptom of dermatologic and systemic diseases. The diagnosis of pruritus is clinical, although additional tests may be necessary to identify or confirm the cause. Translational medicine has led to the discovery of new mediators of itch, or pruritogens, as well as new receptors. Knowing how to properly recognize the main pathway that mediates itch in each patient is the key to successful treatment. Although the histaminergic pathway predominates in conditions like urticaria or drug-induced pruritus, it is the nonhistaminergic pathway that predominates in nearly all other skin diseases covered in this review. Part 1 of this 2-part review discusses the classification of pruritus, additional testing, the pathophysiology of itch and the pruritogens implicated (including cytokines and other molecules), and central sensitization to itch.     

Anästhesieverfahren in der Dermatologie

Zusammenfassung Die Verfahren der Lokalanästhesie sind integraler Bestandteil der operativen Dermatologie. Sie gewährleisten eine effiziente und sichere Analgesie in umschriebenen Haut- und Weichteilregionen und ermöglichen, einen sonst schmerzhaften diagnostischen oder therapeutischen Eingriff bei erhaltenem Bewusstsein zu tolerieren. Einzelne Methoden der Applikation sind "konkurrenzlos", wie die topische Applikation von EMLA^® oder die Kryoanästhesie, andere bieten alternative Optionen zur Allgemeinanästhesie. Die Tumeszenzlokalanästhesie wurde—jenseits der kosmetischen Liposuktion—zu einer effizienten Anästhesieform für größere Operationen bei Tumoren der Haut, plastische Rekonstruktionen und in der Phlebochirurgie weiterentwickelt. Die Wahl des Verfahrens im Einzelfall wird vom Alter, der Kooperationsfähigkeit und der Komorbidität des Patienten bestimmt. Für Infiltrationsanästhesien werden heute vorwiegend Lokalanästhetika vom Amidtyp eingesetzt. Fundierte Kenntnisse über die Anatomie der sensiblen Nerven sind Voraussetzung für erfolgreiche operationsfeldnahe periphere Blockaden. Wenn die Wirkungsweise der Lokalanästhetika, ihre toxischen Effekte und potenzielle Arzneimittelinteraktionen bei ihrem Metabolismus in der Praxis beachtet werden, dann ist das Risiko von Komplikationen relativ gering. Es sollte dennoch nicht unterschätzt, und adäquate Notfallmaßnahmen im Operationsteam sollten regelmäßig trainiert werden.     

Occupational allergic contact dermatitis caused by decorative plants

12 cases of occupational allergic contact dermatitis caused by decorative plants were diagnosed in a 14-year period. The patients were middle-aged, and their average exposure time was 13 years. The plant families and plants causing occupational contact dermatitis were Compositae (5 patients: chrysanthemum, elecampane, gerbera, feverfew), Alstroemeriaceae (5 patients, Alstroemeria ), Liliaceae (4 patients; tulip, hyacinth). Amaryllidaceae (2 patients: narcissus) and Caryophyllaceae (2 patients; carnation, cauzeflower). The known chemical allergens causing dermatitis were tuliposide-A and sesquiterepene lactones, such as alantolactones and parthenolide, in the Liliaceae and Compositae families. 7 of the 12 patients were able to continue their work; 5 were not because of severe relapses of skin symptoms. The plant allergen and extract series currently available are of great help in the diagnosis.     

Leprosy in a University Hospital in Southern Brazil

BACKGROUND

Leprosy is an infectious disease that may lead to irreversible nerve damage, compromising patient''s quality of life and leading to loss of working years.

OBJECTIVES

To evaluate the epidemiological profile of patients followed at a University Hospital.

MATERIALS AND METHODS

This is a retrospective observational study, based on a review of medical records. We studied the clinical and epidemiological features of patients with leprosy monitored at the Hospital de Clínicas of the Federal University of Paraná between January 2005 and January 2010.

RESULTS

The mean age was 47.51, while 35.94% of patients were aged 41-60. The male:female rate was 1.8:1. The most prevalent occupations were: retired, students or rural workers. Patients came mainly from Curitiba or nearby areas, but there were also patients from the countryside. The mean diagnostic delay was 24.57 months. Multibacillary forms prevailed, with the lepromatous variety being the most common, closely followed by the borderline type. Neural enlargement was found in more than 50% of the patients and 48.44% of them developed reactional states. Hemolysis was the most commonly detected drug side effect. Initial functional evaluation was possible in 70% of patients, 55% of whom had disabilities upon diagnosis. The most prevalent associated disease was hypertension.

CONCLUSIONS

This study showed an important diagnostic delay and a high rate of sequelae in this specific population. Brazil is one of the few remaining countries that has not yet eradicated leprosy and it is important to improve health policies in order to prevent sequelae and achieve eradication.     

Therapie der Akne mit Antiandrogenen – Eine evidenzbasierte Übersicht

Background: Increased sebaceous gland activity with seborrhea is one of the major pathogenetic factors in acne. Antiandrogen treatment targets the androgen‐metabolizing follicular keratinocytes and the sebaceous gland leading to sebostasis, with a reduction of the sebum secretion rate of 12.5 – 65 %. Antiandrogens can be classified based on their mechanism of action as androgen receptor blockers, inhibitors of circulating androgens by affecting ovarian function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotropin‐releasing hormone agonists and dopamine agonists in hyperprolactinemia), inhibitors of adrenal function, and inhibitors of peripheral androgen metabolism (5α‐reductase inhibitors, inhibitors of other enzymes). Methods: All original and review publications on antiandrogen treatment of acne as monotherapy or in combination included in the MedLine system were extracted by using the terms “acne”, “seborrhea”, “polycystic ovary syndrome”, “hyperandrog*”, and “treatment” and classified according to their level of evidence. Results: The combinations of cyproterone acetate (2 mg)/ethinyl estradiol (35 µg), drospirenone (3 mg)/ethinyl estradiol (30 µg), and desogestrel (25 µg)/ethinyl estradiol (40 µg) for 1 week followed by desogestrel (125 µg)/ethinyl estradiol (30 µg) for 2 weeks showed the strongest anti‐acne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotropin‐releasing hormone agonists, and inhibitors of peripheral androgen metabolism cannot be endorsed based on current knowledge. Low dose prednisolone is only effective in late‐onset congenital adrenal hyperplasia and dopamine agonists only in hyperprolactinemia. Treatment with antiandrogens should only be considered if none of the contraindications exist. Conclusion: Antiandrogen treatment should be limited to female patients with additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, women with late‐onset or recalcitrant acne who also desire contraception can be treated with antiandrogens as can those being treated with systemic isotretinoin. Antiandrogen treatment is not appropriate primary monotherapy for noninflammatory and mild inflammatory acne.     

Ultraviolet phototherapy for pruritus

Ultraviolet-based therapy has been used to treat various pruritic conditions including pruritus in chronic renal failure, atopic dermatitis, HIV, aquagenic pruritus and urticaria, solar, chronic, and idiopathic urticaria, urticaria pigmentosa, polycythemia vera, pruritic folliculitis of pregnancy, breast carcinoma skin infiltration, Hodgkin's lymphoma, chronic liver disease, and acquired perforating dermatosis, among others. Various mechanisms of action for phototherapy have been posited. Treatment limitations, side effects, and common dosing protocols are reviewed.     

Klinik und Pathogenese UV‐induzierter Pigmentveränderungen

Solar and ultraviolet (UV) radiation, respectively, are the strongest stimuli for the induction of pigmentation in human skin. UV radiation induces pigmentation by exerting direct and indirect effects on melanocytes. Melanogenesis is a very complex process whose molecular mechanisms are not yet completely understood. Acute UV exposure induces the non‐protective immediate pigment darkening as well as delayed tanning which exerts photoprotective effects. Chronic UV exposure causes permanent pigmentary changes by inducing solar lentigines and pigmented actinic keratoses as well hypopigmentated areas. Artificial UV irradiation (UVA, PUVA) can also induce pigmentary disorders, including lentigines. Since the therapeutic options for UV‐induced pigmentary changes are limited consequent protection as a prophylactic measure is recommended.     

Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus vulgaris,or just ‘witnesses of disease'?

Pemphigus vulgaris (PV) is fascinating to dermatologists, epithelial biologists and immunologists alike, as its pathogenesis has been clarified to a much greater extent than that of most other organ-specific autoimmune diseases, and as it has provided abundant novel insights into desmoglein biology and pathology along the way. Historically, the most influential PV pathogenesis concept is that of Stanley and Amagai. This concept holds that autoantibodies against desmogleins are both essential and sufficient for epidermal blister formation (acantholysis) by impeding the normal functioning of these major adhesion proteins. However, as with most good theories, this landmark concept has left a number of intriguing and important questions open (or at least has not managed to answer these to everyone's satisfaction). Moreover, selected dissenting voices in the literature have increasingly called attention to what may or may not be construed as inconsistencies in this dominant PV pathogenesis paradigm of the recent past. The present debate feature therefore bravely rises to the challenge of re-examining the entire currently available evidence, as rationally and as undogmatically as possible, by provocatively asking a carefully selected congregation of experts (who have never before jointly published on this controversial topic!) to discuss how essential anti-desmoglein autoantibodies really are in the immunopathogenesis of PV. Not surprisingly, some of our expert "witnesses" in this animated debate propose diametrically opposed answers to this question. While doing so, incisive additional questions are raised that relate to the central one posed, and our attention is called to facts that may deserve more careful consideration than they have received so far. Together with the intriguing (often still very speculative) complementary or alternative pathogenesis scenarios proposed in the following pages, this offers welcome "food for thought" as well as very specific suggestions for important future research directions--within and beyond the camp of PV aficionados. The editors trust that this attempt at a rational public debate of the full evidence that is currently at hand will constructively contribute to further dissecting the exciting--and clinically very relevant!--immunopathogenesis of PV in all its complexity.