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Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung. Increased CSL levels enhanced the proliferative potential of HKCs and SCC cells, while silencing of CSL induced growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels gave rise to rapidly expanding tumors, while cells with silenced CSL formed smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKCs and SCC cells with silenced CSL revealed major modulation of apoptotic, cell-cycle, and proinflammatory genes. We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. CSL/KDM6B protein expression could be used as a biomarker of SCC development and indicator of cancer treatment.

The incidence of cutaneous malignant melanoma has steadily increased in Caucasian populations over the last decades. With around 1900 new cases each year, Switzerland has one of the highest melanoma rates in Europe (16/100 000 world-standardised rate). Regional differences are emerging within Switzerland, with a higher incidence in the western (French-speaking) region. Observed changes in sun protection attitudes and knowledge in the Swiss population have yet no impact on the incidence trend. Early detection, carried out since the mid 1980s in Switzerland, has led to a substantial increase in survival and rates of thin melanoma, without material change in rates of thick melanoma. Mortality from melanoma has recently decreased, earlier in women than men. The efficacy of prevention campaigns should soon become more blatant if current efforts persist.

Background:Fusarium species are isolated from about 3% of onychomycoses in the Swiss native population. On the basis of macroscopic characters and microscopic examination of the cultures, identification of Fusarium often remains difficult or uncertain because of variations from one isolate to another and overlapping characteristics between species. Objective: To obtain information about the prevailing species of Fusarium collected from onychomycoses. Methods: An analysis of the Fusarium specimens isolated in the Department of Dermatology at the University Hospital of Lausanne was conducted during a 2-year period (71 isolates). A 311-bp fragment of the gene encoding 28S rRNA was amplified by PCR and sequenced. DNA sequences were compared to those available for reference strains. Results:Fusarium oxysporum was the most frequently isolated species, accounting for 54% of the isolates. F. proliferatum and 4 taxons belonging to the F. solani species complex were identified with an appreciable frequency ranging from 4 to 14%. Conclusion: The Fusarium species identified were the same as those known to cause disseminated fusariosis in immunocompromised patients. The presence of these Fusarium species in onychomycoses warrants that careful attention should be paid to abnormal nails before beginning immunosuppressive treatments in patients.

Sirolimus is a new immunosuppressive agent used to prevent rejection in renal allograft recipients in order to reduce the need of potentially nephrotoxic calcineurin inhibitors (cyclosporine, tacrolimus). The cutaneous side effects of sirolimus are not well known and they may have been underestimated. We report 2 cases of follicular acneiform eruptions induced by sirolimus in renal allograft recipients. This dermatologic complication was severe and difficult to treat, and resolved only after discontinuation of sirolimus.

Resume Introduction Nous rapportons une observation d’hidradenite eccrine a Pseudomonas (P.) aeruginosa de l’enfant, ou « Pseudomonas Hot Foot Syndrome », revelatrice d’une leucemie aigue lymphoblastique. Observation Chez une fillette de 10 ans survenaient brutalement des nodules douloureux et necrotiques palmoplantaires dans un contexte febrile avec frissons. L’examen histologique d’une biopsie cutanee trouvait une necrose des glandes eccrines, avec a la culture du P. aeruginosa. Une numeration formule sanguine trouvait une pancytopenie, avec au myelogramme une leucemie aigue lymphoblastique. Toutes les hemocultures et les autres prelevements microbiologiques etaient negatifs. Les signes cutanes etaient apparus 48 heures apres une baignade dans un parc de loisir aquatique. Le diagnostic d’hidradenite eccrine a Pseudomonas, ou « Pseudomonas Hot Foot Syndrome » etait retenu, bien que les autorites sanitaires locales n’aient pu mettre en evidence de contamination par P. aeruginosa de l’eau du centre aquatique. Commentaires Des lesions evocatrices d’hidradenite eccrine plantaire juvenile sans facteur traumatique evident doivent faire rechercher une contamination par du P. aeruginosa a partir d’un milieu aquatique, avec les consequences sanitaires et epidemiologiques qui en decoulent. Par ailleurs, une infection cutanee severe a P. aeruginosa de l’enfant doit faire rechercher une immunosuppression sous jacente, en particulier un processus leucemique aigu.

Background: Dermatophytes are usually identified on the basis of macroscopic characteristics and microscopic examination of the cultures. Identification of dermatophytes often remains difficult or uncertain because there are variations from one isolate to another and overlapping characteristics between species. Objective: To identify dermatophyte species producing numerous microconidia and resembling Trichophyton mentagrophytes by DNA sequence analysis. Methods: The complete ITS1 + 5.6s + ITS2 rDNA region of various dermatophytes isolated in culture was amplified by PCR and sequenced. Results: Nine isolates of a fast-growing dermatophyte species were identified as Arthroderma benhamiae by DNA sequencing. Retrospective investigations revealed that the isolates were from 8 children and 1 adult suffering from inflammatory dermatophytosis. Eight of the 9 patients had had previous contact with rodents, mostly guinea pigs. Conclusion: It is the first time that A. benhamiae is reported in Switzerland. In cases of dermatophytosis attributed to A. benhamiae, a rodent is the most likely cause of infection.

We have shown that dermatophyte species can be easily identified on the basis of a DNA sequence encoding a part of the large-subunit (LSU) rRNA (28S rRNA) by using the MicroSeq D2 LSU rRNA Fungal Sequencing Kit. Two taxa causing distinct dermatophytoses were clearly distinguished among isolates of the Trichophyton mentagrophytes species complex.

Background: The hazards due to sun exposure are well known. Many recent studies have emphasized the protection against the harmful effects of the sun by the use of sunscreens and, moreover, by staying in the shade and wearing long-sleeved shirts, hats and sunglasses. Switzerland has one of the highest rates of skin cancer induction in Europe and the incidence of melanoma in Switzerland is constantly increasing with an incidence of 10–12/100,000 inhabitants/year. Interestingly, some studies have evoked the possibility that sunscreen use can increase the risk of melanoma by increasing overall sun exposure. Objective and Methods: In this context, the aim of our study was to estimate the amount of sun exposure of children, and their parents, living in Switzerland and to give a description of how they protect themselves against sun irradiation. Questionnaires were provided to pediatricians in every state (canton) in Switzerland and were given to families coming for consultation. Results: A total of 328 forms including 1,285 individuals were returned from most of the cantons in Switzerland. The majority of the Swiss families had 2 children under 16 years of age with middle-aged parents (30–45 years) and a central European skin type (light skin of type II–III, brown or blue eyes, and brown to blond hair). An important sun exposure was noted even though the population seems to be conscious of the associated dangers. Sunscreens were the first-line defense against sun exposure with clothing and shielding oneself from the sun not being highly used. Moreover, sunscreens tended to be misused with most people applying them at the beach or swimming pool (instead of 15 min before exposure) and few applications throughout the day. Conclusions: Prevention should imperatively be emphasized for lower overall sun exposure as sunscreens are primarily used at the beach and not in routine daily exposure. In addition, it is agreed that prevention campaigns would be better directed towards children because up to 80% of detrimental sun exposure occurs during childhood.

While the modern use and indication for radiotherapy (RT) of malignant skin disorders is a well-established strategy which includes the treatment of basal cell and squamous cell carcinoma, melanoma, Merkel cell tumors Kaposi’s sarcoma, and cutaneous lymphomas (all, see previous chapters of this book), the use of ionizing radiation for nonmalignant or benign skin disorders is less recognized, is not represented in actual interdisciplinary treatment guidelines, and has clearly decreased as many new and better systemic and local noninvasive and invasive treatment options have become available in the past two decades. Moreover, in many dermatological departments throughout the world, the actual training and knowledge of medical specialists about the possible implementation of ionizing radiation to treat nonmalignant skin disorders has slowly faded away and is dismissed in modern dermatology textbooks. Local surgical methods and/or systemic medication options dominate the actually recommended treatment strategies for most nonmalignant skin disorders.

Background: Conventional oral PUVA therapy is hampered by large inter- and intraindividual variations in the bioavailability of 8-methoxypsoralen (8-MOP), caused by its low solubility in the gastrointestinal juices and large interindividual differences in hepatic metabolism rate (hepatic first pass). Aims: New galenic formulations of 8-MOP based on solid dispersions, suspensions, and saturated solutions containing penetration enhancers were developed for sublingual administration, a drug delivery route which avoids the hepatic first pass metabolism. Methods: Solubility properties of 8-MOP were tested in 22 potential penetration enhancers and solubilizers. Following preliminary in vivo tests of 13 sublingual 8-MOP formulations, five were administered to groups of volunteers at a nominal dose of 0.6 mg/kg body weight: two solid dispersions based on PEG 1540 (with and without Xylitol); a solution in Labrasol® (glyceryl and PEG-8 caprylate/caprate), PEG 400, Transcutol® (ethoxydiglycol) (1:1:1); a micronized suspension in sorbitol, water, ethanol, propylene glycol (ca. 3:1:1:5 w/v); and Oxsoralen® capsules. Pharmacokinetic behaviour of 8-MOP was examined in serum; samples were analysed by HPLC. Photosensitivity was measured in seven subjects. Results: The peak of maximum 8-MOP concentration in blood was sharp, rapid and reproducible: tmax of 8-MOP in blood averaged 23±3 min, independent of the particular formulation. Cmax was higher when 8-MOP was presented in dissolved form (solution and capsule formulations, 85±29 and 85±35 ng/ml, respectively) and lowest with the suspension (42±15 ng/ml). Photosensitivity peaked reproducibly at 45 min. post dosing. Conclusions: Sublingual PUVA therapy is suitable for patients with skin types I and II, in particular patients who are less suitable candidates for standard PUVA therapy (due to hepatic, renal, or cardiac insufficiency) or who have experienced side effects with standard PUVA.

In this study we assessed the expression of the Melan-A/MART-1 antigen by immunohistochemistry using monoclonal antibody A103 in 73 primary cutaneous melanomas and its correlation with tumor staging and patient survival. Melan-A/MART-1 was expressed in 90% of primary tumors, with loss of expression increasing with Breslow thickness. Kaplan-Meier analysis demonstrated a significantly reduced disease-free interval and overall survival rate for patients not expressing this antigen. The poor prognosis of such patients was even worse for those presenting with a primary melanoma and a Breslow thickness of > or = 1 mm. Thus, Melan-A/MART-1 is not only a useful and specific additional marker for the diagnosis of primary cutaneous melanoma, but it may also help refine the prognosis of patients with malignant melanoma.

Background The formation of the cornified cell envelope (CE) during the late stages of epidermal differentiation is essential for epidermal barrier function and protects the body against environmental attack and water loss. Formation of the CE involves the replacement of the plasma membrane by cross-linkage of precursor proteins such as involucrin, small proline rich proteins (SPRR) and loricrin. In normal epidermis, SPRR1 is restricted to appendages, SPRR2 is also expressed in interfollicular areas, while SPRR3 is completely absent; the latter is most abundant in oral epithelium. This differential expression indicates an important part for SPRRs in specific barrier requirements, and reflects their importance in the biomechanical properties of the CE. Objectives We report here on the expression of SPRR1, SPRR2 and SPRR3 in a wide range of cutaneous neoplastic and inflammatory diseases. Methods We used immunohistochemistry; in addition, Northern blot analysis of malignant tumours was performed. Results Increased suprabasal expression of SPRR1 and SPRR2, but no SPRR3 expression, was noted in inflammatory dermatoses with orthokeratotic and parakeratotic squamous differentiation. By contrast, differentiating epidermal tumours such as Bowen's disease, keratoacanthoma and squamous cell carcinoma expressed SPRR3. Conclusions As SPRRs were originally cloned on the basis of their expression in ultraviolet light-irradiated keratinocytes, the expression of SPRR3 in actinic lesions is of interest, and might serve as a diagnostic tool.

Resume Introduction L’infection par des especes du genre Borrelia est responsable de manifestations cutanees variees reparties en trois grands types : erytheme chronique migrateur, lymphocytome borrelien et acrodermatite chronique atrophiante. Nous rapportons un cas d’erytheme infiltre de la face lie a une infection par Borrelia afzelii, mais difficile a integrer dans cette classification. Observation Une femme de 51 ans presentait un erytheme medio-facial infiltre s’etendant au cou et au menton, sans argument clinique pour une rosacee. Le diagnostic de borreliose etait suspecte grâce a la biopsie cutanee, qui montrait un infiltrat inflammatoire dermique riche en plasmocytes. Le diagnostic d’infection par B. afzelii etait confirme par la serologie et la PCR dans la biopsie cutanee, toutes deux positives. Discussion L’erytheme borrelien de la face pourrait representer une forme particuliere d’infection cutanee chronique par Borrelia, a inclure parmi les diagnostics differentiels des erythemes chroniques du visage, en particulier en zone d’endemie borrelienne.

Cannabis arteritis is a serious peripheral vascular disease affecting young adults consuming cannabis. An increasing number of cases have been recently reported in Europe. The risk of amputation is high. Cannabis arteritis is often confused with atherosclerosis. We present a new case in which complete arterial revascularization was obtained with early aspirin treatment. Cannabis arteritis should be therefore distinguished from peripheral arterial disease caused by atherosclerosis, which is typically not reversible. Early diagnosis and treatment are essential to avoid an irreversible vascular occlusion and amputation.

Paronychia is a rare complication of pemphigus vulgaris (PV), and the immunological profile of patients with digital disease has not been assessed so far. We report 2 cases of PV with oral mucosa and periungual involvement, who had high titers of anti-desmoglein (Dsg)-3 circulating antibodies. These observations raise the possibility that expression of Dsg-1 and Dsg-3 in distinct areas of periungual skin is disease specific and that anti-Dsg-3 antibodies alone may have an as yet unrecognized importance for the development of paronychia in PV. Copyright (c) 2008 S. Karger AG, Basel

The diagnosis of lymphoproliferative and melanocytic skin lesions is one of the most vexing problems in dermatopathology, a problem that is compounded by the far-reaching therapeutic and psychosocial consequences of the diagnosis for both patient and physician. On the occasion of a self-assessment slide seminar held during a dermatopathology meeting, 30 unusual lymphoproliferative and melanocytic lesions, each provided with four differential diagnoses, were evaluated by "expert pathologists" and other participants ("nonexperts") of the slide seminar. The final diagnosis was pinpointed by the majority of the experts in 16 of 30 cases (56%). The group of experts returned an unanimous decision on the diagnosis in only 2 of the 30 cases (7%). In contrast to the expert group, the preferred diagnoses given by the nonexperts showed a wider range. In 20 of 30 cases (66%), the final diagnosis could only be established after consideration of clinical, histologic, immunophenotypic, and molecular features. Our findings agree with the results of recent studies indicating quite a high degree of discordance among expert pathologists. The discordance between experts and, to a higher extent, nonexperts may have some crucial consequences for dermatopathology. Full agreement on diagnosis, particularly in unusual skin lesions, cannot be achieved only by an accumulation of expertises. Instead of relying on one single finding or diagnostic procedure ("gold standard") as the main criterion upon which to base a diagnosis, the diagnoses become more reliable if based on the integration of several factors including an evaluation of clinical and histomorphologic features and immunophenotypic and molecular findings ("diagnostic elements"), particularly in the field of lymphoproliferative and melanocytic lesions. In addition, a continuous retrospective work-up of difficult or unusual cases is recommended to ensure a long-term improvement in diagnostic reliability.

As ferritin has been identified as an important factor in antioxidant defense in cultured human skin cells we evaluated the presence of ferritin in human skin in vivo and the modifications following irradiation with UVA I, UVA I + II, and solar simulating light by immunohistochemical analysis. We report that the putative protective protein ferritin is regularly present in the basal layer of unirradiated epidermis in vivo and that the induction of ferritin was dependent on wavelength and cell type. Following UVA I radiation, ferritin increased both in epidermal and in dermal tissue. The same response occurred, although to a lesser extent, with UVA I + II but did not occur following solar simulating radiation. Quantitative analysis for ferritin in cultured keratinocytes and fibroblasts from seven individuals following each UV spectra were also assessed by enzyme-linked immunosorbent assay. The induction of ferritin by UV was highly dependent on the waveband and cell type. UVA I and UVA I + II radiations induced ferritin expression in dermal fibroblasts up to 260% and 200% over basal levels, respectively. Solar simulating radiation produced only a small induction of ≈130% over basal ferritin levels in dermal fibroblasts. Ferritin increased in cultured fibroblasts as early as 3 h post-UVA with a peak at 6 h that remained until 48 h; there was no observable qualitative or quantitative increase seen in the undifferentiated cultured epidermal keratinocytes. Our findings indicate that the putative defense system of ferritin exists in human skin in vivo and its induction is dependent on UV spectra and cell type. The increased concentrations of this antioxidant in human skin following acute UV radiation could afford increased protection against subsequent oxidative stress. Key word: oxidative stress. J Invest Dermatol 111:159–163 1998

DNA damage by UV radiation plays an essential role in skin cancer induction. We report that even sub-erythemal doses of solar simulating radiation, are capable of inducing substantial nuclear damage, namely pyrimidine dimers and p53 induction in human skin in situ . The quantity and distribution of p53 induced in human skin by UV radiation depended highly on the waveband and dose of UV used. Solar simulating radiation induced very high levels of p53 throughout all layers in epidermal keratinocytes 24 hr following an erythemal dose (230 ± 15.9/1000 cells), and the induction followed a dose response. Following UVA I + II and UVA I radiations, p53 expression was approximately half of that seen with equivalent biological doses of solar simulating radiation (63.5 ± 28.5 and 103 ± 15.9, respectively). Expression of p53 was seen in basal cell keratinocytes at lower doses of UVA, but all layers of the epidermis were affected at higher doses. Pyrimidine dimer induction, however, was seen to be the same for equivalent biological doses of UVA I, UVA I + II and solar simulating radiations, which coincides with previous findings that pyrimidine dimers initiate the erythemal response and are implicated in skin carcinogenesis. When equivalent biological doses of pure UVA are used with no UVB contamination, significant nuclear alterations occur in human skin in situ, which can approach those seen with UVB radiation. Our results suggest that DNA damage assessed in vivo by immunohistochemistry could provide a very sensitive endpoint for determining the efficacy of protective measures, such as sunscreens or protective clothing, against both UVB- and UVA-induced damage in human skin. Int. J. Cancer 76:201–206, 1998.© 1998 Wiley-Liss, Inc.

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.

Adhesion molecules are involved in leukocyte recruitment, lymphocyte recirculation, and in several aspects of tumour biology. Recent discoveries of surface proteins on tumour cells involved in tumour metastasis may explain the invasive behaviour, the migration involving reversible adhesive contacts, the release into the circulation and the extravasation of tumour cells. CD44 is a family of glycoproteins involved in cell-cell and cell-matrix interactions. The v6 (variant exon v6) form of CD44 confers a metastatic potential onto some carcinoma cells. In the present study, the expression of CD44v6 on skin biopsies of 10 inflammatory skin diseases, 30 cutaneous lymphomas (CL), 11 reactive lymph nodes, 10 primary nodal non-Hodgkin's lymphomas (NHL) and 5 secondary nodal NHL was investigated immunohistochemically. None of the 10 nodal NHL were CD44v6 positive for the neoplastic B- or T-cells, whereas 11/12 CL with systemic spread showed a distinct CD44v6 expression in the skin. CD44v6 was not expressed on the tumour cells of skin biopsies of patients without systemic spread (18 cases of CL). In conclusion, CD44v6 expression is connected to an aggressive behaviour of CL.

A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.

Minor nail trauma may cause bluish discoloration of the nail, while tangential skin trauma on the heel can result in a so-called black heel. To rule out melanoma in such clinical situations, a biopsy is needed to reveal homogeneous eosinophilic masses deposited under the nail plate or within it (transepidermal elimination). Most dermatopathologists attempt to demonstrate the presence of hemoglobin in these eosinophilic masses with Prussian blue stain, which typically remains negative. In our experience, these traumatically induced blood deposits are always situated in avascular spaces, devoid of degrading phagocytes. Consequently, a histochemical stain for these deposits should be directed specifically toward hemoglobin, not hemosiderin. In the dermatopathologic literature, the various techniques to detect hemoglobin deposits in tissue sections are not well-known. We would like to emphasize benzidine stain, a highly selective and efficient method to demonstrate the presence of hemoglobin deposits in histologic sections. To date, benzidine stain has not been utilized to characterize splinter hemorrhage (subungual hematoma). Of concern, the use of benzidine in histopathology laboratories is restricted because this agent is a known carcinogen, while the non-mutagenic derivative, 3,3',5,5'-tetramethylbenzidine, does not stain histologic sections. Patent blue V, a completely different and less specific agent, stains hemoglobin an intense blue-green.

Patienten mit phanotypischer Sjogren-Syndrom (SS)-Lupus erythematodes(LE)-Uberlappung stellen eine immungenetisch, serologisch und klinisch einheitliche Krankheitsgruppe dar mit polyzyklisch-anularen, erythematosquamosen Hautlasionen, zirkulierenden SSA(Ro)-Antikorpern und hoher Pravalenz des immungenetischen Phanotyps HLA-DR3. Die Sicca-Symptomatologie des SS kann der LE-Symptomatik zeitlich folgen oder vorangehen. Neben Hautveranderungen wie beim subakuten kutanen LE (SCLE) kommt es zu vaskulitischen, purpuriformen und Sweet-Syndrom-artigen Hautlasionen. Die alteren, vornehmlich weiblichen Patienten zeigen ein erhohtes Risiko pulmonaler und neurologischer Komplikationen. Demgegenuber kommt es selten zu einer Nierenbeteiligung. Eine 81jahrige, anti-SSA(Ro)-, HLA-DR3-positive Frau mit 30jahriger Anamnese eines kutanen LE wird vorgestellt, bei der erst Jahre spater neben den Hautveranderungen eines SCLE eine Sicca-Symptomatik, vaskulitische und Sweet-Syndrom-artige Hautveranderungen auftraten. Wenngleich diskutiert werden kann, ob es sich bei der phanotypischen SS-LE-Uberlappung um ein eigenstandiges Krankheitsbild oder um einen LE mit sekundarem SS bzw. ein primares SS mit Hautmanifestationen handelt, scheint das SS-LE-Uberlappungssyndrom hinreichend gut charakterisiert, um es als eine Krankheitsentitat mit eigenen Implikationen fur die Therapie und Prognose anzuerkennen. Die Stellung des SS/LE-Uberlappungssyndroms im Spektrum der anti-SSA(Ro)-, HLA-DR3-positiven Erkrankungen, und die enge immunologische Verwandtschaft zum SS und zum anti-SSA(Ro)-positiven LE werden diskutiert.

Die idiopathische Elastolyse der mittleren Dermis (idiopathic middermal elastolysis=IMDE) ist eine seltene Hauterkrankung mit zwei verschiedenen klinischen Erscheinungsformen, namlich einer grosflachig-konfluierenden Form (Typ I) mit feingefaltelten Effloreszenzen entlang den Hautspaltlinien und einer disseminiert-perifollikularen Form (Typ II) mit Protrusionen. Das histologische Bild mit Fehlen der elastischen Fasern in der mittleren Dermis ist charakteristisch. Betroffen sind uberwiegend Frauen jungeren bis mittleren Alters. Im deutschen Sprachraum hat dieses Krankheitsbild in der Literatur noch keine Erwahnung gefunden. Wir beschreiben einen heute 60jahrigen Patienten mit dem typischen Bild einer IMDE (Typ I). Das besondere Interesse dieser Kasuistik gilt der Tatsache, das keine Lichtabhangigkeit zu verzeichnen ist, was sich auch dadurch gezeigt hat, das unter einer PUVA-Therapie keine Verschlechterung eingetreten ist. Wahrscheinlich handelt es sich bei der IMDE um eine besondere Erkrankung aus dem Formenkreis elastolytischer Erkrankungen, bei der immunologische Mechanismen in der Atiopathogenese diskutiert werden konnen.

Background: Retinoic acid (RA) cream treatment alters epidermal proliferation and differentiation in photoaged skin. Objective: To study the changes in the expression of markers of epidermal differentiation in photoaged skin following RA cream treatment. Methods: Ten subjects with photoaged skin were examined before treatment and at regular intervals during 12 months of once daily application of 0.05% tretinoin cream over the left forearm. Paraffin-embedded biopsy sections from the forearm were stained with loricrin, filaggrin, involucrin and cornifin antisera in addition to hematoxylin and eosin. The various layers were measured using a calibrated optical micrometer. Results: The thickness of the epidermis increased rapidly, reaching a substantial increase after 1 month of retinoid cream application and retaining it during the following 12 months. The stratum granulosum achieved a transient but substantial increase after 1 and 3 months. Except involucrin, the ratio between the layers expressing the various markers of epidermal differentiation and the epidermis significantly increased following tretinoin cream treatment. Conclusion: RA cream treatment not only increases the thickness of the epidermis but also the programming of late terminal epidermal differentiation, as expressed by the markers studied. Thus, RA appears to affect both proliferation and differentiation of keratinocytes in vivo.

Background: The dermatophytes are important in the Swiss medical environment since 5–10% of consultations in dermatology concern mycotic infections. Objective: To obtain information about the prevailing species of dermatophytes in the south-west of Switzerland and their pattern of infection. Methods: An analysis was made of the dermatophytes isolated in the Department of Dermatology at the University Hospital of Lausanne and from samples collected in private practices of Switzerland during an 8-year period (1993–2000). The total number of samples sent for mycological analysis was 33,725. Results: 4,193 cultures revealed a dermatophyte. Trichophyton rubrum was the most frequently isolated species accounting for 62.5% of the strains followed by T. mentagrophytes (24.5%) and Microsporum canis (5.0%). Less frequent isolates included Epidermophyton floccosum, M. langeroni, M. gypseum, T. soudanense, T. violaceum, T. verrucosum, T. gourvili and T. tonsurans. Analysis of the localisation of the isolated fungi confirms that the dermatophyte species have a predilection for certain body areas. Conclusions: The relative frequencies of isolation of the dermatophyte species partially depending of the record of the different tinea vary from one country to another. Our study reveals the importance of T. rubrum and the appreciable frequency of M. canis in the Swiss autochthonous population and the apparition of new species with immigrants.

Background: Surgical excision is the gold standard for cutaneous squamous cell carcinoma (cSCC), however its application is limited in specific cases. Superficial radiotherapy (RTx) is an alternative treatment option, but long-term follow-up data are limited. Objective: To determine the outcome of superficial RTx of cSCC in correlation to histological differentiation grade and tumor localization. Methods: The outcome of 180 large cSCCs after superficial RTx between 1960 and 2004 was retrospectively reviewed. Results: Mean tumor size was 3.5 cm2 (SD 7.5) and mean follow-up period was 4.9 years (SD 4.7). Relapse-free survival was 95.8 and 80.4% after 1 and 10 years. Two-year relapse-free survival was 94.8% for good, 88.9% for moderate and 85.7% for poor differentiated tumors. Five-year relapse-free survival was highest in cSCCs located around the eyes (100%) and cheeks (90.9%). Conclusion: Superficial RTx is an effective alternative for cSCC if surgery is difficult due to localization or concomitant disease.

A 23-year-old woman presented with subcutaneous ossification, which together with short stature, stocky physique, round face and brachydactyly suggested Albright's hereditary osteodystrophy (AHO). Serum calcium and phosphorus levels were normal. AHO refers to the phenotype of the syndromes of pseudo-hypoparathyroidism (PHP) type Ia and pseudopseudohypoparathyroidism (PPHP), both considered genetically related variants with a defect of the alpha subunit of the stimulatory G protein of adenylate cyclase, necessary for the action of parathyroid and other hormones using cyclic AMP as an intracellular second messenger. PPHP differs from PHP in that it lacks parathyroid hormone resistance manifesting itself as hypocalcemia. Other endocrine end organ unresponsiveness, e.g. hypothyroidism and hypogonadism, may also be found with PHP. Both PHP and PPHP usually exhibit characteristic phenotypic abnormalities, of which subcutaneous ossification may be a presenting feature. The differential diagnosis of cutaneous calcification and ossification is outlined.

Syringocystadenoma papilliferum (SP) is a benign tumor most commonly located on the scalp or face, which frequently arises from a nevus sebaceus (NS). Transition of SP to basal cell carcinoma (BCC) and, albeit rarely, to metastatic adenocarcinoma may occur. Allelic deletions of the human homologue of the drosophila patched gene (PTCH) occur in both NS and BCC. To search for genetic changes in SP, a microdissection-based genetic analysis using polymorphic markers at 9q22 (PTCH; D9S15, D9S303, D9S287, D9S252) as well as markers at 9p21 flanking the tumor suppressor gene p16 (IFNA, D9S171) was performed. Glandular epithelium consisting of two rows of cells as well as adjacent normal tissue or inflammatory infiltrates in the stroma, when present, was dissected and subjected to single-step DNA extraction and loss of heterozygosity (LOH) analysis. Two of 10 informative SP cases showed LOH at 9q22 (PTCH). Three of 7 informative SP cases showed allelic deletions at 9p21 (p16). Allelic loss at 9q22 is consistent with the clinical observation of transition of SP to BCC. The finding of frequent allelic loss at 9p21 is unlikely to be related to the rare transition of SP to metastatic adenocarcinoma. Our study supports the hypothesis of a gatekeeper role of the tumor suppressor gene p16 in a variety of benign and malignant tumors, including SP.

Wegener’s granulomatosis is a systemic disease characterized by necrotizing granulomas and vasculitis involving the upper and lower respiratory tract as well as the kidneys. Cutaneous manifestations consist mainly of papules or papulonecrotic lesions. c-ANCA are known to be a valuable adjunct for the diagnosis and follow-up of Wegener’s granulomatosis with systemic involvement. We report the case of a 49-year-old man with Wegener’s granulomatosis who developed two relapses of the disease with cutaneous manifestation and who presented with concomitant elevation of the c-ANCA and more precisely the subset PR3-ANCA during the acute phase of the disease.