Publications by authors named "Isabel Kolm"

35 Publications

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients.

Allergy 2021 Jun 22. Epub 2021 Jun 22.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Background: Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR.

Methods: Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed.

Results: IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8 T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features.

Conclusion: A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8 T cells in severe COVID-19 patients, which in turn may impact the development of MDR.
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http://dx.doi.org/10.1111/all.14983DOI Listing
June 2021

A Problem of Classification: 2 Cases of Epstein-Barr Virus + Primary Cutaneous Plasmacytoma Arising in Immunocompetent Elderly Patients.

Am J Dermatopathol 2021 Jun 2. Epub 2021 Jun 2.

Department of Pathology, Lisbon Institute of Oncology, Lisbon, Portugal; Department of Dermatology, Kempf and Pfaltz Histological Diagnostics, University Hospital Zurich, Zurich, Switzerland; Kempf und Pfaltz Histologische Diagnostik, Zurich, Switzerland; Dermatopathology Friedrichshafen, Friedrichshafen, Germany; and Department of Pathology, St Thomas' Hospital, London, United Kingdom.

Abstract: Primary extramedullary plasmacytoma is rare monoclonal proliferation of plasma cells, which arise in various nonosseous anatomic locations without detectable underlying systemic disease. Historically, cutaneous infiltrates rich in mature neoplastic plasma cells have fallen into one of the following categories, plasmacytoma, lymphoplasmacytic lymphoma, and marginal zone lymphoma, which included immunocytoma. Since 2005, each of these was subsumed under the marginal zone lymphoma umbrella, largely on the basis of acknowledged diagnostic difficulties in some of these cases. We describe 2 cases in which the cutaneous infiltrates consisted of a pure population of light chain-restricted mature plasma cells in the absence of any other evidence for a marginal zone proliferation, or evidence of extracutaneous involvement, including a paraprotein. We propose that primary cutaneous plasmacytoma is the accurate diagnosis and is consistent with wider nomenclature. The unusual observation of widespread Epstein-Barr virus expression in both tumors is also discussed.
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http://dx.doi.org/10.1097/DAD.0000000000001932DOI Listing
June 2021

Golden Lady.

Dermatol Pract Concept 2021 Jan 29;11(1):e2021134. Epub 2021 Jan 29.

Department of Dermatology, University Hospital of Zurich, Switzerland.

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http://dx.doi.org/10.5826/dpc.1101a134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875672PMC
January 2021

Photochemical internalization (PCI)-mediated activation of CD8 T cells involves antigen uptake and CCR7-mediated transport by migratory dendritic cells to draining lymph nodes.

J Control Release 2021 04 17;332:96-108. Epub 2021 Feb 17.

Department of Dermatology, University of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. Electronic address:

Antigen cross-presentation to cytotoxic CD8 T cells is crucial for the induction of anti-tumor and anti-viral immune responses. Recently, co-encapsulation of photosensitizers and antigens into microspheres and subsequent photochemical internalization (PCI) of antigens in antigen presenting cells has emerged as a promising new strategy for inducing antigen-specific CD8 T cell responses in vitro and in vivo. However, the exact cellular mechanisms have hardly been investigated in vivo, i.e., which cell types take up antigen-loaded microspheres at the site of injection, or in which secondary lymphoid organ does T cell priming occur? We used spray-dried poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with ovalbumin and the photosensitizer tetraphenyl chlorine disulfonate (TPCS) to investigate these processes in vivo. Intravital microscopy and flow cytometric analysis of the murine ear skin revealed that dendritic cells (DCs) take up PLGA microspheres in peripheral tissues. Illumination then caused photoactivation of TPCS and induced local tissue inflammation that enhanced CCR7-dependent migration of microsphere-containing DCs to tissue-draining lymph nodes (LNs), i.e., the site of CD8 T cell priming. The results contribute to a better understanding of the functional mechanism of PCI-mediated vaccination and highlight the importance of an active transport of vaccine microspheres by antigen presenting cells to draining LNs.
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http://dx.doi.org/10.1016/j.jconrel.2021.02.014DOI Listing
April 2021

Glucocorticoid Receptor Beta and Its Prognostic Value on Treatment Response in Chronic Vulvar Dermatitis.

Skin Pharmacol Physiol 2021 16;34(1):30-37. Epub 2021 Feb 16.

Department of Gynecology, University Hospital Zurich, University of Zurich, Zurich, Switzerland,

Background: Chronic vulvar dermatitis (CVD) is the most prevalent disease in gynecologic dermatology. The treatment mainly depends on topical glucocorticoids (TGC) but is challenged by insufficient treatment response. On a histological level, the upregulation of the glucocorticoid receptor β (GRβ), an inhibitor of the active glucocorticoid receptor α (GRα), is discussed as mechanism of glucocorticoid insensitivity.

Objectives: To analyze whether the expression of GRβ protein at baseline in keratinocytes may predict responsiveness to TGC in patients with CVD.

Methods: In this retrospective cohort study, clinical and biological data of 25 women with a histological diagnosis of chronic vulvar eczema were analyzed. Randomization was done according to the responsiveness to TGC treatment (responsive vs. nonresponsive). Clinical data and the expression of GRβ in the immunohistochemical stained biopsies were examined.

Results: Fifty-two percent of women with CVD were nonresponsive to TGC. GRβ was abundantly expressed in the cytoplasma of keratinocytes of the vulvar epithelium, but no difference in the level of expression was found among GC responsive and nonresponsive patients in the semiquantitative (p = 0.376) and quantitative analysis (p = 0.894).

Conclusion: GRβ is highly expressed in keratinocytes of the vulvar epidermis affected by CVD, but GRβ expression was not increased in patients nonresponsive to TGC compared to responsive patients. Thus, the failure mechanism in nonresponders still remains to be elucidated.
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http://dx.doi.org/10.1159/000513594DOI Listing
February 2021

Lichen aureus with pseudolymphomatous infiltrate.

J Cutan Pathol 2021 May 18;48(5):669-673. Epub 2021 Jan 18.

Department of Dermatology, University Hospital Zurich, Switzerland.

Lichen aureus is a variant of pigmented purpuric dermatoses. The usual histopathology of lichen aureus is characterized by a subepidermal dense, band-like lymphocytic infiltrate, extravasated erythrocytes, and hemosiderin deposits. We report three patients with lichen aureus on the extremities with similar clinical, dermoscopic, and histopathological findings characterized by a dense band-like relatively deep dermal infiltrate accompanied by extravasation of erythrocytes and hemosiderin deposits occasioning a resemblance to a lymphoproliferative disorder.
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http://dx.doi.org/10.1111/cup.13948DOI Listing
May 2021

Sebaceous Tumors of the Skin: A Study of 145 Lesions From 136 Patients Correlating Pathologic Features and DNA Mismatch Repair Staining Pattern.

Am J Dermatopathol 2021 Mar;43(3):174-181

Sikl's Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic.

Abstract: Sebaceous neoplasms occur sporadically or in the setting of Muir-Torre syndrome. The data regarding the correlation of pathologic features and DNA mismatch repair (MMR) staining pattern in sebaceous tumors of the skin are very scanty and based on relatively small series of patients. The goal of this study was to correlate MMR staining pattern with selected morphological features in a series of 145 sebaceous neoplasms (sebaceous adenoma, sebaceoma, and extraocular sebaceous carcinoma) from 136 patients. Cystic change, intratumoral mucin deposits, squamous metaplasia in the absence of keratoacanthoma-like changes, ulceration, intratumoral and peritumoral lymphocytes (in cases without epidermal ulceration), and intertumoral heterogeneity proved to be significantly associated with MMR deficiency. Identification of any of these changes, alone or in combination, should prompt further investigation of the patient to exclude Muir-Torre Syndrome. Our study also confirms the previously published observation that the diagnosis and tumor location are significantly associated with MMR deficiency.
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http://dx.doi.org/10.1097/DAD.0000000000001691DOI Listing
March 2021

Benralizumab for severe DRESS in two COVID-19 patients.

J Allergy Clin Immunol Pract 2021 01 8;9(1):481-483.e2. Epub 2020 Oct 8.

Faculty of Medicine, University of Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Department of Dermatology, Hochgebirgsklinik Davos, Davos, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.09.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543785PMC
January 2021

The role of macrophages type 2 and T-regs in immune checkpoint inhibitor related adverse events.

Immunobiology 2020 09 21;225(5):152009. Epub 2020 Aug 21.

Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.

Immune checkpoint inhibitory (ICI) therapy represents a novel approach in a variety of cancers, with impressive survival benefit. With ICIs, however, a new spectrum of immune related adverse events (irAE) including life threatening hypohysitis has emerged. This autopsy study aimed to investigate inflammatory cells, PD-1 and PD-L1 expression in cases of patients who developed hypophysitis and involvement of other organs. We analysed 6 patients, who were treated with ICIs and developed hypophysitis. Two received an additional MAP-kinase inhibitor, MEK-inhibitor and cytotoxic chemotherapy. Besides the pituitary gland, all investigated adrenal glands (5/5) were affected; three cases had other organs involved (liver (2/6), thyroid (2/6), lung (1/6), myocardium (1/6), colon (1/6). The inflammatory cells of involved organs were further specified and PD1 and PDL-1 expression was analyzed using immunohistochemistry. We observed that patients treated with ICIs alone showed T-cell predominant lymphocytic infiltrates, whereas patients receiving additional therapies demonstrated an increase in B- and T-lymphocytes. Surprisingly, the dominant inflammatory population was not T-cell, but type 2 macrophages. CD25 positive T-regs were sparse or absent. Our study suggests that T cell activation is only partially responsible for irAE. ICI therapy interaction with CTLA-4, PD-1 and PDL-1 in type 2 macrophages appears to result in disturbance of their control. Furthermore, depletion of T-regs seems to contribute significantly. Our findings with simultaneous pituitary and adrenal gland involvement underlines the systemic involvement as well as the importance of monitoring cortisol levels to avoid potentially life threatening hypocortisolism.
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http://dx.doi.org/10.1016/j.imbio.2020.152009DOI Listing
September 2020

Infliximab for the treatment of recalcitrant bullous Sweet syndrome in a 10-year-old girl.

Pediatr Dermatol 2020 Nov 9;37(6):1183-1184. Epub 2020 Sep 9.

Pediatric Skin Center, Department of Dermatology, University Children's Hospital Zurich, Zurich, Switzerland.

We report the case of a 10-year-old girl with bullous Sweet syndrome, recalcitrant to high-dose systemic corticosteroids. Subsequent treatment with infliximab resulted in a rapid improvement in cutaneous lesions and systemic symptoms. Cutis laxa was noted in the healed skin. We propose early second-line treatment with infliximab in children with steroid-refractory Sweet syndrome.
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http://dx.doi.org/10.1111/pde.14356DOI Listing
November 2020

[Inflammatory Diseases of the Vulva - a Dermatologist's Point of View].

Authors:
Isabel Kolm

Praxis (Bern 1994) 2019 ;108(16):1085-1090

Dermatologische Klinik, Universitätsspital Zürich.

Inflammatory Diseases of the Vulva - a Dermatologist's Point of View Inflammatory vulvar diseases include a variety of disorders - many of which have a chronic course with significant morbidity. Diagnosis and especially treatment can be challenging for the clinician and warrant an interdisciplinary approach. This review covers the most common non-infectious and non-malignant vulvar diseases - from a dermatological point of view. The typical clinical symptoms, clinical appearances, treatment modalities of the main non-infectious vulvar diseases are highlighted; additionally, important dermatological differential diagnoses which should not be forgotten will be mentioned.
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http://dx.doi.org/10.1024/1661-8157/a003330DOI Listing
December 2019

Lineare juckende Plaques, Gelenkschmerzen und Fieber bei einem Kind.

J Dtsch Dermatol Ges 2019 Nov;17(11):1183-1186

Abteilung für Dermatologie, Kinderspital Zürich, Zürich, Schweiz.

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http://dx.doi.org/10.1111/ddg.13932_gDOI Listing
November 2019

A linear pruritic rash, arthralgia, and fever in a child.

J Dtsch Dermatol Ges 2019 11 13;17(11):1183-1186. Epub 2019 Sep 13.

Department of Dermatology, University Children's Hospital Zurich, Zurich, Switzerland.

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http://dx.doi.org/10.1111/ddg.13932DOI Listing
November 2019

Keratinocytic Malfunction as a Trigger for the Development of Solar Lentigines.

Dermatopathology (Basel) 2019 Jan-Mar;6(1):1-11. Epub 2019 Jan 3.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Introduction: Solar lentigines (SL) affect chronically UV-radiated skin. Treatment is often refractory. Deeper knowledge on its pathogenesis might improve therapeutic effects.

Material And Methods: Morphological characterization of 190 SL was performed and epidermal thickness, pigment distribution, dendricity, and cornification grade were measured. Immunoreactivity was investigated using Melan A, Tyrosinase, MITF, p53, and CD20, as well as Notch1 using immunofluorescence.

Results: We found 2 groups of histological patterns, i.e., either acanthotic or atrophic epidermis. Lesions with basket-woven cornification and atrophic epidermis were observed in 6 out of 9 and 14 out of 16 cases from the face, respectively. Consistency of areas with a high pigmentation was observed in 96-97% of the cases. Hyperpigmentation grade and acanthosis or cornification disorders correlated positively in 88.5% of the cases. Overexpressed of p53 was found in 19 out of 20 lesions, presenting in a scattered distribution. A significant correlation of p53 and acanthosis ( = 0.003) and cornification grade ( = 0.0008) was observed. Notch1 was expressed in all SL, with the highest immunoreactivity in atrophic facial lesions. Lesions from the hands expressed Notch1 mainly in acanthotic areas with elongated rete ridges and less compact cornification.

Discussion: We suggest that Notch1-dependent keratinocytic malfunction causes the development of SL. Consequently, hyperpigmentation would be a result and not the primary cause of the pathogenesis. Confirmation of these findings might have clinical implications as hitherto treatment has mainly focused on melanocytes and pigmentation and not on the proliferation/differentiation balance of keratinocytes.
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http://dx.doi.org/10.1159/000495404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381907PMC
January 2019

A Prospective Trial Comparing Q-Switched Ruby Laser and a Triple Combination Skin-Lightening Cream in the Treatment of Solar Lentigines.

Dermatol Surg 2016 Jul;42(7):853-7

Department of Dermatology, University Hospital, Zurich, Switzerland.

Background: Quality-switched (QS) laser therapy is a safe and well-established treatment option for removing solar lentigines. Triple combination therapy (TCT) with the active pharmaceutical ingredients hydroquinone 5%, tretinoin 0.03%, and dexamethasone 0.03% is often used for skin-lightening.

Objective: This prospective, open-label trial compares the efficacy and safety of a QS Ruby laser (QSRL) and a TCT in the treatment of solar lentigines.

Methods: In total, 15 patients with symmetrically distributed solar lentigines on the back of both hands were included. The lesions on the back of the right hand were treated in one or 2 sessions with a QSRL, the ones on the back of the left hand with a TCT for 7 weeks accompanied by UV protection. Clinical results were evaluated 4 weeks, 8 weeks, and 20 weeks after baseline.

Results: Treatment with QSRL provided significant lightening (p = .01) compared with TCT. Both procedures were generally well-tolerated. Comparing the side effects, the laser produced significantly more crusting and hyperpigmentation than the TCT.

Conclusion: Both QSRL and TCT were capable in reducing solar lentigines in Fitzpatrick skin Type I to IV with an acceptable side effect profile. The QSRL provides faster, superior, and long lasting lightening compared with TCT.
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http://dx.doi.org/10.1097/DSS.0000000000000793DOI Listing
July 2016

Cervicofacial actinomycosis: a long forgotten infectious complication of immunosuppression - report of a case and review of the literature.

Dermatol Online J 2014 May 16;20(5):22640. Epub 2014 May 16.

University Hospital Zurich.

Actinomycosis is a rare chronic granulomatous infection caused by Gram-positive, non-acid-fast, anaerobic to microaerophilic bacteria.We report a case of cervicofacial actinomycosis in an 86-year-old woman undergoing immunosuppressive therapy with azathioprine and prednisone for rheumatoid arthritis. She underwent a dental treatment several months earlier. The diagnosis of culture-negative actinomycosis was based on histolopathology findings and the isolation of companion bacteria. The patient was treated with amoxicillin-clavulanic acid for 3 months, which produced complete clearance of her cervicofacial actinomycosis.Our case points out the pitfalls of diagnostic procedures in actinomycosis and the ability of this rare disease to mimic other medical conditions.
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May 2014

Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom.

Hered Cancer Clin Pract 2014 20;12(1):20. Epub 2014 Nov 20.

Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.

Background: Mutations in the CDKN2A and CDK4 genes predispose to melanoma. From three case-control studies of cutaneous melanoma, we estimated the prevalence and predictors of these mutations for people from regions with widely differing latitudes and melanoma incidence.

Methods: Population-based cases and controls from the United Kingdom (1586 cases, 499 controls) and Australia (596 early-onset cases, 476 controls), and a hospital-based series from Spain (747 cases, 109 controls), were screened for variants in all exons of CDKN2A and the p16INK4A binding domain of CDK4.

Results: The prevalence of mutations for people with melanoma was similar across regions: 2.3%, 2.5% and 2.0% for Australia, Spain and the United Kingdom respectively. The strongest predictors of carrying a mutation were having multiple primaries (odds ratio (OR) = 5.4, 95% confidence interval (CI: 2.5, 11.6) for 2 primaries and OR = 32.4 (95% CI: 14.7, 71.2) for 3 or more compared with 1 primary only); and family history (OR = 3.8; 95% CI:1.89, 7.5) for 1 affected first- or second-degree relative and OR = 23.2 (95% CI: 11.3, 47.6) for 2 or more compared with no affected relatives). Only 1.1% of melanoma cases with neither a family history nor multiple primaries had mutations.

Conclusions: There is a low probability (<2%) of detecting a germline CDKN2A mutation in people with melanoma except for those with a strong family history of melanoma (≥2 affected relatives, 25%), three or more primary melanomas (29%), or more than one primary melanoma who also have other affected relatives (27%).
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http://dx.doi.org/10.1186/1897-4287-12-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361137PMC
March 2015

Evaluation of PAX3 genetic variants and nevus number.

Pigment Cell Melanoma Res 2013 Sep 4;26(5):666-76. Epub 2013 Jul 4.

Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain.

The presence of a high nevus number is the strongest phenotypic predictor of melanoma risk. Here, we describe the results of a three-stage study directed at identifying risk variants for the high nevus phenotype. At the first stage, 263 melanoma cases from Barcelona were genotyped for 223 single-nucleotide polymorphisms (SNPs) in 39 candidate genes. Seven SNPs in the PAX3 gene were found to be significantly associated with nevus number under the additive model. Next, the associations for seven PAX3 variants were evaluated in 1217 melanoma cases and 475 controls from Leeds; and in 3054 healthy twins from TwinsUK. Associations with high nevus number were detected for rs6754024 (P values < 0.01) in the Barcelona and Leeds datasets and for rs2855268 (P values < 0.01) in the Barcelona and the TwinsUK sets. Associations (P values < 0.001) in the opposite direction were detected for rs7600206 and rs12995399 in the Barcelona and TwinsUK sets. This study suggests that SNPs in PAX3 are associated with nevus number, providing support for PAX3 as a candidate nevus gene. Further studies are needed to examine the role of PAX3 in melanoma susceptibility.
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http://dx.doi.org/10.1111/pcmr.12130DOI Listing
September 2013

Serum 25-hydroxyvitamin D3 levels and vitamin D receptor variants in melanoma patients from the Mediterranean area of Barcelona.

BMC Med Genet 2013 Feb 16;14:26. Epub 2013 Feb 16.

Background: Serum 25-hydroxyvitamin D3 (Vitamin D) insufficiency and single-nucleotide polymorphisms (SNPs) on its receptor, Vitamin D receptor (VDR), have been reported to be involved in melanoma susceptibility in populations mostly from northern countries.

Objective: To investigate 25-hydroxyvitamin D3 levels and VDR SNPs in melanoma patients from sunny area of Barcelona, two studies were carried out. The first study evaluated the levels of Vitamin D at time of melanoma diagnosis and the second one analyzed the association between VDR genetic variants and risk of having a high nevus number, the strongest phenotypic risk factor for melanoma.

Methods: The levels of 25-hydroxyvitamin D3 in 81 melanoma patients at diagnosis were measured. In a second group of melanoma patients, including 150 with low and 113 with high nevus number, 11 VDR SNPs were analyzed for their association with nevus number.

Results: In the first study, 68% of patients had insufficient levels of 25-hydroxyvitamin D3 (<25 ng/ml). Autumn-winter months and fair phototype were associated with 25-hydroxyvitamin D3 insufficiency; after multivariate analysis, season of sampling remained the only independent predictor of 25-hydroxyvitamin D3 levels. In the second study, VDR variant rs2189480 (P = 0.006) was associated with risk of high nevus number whereas rs2239179 (P = 0.044) and rs7975128 (P = 0.0005) were protective against high nevus number. After Bonferroni adjustment only rs7975128 remained significant. In stratified analysis, SNP rs7975128 was found protective against multiple melanomas (P = 0.021).

Conclusion: This study showed that even in Barcelona, a sunny Mediterranean area, 25-hydroxyvitamin D3 levels were sub-optimal in the majority of melanoma patients at diagnosis. The involvement of VDR in nevi and, in turn, in melanoma susceptibility has also been suggested. Larger studies are needed to confirm our findings.
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http://dx.doi.org/10.1186/1471-2350-14-26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648347PMC
February 2013

Negative pigment network: an additional dermoscopic feature for the diagnosis of melanoma.

J Am Acad Dermatol 2013 Apr 9;68(4):552-559. Epub 2012 Oct 9.

Sydney Melanoma Diagnostic Center, Royal Prince Alfred Hospital and Discipline of Dermatology, University of Sydney, Sydney, Australia.

Background: The negative pigment network (NPN) is seen as a negative of the pigmented network and it is purported to be a melanoma-specific structure.

Objectives: We sought to assess the frequency, sensitivity, specificity, and odds ratios (ORs) of NPN between melanoma cases and a group of control lesions.

Methods: Digitalized images of skin lesions from 679 patients with histopathological diagnosis of dermatofibroma (115), melanocytic nevus (220), Spitz nevus (139), and melanoma (205) were retrospectively collected and blindly evaluated to assess the presence/absence of NPN.

Results: The frequency of occurrence of NPN was higher in the melanoma group (34.6%) than in Spitz nevus (28.8%), melanocytic nevus (18.2%), and dermatofibroma (11.3%) groups. An OR of 1.8 emerged for the diagnosis of melanoma in the presence of NPN as compared with nonmelanoma diagnosis. Conversely, for melanocytic nevi and dermatofibromas the OR was very low (0.5 and 0.3, respectively). For Spitz nevi the OR of 1.1 was not statistically significant. When comparing melanoma with dermatofibroma, melanocytic nevus, and Spitz nevus, we observed a significantly higher frequency of multicomponent pattern (68.1%), asymmetric pigmentation (92.9%), irregularly distributed NPN (87.3%), and peripheral location of NPN (66.2%) in melanomas.

Limitations: Further studies can provide the precise dermoscopic-histopathologic correlation of NPN in melanoma and other lesions.

Conclusions: The overall morphologic pattern of NPN, such as the irregular distribution and the peripheral location of NPN, along with the multicomponent pattern and the asymmetric pigmentation could be used as additional features in distinguishing melanoma from Spitz nevus and other benign lesions.
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http://dx.doi.org/10.1016/j.jaad.2012.08.012DOI Listing
April 2013

Trauma as triggering factor for development of melanocytic nevi.

Dermatology 2010 24;220(4):291-6. Epub 2010 Apr 24.

Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, Zurich, Switzerland.

The mechanisms for the development of acquired melanocytic nevi remain mostly unclear. Here we report a case of eruptive nevi that developed after localized superficial trauma, and review the currently known cellular and triggering factors for acquired melanocytic nevi. A 66-year-old woman presented a linear arrangement of pigmented macules on her left calf that developed after a bloodless skin erosion on the same spot, resulting from friction with the lining of a ski boot. Dermatopathology identified multiple junctional proliferations of single or small nest-forming melanocytes with bridging, pigment incontinence and moderate cellular atypia. The number of a person's nevi correlates with age, race and genetics, but blistering diseases, scarring processes, light exposure and immunosuppression can contribute to nevocellular growth as well. Damaged keratinocytes and inflammatory cells can release growth factors inducing nevus cell proliferation, and immunosuppression could end cellular surveillance keeping preexisting nevus cell nests in check. We conclude that in predisposed patients, the trigger for eruptive nevi can be reduced to a simple localized minor trauma.
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http://dx.doi.org/10.1159/000276983DOI Listing
October 2010

Internet based health promotion campaign against skin cancer - Results of www.skincheck.ch in Switzerland.

Eur J Dermatol 2010 Jan-Feb;20(1):109-14. Epub 2009 Oct 13.

Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.

Conventional skin cancer prevention programs appeal to limited populations, and the middle aged male population responds less frequently. Our objective was to establish a complementary health promotion campaign tool for skin cancer prevention. Internet-based education, instruction for self assessment and teledermatological evaluation of skin lesions by an expert commission of dermatologists was used. Compliance and clinical diagnosis was assessed in a subgroup. 12,000 users visited the educational website. There was strong interest among the middle aged male population (53% (N = 262): male; mean age: 42). 28.5% of examined lesions (N = 494) were considered suspicious. Email requests, sent to the group whose lesions where considered suspicious, were answered by 46.0% of females (N = 29) and 59.7% of males (N = 46) with a female distribution predominantly in younger ages (52.6% of females with known age: < 30 years). Males were predominantly represented over 30 years (86.2% of all males). According to user's declarations, at least 8 (8.5%) malignant lesions (1 melanoma in situ, 1 squamous cell carcinoma, 4 basal cell carcinomas, 2 malignant lesions without declared diagnosis) were finally diagnosed by physicians. We conclude that internet-based, interactive, educational programs, in addition to existing health promotion campaigns, can enhance public participation in the middle aged male population in skin cancer prevention.
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http://dx.doi.org/10.1684/ejd.2010.0827DOI Listing
April 2010

Detection of basal cell carcinoma using color and histogram measures of semitranslucent areas.

Skin Res Technol 2009 Aug;15(3):283-7

Stoecker and Associates, The Dermatology Center, 1702 E. 10th St. Rolla, MO, USA.

Background: Semitranslucency, defined as a smooth, jelly-like area with varied, near-skin-tone color, can indicate a diagnosis of basal cell carcinoma (BCC) with high specificity. This study sought to analyze potential areas of semitranslucency with histogram-derived texture and color measures to discriminate BCC from non-semitranslucent areas in non-BCC skin lesions.

Methods: For 210 dermoscopy images, the areas of semitranslucency in 42 BCCs and comparable areas of smoothness and color in 168 non-BCCs were selected manually. Six color measures and six texture measures were applied to the semitranslucent areas of the BCC and the comparable areas in the non-BCC images.

Results: Receiver operating characteristic (ROC) curve analysis showed that the texture measures alone provided greater separation of BCC from non-BCC than the color measures alone. Statistical analysis showed that the four most important measures of semitranslucency are three histogram measures: contrast, smoothness, and entropy, and one color measure: blue chromaticity. Smoothness is the single most important measure. The combined 12 measures achieved a diagnostic accuracy of 95.05% based on area under the ROC curve.

Conclusion: Texture and color analysis measures, especially smoothness, may afford automatic detection of BCC images with semitranslucency.
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http://dx.doi.org/10.1111/j.1600-0846.2009.00354.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154079PMC
August 2009

Dermoscopy: what's new?

Clin Dermatol 2009 Jan-Feb;27(1):26-34

Department of Dermatology, University Hospital Zürich, Zürich 8091, Switzerland.

Dermoscopy has been described as a useful tool for the early diagnosis of melanoma and the differential diagnosis of pigmented lesions of the skin. This has been proven by three independent meta analyses of the literature. Dermoscopy is a fast evolving field with a high number of new publications every year. Initially, the use of dermoscopy was limited to pigmented lesions, but it is used more and more in other situations. It has become an important tool for the diagnosis of nail pigmentations, hair and scalp disorders, and so forth. In this article we try to provide an update on recent trends and developments in dermoscopy.
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http://dx.doi.org/10.1016/j.clindermatol.2008.09.003DOI Listing
April 2009

The furrow ink test: a clue for the dermoscopic diagnosis of acral melanoma vs nevus.

Arch Dermatol 2008 Dec;144(12):1618-20

Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.

Background: Dermoscopy is a helpful tool that can assist experienced users improve the diagnostic accuracy for pigmented lesions in acral sites. As a simplification, one can assume that if pigment is found predominantly in the furrows, the lesion can be considered benign, and if the pigmentation is present predominantly on the ridges, the lesion should be considered malignant. The differentiation between furrows and ridges is the main clue for the diagnosis, but this can sometimes be difficult to discern. For this reason, we describe a simple in vivo technique that makes this task much easier for the clinician.

Observations: Liquid ink (ie, from a fountain pen) should be applied directly onto the lesion. The ink should be left on the skin for a few seconds to allow the ink to penetrate into the furrows. The excess ink should then be wiped off. The ink will at first diffusely color the entire skin surface. The subsequent cotton swab wiping will only remove the ink on the skin overlying the ridges. The furrows will retain the stain and become clearly visible on dermoscopic examination as thin inked lines. This in turn will make it easy to evaluate whether the melanin pigmentation follows the ink lines (benign pattern) or if the pigmentation is located in between these ink lines (malignant pattern). Conclusion The furrow ink test is a quick and easy method to facilitate the correct identification of furrows and ridges on volar skin and facilitates dermoscopic diagnosis of pigmented lesions in acral sites.
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http://dx.doi.org/10.1001/archderm.144.12.1618DOI Listing
December 2008
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