Androniki D. Tosca

Dermatological Manifestations in Primary Biliary Cirrhosis Patients: A Case Control Study

OBJECTIVES:Primary biliary cirrhosis (PBC), a disease of probable autoimmune etiology that affects the small intrahepatic bile ducts of mainly middle-aged women is commonly associated with pruritus, xanthomatous lesions, and melanosis. We conducted a prospective study to systematically describe the skin disorders of a group of PBC patients.METHODS:A prospective evaluation and analysis of dermatological manifestations including oral and genital lesions was carried out, in 49 PBC patients (45 females and 4 males). Median age 63 yr (range 35–87 yr). They were compared with 45 age and sex matched controls, selected among persons attending the dermatologic outpatient clinic.RESULTS:A total of 330 skin disorders were found in the 49 PBC patients versus 76 in the 45 controls; 31.5% of all lesions were skin fungal infections. Of all lesions analyzed with the Bonferonni rule of multiple comparisons significantly more common in PBC patients were plantar mycoses, onychomycoses, and interdigital mycoses. Pruritus was found in 69.3% of patients versus 22.2% of controls, xerosis in 69.3%versus 2.2%, dermographism in 57.1%versus 4.4%, and melanosis in 46.9%versus 0%. In 38.7% of the PBC patients the dermatologic lesion was the presenting symptom.CONCLUSIONS:PBC patients present with a wide variety of cutaneous manifestations varying in severity. Multiple skin fungal infections have been found even in the early stages. Since in more than one third of our PBC patients the dermatologic lesion was the presenting sign or symptom leading to diagnosis we believe that physicians should be aware so that a prompt and early diagnosis may be achieved.

Mycosis fungoides: Expression of C-myc p62 p53, bcl-2and PCNA Proteins and Absence of Association with Epstein-Barr Virus

The expression of C-myc p62, bcl-2, p53, PCNA and EBV-encoded LMP-1 proteins was studied by immunohistochemistry on paraffin-embedded skin specimens from 14 patients with early stage (premycotic erythema and second stage plaques) mycosis fungoides (MF), 21 patients with advanced stage MF (third stage plaques and tumors), 3 patients with Sezarys syndrome (SS) and 3 patients with pleomorphic medium and large cell cutaneous T-cell lymphomas (PML-CTCL). All 41 cases were also screened for the presence of EBV by using RNA in situ hybridization with EBER 1/2 oligonucleotides. Increased expression of C-myc p62, p53 and PCNA proteins was found in PML-CTCL and advanced stages of MF as compared to early stages of MF. These results suggest a relationship between levels of C-myc p62, p53 and PCNA proteins and aggressiveness of the cutaneous T-cell lymphomas. Furthermore, C-myc p62 and bcl-2 proteins were found to be frequently coexpressed in the present series. In view of the background information from in vitro findings and animal models that cooperation of C-myc and bcl-2 is important for lymphomagenesis, our results suggest that coexpression of these oncogenes may be implicated in the pathogenesis and/or the progression of cutaneous T-cell lymphomas. Neither LMP-1 expression nor EBV EBER l/2 transcripts were detected in our series suggesting that EBV is not involved in the pathogenesis of cutaneous T-cell lymphomas.

In vivo fluorescence kinetics and photodynamic therapy in condylomata acuminata.

Background  Topical application of 5‐aminolaevulinic acid (ALA) to condylomata acuminata leads to accumulation of protoporphyrin IX (PpIX); therefore ALA‐induced photodynamic therapy (ALA‐PDT) appears to be a potential treatment.

STAT4 gene polymorphism is associated with psoriasis in the genetically homogeneous population of Crete, Greece.

Recent genome-wide association studies (GWAS) of many complex diseases have successfully identified novel susceptibility loci, with many of them being associated with more than one condition. Taking into consideration that different autoimmune diseases may share some common pathogenetic pathways, we hypothesized that STAT4, a susceptibility gene found to be associated with increased risk for systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, Sjögrens syndrome, Wegeners granulomatosis, Crohns disease, and ulcerative colitis may also have a role in psoriasis. Psoriasis is an autoimmune, chronic inflammatory skin disease. Here we performed a case-control study in the population of island of Crete and demonstrated for the first time the association of a STAT4 single nucleotide polymorphism (SNP) with susceptibility to psoriasis, thus suggesting a putative key role of STAT4 in multiple autoimmune diseases. We found that mutated allele T of the STAT4 rs7574865 SNP, which previously was implicated in the predisposition to many autoimmune diseases, were more common in individuals with psoriasis than in controls (p = 0.045, odds ratio = 1.42, 95% confidence interval 1.01-2.00), thus concluding that the polymorphism examined is associated with the development of psoriasis in our population.

Low molecular weight heparin; a novel alternative therapeutic approach for lichen planus

Heparin analogues in low doses have antiproliferative and immunomodulatory properties. The aim of this study was to evaluate the effect of low‐dose enoxaparin administered subcutaneously in lichen planus (LP). Eighteen patients with various types of LP were treated in an open study for 6–13 weeks. Efficacy and safety data were recorded. Complete remission was observed in 11 of 18 patients (61%) and marked improvement in two (11%). Widespread cutaneous involvement and reticulated oral LP had the best response, while in LP of the scalp the response was poor. Enoxaparin is a promising alternative therapy for various types of LP.

A simple digital image processing system to aid in melanoma diagnosis in an everyday melanocytic skin lesion unit: a preliminary report.

Background  For early melanoma diagnosis, experienced dermatologists have an accuracy of 64–80% using clinical diagnostic criteria, usually the ABCD rule, while automated melanoma diagnosis systems are still considered to be experimental and serve as adjuncts to the naked‐eye expert prediction. In an attempt to aid in early melanoma diagnosis, we developed an image processing program with the aim to discriminate melanoma from melanocytic nevi, establishing a mathematical model to come up with a melanoma probability.

Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis

Background  Tumour necrosis factor (TNF)‐α blockade using infliximab, a chimeric anti‐TNF‐α antibody, is an effective treatment for plaque‐type psoriasis, inducing remission in about 80% of patients.

The role of endothelial cell apoptosis in the effect of etanercept in psoriasis

Background  Psoriasis is a chronic inflammatory skin disease associated with abnormal vascular expansion in the papillary dermis. Tumour necrosis factor (TNF)‐α is a proinflammatory cytokine that can induce antiapoptotic proteins and endothelial cell activation factors in psoriasis.

Primary care and pattern of skin diseases in a mediterranean island

BackgroundIn Greece where primary health care services are not fully developed, patients with simple or minor conditions have to attend to hospitals to be treated. We analysed the data of patients with cutaneous disorders attending the tertiary referral hospital on the Island of Crete, with the aim to identify the most common conditions that patients complain of, in order to define the areas where the education of General Practitioners in Dermatology must focus.MethodsAll patients attending the Dermatology ambulatory office in the Emergency Department of the University General Hospital of Heraklion from January 2003 to December 2003 were included in this retrospective analysis. The medical records of the patients (history, physical examination and laboratory investigations) were analysed to ascertain the diagnosis and the management of cases. All patients were evaluated by qualified dermatologists.ResultsA total of 3715 patients attended the Dermatology Clinic. Most patients were young adults in the age group 21–40 years (38.4%), and the male to female ratio was 1 to 1.2. Allergic skin diseases, mostly dermatitis and urticaria (35.7%) were the most common for attendance, followed by infectious diseases (26.1%) and insect bites (10.2%). Inflammatory and autoimmune disorders accounted for 7.9% of the cases. Pruritus of unknown origin was diagnosed in 6.3% of patients. Skin tumors were detected in 2.7%. The management of the vast majority of cases (85.0%) consisted of advice with or without a prescription, while only 4.8% of patients required admission.ConclusionAllergic and infectious skin diseases were the most common cutaneous diseases in patients attending this tertiary University hospital, while the management of most patients did not require specialised care. On the basis of the present data, the training of primary health care providers in Dermatology should emphasize these common conditions, with the aim of improving primary care and alleviating the burden on hospital care.

Overview of Merkel cell carcinoma and recent advances in research.

Merkel cell carcinoma is a rare primary neuroendocrine carcinoma of the skin with an aggressive biological behavior and poor prognosis. It was first described in 1972 by Toker 1 as a carcinoma originating in the sweat glands. Six years later, Tang and Toker 2 detected electron-dense neurosecretory granules in the cytoplasm of the tumor cells, thus identifying this tumor as a neuroendocrine carcinoma. This finding was substantiated by the detection of neuropeptide production by the tumor, including production of calcitonin, corticotropin, vasoactive intestinal peptide, met-enkephalin, somatostatin and gastrin. 3–7 Several names have been used in the past to describe this tumor, such as “primary neuroendocrine carcinoma of the skin”, “endocrine carcinoma of the skin”, and “cutaneous APUDoma”, reflecting the neuroendocrine origin of the cells. The terms “primary small-cell carcinoma of the skin” and “extrapulmonary carcinoma of the skin” reflect its resemblance to small-cell lung carcinoma (SCLC), whereas “undifferentiated or anaplastic carcinoma of the skin” and “trabecular carcinoma” reflect some of its histologic features. The designation “Merkel cell tumor” or “Merkel cell carcinoma” (MCC) has been used because of the presumed origin of the tumor from Merkel cells of the skin. Merkel cells were first described in 1875 by Friedrich Merkel 8 as “Tastzellen”. They are neuroendocrine cells of the epidermis, hair follicles and mucosa with epithelial characteristics. Their density has been estimated at 5–100 cells /mm 2 in the basal cell layer, where they are present as single cells or as aggregates. Their presumed function, in combination with existing nerve endings, is that of a slowly adapting mechanoreceptor. The origin of MCC from Merkel cells has been questioned for two main reasons: (a) normal Merkel cells are located in the epidermis, whereas MCC is a tumor growing in the dermis, and (b) normal Merkel cells do not express neurofilaments, which are variably found in MCC. However, both of these arguments have been recently rebutted. First, intraepithelial development of MCC has recently been described with no dermal component, 9,10 while several cases with intraepidermal spread and dermal tumor have been reported. 11,12