Heraklion University General Hospital, Heraklion 711 10, Crete-Greece
derma@med.uoc.gr
II. Education - 1972 MD University of Thessaloniki (Magna cum Laude) - 1977 Doctoral Thesis (Univ. of Athens) (Magna cum Laude) - 1987 Professorship thesis (Univ. of Athens)
III. Post Graduate Education - Academic Appointments 1972-73 Internal Medicine, Greece 1973 Surgery, Greece 1974-77 Residentship, Dept Dermatology, Univ. of Athens, Greece 1977-79 Registrar in Dermatology, Univ. of Athens, Greece 1979-81 Research Fellow, Dept Immunology, Royal College of Surgeons of England, London 1981-82 Lecturer in Dermatology, Dept Dermatology, Univ. of Thessaloniki 1982-86 Senior Registrar, Dept Dermatology, Univ. of Athens, Greece 1984 Research Fellow, Dept Dermatology, Univ. of Lyon, France 1986-89 Head of Dept Dermatology and immunodermatology Laboratory “Andreas Sygros Hospital” Athens, Greece 1987 Research Fellow, Dept Dermatology, Freie Universitat, Univ. of Berlin, Germany 1987 Assistant Professor of Dermatology, Univ. of Athens, Greece 1989-1995 Associate Professor of Dermatology, Head of Dept Dermatology, Univ. of Crete, Greece 1989 Six months seminar in Medical Statistics 1989 Research Fellow, Psoriasis Research Institute “Palo Alto”, California 1990-92 Head of Dept of Pathology, Univ. of Crete, Greece 1995-now Professor of Dermatology, Head of Dept Dermatology
IV. Certification and Licensure Certification Greek Board of Dermatology and Venereology 1977
V. Professional Affiliations -Greek Society of Dermatology and Venereology -International Society of Dermatology -Greek Medical Society -European Academy of Dermatology and Venereology -International Tissue Culture Society -Greek Society for the study of STD -Greek Society of Immunology -Greek Society for Lasers in Medicine VI. Areas of Research Interest -Keratinocyte tissue cultures -Immunocytochemistry and ultrastructural research in Dermatology -Studies on the pathogenesis of mycosis fungoides -Studies on the pathogenesis and diagnosis of skin cancer -Immunopathological mechanisms in allergic vasculitis, development of new therapeutic modalities -Immunological studies in collagen and other autoimmune diseases -Selectivity of photosensitizers and photodynamic treatment
VII. Current Projects -Immunopathology and Immunoserology in Leprosy -Mechanisms in “Aging of the skin” -Biology, Biochemistry Immunopathology and Cytoskeletal studies in skin cancer. Basic Research -HPV Viruses, in situ hybridization in skin premalignancies, malignancies -Immunoserology and Immunopathology in Lupus Erythematosus -Epidemiology of pemphigus and bullous pemphigoid -Pathology-molecular pathology -Immunohistology of cutaneous T-cell lymphomas -Immunopathology of allergic cutaneous vasculitis -Development of photosensitizers and photodynamic treatment of cancer -Photodiagnosis and image analysis of skin disorders
VIII. Teaching activities -1974-now Classroom seminar on Teaching (medical students) Dermatology and Venereology -1974-now Clinical teaching Seminars, Dermatology, Venereology, Immunodermatology (Laboratory, Clinic) -Conferences Grand Rounds, Journal Clubs etc. -Instruction of methods in Immunodermatology -Instruction and Supervision in 35 MD and 3 Professorship theses
IX. Participation in Congresses and Round Tables 120 International (in most of them as invited speaker and chairing sessions) 121 Greek
X. Publications -In Greek literature: 69 -In International Literature: More than 131 -Chapters in Books and Proceedings:23 -Citations:850 -Books :4
XI. Other activities -Member of many advisory scientific committees -Editorial Board in 3 scientific journals -Organizing and Scientific committees of national and international congresses -Foundation in collaboration with F.O.R.T.H and Otorhinolaryngology of the “Center for Photodiagnosis and Phototherapy” at the University Hospital of Heraklion-Crete
XII. Current position Head of the Department of Dermatology and Venereology. Head of the Research Laboratories of Dermatology, University of Crete Medical School, University General Hospital, Heraklion, Crete-Greece
XIII. Financial support through many National and Intermational Competitive Scientific Programs
XIV. Foreign languages: English, French, Italian
Profile of the Medical Department
The Medical Department was founded in 1989 at the University of Crete. 1) Research Laboratories They comprise: A Biochemistry Laboratory, an Immunodermatology Laboratory, Cell and Tissue culture facilities, a Photobiology and a Dermatopathology Laboratory. These Laboratories are located at the building of the Division of Medicine (University of Crete). Four physicians, one biochemist, one biologist and technical stuff, consist the research group at the present time. 2) Dermatology Department It comprises the inpatient section (25 beds) at the University Hospital. Outpatient Clinics: Four outpatient clinics work on a daily basis. Clinical units: Melanoma unit, Photobiology unit, Immediate and Delayed Hypersensitivity unit, Dermatologic surgery unit, Photodection and Photodynamic Therapy unit, Cryosurgery and LASER unit and Medical Informatics unit. Eleven physicians, nurses and tecnical stuff work in the Department of Dermatology at the University Hospital. 3) Research programmes Many research programmes are in progress, financially supported by National and International sources. Many publications have appeared in peered reviewed journals in recent years. 4) Teaching activities Undergraduate seminars, practical exercises grand rounds, physician training in Dermatology, organization of Symposia, Round Tables, Congresses, Lectures and supervision of Doctorate Theses.
Abstract: BACKGROUND: Erysipelas is a superficial form of cellulitis affecting the upper dermis and superficial lymphatics. The widespread use of antibiotics may affect clinical findings and response to therapy of infectious disorders. The purpose of the study was to investigate the epidemiological, clinical, and laboratory features of erysipelas and to compare the results of treatment with penicillin vs. other antibiotic regimens. METHODS: All charts of erysipelas patients treated at the University Hospital of Heraklion, Crete, Greece from 1994 to 2002 were retrospectively studied. RESULTS: Median age of the 99 patients was 54.5 years; 59% were females. The most frequent site involved was the lower extremity (76%), followed by the face (17%) and upper extremity (6%). In 61 patients (62%), a possible entry portal was identified. The most common manifestation of erysipelas was local symptoms and signs (pain, erythema, and swelling) in all patients, together with elevated erythrocyte sedimentation rate (ESR) (60%). Fever was present in 25% of patients. The most commonly used antibiotic was intravenous penicillin G (64%). In the penicillin group, mean duration of fever after treatment initiation was shorter than in the nonpenicillin group (1.7 vs. 4.5 days, P = 0.002). Both treatment failures and recurrences were the same between the two groups. DISCUSSION: The diagnosis of erysipelas can be based on careful examination for local signs and symptoms. The role of ESR in primary diagnosis needs further investigation. Penicillin seems to preserve its fundamental role in the treatment of disease.
Abstract: Recent whole-genome and candidate-gene association studies in patients with psoriasis (PS) have identified a number of single-nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. Predisposition to PS is known to be affected by genetic variation in human leukocyte antigen-C as well as other non-human leukocyte antigen genes. We recently reported for the first time as a PS-associated SNP the signal transducer and activator of transcription-4 (STAT4) rs7574865 polymorphism, which is also associated with several autoimmune diseases. The aim of this study was to assess whether the functional R620W polymorphism of protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene encoding the lymphoid-specific tyrosine phosphatase, which is known to be associated with various autoimmune diseases, also confers increased risk for PS in the genetic homogeneous population of Crete. A case-control study was performed with 173 PS patients consecutively recruited and 348 healthy controls, all of them from the island of Crete. We found that the mutated T allele of the PTPN22 1858T SNP was more common in control individuals than in patients with PS (odds ratio = 0.39, 95% confidence interval = 0.11-1.04, p = 0.09). No considerable difference was observed in terms of sex, age of onset, or clinical presentation of psoriatic arthritis. Our results provide evidence that the PTPN22 1858T allele is not a susceptibility factor for PS in the Cretan population.
Abstract: Backgroundâ 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. Objectivesâ The present study investigated the effect of the anti-TNF-α agent etanercept on the expression of endothelial nuclear factor-κB (NF-κB), angiogenic vascular endothelial growth factor (VEGF), endothelial cell marker CD31, antiangiogenic factor thrombospondin-1 (TSP-1), and antiapoptotic factors Bcl-2 and Bcl-xL in psoriasis. Methodsâ Sixteen patients with moderate-to-severe psoriasis were included in the study and treated with etanercept 50âmg twice weekly subcutaneously for 12âweeks. Biopsies of lesional skin (baseline, weeks 3, 6 and 10) were obtained and immunohistochemically stained with antibodies for CD31, VEGF, TSP-1, NF-κB, Bcl-2 and Bcl-xL. Double immunofluorescence staining for VEGF and CD31 was evaluated with confocal laser microscopy. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was applied for apoptosis detection. Resultsâ Etanercept caused a statistically significant time-dependent reduction in the number of dermal blood vessels, the number of CD31+ cells and VEGF in psoriatic lesions, with induction of endothelial cell apoptosis and statistically significant upregulation of TSP-1 in psoriatic vessels. Immunohistochemical analysis showed significant reduction of NF-κB, Bcl-2 and Bcl-xL expression in endothelial cells during treatment. These changes were accompanied by a marked clinical response. Conclusionsâ The present findings suggest that treatment with etanercept induces apoptosis, reduces apoptosis-inhibiting factors in psoriatic endothelial cells, and decreases angiogenesis in psoriatic skin.
Abstract: BACKGROUND/AIMS: KIT receptor has been implicated in the pathogenesis of cancer, either by mutation or autocrine activation. Merkel cell carcinoma (MCC) is a rare KIT-positive cutaneous tumor. We investigated the co-expression of KIT and its ligand stem cell factor (SCF) in MCC. METHODS: Sixteen specimens from 13 MCC patients of various tumor stages were examined by immunohistochemistry for SCF, KIT, Ki67/MIB-1 and cleaved caspase 3 expression, and for apoptosis by TUNEL. RESULTS: KIT was expressed in 13 of 16 tumors, and SCF in 15 of 16 specimens. Co-expression of KIT and SCF was detected in 12 of 16 tumors. KIT and SCF immunoreactivity scores were independent of tumor stage. Ki67/MIB-1 proliferation rates were high, whereas apoptosis rates were low, and did not depend on KIT or SCF expression. CONCLUSION: Co-expression of KIT and SCF in a high percentage of MCC tumors hints to an autocrine mechanism. KIT and SCF expression in primary tumors and in metastases suggests an early event in Merkel cell transformation.
Abstract: 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, Sjögren's syndrome, Wegener's granulomatosis, Crohn's 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.
Abstract: BACKGROUND: Treatment of multiple cutaneous piloleiomyomas which are rare, frequently painful, benign tumors originating from the arrector pilorum muscle of hair follicles is difficult. OBJECTIVE: To determine the efficiency of botulinum toxin type A (BT-A) treatment for pain relief of cutaneous piloleiomyomas. Methods: A patient with multiple painful piloleiomyomas was treated with local injections of 200 units of BT-A. RESULTS: There was a rapid and sustained decrease in pain. Treatment was repeated every 3 months for 2 years with the same efficacy. CONCLUSION: BT-A may be a promising new treatment option for multiple painful cutaneous piloleiomyomas.
Abstract: Quantitative immunohistochemistry is needed in order to reliably and accurately assess the expression of cellular proteins in tissue. Skin is a difficult tissue for automated image analysis due to its heterogeneous composition and its architecture. In the present study we used a psoriatic skin model to compare the expression of p53 and bcl-2 before and after treatment with anti-tumor necrosis factor-alpha using digital image analysis. Digital photomicrographs were acquired and analyzed with Scion image software in order to obtain the fraction of p53 and bcl-2 immunoreactive cells' area out of the total area investigated. Statistical analysis with ANOVA revealed a significant increase of p53 expression and a decrease of bcl-2 expression in all 3 epidermal layers during the course of therapy (p<0.001). The results were in line with the conventional histopathological evaluation using an arbitrary scale to grade the extent and intensity of the staining. So, the estimation of volume fraction of immunohistochemically labelled cells in skin tissue can be performed easily and rapidly using commonly available image analysis software and provides reproducible and unbiased numerical estimations of the amount of cell labelling.
Abstract: Transforming growth factor-beta (TGF-beta), a potent inhibitor of normal melanocyte growth, does not significantly suppress growth of melanoma cells. The mechanism of melanocyte desensitization to TGF-beta in the transformation process remains largerly unknown. We investigated whether the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) may induce melanocyte resistance to TGF-beta. Cell proliferation and DNA synthesis of normal human melanocytes were strongly inhibited by TGF-beta, whereas in the presence of TPA remained largerly unaffected. The inactive phorbol ester 4alpha-phorbol 12,13 didecanoate did not modify the TGF-beta antiproliferative effect, whereas the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol counteracted TGF-beta effects. Protein kinase C (PKC) is the major cellular receptor of tumor promoting phorbol esters. PKC-alpha expression and phosphorylation were almost completely downregulated under combined treatment with TGF-beta + TPA at 24 and 72 h, as shown by immunoblots. Confocal microscopy demonstrated that TGF-beta-induced nuclear accumulation of PKC-alpha was abolished in the presence of TPA at the same time points. The selective PKC inhibitor Ro-31-8220 weakened the TGF-beta antiproliferative effect. Smads are central mediators for TGF-beta signal transduction. Smad-dependent transcriptional activity was suppressed in TGF-beta-treated melanocytes in the presence of TPA, as well as in ALK5 (constitutively active type I TGF-beta receptor)- or Smad3 + Smad4-transfected melanocytes in the presence of Ro-31-8220. In addition, an antisense oligodeoxynucleotide against PKC-alpha abolished TGF-beta-driven Smad-mediated transcription. These findings show that tumor promoting phorbol esters induce melanocyte resistance to TGF-beta, associated with downregulation of PKC-alpha and suppression of Smad-dependent transcription. This may represent an important mechanism for expansion of melanocytes exposed to PKC-targeting tumor promoters.
Abstract: Merkel cell carcinoma is a tumor with aggressive biological behavior and limited response to chemotherapy. The present study investigated the effect of interferon (IFN)-alpha on growth and apoptosis of Merkel carcinoma cells in vitro. Proliferation of MCC-1 cell line was reduced dose-dependently by IFN-alpha and diminished when higher IFN-alpha concentrations were used. Additionally, IFN-alpha potently decreased DNA-synthesis and Ki67/MIB-1 proliferation index of MCC-1 cultures. Furthermore, IFN-alpha induced dose-dependently apoptosis of MCC-1 cells as shown by caspase-3 activation, and detection of apoptotic DNA strand breaks and fragmented nuclei. These findings suggest that IFN-alpha may have antitumor activity against Merkel cell carcinoma.
Abstract: A 64-year-old woman presented with erythematous, infiltrative plaques with a central atrophic area on both zygomatic regions. Several yellow-reddish papules were seen at the periphery of the plaques and showed an "apple-jelly" color on diascopy (Fig. 1). No visceral involvement was detected. The past medical history revealed that, at 3 years of age, she had developed an "Oriental sore" on both cheeks that healed with permanent scars. Thirty years later, she noticed an erythematous patch around the scars. She reported a hospital admission 22 years earlier for cutaneous leishmaniasis (CL); this was treated with pentavalent antimonial therapy for 10 days with partial improvement, when she refused further treatment. The lesions worsened in the summer and gradually became disfiguring, which prompted her to seek medical consultation. Laboratory findings were normal. Leishmania antibody titers were negative. Tissue samples were obtained by biopsy from the border of the lesion for culture, polymerase chain reaction (PCR), and histopathologic examination. Histology revealed a dermal infiltrate with tuberculoid granulomas surrounded by lymphocytes, histiocytes, and some plasma cells, but no caseation necrosis. A few Leishmania organisms were found on careful searching (Fig. 2). Leishmania tropica was identified by culture and PCR. A diagnosis of leishmaniasis recidiva cutis (LRC) was made on the basis of the anamnestic data together with the clinical, histopathologic, biologic, and molecular findings. Complete regression was achieved with meglumine antimoniate (Glucantime) given intramuscularly (15 mg Sb(V)/kg/day for 15 days) and cryosurgery with liquid nitrogen. No recurrence was noted during a 12-month follow-up period.
Abstract: A rare case of an invasive cutaneous infection by Geotrichum candidum in an 80-year-old male patient with diabetes mellitus is reported. The primary site of infection manifested after trauma as an ulcerative lesion on the distal phalanx of the midfinger and extended throughout the right hand. Histological examination showed fungal invasion in the deep dermis without vascular involvement and G. candidum was grown in cultures from the biopsy material. Angiography revealed severe obstructive disease of the right brachial artery and its branches. Treatment, after susceptibility testing of the isolated strain, consisted of sequential administration of intravenous liposomal amphotericin B with oral voriconazole followed by liposomal amphotericin B, resulting in substantial improvement of the infection.
Abstract: BACKGROUND: For Greece, no data regarding the incidence of cutaneous melanoma (CM) have been reported. In this report, we present epidemiologic data for CM on Crete, an island in southern Greece, during the years 1999-2002. We attempt a comparison with corresponding data reported for the Italian population. METHODS: One hundred and two CM patients of Cretan origin with primary CM first diagnosed between the years 1999-2002 were interviewed and underwent complete skin examination by the same two experienced dermatologists. Crude and/or age-standardized incidence rates were calculated for Crete as a whole, as well as for each one of the four prefectures of the island. RESULTS: The age-standardized incidence rate according to the Greek population was 4.6 per 100,000 person-years for men and 4.7 per 100,000 person-years for women. The crude incidence rates did not differ significantly between the four prefectures. Significant differences between Cretan and Italian CM patients were found in terms of gender, age at diagnosis, anatomic site and histogenetic type of CM, hair color, skin reaction to sun exposure, history of sunburn before the age of 15 years, presence of solar lentigines, and total common nevus count. CONCLUSIONS: The incidence of CM on Crete is higher than that estimated for the whole of Greece and comparable with the incidence reported for other southern European countries.
Abstract: BACKGROUND: Comparative analysis of the incidence rates and epidemiological features of cutaneous malignant melanoma (CMM) between different ethnic groups exposed to varying environmental factors is critical for consideration of the causes of CMM but can also be utilized in a public health approach to control of the disease. OBJECTIVES: To compare incidence rates and clinical features of CMM in a Greek and a central European population (central Baden-Württemberg, Germany). METHODS: Incident cases of CMM were traced in all hospitals of the island of Crete for the period 1999-2002. Age-standardized incidence rates per 100 000 inhabitants per year for the European Standard Population were calculated based on the Cretan population statistics. A comparison was performed between the Cretan findings and those of southern Germany as registered by the hospital-based Central Malignant Melanoma Registry, which likewise documents more clinical features than normally recorded by population-based cancer registries. RESULTS: Mean incidence rates in Crete for 1999-2002 were 4.01 per 100 000 inhabitants per year for males and 4.05 for females as compared with 10.6 for males and 11.1 for females in southern Germany. There were striking differences in the clinical characteristics of CMMs, with significantly higher tumour thickness in Crete (median 1.4 mm vs. 0.7 mm in southern Germany). Correspondingly, significantly more nodular melanomas were observed in Crete (29%) as compared with southern Germany (11%). CONCLUSIONS: Incidence of CMM in Crete, with about four cases per 100 000 inhabitants per year, is clearly higher than previously estimated, and there is an urgent necessity for earlier recognition of CMM in Crete. However, the incidence of CMM in southern Germany is much higher.
Abstract: Melanocytic nevi are recognized as precursors of melanoma. Aiding in early recognition of melanoma, we estimated color texture parameters, fractal dimension and lacunarity of melanoma and other melanocytic nevi. Digital images of the lesions were processed. Graphic three-dimensional pseudoelevation images of the lesions and surrounding skin were produced to identify irregularities in color texture within the lesions. Estimation of lacunarity and fractal dimension followed in order to produce a numerical estimate of the coarseness of color texture. Clinicians readily perceive the resulting "geographical" images. Irregularity in the anaglyph, which might veil malignancy, is effortlessly identified through these images, and therefore an early excision of a suspect lesion is indicated.
Abstract: 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 Bonferroni 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.
Abstract: BACKGROUND: Onychomycosis represents the most frequently encountered nail disease, which is difficult to eradicate with drug treatment. Epidemiological studies concerning onychomycosis have been performed in many countries worldwide. Differences in the incidence of onychomycosis have been reported not only for various geographical areas, but also for different regions of the same country. OBJECTIVE: This survey was undertaken to determine the epidemiology of onychomycosis in the population of Crete, Greece. METHODS: In a prospective study, the fingernails and toenails of all new patients presenting to the outpatient Dermatology Department of the University Hospital of Crete were examined by certified dermatologists. If they appeared abnormal, nail material was obtained for mycologic examination. RESULTS: A total of 23,477 patients were examined during the study period (1992-2001). Of them, 19,556 (83.3%) participated in the investigation. Clinical abnormal nails were observed in 2098 (10.7%) patients, 36.7% males and 63.3% females. Mycologically confirmed onychomycosis was detected in 511 (24.3%). Toenail onychomycosis was found in 283 (55.4%) patients, fingernail onychomycosis in 210 (41%), and both toenail and fingernail onychomycosis in 18 (3.6%). In the toenail infections, dermatophytes were most frequently isolated (52%), followed by yeasts (24.7%) and moulds (15.5%); 7.8% of the infections were mixed. In the fingernail infections, yeasts were most often isolated (82.9%), followed by dermatophytes (10%), and moulds (1.9%); 5.2% of the infections were mixed. CONCLUSION: Because the pattern of onychomycoses in a country is changing with time, epidemiological studies are necessary for determining the prevalence and the causative agents of the infection.
Abstract: 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. METHODS: Digital images of 132 melanocytic skin lesions (23 melanomas and 109 melanocytic nevi) were studied in features of geometry, color, and color texture. A total of 43 variables were studied for all lesions, e.g., geometry, color texture, sharpness of border, and color variables. Univariate logistic regression analysis followed by "-2 log likelihood" test and Spearman's rank correlation coefficient were used to eliminate inappropriate variables, as the presence of multi-collinearity among variables could cause severe problems in any stepwise variable selection method. Initially, "-2 log likelihood" and nonparametric Spearman's rho picked five variables to be included in a multivariate model of prediction. The five-variable model was then reduced to three variables and the performance of each model was tested. The "jackknife" method was performed in order to validate the model with the three variables and its accuracy was weighed vs. the five-variable model by receiver-operating characteristics (ROC) curve plotting. It was concluded that the reduced model did not compromise discriminatory power. RESULTS: Not all variables contributed much to the model, therefore they were progressively eliminated and the model was finally reduced to three covariates of significance. A predictive equation was calculated, incorporating parameters of geometry, color, and color texture as independent covariates for the prediction of melanoma. The proposed model provides melanoma probability with a 60.9% sensitivity and 95.4% specificity of prediction, an overall accuracy of 89.4% (probability level 0.5), and 8% false-negative results. CONCLUSIONS: Through a digital image processing system and the development of a mathematical model of prediction, discrimination between melanomas and melanocytic nevi seems feasible with a high rate of accuracy using multivariate logistic regression analysis. The proposed model is an alternative method to aid in early melanoma diagnosis. Expensive and sophisticated equipment is not required and it can be easily implemented in a reasonably priced portable programmable computer, in order to predict previously undiagnosed skin melanoma before histopathology results confirm diagnosis.
Abstract: BACKGROUND: Erysipelas is a bacterial infection of the dermis and hypodermis, mostly of streptococcal origin. Bullous erysipelas represents a severe form of the disease. OBJECTIVE: To evaluate the clinical and microbiological characteristics and treatment of bullous erysipelas. METHODS: Patients with a diagnosis of bullous erysipelas who were treated at the Department of Dermatology, University Hospital of Heraklion, Crete, Greece, between the years 1996 and 2001 were retrospectively studied. RESULTS: Fourteen patients (11 women, 3 men) with bullous erysipelas were evaluated. The lesions were located on the legs and face in 9 and 4 patients, respectively. The median duration of disease before hospital admission was 4 days. Eight patients had fever at presentation. Local trauma and various lesions were common causes for pathogen entry. The initial empirical antibiotic treatment included intravenous beta-lactams and was modified according to the sensitivities of the isolated strains. Staphylococcus aureus was isolated from 7 (50%), while S. warneri, Streptococcus pyogenes and Escherichia coli grew from the lesions of 3 other patients. Six out of 7 S. aureus strains were methicillin resistant (MRSA) but susceptible to several other non-beta-lactam antibiotics such as quinolones, vancomycin, rifampicin and trimethoprim/sulfamethoxazole. CONCLUSION: Our findings suggest that S. aureus is frequently involved in and probably contributes in synergy with beta-hemolytic streptococci to the complicated course of bullous erysipelas. The frequency of MRSA isolation suggests that beta-lactam antibiotics may not be sufficient for the treatment of bullous erysipelas anymore, at least in areas with a high incidence of MRSA strains. The role of other classes of antibiotics providing adequate coverage for MRSA has to be evaluated in prospective clinical trials.
Abstract: BACKGROUND: In 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. METHODS: All 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. RESULTS: A 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. CONCLUSION: Allergic 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.
Abstract: BACKGROUND: Tumour necrosis factor (TNF)-alpha blockade using infliximab, a chimeric anti-TNF-alpha antibody, is an effective treatment for plaque-type psoriasis, inducing remission in about 80% of patients. OBJECTIVES: To examine infliximab-induced programmed cell death (PCD) of keratinocytes in psoriatic plaques on serial skin biopsy samples. METHODS: Five patients with moderate to severe plaque-type psoriasis received infliximab infusions intravenously (5 mg kg(-1)) at weeks 0, 2 and 6. Biopsies of nonlesional and lesional skin (days 0, 5, 14 and 21) were obtained. Conventional microscopy was used to examine the morphology of the psoriatic keratinocytes. In situ detection of apoptosis was performed by electron microscopy and by immunohistochemical staining with anti-p53 and anti-caspase-3 antibodies. Results Infusion of infliximab induced a clinical response in all five patients with psoriasis, with a mean Psoriasis Area and Severity Index improvement of 24.8% already at day 5. This was accompanied by significant histopathological changes in the skin biopsy samples after infliximab treatment. Light and electron microscopic evaluation revealed apoptosis-like morphological changes in lesional keratinocytes, i.e. nuclear condensation, chromatin fragmentation and cytoplasmic vesiculation, visible already after the first infusion. These damaged keratinocytes stained positively for p53, but not for active caspase-3. CONCLUSIONS: The effects of infliximab in psoriasis extend beyond merely anti-inflammatory actions, and may include caspase-independent PCD of lesional keratinocytes. The PCD of keratinocytes may be an important mechanism that could explain at least in part the rapid and sustained therapeutic effect of infliximab in psoriasis.
Abstract: Scleredema adultorum is a rare sclerotic disorder characterized by diffuse swelling and nonpitting induration of the skin. Its occurrence has been documented in association with infections, diabetes mellitus, paraproteinemia, multiple myeloma, and monoclonal gammopathy. We report an unusual case of a 48-year-old man with an asymptomatic bilateral eyelid edema of sudden onset. During a period of 6 months, the condition slowly progressed to extensive nonpitting edematous swelling restricted to the periorbital sites. The presumptive diagnosis of scleredema adultorum was confirmed by the presence of typical histologic findings. This case is unique in that the periorbital swelling remained as the sole clinical manifestation of scleredema during the 5-year follow-up and was complicated with partial vision blockage.
Abstract: We report a case of cutaneous alternariosis in a 69-year-old male patient. During hospitalization for treatment of the skin disorder, acute myeloid leukaemia was diagnosed. He received multiple chemotherapeutic agents but the leukaemia remained refractory to therapy and the patient died. The clinical picture, diagnosis and treatment of cutaneous alternariosis will be discussed and a review of the literature regarding patients with haematological diseases will be given.
Abstract: The aim of this study was to reveal differences in the epidemiology and to identify significant risk factors for cutaneous melanoma (CM) in a relatively dark-skinned, chronically sun-exposed Caucasian population. This group is considered to have a low risk for this tumour. One hundred and ten newly diagnosed patients with primary CM and 110 age- and gender-matched controls, all of Cretan origin, were interviewed and underwent a complete skin examination. Solar keratoses odds ratio (OR) 6.2 and lentigines (OR 2.2), common and atypical naevi (OR 5.4 and 3.0, respectively), blonde or red hair colour (OR 3.1), skin phototypes I/II (OR 1.8), as well as total sun exposure (weeks per year) (OR 1.03), were all significantly associated with CM risk in a multivariate logistic regression analysis. In the relatively dark-skinned Cretan population, sun exposure indices represent the most important risk markers for CM which contrasts with data from fair-skinned Caucasian populations where melanocytic naevi are the main risk factors.
Abstract: We report a case of Netherton syndrome manifested as congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy, who in early adulthood developed multiple, aggressive epithelial neoplasms in sun-exposed areas of the skin, in areas with papillomatous skin hyperplasia and at the left parotid region. The occurrence of cutaneous neoplasia has been reported in syndromes with congenital ichthyosis and suggests that the underlying genetic defects may cause the development of cancer in prone patients.
Abstract: 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. OBJECTIVES: To investigate in vivo the PpIX fluorescence time course after topical application of ALA in order to determine the optimal time for irradiation, and to assess the efficacy of subsequently performed ALA-PDT. METHODS: Fluorescence kinetics was studied in 12 male patients with condylomata acuminata. Confirmation of diagnosis was established with conventional histology and polymerase chain reaction. Lesions were treated with 20% ALA and irradiated at the optimal time with a dose of 70 J cm-2 or 100 J cm-2 light. An additional session with 100 J cm-2 was administered 1 week later to lesions that persisted. RESULTS: The in vivo study of fluorescence kinetics indicated that the optimal time for irradiation varied among patients from 6 to 11 h. The overall cure rate was 72.9%, 12 months after treatment. CONCLUSIONS: Topical ALA-PDT is a potentially effective treatment for condylomata acuminata.
Abstract: The aim of this work was to present an efficient and objective method of wound healing assessment based on serial measurements of ulcer dimensions and calculation of wound margin advancement towards the center of the lesion. The method is implemented via computer software, which permits clinicians to perform necessary computations. The proposed method of wound assessment integrates pieces of work that have been published in the past into a user-friendly environment. The high accuracy of computations may help clinicians to make objective decisions in the management of difficult to heal ulcers.
Abstract: BACKGROUND: Milia en plaque (MEP) is an unusual entity with a distinctive clinicohistologic appearance. Optimal treatment is unestablished, particularly for MEP located on difficult anatomic areas. OBJECTIVE: To illustrate by a case report the clinical presentation and management of MEP. METHODS: A 35-year-old woman with numerous tiny cysts within an slightly erythematous base in unilateral periorbital distribution is described. Histology revealed epidermal cysts arranged within the entire dermis. RESULTS: Treatment with chemical exfoliating agents, manual extraction, and topical photodynamic therapy resulted in partial improvement. CONCLUSION: Dermatologists should become familiar with this peculiar condition, being significantly rare possibly because of underreporting or misdiagnosis. New treatment procedures must be tried to achieve a successful cosmetic result with minimal risks.
Abstract: Human papilloma virus infection is increasing at an alarming rate. The ability of the virus to establish a subclinical infection and its association with malignancy of the lower genital tract make the statistics even more worrisome. Topical application of acetic acid solution provokes temporal alterations of the light-scattering properties of human papilloma virus-induced lesions of anogenital area. For the in vivo study of the phenomenon, an imaging system has been employed, which performs time-lapse imaging and enables the calculation and display of the kinetics of the provoked alterations in any point within the examined area. Confirmation of diagnosis has been established with conventional histology and polymerase chain reaction. It has been shown that the method provides early detection and staging of skin alteration or transformation due to human papilloma virus infection and enables mapping of the infected area.
Abstract: Photodynamic therapy (PDT) with topical d-aminolevulinic acid (ALA) has become a therapeutic option of growing interest for superficial non-melanoma precancerous and malignant lesions. After application of ALA, in situ conversion to endogenous porphyrins is accomplished in a gradual manner. Therefore, the determination of fluorescence kinetics and spatial distribution in vivo versus time is a crucial point for the success of ALA-PDT. Seventeen basal cell carcinomas (BCC) and 20 actinic keratoses (AK) were enrolled in this study. In 5 BCC and 4 AK, in vivo fluorescence kinetics were performed over 24 hrs and for the remaining lesions between 2 and 7 hrs after ALA application. In vivo spatial and quantitative detection of the fluorescence intensity versus time showed considerable variations among tumors of the same type, so light irradiation was performed according to patient individualities. Both BCC and AK showed maximal median fluorescence intensity at 4-6.5 hrs post-application. In the present study, a high cure rate was proven after topical ALA-PDT (70.6% in BCC and 85% in AK). The results of fluorescence studies suggest that optimum irradiation time for BCC is approximately 3.5-5 hrs and for AK 5 hrs after ALA application, when relative maximal fluorescence intensity in correlation with fluorescence selectivity on the lesion, is obtained.
Abstract: A 78-year-old farmer presented with symptomless skin lesions for evaluation. Two years prior, he had developed idiopathic pulmonary fibrosis (IPF) and had been treated thereafter with oral prednisolone 20 mg/day and occasionally with colchicine 1 mg/day. On examination, erythematoviolaceous, slightly infiltrated plaques, measuring approximately 5 x 9 cm, rubbery in consistency, intermingled with pustules, sometimes eroded, with distinctive borders, were noted on the dorsum of both hands and on the extensor surface of both forearms. The lesions had developed over a 20-day period. The skin of these areas was atrophic or eroded with multiple ecchymoses (Fig. 1). The abnormal laboratory findings included an elevated white blood cell count of 17,100/mm3, with 79% neutrophils, 16% lymphocytes, and 5% monocytes, C-reactive protein of 33.15 mg/dL (normal, <0.8 mg/dL), and immunoglobulin G of 598 mg/dL (normal, 701-1545 mg/dL). Other blood and urine tests performed were within normal limits. The diagnosis of IPF was reconfirmed through radiology, high-resolution computed tomography, and spirometry, as well as bronchoscopy and bronchoalveolar lavage fluid analysis. Coexistence of presumptive pulmonary alternariosis was excluded. Hematoxylin and eosin stained sections of the excised cutaneous specimen showed focal ulceration of the epidermis adjacent to a mainly intradermal abscess cavity. Within the latter, remnants of a partly destroyed hair follicle were seen amongst degenerating polymorphonuclear leukocytes, as well as many histiocytes and a few Langhans-type multinucleated giant cells. Minute collections of polymorphonuclear leukocytes were seen in the adjacent epidermis. Periodic acid-Schiff (PAS) and Gomori's silver methenamine stains showed a multitude of broad branching fungal hyphae and large spores within the aforementioned cavity, both free and within the cytoplasm of giant cells (Fig. 2). Immunohistochemistry was performed by means of the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Sections showed that the infiltrate consisted of an almost equal number of B and T lymphocytes, whereas histiocytes and the few giant cells were labeled with anti-CD68 antibodies. Skin smears and biopsy specimens taken twice from all lesions were used for mycologic examination. Wet mounts revealed numerous, brownish, septate hyphae and ovoid Skin smears and biopsy specimens taken twice from all lesions were used for mycologic examination. Wet mounts revealed numerous, brownish, septate hyphae and ovoid structures. Biopsy material was plated on Sabourand's dextrose agar with cloramphenicol (0.05 mg/mL). After 7 days at 27 degrees C, dark, gray-white colonies with a dark brown underside appeared. Microscopic examination of the colonies revealed hyphae with typical conidia having transverse and longitudinal septa. Based on macroscopic and microscopic examination, the isolates were identified as Alternaria alternata (Fig. 3). Treatment with prednisolone was reduced to 10 mg/day and the patient received oral itraconazole (200 mg/day). This resulted in progressive improvement of alternariosis, and the lesions healed completely within 3 months, when treatment was interrupted. Two years later, there is no evidence of recurrence.
Abstract: 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.
Abstract: In this article we present a method for the objective assessment and monitoring of tissue blood supply using a specially developed endoscopic imaging colorimeter that enables quantitative color modeling of the back-scattered light during endoscopic examination. Tissue blood volume changes in the nasal mucosa, induced by xylometazoline hydrochloride nasal spray, were evaluated with this method. It was found that quantitative imaging provides sensitive, reproducible, and reliable means for the monitoring and mapping of tissue blood supply and is easy to use routinely. The results showed that saturation decreases with time, being the most sensitive color parameter to the vasoconstriction procedure. It appears that objective indexes for optical tissue characterization and analysis may be promising in the understanding of the pathophysiology of tissue changes and in the objective evaluation of their response to different therapeutic schemes.
Abstract: BACKGROUND: Few studies of prospectively collected data regarding the natural course of bullous pemphigoid have been performed. METHODS: The following factors were combined both quantitatively and qualitatively to obtain results: gender, clinical activity based on the estimation of the body area involvement, disease duration, relapses, coexistence with other disease states, and serology Twenty-seven consecutive patients were followed up for 1 year. RESULTS: Most disease activity (85.2%) is exhibited in the first year after onset. There is a lack of parameters with clear predictive significance. The extent and severity of skin involvement are equally distributed between the sexes and not affected by the disease duration. The generalized form of the disease is predominant (86.5%). The average clinical activity in relapses within the year of follow-up is 48% of the initially observed attack. The probability for recurrence is higher in seropositive patients (overall 37%). Coexistence with other disease states seems to be a random chance event. CONCLUSIONS: The lack of parameters with predictive importance underlines the necessity of a thorough follow-up to prevent treatment-related complications in elderly patients.
Abstract: BACKGROUND: During the last 20 years, few prospective studies on the natural course of pemphigus vulgaris (PV) have been performed. METHODS: Various correlations of disease duration, clinical activity fluctuations, serology, and coexistence with other disease states were analyzed with regard to their impact upon the natural history of pemphigus. Thirty-seven consecutive PV patients were involved in this 1-year retrospective follow-up study. RESULTS: The disease activity decreases with time, but when exacerbated it is of unpredictable intensity; skin involvement is equally distributed between the sexes; relapses occur mostly during the first 2 years after disease onset, and can be marginally predicted by autoantibody titers. CONCLUSIONS: Notice should be taken of the relative frequencies of PV associated with neoplasia, ionizing radiation, and familial occurrence.
Abstract: Amicrobial pustulosis (AP) is a recently defined entity associated with connective tissue diseases. Few cases have appeared in the literature. We report a case of AP coexisting with a systemic lupus erythematosus-scleroderma overlap syndrome and marked photosensitivity. The patient presented prominent pustular skin lesions and a few discoid lupus ones. No significant differences in the inflammatory infiltrate were found between the two clinical variants. The infiltrate consisted mainly of CD4+ lymphocytes and many neutrophils. CD1a+ dendritic cells were few in both epidermis and dermis. AP introduces a potential source of diagnostic confusion, but increasing experience of this syndrome will improve the awareness and diagnostic potential among dermatologists.
Abstract: BACKGROUND: Photodynamic therapy with delta-aminolevulinic acid is a promising alternative treatment for superficial skin malignancies. OBJECTIVE: Further clinical experience, study of tissue alterations leading to recovery, and correlation/prediction of the therapeutic response through in vivo skin color changes as represented by erythema development. METHODS: The therapeutic procedure, sequential histology and histochemistry, and the development of a remote machine vision system to measure, map, and monitor the erythema development. RESULTS/CONCLUSIONS: A high cure response rate with adequate follow-up was shown. A significant correlation of the clinical-histologic response of tumors subjected to treatment with the erythema measurements implies that erythema inspection and quantitative analysis offer a reliable predictor of the therapeutic outcome and a clue for optimization of this treatment modality.
Abstract: BACKGROUND: The finite element analysis (FEA) is a recently introduced method in biomechanics that permits modeling of complex structures considering them as an aggregate of small elements. Skin flaps are highly suggested to be amenable to the continuum mechanic laws that underly the development of FEA. OBJECTIVE: A combination of "large deformation analysis," based on FEA with the criteria for skin flap selection, was attempted. METHODS: Serial defects were experimentally created on piglet skin stripes, which were consequently covered through designing appropriate flaps. Skin samples were modeled after the development of a computer FEA program and they were scanned by incorporating their photographs. RESULTS AND CONCLUSION: On the graphic interfaces the flap movement, the closure of the defect, and the whole deformation were found to match with the skin stripe postincisional alterations. This work permits the prediction and offers planning guides for different skin reconstructions.
Abstract: BACKGROUND AND DESIGN: Sunlight and air temperature are environmental parameters with considerable influence upon autoimmunity. Their impact on idiopathic bullous pemphigoid (BP) was studied 1) in a prospective series of 27 patients with regard to clinical activity and 2) in a retrospective series of 232 cases during a 7-year period with regard to immunoserology. RESULTS: Skin involvement and the onset of disease showed an immediate and cumulative pattern of response to sunlight and air temperature. Immunoserologic analysis showed a strong correlation of autoantibody expressivity with these two environmental measurements. CONCLUSIONS: This study verifies previous sporadic clinical and experimental data concerning the influence of environmental factors on BP. Accordingly, preventive measures against exposure to sunlight and high temperature are recommended.
Abstract: In 30 male patients suffering from recurrent condylomata acuminata, immediate hypersensitivity parameters (total IgE, PTT and prick tests) and delayed hypersensitivity against seven recall antigens (multi test) were studied. Thirty healthy male volunteers, matched in age, were the controls. Significantly higher immediate hypersensitivity activity was shown in the patient group. Qualitative evaluation of delayed type hypersensitivity showed that controls had a positive test 16 times more often than patients. A rather homogeneous suppression of delayed type hypersensitivity was found in the patient group mainly as regards the presumably most common antigens vs. the control group. This suppression was proved to be related to disease duration. The hypothesis of a CD4+ Th-2 lymphocyte predominance in recurrent condylomata, owed to longstanding or repetitive antigenic stimulation seems to adequately explain the findings of the present study.
Abstract: BACKGROUND: Histoid leprosy is a rare form of multibacillary leprosy as the result of secondary or even primary resistance to dapsone. The etiopathogenesis has not been clarified up to now. METHODS: An immunohistochemical study was carried out for the expression of various markers on epidermal and dermal cell populations using sections of frozen skin specimens from 5 patients with histoid leprosy as compared to specimens from 7 tuberculoid and 7 lepromatous patients. RESULTS: Dendritic epidermal cells, identified by monoclonal antibodies against CD1, HLA-DR, CD45, and CD36, were found reduced in histoid leprosy as compared to both tuberculoid and lepromatous groups. A gradual reduction of keratinocytic HLA-DR expression from tuberculoid to lepromatous to histoid leprosy was observed. The pattern of CD36, CD4, and CD8 expression of lymphomonocytic cells in the dermis of histoid lesions was similar to that of tuberculoid leprosy, but without the formation of an organized granuloma. CD45+ cells as well as activated lymphocytic cells, expressed by the activation immunophenotype (CD1, HLA-DR, CD25, CD71, EGF-R) were found frequently in all groups. CONCLUSIONS: The in situ immunohistochemical findings support a modified hypersensitivity reaction of the cellular type that results in an inhibition of the lesional expansion, but not in the destruction of the bacilli within the histoid lesion.
Abstract: BACKGROUND: Pemphigus vulgaris is an autoimmune disorder, in which environmental factors seem to play a role, both in the pathogenesis and the activity of the disease. The purpose of the study was to correlate the biologic activity of pemphigus vulgaris with sun exposure and air temperature. METHODS: An epidemiologic study was carried out, analyzing results of serology, skin involvement, and proportional morbidity rates, related to sun exposure and air temperature. The study was based on retrospective and prospective series of patients. All data were evaluated in a yearly seasonal distribution. RESULTS: Strong correlations were shown between climatologic data and pemphigus activity in the populations studied. CONCLUSIONS: Environmental factors have a significant impact on the disease expression. This stresses the necessity of preventive measures against exposure to sun and high temperature.
Abstract: DNA samples from recurrent condylomata acuminata biopsies of Greek males and females were examined for the presence of human papillomavirus (HPV) DNA using high-stringency Southern blot hybridization analysis. Of the twenty-six biopsies, 25 were positive for the HPV 6/11-related DNA sequences, and when further analyzed with the polymerase chain reaction (PCR) the HPV-negative biopsy was also positive for HPV 6/11 DNA. Nineteen specimens were further characterized based on their Pstl restriction endonuclease hybridization pattern. Twelve biopsies were positive for HPV 6a, one biopsy was positive for HPV 11a, and one biopsy was positive for HPV 6c DNA. Three specimens contained HPV 6/11 related DNA that gave an unusual Pstl pattern, and one specimen appeared to represent a multiple HPV infection containing HPV 6/11- and HPV 31/35/39-related sequences. Finally, one sample contained a mixture of HPV 6a DNA and an HPV 6a-like genome. Biopsies were also taken from adjacent apparently normal tissue, 0.5 cm away from the lesion, in 19 of the patients. Only one of these was found to be positive for HPV 6a DNA by Southern blot analysis.
Abstract: 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 Sezary's 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.
Abstract: Physical properties of hematoporphyrin-enriched collagen gels relevant to the photodynamic treatment of cancer are characterized. The incorporation of the sensitizer within the gels does not affect either the structure of the gel or the absorption and fluorescence spectra of the sensitizer. The gel-embedded sensitizer photodegrades efficiently with the formation of a product emitting near 635 nm. Differences in the collagen scattering are observed following sensitization vs. prolonged irradiation with Ar+ laser, indicating contrasting structural modifications effected to the biopolymer matrix in the two cases. The results correspond well to in vivo observations, suggesting that hematoporphyrin-enriched collagen gels may be appropriate systems for modeling the influence of the semisolid nature of tissues, and in particular of the tumour stroma collagen, on the photodynamic phenomenon.
Abstract: The state of polymerization of actin and the organization of actin filaments is widely believed to be related to cellular transformation. Since the intracellular monomer (G) and filamentous (F) actin content reflects the state of microfilament polymerization, we measured the G/total actin ratio in primary cultures of normal and malignant human keratinocytes. In normal keratinocytes the mean value of this ratio was 0.30 +/- 0.03 (mean +/- SE, n = 15), while in basal cell carcinoma (BCC) keratinocytes it was 0.49 +/- 0.03 (n = 8) and in squamous cell carcinoma keratinocytes (SCC) 0.5 +/- 0.07 (n = 4), indicating a 1.7-fold increase of the G/total actin ratio in malignant cells. These results imply that the proportion of polymerized actin is decreased markedly in malignant keratinocytes, suggesting alterations of microfilament structures which probably occur during the transformation process. This was supported by the morphological changes of microfilament structures as assessed by fluorescence microscopy. A different distribution of actin filaments in normal and malignant cells became evident; stress-fibres were converging in patches at several points in SCC cells, when compared to normal keratinocytes. Furthermore, incubation of normal and malignant keratinocytes with cytochalasin B indicated differences in the resistance of their microfilament networks. After 1 h exposure to 10(-6) and 10(-5) M cytochalasin B, microfilaments in normal cells appeared to be less affected than their counterparts in neoplastic cells. Even in a high excess of cytochalasin B (10(-4) M), normal keratinocytes preserved their shape, while both basal cell and SCC were totally disrupted.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Thirty four sera from: 12 patients with Systemic Lupus Erythematosus (SLE), 9 with Subacute Cutaneous Lupus Erythematosus (SCLE) and 13 with Discoid Lupus Erythematosus (DLE) (disseminatus 3, localised 10) were tested for the presence of: (a) anti-thyroglobulin and anti-microsomal autoantibodies (b) anti-Sm/RNP, anti-doublestranded. DNA (anti-ds. DNA), anti-single-Stranded. DNA (anti-ss. DNA), anti-cardiolipin (anti-Cl), anti-SSA, anti-SSB, Antinuclear Antibodies (ANA). T3, T4, TSH levels were also determined. Five patients with SLE (41.6%), 4 with SCLE (44.4%), and 2 with DLE (15.3%) had thyroid autoantibodies and only three of the 41 controls (7.3%). Five patients (14.7%), especially from SLE and SCLE groups, had biochemical hypothyroidism whereas only one had hyperthyroidism. Statistical evaluation for the possible coexistence of thyroid autoantibodies with a panel of lupus characteristic autoantibodies, revealed highly significant correlations with anti-Sm/RNP, IgG (p = 0.003) and anti-ds. DNA, IgM (p = 0.012). It may be concluded, that not only SLE but also SCLE predisposes to autoimmune thyroid disease and the prevalence of the latter is related to a great extent to the subset of the LE spectrum. From these results and from the inhibition experiments, it seems that some of the specific mono- or polyclonal autoantibodies may be multiple organ reactive.
Abstract: The serum levels of soluble interleukin 2 receptor (SIL-2R) and tumor necrosis factor (TNF) were assessed in 69 children from 6 months to 14 years old who suffered from acute lymphoblastic leukemia (39), Hodgkin's disease (15), non-Hodgkin's lymphoma (15) and in 54 normal age-matched controls prior to any therapy and at remission. Both SIL-2R and TNF levels were significantly higher at diagnosis compared with normal controls (P < 0.001), but decreased significantly at remission. The SIL-2R and TNF levels were significantly higher in an advanced stage of lymphoma than in an early stage. In the patients with acute lymphoblastic leukemia (ALL) and lymphoma, higher levels of SIL-2R (> 1030 units/ml) and TNF (> 30 pg/ml) were associated with a poorer treatment outcome (P < 0.01). Our findings indicate that elevated TNF serum secretion together with SIL-2R are useful markers in childhood ALL and lymphoma and can be used to assess both disease activity and prognosis in this group of malignancies.
Abstract: Immunological responses to a panel of antigens were evaluated in 27 patients with lepromatous and 20 patients with tuberculoid leprosy and compared with 24 pulmonary tuberculosis patients, 25 systemic lupus erythematosus patients and 41 healthy blood donors. Some autoantibody specificities were extensively studied for the first time in mycobacterial infections. Striking immunoserological abnormalities were found in patients with lepromatous leprosy, particularly in those presenting with relapse. Inhibition assays were performed, providing a tool for further analysis of the binding range of specific anti-N.D.O. BSA antibodies and strengthening the suggestion of molecular mimicry reactions between cytoskeletal proteins, host stress proteins and Mycobacterium leprae antigens or stress proteins. A significant serological overlap between lepromatous leprosy and autoimmune diseases is indicated.
Abstract: We have examined various autoimmunity parameters in AIDS with special emphasis on the expression of pemphigus and bullous pemphigoid antibodies. Sera from healthy seropositive individuals without syphilis (CS-, n = 17), seropositive individuals with syphilis (cs+, n = 11), and patients with AIDS (n = 6) were studied and compared with normal controls (n = 30); autoimmunity parameters related to dermatology were evaluated. Indirect immunofluorescence (IIF) for pemphigus and pemphigoid antibodies, antinuclear antibodies (ANA), anti-DNA antibodies, antismooth muscle antibodies (ASMA) antimitochondrial antibodies (AMA), and antithyroid antibodies (ATA) was carried out and findings were graded with a cumulative index (CI) for each patient group. Pemphigus and bullous pemphigoid-like antibodies (IgG, PV + BP) were detected in 33% of the AIDS patients. Statistically increased CI (P less than 0.01) was found in the CS- group compared with the CS+ group and in the AIDS group compared with CS- (P less than 0.01).
Abstract: A 53-year-old female patient with pemphigus vulgaris under continuous immunosuppressive therapy for about 2 years presented a superficial spreading malignant melanoma on a pre-existing melanocytic naevus. After surgical removal of the inguinal lymph node group, a diffuse low-grade polymorphous immunocytoma was proved both histologically and immunocytochemically. The possible induction mechanisms are discussed.
Abstract: In the present work, we studied the expression of the c-myc oncoprotein p-62 and the ras oncoprotein p-21 in the dermal cellular infiltrate of paraffin embedded skin specimens, obtained from patients suffering from Mycosis Fungoides and Sezary syndrome. Nineteen specimens from early stage Mycosis Fungoides, nineteen from advanced stage Mycosis Fungoides and four from Sezary syndrome were included in the study. The oncoprotein detection was achieved immunohistochemically, using the mouse monoclonal antibody myc 1-9E10 and the rat monoclonal antibody Y13-259 for p-62 and p-21 respectively. Increased detection of both p-62 and p-21 in atypic lymphoid cells was shown in advanced stages of Mycosis Fungoides (third stage plaques and tumors) as compared to early stages (premycotic erythema, second stage plaques). In advanced stages, however, the percentage of P-62+ atypic cells proved to be higher than that of p-21+ atypic lymphoid cells. The implication of increased p-62 and p-21 oncoprotein expression in the process of lymphomagenesis in cutaneous T-cell lymphomas is discussed.
Abstract: In the present work, we have attempted to pay special attention to epidermal and dermal cellular events in Mycosis fungoides (MF). In the epidermis, the two dendritic cell populations, CD1+ and OKM5+, HLe-1+, the adhesion molecules OKM5 and DR on the surface of epidermal cells (Ecs), and cytoskeletal proteins were studied. CD1+ dendritic epidermal cells were generally more abundant than OKM5+, HLe-1+ ones with no interrelationship in their presence. OKM5+, HLe-1+ dendritic cells prevailed in the second stage plaques. The staining pattern with anti-spectrin polyclonal antibody gradually presented increased intensity from Pre-MF to tumor stage. The activation-proliferation related immunophenotype was also examined, as well as other useful markers, in an attempt to correlate their presence in different stages of MF. Special emphasis was given to the staining pattern with the epidermal growth factor receptor (EGF-R) monoclonal antibody against three targets: epidermal, endothelial, and lymphoid cells. The presence of Ki-67 proliferation marker in suprabasal epidermal layers and lymphoid cells in the dermal infiltrate was also of interest.
Abstract: In a five year period 73 cases of pemphigus vulgaris (PV) and 94 of bullous pemphigoid (BP) were studied to investigate important parameters for these diseases. From the results it was found that the incidence of PV was higher in women whereas that of BP was almost equal in both sexes. The incidence of PV was highest in the sixth decade but was highest in the eighth decade for BP. Indirect immunofluorescence (IIF) was more sensitive in PV whereas direct immunofluorescence (DIF) was more sensitive in BP. The present study provides a basis for comparison with results of previous or future studies in Greek and other populations.
Abstract: In this work, the incidence of nuchal nevus flammeus was studied in 205 patients suffering from various forms of alopecia areata, as well as in a group of 555 volunteers without alopecia areata examined in our outpatient clinic. The incidence of nuchal nevus flammeus in the totalis-universalis form of alopecia areata was 58.2% (examined patients, n = 79), in ophiasis-extensive forms 22.8% (examined patients, n = 70) and in simple forms of alopecia areata 3.6% (examined patients, n = 56). In the group of 555 volunteers without alopecia areata the incidence of nuchal nevus flammeus was 4.5%. Our results show that nuchal nevus flammeus could be a valuable skin marker indicating a more severe course of alopecia areata.
Abstract: During the topical treatment of 45 patients, who had extensive forms of alopecia areata, with the allergen diphencyprone, 3 of them (6.7%) developed vitiligo. Two were females and 1 male aged 53, 19 and 28 years respectively. None of these patients had a personal or family history of vitiligo. Vitiligo appeared 3-5 months after the onset of treatment and was localized only to the areas of topical application in the younger woman and the man. In the older woman, vitiligo extended to several areas apart from those where the medicament was applied. After the end of diphencyprone treatment, vitiligo had a spontaneous significant improvement only in the man. Mitochondrial autoantibodies were found in the older woman only. To our knowledge, vitiligo due to diphencyprone has not been previously reported.
Abstract: Fourteen patients with allergic cutaneous vasculitis of either the polymorphonuclear (PMN)- or the mononuclear (MN)-predominant type were studied as regards the following parameters: the disease duration, histology, monoclonal antibody typing of the mononuclear cell infiltrate from recent lesions, and the delayed hypersensitivity (DH) response, assessed both by recall antigens (tuberculin type) and the dinitrochlorobenzene skin test. From the results, it was shown that in PMN-predominant vasculitis, DH reactions were well elicited, whereas in MN-predominant vasculitis, DH skin reactions were somehow impaired. In MN-predominant cases, many OKT3+, OKT4+, OKT8+, and OKM1+ cells were usually seen to surround the skin vessels, whereas in PMN-predominant cases, rare OKT8+, OKT4+, or OKM1+ cells were seen in the dermis. The epidermal dendritic cell system, as revealed by the Na(1)34 monoclonal antibody, was unaffected in both types of allergic cutaneous vasculitis.
Abstract: An immunohistological study of skin biopsy specimens from patients with early syphilis was undertaken before and after treatment (one day after intramuscular administration of 2.4 MIU benzathine penicillin and eight days later, after a total administration of 3.6 MIU. In chancres from seronegative patients treatment with 3.6 MIU usually resulted in fewer immunocompetent cells in the infiltrate. In lesions of secondary syphilis treatment with 2.4 MIU benzathine penicillin produced a significant decrease in immunocompetent cells. After treatment with 3.6 MIU there was no further decrease. It was worth noticing that even eight to nine days after the initial pretreatment biopsy, when 3.6 MIU had been administered, the overall lymphohistiocytic infiltrate was not substantially diminished. Significantly more suppressor (T8+) cells were found in lesions of primary syphilis than of secondary syphilis, and they showed remarkable exocytosis. Activated local T8+ cells may release immunosuppressive lymphokines.
Abstract: We have shown that skin surface marking exists on the prickle cell layer after provocation of intra-epidermal vesiculation with a 50% solution of NH4OH.
Abstract: Lesional skin specimens from twenty-eight patients with mycosis fungoides were studied by evaluating immunohistochemical criteria, primarily with monoclonal antibodies. It was demonstrated that significant differences exist between the control and the premycotic-stage group in regard to the monoclonal antibodies BE1, BE2, and OKT9. The detection of specific antigenic determinants on the surface of cell populations early in the course of the disease seems to be of considerable value for the early diagnosis of the disease. Statistically significant differences were found between the premycotic stage and the plaque stage in regard to T lymphocytes, macrophages, OKT6+, OKT4+, OKT8+, and BE2+ cells in the dermal infiltrate. Significant differences were also shown between the plaque and tumorous groups, concerning macrophages, T cells, and OKT9+ cells in the dermis, as well as epidermal dendritic cells. Differences between stages may supplement histologic data for the follow-up of the disease with or without treatment.
Abstract: Two further methods for the characterization of epidermal skin tumors are described: the antinuclear antibody (ANA) immunofluorescent test, which consists of indirect immunofluorescence with known high titer sera containing homogenous ANAs on epidermal skin tumors, and the ammoniacal-silver cytochemical method, which specifically stains nuclear histones. Squamous cell carcinomas (SCCs), basal cell epitheliomas (BCEs) as well as control specimens from normal skin and benign epidermal hyperplasias were studied. The ANA immunofluorescent test was positive for most SCCs, mixed SCC and basal cell carcinomas and metatypical BCEs. The ammoniacal-silver method gave a characteristic staining pattern shared among SCCs, mixed carcinomas and metatypical BCEs. BCEs, besides metatypical ones, were always negative by the ANA immunofluorescent test and the same applied for the control specimens. The ammoniacal-silver method gave a characteristic staining pattern for BCEs and control sections quite different from the staining pattern of the more aggressive forms of epidermal tumors. The two methods usually yielded parallel results.
Abstract: Peripheral blood lymphocytes from 21 patients with aleukaemic stages of mycosis fungoides were studied with monoclonal T cell antibodies. Patients with erythematous eruptions or infiltrated plaques (group I) had a higher percentage of OKT4+ cells than patients with a tumorous stage (group II) or normal subjects (p = 0.05). OKT8+ cells were decreased in group I patients whereas in group II they were usually normal or increased (p less than 0.02). These data indicate that with advancing stage of the disease a different pattern of imbalance of T-cell subsets is being established.
Abstract: In this study, the in situ immunological typing of cell populations in lichen planus was attempted. T lymphocytes and suppressor/cytotoxic subsets, B lymphocytes, macrophages, immunocytes and Langerhans' cells were studied by one or more technical parameters and semiquantitative assessment of T cell populations were carried out. A critical evaluation of assays for T cell characterization was also attempted. T cells were found predominant in lichen planus infiltrate but macrophages were also many. Langerhans' cells were increased in the epidermis compared to normal skin and contact dermatitis.
Abstract: We studied sweat gland distribution, density and activity in thirteen cases of granuloma annulare and ten cases of necrobiosis lipoidica, using a combination of the plastic impression and starch-iodine methods. The pattern of sweat gland disturbance in the two diseases was entirely different. In necrobiosis lipoidica an intense and uniform hypohidrosis was detected throughout the lesion, whereas in granuloma annulare the disturbance followed the morphology of the lesion (the papular border showed complete anhidrosis, whereas the flat central part of the lesion showed only moderate hypohidrosis or normal sweating). The method assigns numerical values to the 'relative density' and the 'relative activity' of the functioning sweat glands compared with normal skin, thus permitting statistical evaluation of the results.
Abstract: In 54 cases of dermatophytosis, sweat gland disturbances and their possible mechanisms were studied. The basic perspiratory malfunction was intense hypohidrosis, with some hyperhidrotic phenomena being observed at particular points of the exanthem (margin and disc) in a few cases. It is worth noting that in 51.85% of the cases, hypohidrotic phenomena were also observed in areas of normal skin adjacent to the lesions. One of the most important forms of perspiratory disturbances was the closure of sweat ducts at the keratin level. The inflammatory process in the dermis may also affect gland function. Finally, there is a discussion of the significance of perspiratory disturbances in relation to special aspects of the disease.
Abstract: In 2 patients with anhidrotic ectodermal dysplasia, we were able to show that the hypoplastic eccrine glandular elements may give rise to normal eccrine glands both anatomically and functionally, after repeated local application of acetylcholine. The perspectives of our findings for the therapeutic management of the anhidrotic ectodermal dysplasia are discussed and special attention is paid to the genetic background of the defect as well as the possible mode of action of acetylcholine.
Abstract: The present study deals with the evaluation of some substrates for the detection of nuclear antibodies by the indirect immunofluorescence method. We have examined white male mouse liver imprint, white female pregnant mouse liver imprint, compound substrate consisting of male mouse liver, kidney and gastric wall sections, skin sections from psoriatic patients, skin sections from squamous cell carcinomata, male rabbit spleen imprint, skin sections from healthy adults people, skin sections from basal cell epitheliomata, skin sections from patients with lichen planus, male mouse spleen imprint and male guinea pig spleen imprint. To evaluate the substrates, we have employed 4 selected sera from patients with collagen disease. It was observed that some types of antinuclear antibodies demonstrate greater affinity for certain substrates and the fluorescent nuclear pattern might change on serial dilutions. From all the substrates studied, the white male mouse liver imprint and the male rabbit spleen imprint were considered as the most efficient for routine purpose as they are both sensitive and easily obtainable.
Abstract: In the present study, the development of pemphigus and bullous pemphigoid antigens was investigated by means of the indirect immunofluorescence technique using sera of pemphigus and bullous pemphigoid patients, respectively, on human foetus skin antigenic substrate. Seventy skin specimens from embryos of 9-38 weeks of gestation were studied. Both pemphigus and bullous pemphigoid antigens were observed for the first time at about 16 weeks of gestation. Pemphigus antigen has a slower rate of evolution. Between 30 and 38 weeks both antigens were detected as strongly positive.
Abstract: Twelve patients with keratoacanthoma were studied to assess the role and importance of immunological factors in tumor regression. Direct immunofluorescence was determined with immunoglobulins, complement (C3), and fibrin to estimate the deposition of these factors in the lesion area. Indirect immunofluorescence was also undertaken using pemphigus and bullous pemphigoid sera against the keratoacanthoma lesion to study the presence or absence of tissue-specific antigens (T.S.A.) in intercellular substance and basement membrane. Finally, the cell-mediated immunity was studied using two in vitro parameters: (a) The estimation of T-lymphocytes through the formation of E-rosettes and (b) the estimation of the leukocyte migration inhibition factor (LIF). Our findings show that specific humoral immune mechanisms are apparently not involved in the spontaneous regression of keratoacanthoma. Cell-mediated immune mechanisms are evidently not responsible for the resolution of the tumor.
Abstract: A case of local hyperhidrosis at the ulnar aspect of the left forearm-carpal region with exacerbation, especially during summer, is presented. The sweat function is normal on the remainder of the body. This case is rare, and few similar cases are known in the literature. The possible pathogenetic mechanisms are discussed.
Abstract: Cutaneous leishmaniasis is a disease endemic in Greece. Cases collected between the years 1975 and 1979 are analyzed from a clinico-epidemiologic point of view. Prevalence is highest in the Ionian islands and Crete. The disease most commonly affects individuals 10 to 20 years of age. The exposed parts of the body are most commonly involved, particularly the face. The period of highest incidence is mid-winter.
Abstract: One hundred tumors of epidermal origin were studied by means of indirect immunofluorescence technique with sera from patients with proven pemphigus and bullous pemphigoid. We found that in tumors of epidermal origin, there was a loss of antigenicity of the intercellular substance and basement membrane; this was minimal for benign tumors, greater for premalignant tumors, and very clear for malignant tumors. We also found a gross correlation between the histologically proven malignancy of squamous cell carcinoma and the grade of antigenic loss; both for the intercellular substances and for the basement membrane antigens. However, this did not yeild definite results in the group with basal cell carcinoma. With regard, especially, to the intercellular substance antigen, it seemed to be completely independent of histologic type of basal cell carcinoma. We found that the duration of the epidermal tumor did not correlate with the percentage of intercellular substance and basement membrane antigenic loss. This suggested that the antigenic loss was an early feature of neoplastic behavior. The deeper parts of the malignant tumors in the dermis showed a lower percentage of antigenicity for both antigens.
Abstract: An immunohistochemical study has been undertaken on 25 biopsy specmens taken from lichen planus lesions, using antisera against human fibrin, immunoglobulins IgG, IgA, IgM and C3 (B1C/B1A) complement component. The findings of the present research are discussed and evaluated in relation to the problem of the etiopathogenesis of the disease.
Abstract: A case is described with features both of Hailey-Hailey and Darier's disease in a male patient who presented skin lesions since he was 8 years old. The present case is discussed in relation to data obtained from the literature, and a differential diagnosis from Grover's disease is made.
Abstract: Sixty-five cases of proved cutaneous Leishmaniasis have been studied on clinical, histological and laboratory grounds. A new histological classification is proposed and emphasis is given to specific histological changes and their correspondence to distinct clinical signs.
