Psoriasis and oral lesions: multicentric study of Oral Mucosa Diseases Italian Group (GIPMO).

OBJECTIVE: This is a multicentric, observational and controlled study designed to verify the existence of a significant association between plaque-type psoriasis and oral lesions, such as geographic tongue and/or fissured tongue. STUDY DESIGN: during a period of 9 months all consecutive patients with plaque-type psoriasis were enrolled using simple nonrandom (sequential) sampling. The control group included healthy subjects presenting to the same Dermatology centers to monitor pigmented skin lesions; the patients were matched for age and sex. All patients were examined for oral lesions. RESULTS: Out of a total of 535 psoriatic patients and 436 control group patients, oral mucosal lesions were detected in 188 (35.1%) and 86 (19.7%) cases, respectively, and the difference is statistically significant. Fissured tongue (FT) and geographic tongue (GT), which were most frequently detected, were seen more frequently in psoriatic patients (FT: 22.6%; GT: 9.1%) than the control group (FT: 10.3%; GT: 5.2%) (p<0.05). CONCLUSIONS: On the basis of the similar studies reported in the literature and the large number of patients involved in our study, we can conclude that FT and GT can be clearly suggested as oral manifestations of plaque-type psoriasis, although the reason for this association is not clear.

Osteopontin, a protein with cytokine-like properties: a possible involvement in pemphigus vulgaris.

Pemphigus is an autoimmune blistering disease characterized by severe and chronic course, histopathologically characterized by infiltration of a large quantity of eosinophils, neutrophils, and activated Th1 and Th2 cells around the blister. Polarization of Th cells to Th1 or Th2 phenotypes, a critical aspect of cell-mediated immunity, is influenced by production of early cytokines, including osteopontin. To determine the involvement of osteopontin in pemphigus vulgaris patients in active stage of the disease, auto-antibodies to desmoglein-1 and desmoglein-3 and plasmatic osteopontin levels were examined by ELISA tests. In this work, significant plasmatic level of osteopontin in PV patients with active stage of disease were found particularly in those patients with both skin and oral pemphigus. OPN might drive the immune responses playing an important role in pemphigus onset.

Tinea capitis mimicking tufted hair folliculitis.

We report a case of tinea capitis mimicking tufted hair folliculitis in a 56-year-old European man, who presented with a 4-year history of pain and erythema in an area of scarring alopecia of the occipital scalp, with scales and tufts of hair emerging from individual follicles. Histological examination showed hair plugging, and a dense perifollicular infiltrate of plasma cells, lymphocytes, and neutrophils. There was widespread scarring and fibrosis. Bacterial cultures were negative for Staphylococcus aureus, but fungal cultures and periodic-acid-Schiff stain were positive for Trichophyton tonsurans. Videodermatoscopy of the lesion showed a pattern consistent with folliculitis decalvans. Diagnosis was made on the basis of the clinical, histological, microbiological and videodermatoscopy data. After 30 days of systemic antifungal treatment, there were a substantial clinical improvement and disappearance of pain. After 5 months, a residual cicatricial area was seen with some hair tufts emerging from a single orifice.

Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells.

Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions. Our previous investigations suggest that keratinocytes play an important role in conditioning the therapeutic effects of the PT in psoriasis. However, peptides are not good therapeutic agents, because they exhibit poor absorption, are easily metabolized and are immunogenic. Using computational methods, the natural product amygdalin was identified as peptidomimetic of PT. However, amygdalin exhibits a toxic profile due to its cyanide group. To overcome this deleterious effect, we synthesized analogues lacking the cyanide group. Human keratinocytes were treated with PT or with three different peptidomimetics of PT. To study its effects on the expression of HSP-70, TGF-beta, alpha-v integrin, ICAM-1 and cytokines, we analysed the protein levels by Western blot and ELISA. Our results show that the different peptidomimetics of PT tested exhibit a similar biological behaviour in regard to the overexpression of HSP-70, TGF-beta and alpha-v integrin than the native peptide. TNF-alpha is overexpressed by PT and SVT-03018; between the other two analogs, SVT-03016 do not produce any significant change in regard to the control, while SVT-03017 shows only a moderate increase in regard to control. SVT-03018 provokes a remarkable upregulation of IL-10, stronger than SVT-03016, SVT-03017 and PT. All the other three analogues reduce comparably to the PT, the expression of ICAM-1 and do not increase the release of proinflammatory cytokines. The results highlighted that the three analogues of amygdalin with the cyanide group removed exhibit the same biological effects of PT. Therefore, they can be considered peptidomimetics, suggesting their possible use in the treatment of psoriasis.

Kaposi's sarcoma of the tongue associated with median rhomboid glossitis in a non-AIDS patient. A case report.

Kaposi's sarcoma (KS) of the tongue is extremely rare in immunocompetent patients. We report a case of KS of the tongue associated with a median rhomboid glossitis. The main clinical, pathological and immunohistochemical features allowed the differential diagnosis.

Effectiveness of small-volume, intralesional, delayed-release triamcinolone injections in orofacial granulomatosis: a pilot study.

BACKGROUND: Orofacial granulomatosis (OFG) is an idiopathic disorder characterized by chronic orofacial swellings causing significant cosmetic and functional problems. Treatment with high-volume triamcinolone injections has been shown to be effective but requires nerve block anesthesia and causes a dramatic temporary increase of lip swelling. OBJECTIVE: We have performed a noncomparative open-label pilot study in 7 patients with OFG in order to evaluate the effectiveness of small volumes of extended-release high-concentrate triamcinolone injections in reducing lip swelling and preventing recurrences. METHODS: Seven patients with OFG were studied. Small-volume, intralesional, high-concentrate, extended-release triamcinolone was injected on the basis of a weekly schedule. A standard cycle consisted of 2 or 3 injection sessions over 14 or 21 days, depending on the clinical response. RESULTS: After cycle completion, all patients remained without recurrences or with cosmetically acceptable slight lip enlargement for a mean time of 19 months (range, 8-30 months). No side effects were observed, except in one patient with hypopigmentation of the skin of the upper lip. CONCLUSIONS: Slow-volume, intralesional, high-concentrate, extended-release triamcinolone injections appear to be effective in reducing lip enlargement in patients with OFG and do not require nerve block anesthesia or cause a temporary troublesome increase of swelling. A long disease-free period is generally obtained.

Kaposi's sarcoma: aetiopathogenesis, histology and clinical features.

UNLABELLED: Kaposi's sarcoma (KS) represents today one of the most common skin cancers in transplanted Mediterranean subjects and, since the epidemic of human immunodeficiency virus/acquired immune deficiency syndrome, in young unmarried single men. The disease has been associated with the recent identified human herpesvirus (HHV)-8 or KS herpesvirus and its incidence in the general population shows a north to south gradient that parallels the HHV-8 increasing prevalence from Nordic countries to sub-Saharan regions. The identification of the aetiopathogenetic mechanisms (viral agents and immunodeficiency) involved in the pathogenesis of KS, are relevant for identifying susceptible subjects (HHV-8 seropositive subjects), monitoring the immune levels in iatrogenic immune suppressed patients, and developing new therapeutic approaches based on antiviral and immune modulators. LEARNING OBJECTIVE: This article should enable the reader: (i) to learn about the clinical and molecular aspects of KS in order to have a multidisciplinary approach to a tumour that shows unique features; (ii) to consider the role of viral agents and immunity; and (iii) to recognize properties of an opportunistic neoplasm. The identification of the HHV-8 role in KS pathogenesis should establish a relevant tool in the clinical management of KS patients.

Molecular predictors of survival after adjuvant chemotherapy for colon cancer.

BACKGROUND: Adjuvant chemotherapy improves survival among patients with stage III colon cancer, but no reliable molecular predictors of outcome have been identified. METHODS: We evaluated loss of chromosomal material (also called loss of heterozygosity or allelic loss) from chromosomes 18q, 17p, and 8p; cellular levels of p53 and p21(WAF1/CIP1) proteins; and microsatellite instability as molecular markers. We analyzed tumor tissue from 460 patients with stage III and high-risk stage II colon cancer who had been treated with various combinations of adjuvant fluorouracil, leucovorin, and levamisole to determine the ability of these markers to predict survival. RESULTS: Loss of heterozygosity at 18q was present in 155 of 319 cancers (49 percent). High levels of microsatellite instability were found in 62 of 298 tumors (21 percent), and 38 of these 62 tumors (61 percent) had a mutation of the gene for the type II receptor for transforming growth factor beta1 (TGF-beta1). Among patients with microsatellite-stable stage III cancer, five-year overall survival after fluorouracil-based chemotherapy was 74 percent in those whose cancer retained 18q alleles and 50 percent in those with loss of 18q alleles (relative risk of death with loss at 18q, 2.75; 95 percent confidence interval, 1.34 to 5.65; P=0.006). The five-year survival rate among patients whose cancer had high levels of microsatellite instability was 74 percent in the presence of a mutated gene for the type II receptor for TGF-beta1 and 46 percent if the tumor did not have this mutation (relative risk of death, 2.90; 95 percent confidence interval, 1.14 to 7.35; P=0.03). CONCLUSIONS: Retention of 18q alleles in microsatellite-stable cancers and mutation of the gene for the type II receptor for TGF-beta1 in cancers with high levels of microsatellite instability point to a favorable outcome after adjuvant chemotherapy with fluorouracil-based regimens for stage III colon cancer.

Detection of occult melanoma cells in paraffin-embedded histologically negative sentinel lymph nodes using a reverse transcriptase polymerase chain reaction assay.

PURPOSE: Detection of occult metastasis before the development of clinical disease could allow more accurate staging, appropriate follow-up procedures, and adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph node (SLN) has been proposed as a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. In this study, we screened both paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at various stage of disease using a multimarker reverse transcriptase polymerase chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR-positive markers was also evaluated. PATIENTS AND METHODS: Total RNA was obtained from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was performed using tyrosinase and MelanA/MART1 as melanoma-associated markers. Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels. RESULTS: Good sensitivity of the RT-PCR assay on archival tissues was demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded SLNs from 16 MM patients. Significant correlation between the disease stage and marker expression in both PB and SLN samples was observed; the highest value was for patients who were positive for both markers in SLN (P =.006). Progression of disease was significantly associated with the total number of PCR-positive markers in both PB (P =.034) and SLN (P =.001) samples. CONCLUSION: Although sensitivity is lowered by the use of paraffin-embedded specimens, our data indicate that RT-PCR analysis of serial sections from archival SLNs may be helpful in improving detection of occult micrometastases, thus improving staging of patients with melanoma.

Sensitivity and specificity of epiluminescence microscopy: evaluation on a sample of 2731 excised cutaneous pigmented lesions. The Melanoma Cooperative Study.

To evaluate the role of epiluminescence microscopy (ELM) in the differential diagnosis of cutaneous pigmented lesions, and to improve the early diagnosis of cutaneous malignant melanoma (CMM), 15,719 pigmented lesions from 8782 consecutive patients were evaluated using ELM with a hand-held video microscope imaging system (MS 500B Micro-Scopeman, Moritex). Comparison between risk levels as inferred from ELM screening and histology was performed on 2731 surgically excised lesions. ELM sensitivity, specificity, positive and negative predictive values, as well as agreement with histological results for the different subgroups of lesions, were determined. Overall agreement was 87.3% (ranging from 85.1% to 92.2% for melanocytic and non-melanocytic lesions, respectively); sensitivity and specificity were high (values ranging from 87.3% to 96.3% among different subsets of ELM-analysed lesions) and statistically significant (P < 0.0001). ELM screening identified 165 new cases of CMM with a high proportion of lesions (115; 70%) in an early phase of tumour growth (Breslow thickness

Acitretin and treatment of the oral leucoplakias. A model to have an active molecules release.

AIMS: The aim of this study was to investigate the effectiveness of acitretin in a new topical formulation (mucoadhesive two-layer tablets) for the treatment of oral leucoplakias. METHODS: Twenty-one volunteers, 16 men, five women, with oral leucoplakia (histologically diagnosed), were included in this double-blind placebo-controlled study. Patients were randomized in three groups (A, B, C) of seven patients each. Groups A and B received tablets with different in vitro release profiles, and group C subjects (controls) received tablets without acitretin. The acitretin dose was 20 mg/day (two 10 mg tablets daily). Serum aspartate aminotransferase, alanine aminotransferase, cholesterol and triglycerides were evaluated before and after treatment. At the end of therapy the concentrations of acitretin in plasma, saliva and tissue were measured by high-performance liquid chromatography. RESULTS: At the end of the study 71% (groups A and B) of patients showed clinical remission or marked improvement. No improvement was noted in the control subjects (group C). These results were further confirmed by histological findings. There were no significant changes in laboratory values in the three groups. The acitretin concentration in plasma and tissue ranged from 0 to 50 mg with no difference between groups A and B, and it was very high in saliva (ranging from 4.9 to 43 mg) with higher concentrations in group A than in group B (due to a longer adhesion time in group A). Patients' compliance was excellent. The results show that mucoadhesive tablets of topical acitretin are efficacious in the treatment of oral leucoplakia without systemic side-effects.

Oral manifestations of idiopathic lenticular mucocutaneous pigmentation (Laugier-Hunziker syndrome): a clinical, histopathological and ultrastructural review of 12 cases.

OBJECTIVE: To present a clinical, histopathological and ultrastructural study on a group of patients affected by idiopathic mucocutaneous pigmentation (Laugier-Hunziker syndrome: LHS). MATERIALS AND METHODS: Twelve patients were investigated: clinical examination, laboratory tests, and X-ray studies together with light microscopy and electron microscopy were performed in order to diagnose LHS. RESULTS: All cases showed acquired, benign, macular hyperpigmentation of buccal mucosa lips and nails. Histologically, pigmentations are due to an accumulation of melanin in the basal layer keratinocytes and an increase in the number of melanophages in the submucosa and/or papillary dermis. Ultrastructurally there were increased numbers of normal-appearing melanosomes in keratinocytes of the lower epithelium. No evidence of malignant changes were detected. CONCLUSIONS: The importance of this condition relates to it being included in the differential diagnoses of pigmentary disorders of the oral mucosa with associated nail involvement. It is important to recognize this acquired benign disorder to avoid unnecessary investigations and treatments.

Epiluminescence microscopy as a useful approach in the early diagnosis of cutaneous malignant melanoma.

The aim of this study was to evaluate the role of epiluminescence microscopy (ELM) in the differential diagnosis of cutaneous pigmented lesions in order to improve the detection of cutaneous malignant melanoma (CMM) at earlier stages of the disease. In total, 3865 pigmented lesions from 2121 selected patients were evaluated using ELM with a hand-held video microscope imaging system (MS 500B Micro-Scopeman, Moritex). Comparison with histology was performed on the 476 surgically excised lesions. ELM sensitivity, specificity, positive and negative predictive values as well as agreement for the different risk levels of the lesions were determined. Of the 476 cutaneous pigmented lesions removed and histologically examined, 101 (21.2%) were non-melanocytic lesions and 375 (78.8%) were melanocytic lesions. Overall agreement was 83.4% (93.1% and 80.8% for non-melanocytic and melanocytic lesions, respectively). Sensitivity and specificity of ELM in the analysis of melanocytic lesions with a pigment network were both very high (92.3% and 91.2%, respectively). Sixty new cases of CMM were identified. A high proportion of melanoma at stage AJCC IA (23 out of 32; 71.8%) was diagnosed exclusively by ELM (four of these were in situ CCM lesions). ELM is therefore a powerful tool to discriminate between melanocytic and non-melanocytic lesions in order to avoid inopportune surgical treatments for low risk lesions. Unfortunately, ELM did not show 100% sensitivity in diagnosing CMM and therefore ELM features should be integrated with data from both the history and clinical evaluation. However, ELM is much more accurate than clinical examination in detecting thin CMM.

Oral pemphigus: clinical significance of esophageal involvement: report of eight cases.

The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.

[Classical Kaposi sarcoma and volcanic soil in southern Italy: a case-control study]. / Sarcoma di Kaposi classico e suolo vulcanico nel Sud Italia: uno studio caso-controllo.

We tested the hypothesis of a relationship between Kaposi's sarcoma (KS) and volcanic soil by means of a case-control study based on 70 cases of classic KS and 280 hospital controls from the Campania region, an area of active volcanism in the South of Italy. Birth and residence in volcanic areas were associated with approximately two-fold elevated KS risks. If not due to chance, increased risk in the presence of volcanic soil can have different interpretations, including local immune impairment and correlation with unknown environmental or genetic KS predisposing factors.

Mucocutaneous diseases in drug addicts with or without HIV infection. A case-control study.

A case-control study was performed to evaluate the prevalence of mucocutaneous diseases in 106 male drug addicts (age 21-38 years) with or without HIV infection. A mucocutaneous disease was recorded in ten out of 64 HIV-negative and in 20 of 42 HIV-positive patients (OR = 4.9; p < 0.01). Some mucocutaneous diseases were present in similar proportions in both groups (i.e. fungal skin lesions), while others were typically present only in HIV-positive patients. Stratification for possible confounding factors, such as years of drug addiction and number of sexual partners, confirmed that HIV infection is the main risk factor for mucocutaneous disease. Stratification according to the number of CD4-positive cells showed that the more advanced the HIV disease, the more frequently mucocutaneous disease was present (p = 0.02). The study demonstrates that many, but not all, mucocutaneous diseases are associated with HIV infection.