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Melanoma is the most aggressive form of skin cancer, it originates from melanocytes and its incidence has increased in the last decade. Recent advances in the understanding of the underlying biology of the progression of melanoma have identified key signalling pathways that are important in promoting melanoma tumourigenesis, thus providing dynamic targets for therapy. One such important target identified in melanoma tumour progression is the Nuclear Factor-kB (NF-kB) pathway. In vitro studies have shown that NF-kB binding is constitutively elevated in human melanoma cultures compared to normal elanocytes. It has been found that a short cell-permeable peptide spanning the IKK-beta NBD, named NBD peptide, disrupted the association of NEMO with IKKs in vitro and blocked TNFalpha-induced NF-kB activation in vivo. In the present study we investigated the effect of the NBD peptide on NF-kB activity and survival of A375 human melanoma cells. We found that NBD peptide is able to inhibit the proliferation of A375 cells, which present constitutively elevated NF-kB levels. Inhibition of cell proliferation by NBD peptide was associated with direct inhibition of constitutive NF-kB DNA-binding activity and induction of apoptosis by activation of caspase-3 as confirmed by the cleavage and consequently inactivation of poly (ADP ribose) polymerase (PARP-1) known as the best marker of this process.

Hereditary benign intraepithelial dyskeratosis, a very rare disease affecting oral and conjunctival mucosae, is often familial and is determined by an autosomal dominant gene. Seven subjects belonging to three generations of a Neapolitan family presented the disease with a different expressivity. Cytohistological aspects and differential diagnosis are pointed out.

Lymphoscopy and lymphography revealed important changes in the lymph circulation of 4 out of 5 patients (dermal backflow on lymphoscopy and pictures of lymph 'lakes' on lymphographies). In the same patients the results of the challenge test were continuously negative on the diseased leg and positive on the arm after 48 hours. The DNCB test was positive on the arm as well as on the leg in the patient with an adequate lymph circulation. The Tranc smears showed an increased number of lymphocytes and several tadpole cells in all positive reactions to DNCB.

Purpose: Factors that are predictive of prognosis in patients who are diagnosed with malignant melanoma (MM) are widely awaited. Detection of circulating melanoma cells (CMCs) by reverse transcriptase-polymerase chain reaction (RT-PCR) has recently been postulated as a possible negative prognostic factor. Two main questions were addressed: first, whether the presence of CMCs, defined as the patient being positive for any of the three markers, had a prognostic role; and second, what the predictive value of each individual marker was. Patients and Methods: A consecutive series of 200 melanoma patients observed between January 1997 and December 1997, with stage of disease ranging from I to IV, was analyzed by semiquantitative RT-PCR. Tyrosinase, p97, and MelanA/MART1 were used as markers to CMCs on baseline peripheral blood samples. Progression-free survival (PFS) was used as a unique end point and was described by the product limit method. Multivariable analysis was applied to verify whether the auspicated prognostic value of these markers was independent of the stage of disease, and a subgroup analysis was performed that excluded patients with stage IV disease. Results: Overall, 32% (64 of 200) of patients progressed, and a median PFS of 52 months in the whole series was observed. The presence of CMCs and the markers individually or combined was predictive of prognosis in the univariate analysis but did not provide additional prognostic information to the stage of disease in multivariable models. In the subgroup analysis of stage (ie, I–III subgroup), similar results were observed. Conclusion: Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.

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; p0.01). 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.

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.

An 11-month-old male infant was referred to our clinic because of a painful ulcer of approximately 5 months' duration on the ventral surface of the tongue (Fig. 1). On physical examination, the lesion was circular (3 cm x 2 cm) with erythematous, raised, and indurated borders. No pathologic findings emerged from the laboratory data, neurologic examination, or clinical history. The family history was also negative for developmental disorders and congenital syndromes. No biopsy was performed in view of the age of the infant, the particular site of the lesion, and the clinical evidence of diagnosis. The treatment included odontologic cream (methylvinylether/maleic acid) as a protective shield, a collutorium (chlorhexidine 0.2%), and the use of a teething ring. Complete healing of the lesion (Fig. 2) occurred within 3 weeks.

The aim of the present study was to assess the prognostic value of soluble interleukin-2 receptor (sIL-2R) serum levels in stage I-III melanoma patients. The levels of sIL-2R were determined using an enzyme immunometric test kit in 329 patients affected by malignant melanoma (MM) from 1995 to 2004. Correlations between sIL-2R values, baseline patients and tumour features were studied by contingency tables and the chi-square test. The Kaplan-Meier product limit method was applied to plot disease-free survival (DFS) curves. Univariate analysis was performed with the Log-rank test. Cox proportional-hazards regression was used to analyse the effect of several risk factors on DFS. In total, 2330 blood samples were collected during follow-up of 329 MM patients. Forty-five (13.7%) patients had Breslow tumour thicknessor=1.00, 83 (25.2%) patients1.00 andor=2.00 mm, 72 (21.9%) patients2.00 andor=4.00 mm, and 47 (14.3%) patients4.00 mm. Ulceration was present in 64 cases (19.4%). Thirty-nine sentinel lymph nodes (SLNs) (11.8%) were infiltrated by MM. Soluble IL-2R values ranged from 130 to 1420 U/ml; median value was 500 U/ml. One hundred twenty-one (36.8%) patients presented with sIL-2R600 U/ml at first measure (FM), 194 patients (58.9%) with values increasing up to or more than 600 U/ml [increasing values (IV) pattern]. A correlation was found between Breslow's tumour values and the IV sIL-2R pattern group (P=0.0304 with chi2 test). Gender, presence of ulceration, Breslow tumour thickness, FM and IV sIL-2R pattern groups had a significant prognostic value for DFS. At multivariate analysis, presence of ulceration, gender, FM and IV sIL-2R pattern groups emerged as independent prognostic factors for DFS. The 5-year DFS rate was 88% for patients with FM600 U/ml and 76.9% for patients with FM600 U/ml. In IV pattern, the 5-year DFS rate was 69.5% compared to 87% for patients with no sIL-2R values600 U/ml during follow-up. sIL-2R values are associated with progression of MM. Further studies are needed to address the role of the IL-2/IL-2R/sIL-2R axis in melanoma biology.

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.

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.

Melanocytes have their embryologic origin in the neural crest and, during fetal life, migrate to the basal layer of the skin and mucosa through the peripheral nerves. They exhibit dendritic processes that extend to adjacent keratinocytes, where they transfer pigment. Melanocytes synthesize melanin in specialized granules, that is, the melanosomes, which deliver the pigment to the surrounding keratinocytes and sometimes to the macrophages. Genetic constitution, hormone production, and sun exposure usually influence the amount of pigment production. Oral pigmentations represent a group of several entities ranging from physiologic pigmentation to malignant melanoma. The clinical appearance of oral pigmentation ranges from brown to black, depending on the amount of melanin production and depth of the pigment location (usually brown lesions are related to a superficial pigment location and black/gray lesions to deep pigment location). Oral pigmented lesions are due to

ejd.2010.1217 Auteur(s) : Adone BARONI adone.baroni@gmail.com, Vincenzo PICCOLO, Rosa Di MAIO, Francesca ROMANO, Fiorenzo Di GIROLAMO, Rocco Alfredo SATRIANO Department of Dermatology and Venereology, Second University of Naples, II Policlinico, Edificio 3, Quarto piano, Via Pansini 5-80131 Napoli, Italy Mal de Meleda (MdM) is an autosomal recessive genodermatosis characterized by diffuse and “transgrediens” palmoplantar keratoderma (PPK). It starts at infancy in association with a severe evil-smelling [...]

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.

A 35-year-old man presented with a 7-year history of gradually enlarging plaques on his face and trunk. The first lesions had developed on both sides of the forehead and the left cheekbone (Figure 1). Four years later similar lesions appeared on his neck and back. He presented a histologic report of a biopsy specimen from a facial plaque performed 5 years earlier that was diagnostic for granuloma faciale. He had different treatments such as topical steroids and cryotherapy without improvement. The appearance of new lesions on his trunk and the gradual enlarging of the old lesions convinced the patient to seek further treatment. Physical examination revealed dusky, violaceous plaques and papules, 0.5 to 2 cm, well-circumscribed, slightly elevated, and located on the face and trunk, with mild pruritus (Figure 1 and Figure 2). Laboratory investigations, including complete blood cell count, VDRL test, antinuclear antibody test, biochemical parameters, and chest x-ray, did not reveal any abnormalities. A skin biopsy taken from the upper part of the back showed similar features to the facial lesion, detected 5 years before, revealing a dense, polymorphous infiltrate involving mid and deep dermis and displaying a diffuse and perivascular pattern (Figure 3A). A narrow grenz zone of normal collagen was consistently observed between dermal infiltrate and epidermis as well as around the pilosebaceous follicles (Figure 3A). The infiltrate mainly consisted of eosinophils and lymphocytes, but neutrophils (often displaying leukocytoclasis), macrophages, and plasma cells were also present (Figures 3B, 3C). Some mast cells were also identified by staining with toluidine blue (Figure 3D). Perivascular infiltrates were often seen, sometimes penetrating vessel walls and in association with leukocytoclasis. Hyalinization of vessel walls, extravasation of red blood cells around capillaries, and nuclear dust were also noted. The epidermis did not show any remarkable change except for slight acanthosis. A diagnosis of granuloma faciale with extrafacial lesions was made, and a systemic therapy with hydroxychloroquine (200 mg twice daily for 6 weeks) was recommended.(1,2).

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.

The increased incidence of disease, the relative unresponsiveness of advanced tumour to conventional therapies, and high socioeconomic costs make the malignant melanoma an aggressive cancer. During the last decade, several new biological agents have been developed, some of which have shown significant activity in the treatment of disease. However, the impact on the management of melanoma patients is still far from being conclusive. Among biological response modifiers (BRMs), interferons (IFNs) have generated a great deal of interest and have been extensively employed, although incorrectly. IFNs have been used without a specific rationale and at antiproliferative rather than biologically active doses; no extensive laboratory monitoring has been performed. In this paper data available in the current literature are reviewed and the efficacies of the different IFNs, used alone or in combination and in various treatment regimens, are compared in order to understand what is the place of IFNs in the management of patients with metastatic melanoma. Results are encouraging but still disappointing with the most effective treatment, with an overall response rate of 28.5% (10.5% complete responses). However, these results need confirmation. In conclusion, IFN is effective in the therapy of advanced melanoma, but improved response rates are necessary before it may be suitable for general, rather than investigative, use. Alternative biotherapeutical approaches and strategies are suggested.

Pemphigus lesions appeared in a 58‐year‐old man who was talking captopril for his hypertension. Drug withdrawal resulted in complete remission of the eruption. The subsequent use of enalapril as an antihypertensive agent caused a recurrence of pemphigus lesions along with onset of itching and dermographism. Intercellular antibodies were not found. Discontinuance of enalapril therapy had no effect on the clinical course. Steroid treatment was needed to resolve the eruption. Recently repeated immunofluorescent studies disclosed intercellular IgG antibodies in the serum at a low titer. Pemphigus induction could be initially related to the thiol acantholytic property of captopril. Subsequent production of intercellular antibodies and drug‐activation of the kinin system could be responsible for relapsing. Copyright © 1992, Wiley Blackwell. All rights reserved

The exponential increase in incidence, high socio-economic costs, and relative unresponsiveness to conventional therapies make malignant melanoma an aggressive cancer. 1–4 When metastases are already disseminated, the activity of currently available drugs is limited, achieving a response rate of 15 to 25%. 3 Consequently, development of an effective treatment for advanced melanoma (AM) is a pressing problem. In recent years, genetic engineering and related technologies have made possible the large-scale production of pure biomodulators, also known as biologic response modifiers (BRMs). Use of these agents has offered the potential for significant advances in the treatment of cancer.

A 53-year-old man presented porokeratosis palmaris, plantaris et disseminata with some features (exacerbation of lesions, in the sun light , zosteriform fashion of them on the trunk and extremities) distinctive of other variants of porokeratosis. Lately, four squamous cell carcinomas had arisen on the areas involved by disease. Histologic study of porokeratosis lesions showed epidermal changes typical of the desease ('cornoid lamella'), but also a mild disorder of malpighian stratification. Neoplasms were removed surgically and the patients was given etretinate orally (75 mg/day for a week, 50 mg/day for a month, 25 mg/day for six months, i.e. up to now), which proved to be effective in improving porokeratosis lesions and preventing the occurrence of other squamous cell carcinomas.

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.

A 3 1/2-year-old haemophilic child, repeatedly transfused with blood products, developed pemphigus foliaceus with presence in serum of both intercellular and anti-cytomegalovirus antibodies at high titre. The locus A26, which seems to be a genetic marker of pemphigus, was detected in his haplotype. Cytomegalovirus infection of transfusional origin is suspected to have triggered the outbreak of pemphigus.

Kaposi's sarcoma appeared on a chronically lymphedematous leg oi a 75-year-old man. lmrnunologic investigations revealed a lack of cellular immune response confined to the involved lower limb. Regional disorders of immune surveillance are thought to play an important role in the early stages of Kaposi's sarcoma.