Marcello Monti

Ceramide composition of the psoriatic scale

This paper investigates the ceramide composition of the psoriatic scale compared with that of normal human SC. A method was optimalized, based on TLC separation followed by densitometry, allowing the provision of good resolution and quantification of ceramide fractions from both normal and pathological specimens. Seven ceramide fractions were isolated and submitted to compositional analysis. The obtained results suggested a revisitation of previous ceramide designation. Therefore a simple classification is suggested, based on grouping ceramides carrying structural similarities under common codes. According to these rules, ceramides were grouped into five classes designated as: (1) Cer[EOS], which contains ester-linked fatty acids, omega-OH fatty acids and sphingosines; (2) Cer[NS], which contains non-OH fatty acids and sphingosines; (3) Cer[NP], which contains non-OH fatty acids and phytosphingosines; (4) Cer[AS], which contains alpha-OH fatty acids and sphingosines; (5) Cer[AP], which contains alpha-OH fatty acids and phytosphingosines. Analysis of ceramides from the psoriatic scale, compared to those from normal human SC, resulted in an impairment of the Cer[EOS] content as well as of the ceramides containing phytosphingosine, with concurrent increase in ceramides containing sphingosine, being the total amount maintained identical. Since one of the suggested pathways for phytosphingosine biosynthesis involves the water addition to the corresponding sphingosine double bond, we can speculate that the observed alteration is due to a deranged water bioavailability, associated with psoriasis.

Cutaneous manifestations of tetrachlorodibenzo-p-dioxin in children and adolescents: Follow-up 10 years after the Seveso, Italy, accident

After an accident in a chemical plant in Seveso, Italy, on July 10, 1976, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) spread over a populated area. The event was exceptional because children were also affected and because the contamination took place not only through direct exposure but also through inhalation and the ingestion of contaminated foods, especially fruits and vegetables. This paper illustrates the early dermatologic lesions, the late acneic (chloracne) lesions, and their evolution during a 10-year period. Peculiar cutaneous findings, histologic data, and a comparison with previously reported similar accidents are also included.

Content of the different lipid classes in psoriatic scale.

Studies on stratum corneum have demonstrated that interlamellar lipids are functionally involved in the maintenance of barrier function [ 1 ]. In addition, recent investigations have Correlated interlamellar lipid synthesis with the desquamation rate and the mitotic activity, of keratinocytes [2]. The complexity of the functions of the horny layer lipid compartment are strictly related to a constant and well-defined proportion of the different lipid classes as hypothesized in previous reports [3-5]. Psoriasis is characterized by both increased desquamation and keratinocyte hyperproliferation as a consequence of an increased mitotic rate of basal cells [6]. In addition horny layers are deranged, causing an increase in water flux and absorption [7]. Recently, we reported significant variations in the ceramide composition of psoriatic scale compared with normal human stratum corneum [8]. In the present study we determined the relative proportions of the lipid classes present in scales from psoriatic skin and compared them with those in normal human stratum corneum in an attempt to correlate psoriatic barrier alteration with the content and/or relative proportion of each lipid class. Different lipid classes in both normal and psoriatic specimens were analysed by a procedure involving extraction of total lipids, separation of individual classes by thin-layer chromatography and quantification by densitometry. Normal human stratum corneum was obtained by trypsinization of abdominal skin samples obtained during plastic surgery from six subjects (both sexes), Psoriatic scale samples were obtained using tweezers from abdominal lesional areas of ten subjects (all male). Both normal and psoriatic samples were processed for lipid extraction

Cytotoxic γ/δ subcutaneous panniculitis-like T-cell lymphoma: Report of a case with pulmonary involvement unresponsive to therapy

Peripheral subcutaneous panniculitis‐like T‐cell lymphoma (PSPTCL) is a rare form of cutaneous lymphoma recently proposed as a distinct clinicopathological entity. It usually presents with multiple indurated subcutaneous plaques or tumours, most commonly located on the extremities and trunk and clinically mimicking lobular panniculitis. Associated constitutional symptoms due to haemophagocytic syndrome may advance or, more often, complicate the clinical course in about 40–70% of cases. Finding of TIA‐1+ and perforin + cytolytic granules in atypical pleomorphic lymphocytes suggests PSPTCL origin from granular cells of T‐cell or natural killer cell phenotype. Cells have a CD3+ CD4+ CD8– or CD3+ CD4– CD8+ T‐cell phenotype. Moreover, these lymphomas can express natural killer cell associated antigens, such as CD56, especially in γ/δ variants. PSPTCL following an indolent clinical course with recurrent self‐healing lesions have been described. The prognosis of most PSPTCL is poor even when treated with aggressive chemotherapy. This paper reports a case of PCTCL in a young woman with T‐cytotoxic differentiation, with rapid progression unresponsive to several treatments.

Early detection, prevention and management of cutaneous adverse events due to sorafenib: Recommendations from the Sorafenib Working Group

Cutaneous adverse events commonly reported with tyrosine kinase inhibitors (TKIs) in the treatment of malignancies, represent an important clinical concern since they can limit the optimal use of these novel drugs. Although there are numerous reports in the literature of these events there are no practical guidelines on how they should be managed. The Sorafenib Working Group (SWG) was established with the objective of developing recommendations to allow the early detection, prevention and management of cutaneous adverse events in everyday clinical practice. The SWG was a multidisciplinary team made up of experts in the field who were closely involved in the sorafenib clinical development program. This review provides an overview of the nature and incidence of cutaneous adverse events which manifest with sorafenib treatment and provides recommendations for their early detection and effective management in clinical practice.

Clinical management of cutaneous toxicity of anti-EGFR agents

Cutaneous toxicity is the most evident adverse effect of epidermal growth factor receptor (EGFR) inhibitors because of the specific role played by EGFR in skin biophysiology. Dermatological adverse reactions, mainly folliculocentric, have been widely reported in the literature. However, the mechanism of these reactions is not well defined and their management is still a matter of debate. In this paper keratinocyte differentiation, activation and pathways regulating gene expression are reviewed in order to improve the understanding of adverse skin reactions and obtain success in their management. The authors had the opportunity to treat skin reactions induced by cetuximab in a cohort of patients affected by metastatic colorectal carcinoma. The aims of this clinical approach were to control the signs and symptoms of skin toxicity in order to avoid delay in cancer therapy and to use nondrug agents for the treatment of drug-induced skin reactions.

The avidin-biotin peroxidase complex (ABCPx) in skin immunoelectron microscopy

SummaryThe interaction between avidin and biotin can be exploited in immunoperoxidase techniques in three main ways: the labeled avidin-biotin technique (LAB); the bridge avidin-biotin technique (BRAB); the performed avidin-biotin complex (ABCPx). In a comparative study of these three methods and the peroxidase antiperoxidase method using serial dilutions of antinuclear positive serum, the ABCPx method yielded the most intense staining. For this reason, the ABCPx method has been applied in immunoelectron microscopy (IEM) techniques on normal and pathological skin employing monoclonal. OKT4, OKT6, and OKT8 antibodies to detect target membrane antigens. The authors notes that the ANCPx method allows strong staining both in normal and pathological skin and improves tissue preservation.

Atypical Early Syphilis in an HIV-Infected Homosexual Male

A homosexual male, seropositive to HIV and with previously documented syphilitic infections, developed a slowly growing nodule on his left wrist (possibly a chancre) followed, after 2 months, by a few scattered, large papular lesions. Serological evidence of active syphilis was obtained and treponema were identified in the initial lesion by means of immunofluorescent staining. Treatment with both aqueous crystalline penicillin G and benzathine penicillin G healed the lesions. This represents a further case of an atypical presentation of early syphilis in an immunocompromised host.

Heterogeneity of dermal OKT6+ cells in inflammatory and neoplastic skin diseases

This immunopathologic study of both normal and pathologic skin specimens (contact dermatitis [CD], lichen planus [LP], cutaneous T cells lymphoma [CTCL], and histiocytosis X [HX]) allowed as to differentiate four types of dermal OKT6+ cells: (1) cells with the same morphologic features as epidermal Langerhans cells (LCs), rarely found in either normal or pathologic dermis; (2) cells structurally similar to LCs but lacking Birbeck granules (BGs), found mainly in CD and LP; (3) larger cells rich in cytoplasmic organelles, only 5% of which contained BGs. They were especially common CTCL; and (4) cells typical of HX.

Letterer-Siwe disease in an octogenarian

The case of an 81-year-old woman suffering for about 1 year from a typical form of Letterer-Siwe disease (LSD) is reported. The only important systemic involvement was hepatosplenomegaly. The patient was treated with steroids and vinblastine and then with thymopoietin pentapeptide. This last drug proved useful for decreasing the dose of steroid and thus for checking the appearance of new skin lesions. The ultrastructural investigations, carried out before and after vinblastine, showed the presence in some histiocytosis X cells (HXC) of coated Birbeck granules (BG). Immunoelectron microscopy showed about 90% of HXC to be OKT6+ and the OKT6 labeling of these cells to be similar to that of the Langerhans cells of normal skin. Five percent of OKT6+ cells apparently contained no Langerhans granules.