C. Mazzatenta

Extracorporeal photochemotherapy induces apoptosis of infiltrating lymphoid cells in patients with mycosis fungoides in early stages. A quantitative histological study

Extracorporeal photochemotherapy (ExP) is a well‐tolerated new form of chemoimmunotherapy, which is considered to be effective for cutaneous T‐cell lymphoma (CTCL) and the treatment of choice for Sézary syndrome. Improvements have also been seen in patients with non‐erythrodermic mycosis fungoides (MF) in the early stages, even when tumour cells are not detectable in the peripheral blood. In this study, we used ExP as a monotherapy in seven patients who had early stage (Ib) MF, and who were no longer responsive to or had contraindications for other therapies. We observed a clinical improvement in the disease after 12 months of treatment: one patient showed a complete response, five a partial response, and one remained stable. In each patient we compared skin biopsies of large plaque lesions before and after the treatment. We undertook a histological evaluation of the infiltrate. The lymphoid cell proliferation and death rates were quantified using the following parameters: lymphoid cell density (LCD), Ki67+ lymphoid cell nuclei percentage (Ki67+ Lcn percentage), and apoptotic index (AI). Significant decreases in the lymphoid cell infiltrate and in cell proliferation, and a significant increase in AI were observed after therapy. The mean LCD decreased from 187 ± 33 to 34 ± 17·7, Ki67+ Lcn mean percentage decreased from 16·9 ± 3·9 to 4·9 ± 2·4, and the AI mean value increased from 0·05 ± 0·03 to 2·41 ± 1·54. Our results suggest a role for apoptosis in the improvement of the skin lesions and are in line with some reports on the mode of action of ExP. Although the way in which ExP works needs to be clarified further, it does seem to stimulate a CD8+ cell‐mediated anticlonotypic activity against circulating pathogenic clones. Furthermore, a release of tumour necrosis factor α (TNF‐α) by circulating monocytes has been demonstrated after ExP. Both are known to induce cell death by apoptosis.

Mid-dermal elastolysis: an ultrastructural and biochemical study

Mid-dermal elastolysis (MDE) is a particular elastic tissue disorder in which selective loss of elastic fibres occurs in the mid-dermis. It is clinically characterized by the appearence of fine wrinkling of the epidermis and perifollicular protrusion which gives the skin an aged appearence. It is sometimes associated with an inflammatory event such as urticaria while other cases are regarded as idiopathic. The pathogenesis of MDE is still obscure. Some authors have underlined the role of macrophage activation and others have imputed UV radiation. We report here a typical case of MDE arising after several attacks of solar urticaria. Electron microscopic and biochemical studies were carried out. Ultrastructural examination showed active elastophagocytosis by macrophages and mast cells, often degranulated, near phagocytosing cells. Biochemical studies demonstrated that fibroblasts derived from lesional skin of the MDE patient produced high levels of elastase and cathepsin G compared with fibroblasts from a healthy sex- and age-matched control. Phagocytosis of morphologically normal elastic tissue is a noticeable characteristic feature of MDE. In our case mast-cell activation and the abnormal synthesis and/or release of fibroblast elastolytic enzymes seemed to play a role in the pathogenesis of the MDE.

UVA Light Stimulates the Production of Cathepsin G and Elastase-Like Enzymes by Dermal Fibroblasts: A Possible Contribution to the Remodeling of Elastotic Areas in Sun-Damaged Skin

Abstract Solar elastosis is characterized by accumulation of large amounts of material staining similarly to elastin in the dermis. The nature of this material and the process responsible for its accumulation are still unknown. Elastolytic proteases have important functions in the catabolism of the interstitial matrix and can also generate, by the digestion of the interstitial proteins, soluble peptides which can induce collagen and elastin synthesis and deposition. We investigated whether (i) elastolytic enzymes can be detected in samples from sunexposed and nonexposed skin, and (ii) ultraviolet (UV) rays influence the production of elastolytic activities in cultured dermal fibroblasts. Immunoelectron microscopy showed a positive reaction for neutrophil elastase and cathepsin G in fibroblast like cells from specimens of sunexposed areas. Little or no reaction was found in biopsies of sunprotected skin. Fibroblast cultures from sunexposed skin expressed higher levels of hydrolytic activity against synthetic substrates of elastases and cathepsin G than those obtained from sunprotected areas. Irradiation with UVA strongly stimulated the production of these activities in fibroblasts from sunprotected sites. No significant change was detected in parallel sets of cultures after UVB irradiation. Inhibition experiments indicated that the elastaselike activity expressed by fibroblasts can be attributed to at least two enzymes.

Clinical Evaluation of the Trophic Effect of Polydeoxyribonucleotide (PDRN) in Patients Undergoing Skin Explants. A Pilot Study

SUMMARY Objective: The purpose of this double-blind, randomised, placebo-controlled study was to assess the effects of intramuscular and subcutaneous PDRN in favouring the wound-healing process in donor sites of grafts. Methods: 26 adult patients of both sexes (15 males and 11 females; mean age: 68.2 ± 16.1 years) subjected to skin explants due to plastic surgery were eligible to participate in this double-blind, placebo-controlled study. Patients were randomly allocated into the PDRN group (14 subjects) or the placebo group (12 subjects). PDRN (5625 mg/vial) or placebo were administered by the intramuscular route once daily, associated with a subcutaneous administration of the same dosage form (2 vials every 3 days) for 10 consecutive days. The primary end point for efficacy was the evolution of wound healing in donor sites, which was evaluated measuring wound surface area and then calculating percentage re-epithelialisation. Secondary end points were local subjective symptoms, such as pain and itching, and objective signs such as perilesional erythema and blisters. Signs and symptoms were quantified through an analogue scale. Results: At day 7 of the treatment period, the difference in percentage of re-epithelialisation was statistically significant (p < 0.008) in; favour of the PDRN group. At the end of the observational period, between-group comparison demonstrated that patients treated: with PDRN had a more prompt trophic effect. No adverse events were reported during the trial. Conclusions: The findings of our study demonstrated that PDRN is able to modify positively the repair processes in donor sites of autologous skin grafts. This could improve the clinical outcome and decrease the need for additional therapies or hospital stay.

Detection and typing of genital papillomaviruses in men with a single polymerase chain reaction and type-specific DNA probes

BACKGROUND Human papillomavirus (HPV) infection of the genitalia can produce both visible and subclinical lesions. Because different genotypes are preferentially associated with benign or malignant lesions, HPV detection and typing is clinically important. OBJECTIVE Our purpose was to assess a polymerase chain reaction (PCR)-based, noninvasive procedure for HPV diagnosis and evaluate the reliability of the acetic acid test for revealing subclinical HPV lesions. METHODS Mucosal samples were collected by gentle scraping, and PCR-positive samples were typed by hybridization with specific DNA probes. RESULTS Seventy-eight men were assessed. The PCR procedure was reliable and easy to perform. No significant difference was found in the prevalence of HPV infection between patients whose results were acetowhite-positive and those whose results were acetowhite-negative. CONCLUSION Detection of acetowhite epithelium, although useful for clinical examination, is not sufficiently specific and should not be used as a sole criterion for the diagnosis of HPV infection.

Vulvar squamous papillomatosis and human papillomavirus infection. A polymerase chain reaction study

Squamous papillae of the vulvar vestibule and introitus are quite a common clinical finding, however their origin is uncertain. They were formerly described as a normal variant of the mucosal epithelium, but recently they have been attributed to human papillomavirus (HPV) infection. Eight women with clinical findings compatible with a diagnosis of vulvar squamous papillomatosis were studied. All were free of other clinically evident HPV-related diseases. Vulvar scrapes and biopsy specimens were collected and used for DNA extraction and microscopic examination. DNA extracted from vulvar scrapings and from paraffin-embedded tissue was subjected to polymerase chain reaction (PCR). The reactions were performed with two sets of primers designed for the amplification of numerous HPV genotypes including those most commonly encountered in the genital area. Histological examination failed to reveal clear-cut signs of HPV infection in any subject. The PCR on the DNA extracted from vulvar scrapings revealed HPV infection in two cases. PCR performed on the DNA extracted from the paraffin-embedded tissue failed to detect HPV-DNA in any case. A 6-month follow-up showed no changes in the lesions. These results along with literature data, which is clearly inconsistent, indicated that the presence of HPV is coincident to, rather than causal of, vulvar squamous papillomatosis lesions. Patients with symmetrically distributed, long-standing vulvar papillae should, therefore, be carefully evaluated before starting therapy.

Cyclosporin A in the treatment of severe allergic contact dermatitis

Background Allergic contact dermatitis is sometimes difficult to treat because the patients are unable to effect prevention. Contact dermatitis can then become chronic and progressive, posing serious therapeutic problems.

Treatment of disseminated granuloma annulare with allopurinol: case report.

Granuloma annulare (GA) is a rare disease characterized by granulomatous inflammation of the dermis. A variant form of the disease, disseminated granuloma annulare (DGA), can be observed in about 15% of affected patients. Localized GA is likely to resolve spontaneously within months or a few years, whereas DGA can persist for decades. Various therapies have been suggested in these cases, but none of them has been demonstrated to be consistently efficacious. Allopurinol has been successfully used in granulomatous diseases such as sarcoidosis or reactions to polymethylmethacrylate spheres; therefore, we decided to evaluate the possible efficacy of this drug in three patients with long‐lasting, therapy‐resistant DGA.

Treatment of psoriasis with topical agents: Recommendations from a Tuscany Consensus

Psoriasis is a chronic and relapsing inflammatory skin disease, clinically characterized by erythematous and scaly plaques. Treatment approach is mainly driven by disease severity, though several factors should be considered in order to identify the optimal therapeutic choice. Mild psoriasis may be treated with a wide array of topical agents including corticosteroids, vitamin D analogs, keratolytics, and calcipotriol/betamethasone propionate compound. Because guidelines may not provide practical indications regarding the therapeutic approach, the use of topical agents in psoriasis is more individually tailored. In order to homogenize the standard of care, at least in a local setting, we collected the real‐life‐based recommendations for the use of topical therapies from an expert panel, the Tuscany Consensus Group on Psoriasis, representing all leading centers for psoriasis established in Tuscany. With this document, this consensus group sought to define principles guiding the selection of therapeutic agents with straightforward recommendations derived from a real‐life setting.

Modifications in Cutaneous Infiltrate and Death Rate of Lymphoid Cells in Mycosis Fungoides Patients Treated with Photopheresis

Extracorporal photochemotherapy (ECP), also known as photopheresis, is one of the most recent and interesting methods of treating cutaneous T cell lymphoma (CTCL) [1]. It consists in extracorporal exposure of a sample of peripheral blood leukocytes to 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) radiation followed by the reinfusion of the treated cells [2]. Introduced by Edelson in 1987 [2], it is now used in various European and US centres for the treatment of leukemic forms of CTCL [3].