Biagio Guarneri

Treatment of Psoriatic Nails with Topical Cyclosporin: A Prospective, Randomized Placebo-Controlled Study

Background: Nail involvement is a frequent event in the course of psoriasis causing severe distress. While systemic cyclosporin (CsA) represents a well-established therapy of psoriasis, its topical use is limited by the difficult penetration of the molecule through the skin and the nail because of its highly lipophilic nature. Objectives: We carried out a prospective randomized placebo-controlled study in order to analyze the effectiveness and tolerability of topical oil-dissolved 70% CsA solution in nail psoriasis. Methods: Sixteen adult patients with nail psoriasis, divided randomly into two groups of 8 patients (group A and group B), were treated respectively with a 70% maize-oil-dissolved oral CsA solution and maize oil alone. To compare the therapeutic effectiveness, all patients were evaluated, before starting the treatment and after 12 weeks of therapy, by the same dermatologists. The patients were also asked to assess the severity of their nail involvement at baseline and at the end of the treatment. Results: In group A, 3 patients came to a complete resolution of nail lesions and 5 showed a substantial improvement of the overall severity score. In group B, a slight improvement was noted in only 1 patient. All the patients of group A judged positively the results of the therapy, while in group B only 1 patient reported a moderate improvement. Conclusion: Our results show that topical therapy with oral CsA solution is a safe, effective and cosmetically highly acceptable treatment modality for nail psoriasis. The ability of CsA to influence keratinocyte proliferation and T-cell lymphokine release, reducing the cornification of the upper layers of the epidermis, may prevent the typical alterations observed in nail psoriasis.

Correlation between endocrinological parameters and acne severity in adult women.

Many studies demonstrate increased androgen levels and high prevalence of polycystic ovaries in women affected by acne. We evaluated the relationship between clinical features, ultrasonographic data on polycystic ovaries and hormonal parameters in 129 women >17 years of age with acne. Serum levels of androgens of ovarian and adrenal origin were measured. Menstrual cycle regularity, hirsutism, body mass index and ultrasonographic evaluation of ovaries were recorded. Raised levels of at least one androgen were evident in a majority of our patients. Only 19% of them had polycystic ovary syndrome. Hirsutism and acne severity correlated negatively with serum sex hormone-binding globulin (SHBG) levels (p<0.05). No correlation between acne severity and hirsutism was found. In post-pubertal women, severity of acne seems to depend on peripheral hyperandrogenism, with a negative relationship between the acne severity and serum SHBG levels. We strongly recommend the evaluation of serum SHBG levels in women with acne in order to select patients who can have a better response to appropriate hormonal regimes.

Skin pathology findings in a cohort of 1500 adult and elderly subjects

Background No extensive studies are available in the literature on the eventual skin pathology induced by neurologic or systemic diseases in elderly individuals. Other factors, such as health and hygiene, socioeconomic status, and climate can also play an important role.

Behaviour of laminin 1 and type IV collagen in uninvolved psoriatic skin. Immunohistochemical study using confocal laser scanning microscopy

Previous studies have demonstrated the presence in psoriatic lesions of ultrastructural and molecular alterations of the basement membrane and an altered polarized distribution of the integrins; this latter alteration has also been observed in uninvolved skin. The aim of the present study was to determine, by means of immunolocalization with monoclonal antibodies directed against laminin 1 and type IV collagen and using confocal scanning laser microscopy, whether there are also alterations of the main components of the basement membrane in uninvolved skin. The findings showed a discontinuous and fragmented staining of laminin 1 and a normal distribution of type IV collagen. Taking into account both these results and the results of studies on epithelial cell lines, the authors hypothesize the existence of a functional deficit in psoriatic keratinocytes affecting the synthesis of the α1 subunit of laminin. This deficit would explain: (1) the incapacity to produce mature trimeric laminin; (2) the altered assembly into a distinct basal lamina; (3) the loss of keratinocyte adhesion to the basement membrane; (4) alterations in the polarized distribution of the integrins; and (5) the consequent total or partial block of the cell signals regulating the processes of cytomorphosis. Already present in uninvolved skin, and enhanced by various irritative stimuli, this situation could be decisive for the appearance of psoriatic lesions.

Immunohistochemical study of epidermal nerve fibres in involved and uninvolved psoriatic skin using confocal laser scanning microscopy.

Abstract Psoriasis is a typical hyperproliferative epidermal disease whose aetiopathogenesis is still to be defined. One of the most likely hypotheses is that it has a neurogenic origin correlated with an altered release of some neuropeptides by sensitive cutaneous nerves via antidromic pathways. As there are conflicting reports about the existence of cutaneous nerve alterations in psoriasis, we carried out an immunolocalization study using the protein gene product 9.5 as a marker for neuronal structures observed by confocal laser scanning microscopy in order to determine the pattern of sensory nerves in psoriatic skin. The investigation was carried out on cutaneous biopsies taken from involved (mature and long-established lesions) and uninvolved skin of ten patients with extensive chronic plaque psoriasis. In uninvolved psoriatic skin a significant decrease in epidermal nerve fibres was found, a further decrease was observed in mature lesions and almost a complete lack of epidermal nerve fibres in long-established psoriatic lesions. The reduction in epidermal nerve fibres and the consequent loss of relationship between these nerve structures and the skin immunocompetent cells (antigen-presenting cells, Langerhans cells, keratinocytes) might be a factor of fundamental importance in the self-maintenance of the disease.

Trichomegaly of the eyelashes following treatment with cetuximab

Cetuximab is a chimeric monoclonal antibody that effectively binds epidermal growth factor receptor (EGFR), blocking its signal-transduction pathway and causing downregulation of EGFR. EGFR, constitutively expressed in many normal epithelial tissues, including the skin and hair follicle (regulating the growth and division of cells, the repair of cellular damage and the movement of cells within surrounding tissue), is also found in many human cancers including those of the head and neck, colon and rectum. In tumours, the effects of EGFR are enhanced; this leads to tumour growth, increased resistance to chemotherapy or radiotherapy, and metastasis formation. In vitro assays and in vivo animal studies have shown that cetuximab induces inhibition of cell growth, apoptosis and decreased production of vascular EGF. We report a case of overgrowth of the eyelashes, which occurred in a 63-year-old man with stage IV metastatic colon adenocarcinoma (G2 ⁄ T3N2M1). The patient had undergone a left colectomy with lymph-node dissection and partial hepatectomy for treatment of the metastatic tumour in the posterior segment of the liver, and since then had been treated with 5-fluorouracil, in combination with oxaliplatin and irinotecan. Owing to a recalcitrant course of disease, these agents were discontinued and combined therapy with cetuximab and irinotecan was started. After 3 weeks of treatment, the patient developed on the face, upper chest and back the typical acneiform erythematous rash commonly described in patients on cetuximab and other EGFR inhibitors. A marked increase in the length of his eyelashes (Fig. 1) and development of occipital alopecia after about 10 weeks of treatment was also seen. Skin toxicity is the most important side-effect of cetuximab, presenting as a follicular eruption on the face and trunk. The severity of the follicular eruption appears to be a dose-dependent phenomenon, and is increasingly considered an indirect marker of relevant in vivo EGFR targeting. Other cutaneous reactions include nail and periungual changes, abnormalities of hair growth, stomatitis ⁄ mucositis, xerosis, desquamation and pruritus. Trichomegaly is an uncommon clinical feature, which can be familial, paraneoplastic, associated with acquired immunodeficiency syndrome or dermatomyositis, or as a result of treatment with various drugs including EGFR inhibitors. Trichomegaly induced by EGFR inhibitors, due to the increased terminal differentiation caused by these drugs, usually occurs after 2–5 months of treatment, and can be associated with hypertrichosis in other areas. Patients receiving cetuximab in combination with irinotecan, as with our patient, can exhibit a simultaneous occurrence of hair loss, which is a side-effect of irinotecan (a)

Photodistributed eruptive telangiectasia: an uncommon adverse drug reaction to venlafaxine

cians) and time spent informing patients during dermatologist visits could sustain the increased awareness regarding onychomycoses that the PSA achieved. In addition, studies could be undertaken to compare the television time-rental cost along with the cost of unnecessary consultations vs. the decrease in treatment cost through early diagnosis in order to evaluate the cost-benefit ratio of the onychomycosis PSA campaign.

Changes in the distribution of laminin α1 chain in psoriatic skin: immunohistochemical study using confocal laser scanning microscopy

Summary Background Recent studies have demonstrated the presence in psoriatic skin of ultrastructural and molecular alterations in the basement membrane and an altered polarized distribution of the integrins. Previous studies have demonstrated the existence of some epithelial cell lines synthesizing only laminin β and γ chains that, in the absence of the laminin α chain, do not form a distinct basal lamina.

Pretibial myxoedema associated with Hashimoto's thyroiditis.

Pretibial myxoedema is a cutaneous mucinosis typically associated with Graves’ disease, although it may also develop in subjects with non‐thyrotoxic thyroid pathologies. This report presents a rare case of pretibial myxoedema occurring in a 58‐year‐old woman with biopsy‐proven Hashimotos thyroiditis. The hypothetical pathogenetic link between the two disorders is discussed with particular attention to the role of thyroid stimulating hormone receptor antibodies.

Multiple Familial Basal Cell Carcinomas Including a Case of Segmental Manifestation

Background: A tendency to develop multiple basal cell carcinomas at an early age is a characteristic feature of some rare hereditary disorders; moreover, multiple basal cell carcinomas are sometimes observed as a corollary of familial basaloid follicular hamartomas or familial multiple trichoepitheliomas. Observation: We report 3 cases of multiple basal cell carcinomas involving 3 successive generations of a family, with a segmental manifestation of lesions in one of these patients. No additional cutaneous or extracutaneous anomalies were found. Conclusions: We hypothesize that a gene mutation may have caused the tumors observed in this family as an autosomal dominant trait. The segmental arrangement of tumors may reflect loss of heterozygosity: at an early stage of embryogenesis, a postzygotic mutation would give rise to a population of cells either homozygous or hemizygous for the underlying gene. The segmental arrangement following the lines of Blaschko would visualize the dorsoventral proliferation of a cell clone characterized by loss of the corresponding normal allele.