Efficacy of topical imiquimod 3.75% in the treatment of actinic keratosis of the scalp in immunosuppressed patients: our case series.

Background: Actinic keratoses (AK) represent common cutaneous lesions, appearing in 'Field cancerization areas' and potentially evolving toward invasive neoplasm. Immunosuppressed patients frequently develop numerous and aggressive AKs.Aim: In this observational study, we report our experience with topical Imiquimod 3.75% as 'Field-directed therapy' in a cohort of immunosuppressed patients.Methods: A group of 13 immunosuppressed patients presenting multiple AKs of the balding scalp was treated with topical Imiquimod 3.75%. Each patient underwent clinical examination at fixed timepoints during the treatment (T0, T14, T28, T42) and eight weeks after the end.Results: In our cohort, the treatment was well tolerated, with minimal local adverse events. We observed a good clinical response, in terms of Lmax lesions (maximum lesion count during the course of therapy) and of AK clearance. In our group, 46% of patients showed no detectable lesions at the end of the observation period, and this result was maintained up to 1 year after the end of treatment.Conclusion: Topical Imiquimod 3.75% represents an effective and safe treatment for multiple AK of the scalp also in immunosuppressed patients. To the best of our knowledge, this is the first report on the use of this drug in this category of subjects.

Intense Foxp3+ CD25+ regulatory T-cell infiltration is associated with high-grade cutaneous squamous cell carcinoma and counterbalanced by CD8+/Foxp3+ CD25+ ratio.

BACKGROUND: Recent reports have revealed the therapeutic potential of cell-mediated immunity in neoplasms such as cutaneous squamous cell carcinoma (SCC). OBJECTIVES: To define the antigenic coexpression of regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) and assess the CD8(+) /Foxp3(+) CD25(+) cell ratio at peritumoral and intratumoral levels in order to investigate a correlation with the aggressiveness of SCC tumours. METHODS: We evaluated the content and distribution of Foxp3(+) CD25(+) Treg and CD123(+) pDC infiltration and assessed CD8(+) /Foxp3(+) CD25(+) cell ratio at peritumoral and intratumoral levels in 40 SCCs (20 well-differentiated, G1; and 20 moderately to poorly differentiated, G2-G3) to investigate a correlation with their aggressiveness. We determined the profiles of Tregs and CD123(+) cells; immunostained for CD4, CD8, CD123, interleukin (IL)-1 and transforming growth factor (TGF)-ß1; and unequivocally double stained for Foxp3CD25. RESULTS: Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123(+) cells were fewer in G2-G3 (P = 0·0005), while Foxp3(+) CD25(+) cells were more numerous (P = 0·0005). The Foxp3(+) CD25(+) /Foxp3(+) ratio was higher in G2-G3 cases (P = 0·0005), confirming the trend in this group of activated T lymphocytes towards total Treg Foxp3(+) cells, while the CD8(+) /Foxp3(+) CD25(+) ratio was higher in G1 (P = 0·0005). Intratumorally, CD4(+) and CD8(+) cells infiltrated G2-G3 (P = 0·048) more than G1 (P = 0·004), whereas almost all cells were CD123 negative. Regarding Foxp3CD25, TGF-ß1 and IL-10, they were less expressed in G1, whereas they were positive in G2-G3 (P < 0·05). The CD8(+) /Foxp3(+) CD25(+) ratio was similar to that observed in peritumoral infiltration. CONCLUSIONS: Our data suggest that intratumoral recruitment of Tregs, high expression of TGF-ß1 and IL-10, almost negative CD123+, and a low CD8(+) /Foxp3(+) CD25(+) T-cell ratio may contribute to the aggressiveness of cutaneous SCC, as already evidenced for other solid tumours.

Analysis of human ß-papillomavirus and Merkel cell polyomavirus infection in skin lesions and eyebrow hair bulbs from a cohort of patients with chronic lymphocytic leukaemia.

BACKGROUND: Research demonstrates an increased incidence of skin cancer in immunocompromised hosts, including patients with chronic lymphocytic leukaemia (CLL) and organ transplant recipients (OTRs). Active human ß-papillomavirus (ß-HPV) infection has been found in OTR skin lesions, suggesting its possible involvement in skin carcinogenesis. Merkel cell polyomavirus (MCPyV) has also been reported in cases of skin cancer. OBJECTIVES: To investigate the potential correlations between patient clinical features and skin cancer development, and the presence of ß-HPV and MCPyV DNA and protein markers in skin lesions and hair bulbs from patients with CLL. METHODS: The clinical features of 293 patients with CLL were analysed according to the presence or absence of skin lesions. ß-HPV and MCPyV infection was investigated in skin lesions and hair bulbs from the study cohort by both polymerase chain reaction (PCR) analysis and immunohistochemical screening. RESULTS: No significant correlations were observed between any of the analysed haematological parameters and the development of skin cancer. PCR analysis revealed the presence of ß-HPV and MCPyV DNA in skin lesions, and 83% of positivity for MCPyV DNA in hair bulbs, while systematic immunohistochemical analysis of all the lesions failed to detect any expression of the viral proteins ß-HPV E4, L1 or MCPyV LTAg. CONCLUSIONS: Overall, the data indicate that carriage of ß-HPV and MCPyV in the lesional skin and hair bulbs from patients with CLL without any evident reactivation at skin tumour sites most likely represents coincidental rather than causal infection. This contrasts with previous findings in relation to OTR-derived skin lesions.

Basal cell carcinoma of the head region: therapeutical results of 350 lesions treated with Mohs micrographic surgery.

BACKGROUND: Basal cell carcinoma (BCC) is a non-melanocytic skin tumour with a high risk of recurrence after incomplete treatment, especially the aggressive subtypes (basosquamous, micronodular and morphea BCC). The percentage of recurrence also depends on the anatomical site of the tumour. Nose-cheek fold, paranasal fold, retroauricular fold and internal canthus are considered to be critical sites. OBJECTIVE: The aim of this study was to report on recurrence rates for BCC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: We retrospectively studied 350 BCCs of the head region treated with MMS. Results were analysed with chi-squared test and Fisher test and were considered significant when P value was ≤0.05. RESULTS: In our study, the percentage of BCC recurrence rate after MMS was of 3.4% for primary BCC and 4.9% for recurrent BCC; these were similar to the recurrence rates reported in the literature. CONCLUSIONS: Low recurrence rate can be achieved when treated with MMS; it is the treatment of choice for many BCC of the head. Aggressive histopathological subtypes, critical head sites and recurrence after incomplete excision are the most important indications for MMS.

Micrographic surgery (Tubingen torte technique) for the treatment of an invasive dermatofibrosarcoma protuberans with muscular involvement.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumour characterized by a slow, infiltrative growth and marked tendency towards local recurrences. Wide surgical excision of 3-5 cm from the margins including the fascia is the recommended treatment. Mohs Micrographic Surgery has been shown to afford lower rates of recurrence. The Mohs-Tübingen technique is a variant indicated for very large excisions that allows a complete eradication of the tumour, preserving healthy tissues. We report the case of a 45 year-old man affected by DFSP of the right shoulder deeply infiltrating the muscles, referred to us for a recurrence after a large excision. We submitted the patient to Mohs-Tübingen surgery in collaboration with an orthopaedic surgeon due to the presence of muscular involvement of DFSP. Two surgical operations were necessary to obtain negative histology as the tumor was deeply infiltrating the prescapular muscles. After three years of follow-up, the patient did not have any recurrence and the normal mobility of the shoulder was preserved. Precocious diagnosis and adequate therapy are necessary for DFSP as not only the margins, but also the deep invasion of the tumor have to be carefully controlled.

The relationship between glycated hemoglobin and polymorphonuclear leukocyte leukotriene B4 release in people with diabetes mellitus.

In order to evaluate polymorphonuclear leukocyte (PMN) activity in diabetes mellitus, leukotriene B4 (LTB4) levels were measured in sixty patients, 31 affected with Type 1 diabetes mellitus and 29 affected with Type 2 diabetes mellitus. The LTB4 levels (12.1+/-0.2 pg/100 microl) in diabetic patients were higher compared to those of the control group (7.9+/-0.1 pg/100 microl) (P < 0.001), and remained significantly higher (P < 0.001) (12.8+/-0.2 pg/100 microl) than in the control group (11.0+/-0.2 pg/100 microl) after stimulation with calcium ionophore. A significant and positive correlation between glycated hemoglobin and LTB4 was demonstrated (P < 0.001, r = 0.80). This study demonstrates that in diabetic patients there is a PMN activation and that this activation is correlated to glycated hemoglobin level.

ET-1 plasma levels during cold stress test in sclerodermic patients.

Endothelial cell injury in blood vessels of small arteries and capillaries is considered the primary event in the pathogenesis of systemic sclerosis (SSc). Because endothelin-1 (ET-1) is mainly released in the site of endothelial cell damage, thereby inducing a potent vasoconstriction, it was our intention to study ET-1 release in a group of SSc patients during a cold pressor test (CPT). Twelve SSc patients and a control group of 10 healthy subjects underwent CPT. Blood samples for ET-1 assay were collected at 90 and 180 seconds of exposure to cold stress. Heart rate and blood pressure were recorded at the same intervals. A capillaroscopic examination was performed in both groups before and after CPT. We observed significantly higher levels of plasma ET-1 in SSc patients compared with those of the control group at baseline (P=0.007) and at 90 (P=0.006) and 180 seconds (P=0.03) of CPT. During the test, the capillaroscopic examination showed a dramatic worsening of the vascular picture that was parallel to the increase in ET-1 plasma levels. This suggests that higher ET-1 plasma levels can have a part in the acute vascular reactivity of SSc patients undergoing CPT.

[Lipoprotein (a) and plasminogen in atherosclerosis]. / Lipoproteina (a) e plasminogeno nella malattia aterosclerotica.

The aim of this study was to evaluate plasma levels of lipoprotein (a) [LP(a)] and plasminogen in patients affected with atherosclerotic disease and to understand the mutual relationships. Eighty-four patients affected with atherosclerosis were examined and divided as follows: group I, 24 patients with peripheral arteriopathy; group II, 40 patients with ischemic heart disease (myocardial infarction and/or angina pectoris); group III, 20 patients with multi-infarct dementia; group IV (control group) with 20 healthy young subjects. The results show that Lp(a) plasma levels, in atherosclerotic patients, are higher than 30 mg/dl, while the plasminogen levels are lower than 80 mg/dl. There is an inverse correlation between these two data. Moreover, a different behaviour of Lp(a) and plasminogen rate related to age of patients, to number of atherosclerotic lesions or to acuteness of ischemic heart disease, was observed.

[Systemic sclerosis after a long-term follow-up]. / Riflessioni sulla sclerosi sistemica dopo un follow-up a lungo termine.

The authors suggest some remarks on the aetiopathogenesis of systemic sclerosis through a critical review of a group of 51 patients affected by this disease for many years. In this paper the authors report their previous studies regarding the correlation of immunological response, both cell-mediated and humoral, hemocoagulative aspects and haemorheological changes. From the results of immunological studies, the authors report a long-term treatment with an immunomodulating drug: thymopentin. Moreover they report a recent work about the connection among stressor event, production of endothelin-1 (ET-1) and serum levels of some stress hormones such as possible pathogenetic factors of Raynaud's phenomenon and of scleroderma. This work ends with a proposal of a pathogenetic scheme that, even if it doesn't exclude an infective pathogenesis, considers stress as a factor able to switch on a series of psycho-neuro-immunoendocrinological reactions that can support, through the activation of lymphocytes, fibroblastic proliferation and finally fibrosis.

Long-term thymopentin treatment in systemic scleroderma.

A study was carried out to investigate whether thymopentin treatment is capable of inducing changes in the immunological status of patients with systemic scleroderma and to compare any such changes with modifications in clinical condition. Nine patients were given thymopentin, 1 ml in 10 ml saline solution, by slow intravenous infusion 3-times weekly for 5 weeks (cycle). The cycles were repeated at 3-month intervals. Treatment duration ranged from 1 to 5 years. Blood samples were drawn at the beginning and at the end of each cycle and the patients' lymphocytic sub-populations were examined. A control group of 9 comparable healthy subjects were similarly tested. Data analysis showed that a statistically significant decrease of CD16+ and CD25+ lymphocytes compared to pretreatment was already apparent at the end of the first thymopentin treatment cycle. An improvement was found in the clinical condition of 7 of the 9 patients at the end of the follow-up period with a significant correction of unbalanced lymphocytic subsets.

Rheological leukocyte indexes in diabetes mellitus type II.

Eleven healthy volunteers were examined, as well a thirty-five diabetic subjects divided into three groups according to the presence or absence of macro-microvascular complications and according to whether or not these complications were chronic. The results of our study show a marked unfavorable in cell rheology in the diabetic subjects, as studied using the St. George filtrometer. In particular, polymorphonuclear (PMN) cells, in the diabetic subject showed a substantial decreases in viscosity and elasticity, reflected by decreased IrFr and increased CR values. These changes were most marked in the group of diabetics with acute vascular events, i.e., AMI and stroke. Rheological indexes studied appeared to be independent from the simultaneous blood glucose level.