Biomedical subjects

Giampiero Girolomoni

Publications and source records attributed to Giampiero Girolomoni.

At least 19 recordsLinked to original sources

PubMed2007

Videocapillaroscopy in the differential diagnosis between psoriasis and seborrheic dermatitis of the scalp.

BACKGROUND: Videocapillaroscopy (VCP) can be used to explore microcirculatory modifications in skin diseases. Psoriasis shows specific capillary alterations reflecting typical histopathological changes. OBJECTIVE: To compare capillary morphology, distribution and density in psoriasis and seborrheic dermatitis of the scalp for differential diagnosis. METHODS: VCP was performed on histology-confirmed scalp lesions of 30 patients with chronic plaque psoriasis, 30 age- and sex-matched patients with seborrheic dermatitis and 30 healthy subjects. The morphology, mean density per mm(2) and mean diameter of capillary loops was measured. RESULTS: Scalp psoriasis exhibited homogeneously tortuous and dilated capillaries (bushy pattern), with a 73 +/- 17 mum (mean +/- standard deviation) diameter of capillary bushes. In contrast, scalp seborrheic dermatitis presented a multiform pattern, with mildly tortuous capillary loops and isolated dilated capillaries, but a substantial preservation of local microangioarchitecture. Mean diameter of capillary bush was significantly lower (27 +/- 4 microm; p < 0.001) and similar to that of the scalp of healthy subjects (21 +/- 5 microm). Capillary loop density was similar in patients with psoriasis (23 +/- 5/mm(2)) seborrheic dermatitis (24 +/- 2/mm(2)) and healthy scalp skin (24 +/- 3/mm(2)). CONCLUSION: VCP could be a useful noninvasive approach for differentiating between psoriasis and seborrheic dermatitis, especially when the scalp is the only affected site.

Adult↗

PubMed2006

Stimulation of purinergic receptors modulates chemokine expression in human keratinocytes.

ATP is abundantly released from stressed or damaged cells in response to mechanical stimulation, bacteria, or noxious agents. In this study, we have investigated the possible involvement of P2 receptors (receptor for extracellular nucleotides) in the expression and release of inflammatory mediators by human keratinocytes. Notably, extracellular ATP displayed a complex regulation of IFN-gamma-stimulated chemokine expression, with upregulation of CC chemokine ligand 2 (CCL2), CCL5 and CXC chemokine ligand 8 (CXCL8), and suppression of the receptor CXC chemokine receptor 3 (CXCR3), CXCL9, CXCL10, and CXCL11. The effect of ATP was mimicked by ADP and adenosine-5'-O-3-thiotriphosphate, whereas 2',3'-O-(4-benzoylbenzoyl) ATP (BzATP) downmodulated all chemokines investigated. UTP had no effect on IFN-gamma-stimulated chemokine secretion. The broad-spectrum P2 receptor antagonist suramin and the selective P2Y1 inhibitor adenosine 3'-phosphate 5'-phosphosulfate counteracted the effect of ATP on secretion of all the chemokines examined, whereas pyridoxal phosphate 6-azophenyl 2',4'-disulfonic acid and KN62 (1-[N,O-bis(5-isoquinoline sulfonyl)-N-methyl-L-tyrosyl] 4 phenylpiperazine) partially prevented the inhibitory effect of ATP on CXCL10 secretion, but on the other hand potentiated the ATP-stimulatory effect on CCL5, CCL2, and CXCL8 release. In lesional skin of psoriasis and atopic dermatitis patients, intense P2X7 reactivity was confined to the cell membrane of the basal layer, whereas diffuse P2Y1 immunostaining was found throughout the epidermis. Collectively, our data suggest that the orchestrated activation of distinct P2Y and P2X receptors modulates skin inflammation.

Adenosine Triphosphate↗

PubMed2006

Mechanism of HBD-3 deficiency in atopic dermatitis.

Extrinsic atopic dermatitis (EAD) and intrinsic atopic dermatitis (IAD) patients suffer from recurrent bacterial and viral infections. In this study, we demonstrate significantly decreased expression of human beta defensin (HBD)-3, a potent antimicrobial peptide (AMP), in lesional skin of both IAD (p<0.01) and EAD patients (p<0.01), as compared to psoriasis patients. Using primary keratinocytes from EAD and IAD patients, we determined that the deficiency in HBD-3 expression is an acquired rather than a constitutive defect. Furthermore, we demonstrate the down-regulatory effect of IL-4, IL-10, and IL-13 - which are over-expressed in the skin of AD patients - on HBD-3 expression in keratinocytes. Additionally, treatment of EAD skin explants with antibodies against IL-4, IL-10, and IL-13 augmented the expression of HBD-3. These studies suggest that neutralizing the Th2 cytokine milieu in AD skin may augment the innate immune response against bacterial and viral pathogens.

Adult↗

PubMed2006

Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic dermatitis (ATOD2) on human chromosome 1q21.

Psoriasis (PS) is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and altered differentiation. Atopic dermatitis (ATOD) is a chronic inflammatory, pruritic and eczematous disease frequently associated with respiratory atopy. These diseases are associated with distinct immunologic abnormalities and represent typical examples of complex diseases triggered by both genetic and environmental factors, as demonstrated by independent twin studies. Genome wide linkage studies have mapped susceptibility loci on several chromosomes (PSORS1-9; ATOD1-5). Four of them overlap on chromosomes 1q21, 3q21, 17q25 and 20p although ATOD is quite distinct from PS and these two diseases rarely occur together in the same patient. An association fine-mapping study has been performed to refine PSORS4 and ATOD2 susceptibility loci on chromosome 1q21 analyzing two independently collected cohorts of 128 PS and 120 ATOD trios. Genotype and haplotype analysis of PSORS4 and ATOD2 led us to detect significant p value for haplotypes defined by MIDDLE and ENDAL16 markers in both PS (p = 0.0000036) and ATOD (p = 0.0276), suggesting a strict co-localization within an interval of 42 kb. This genomic interval contains a single gene, LOR, encoding for loricrin. Polymorphic markers mapping in regulatory and coding regions did not show evidence of association in neither of the two diseases. However, expression profiles of LOR in skin biopsies have shown reduced levels in PS and increased levels in ATOD, suggesting the existence of a specific misregulation in LOR mRNA production.

Chromosome Mapping↗

PubMed2006

CD56brightCD16(-) NK cells accumulate in psoriatic skin in response to CXCL10 and CCL5 and exacerbate skin inflammation.

Psoriasis is an immune-mediated skin disease characterized by lymphocytic infiltration and altered keratinocyte differentiation. Using immunohistochemical techniques we found that the cellular infiltrate in acute psoriatic plaques includes 5-8% CD3(-)CD56(+) natural killer (NK) cells, mostly localized in the mid and papillary dermis. NK lymphocytes isolated from punch biopsy specimens of psoriatic plaques showed a CD56(bright)CD16(-)CD158b(-) phenotype, failed to express the skin homing cutaneous lymphocyte-associated antigen and released abundant IFN-gamma upon stimulation. Supernatants from psoriatic NK cells induced MHC class II and ICAM-1 expression and release of CXCL10 and CCL5 by cultured psoriatic keratinocytes. Skin NK cells expressed high levels of the chemokines receptors CXCR3 and CCR5, intermediate amounts of CXCR1, CCR6 and CCR8, and low levels of CCR1, CCR2, CCR4, CCR7 and CX3CR1. In addition, they promptly migrated in vitro toward CXCL10, CCL5, supernatants of IFN-gamma-activated psoriatic keratinocytes and, to a lower extent, CCL20 and CCL4. In contrast, they failed to migrate toward CXCL8, CCL1, CCL2, CCL3, CCL17, CCL19 and CX3CL1. Taken together, our results implicate NK lymphocytes as newly identified protagonists in the pathogenesis of psoriasis. Their distinctive homing properties should be taken into account in the design of specific therapy aimed at blocking pathogenic cell accumulation in the skin.

CD56 Antigen↗

PubMed2006

Autoimmune progesterone dermatitis.

Autoimmune progesterone dermatitis (APD) is a rare disorder characterized by recurrent polymorphous skin manifestations, which appear or are exacerbated during the luteal phase of the menstrual cycle. The hallmarks for diagnosis include premenstrual flare, its prevention with the inhibition of ovulation, and positive skin reaction to intradermal injection of progesterone. The mainstay of treatment is to inhibit the secretion of endogenous progesterone by suppressing ovulation. Bilateral oophorectomy may be necessary in patients with severe and refractory symptoms. We report herein the case of a 38-year-old woman who developed recurrent and cyclic vesiculobullous eruptions clinically suggestive of erythema multiforme or autoimmune bullous diseases. The skin manifestations turned out to be APD. The patient was treated with tamoxifen 20 mg daily with complete symptom remission after 4 months.

Adult↗

PubMed2006

Effective management of psoriasis symptom worsening during efalizumab therapy without discontinuing treatment: a case study.

Efalizumab is an effective therapy for the long-term treatment of chronic plaque psoriasis. However, regardless of the type of antipsoriatic treatment a patient is receiving, natural fluctuations in symptom severity occur throughout the course of the disease, and need to be managed appropriately. Here, we report the case of a patient with moderate chronic plaque psoriasis resistant to conventional treatments, who initially showed an excellent response to efalizumab (1 mg/kg per week, subcutaneous injection), but then experienced symptom exacerbation after 8 weeks of treatment. This worsening of symptoms was successfully controlled using a short course of concomitant methotrexate treatment (15 mg/week, intramuscular injection). After 1 month, the clinical signs had cleared, methotrexate treatment was stopped and efalizumab therapy was continued. These results show the effective use of a short course of concomitant methotrexate to control fluctuations in psoriasis severity in a patient receiving efalizumab therapy in general clinical practice.

Antibodies, Monoclonal↗

PubMed2006

Analysis of IFN-kappa expression in pathologic skin conditions: downregulation in psoriasis and atopic dermatitis.

Interferon-kappa (IFN-kappa) is a type I IFN expressed by keratinocytes, monocytes and dendritic cells (DCs). In human keratinocytes, it is produced in response to double-stranded RNA (dsRNA) and other IFNs and protects from viral infections. In monocytes and DCs, IFN-kappa induces tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) and inhibits lipopolysaccharide (LPS)-induced IL-12. In this study, we evaluated IFN-kappa expression in skin lesions of patients with common immune-mediated inflammatory disorders using immunohistochemical techniques. IFN-kappa was not detectable in healthy skin but was strongly expressed in allergic contact dermatitis and lichen planus-affected skin. IFN-kappa was localized mainly in basal and suprabasal keratinocytes and in some leukocytes infiltrating the dermis. In contrast, IFN-kappa expression in psoriatic or atopic dermatitis (AD) pidermis was weak and detectable in only 2 of 5 patients examined. Consistently, cultured keratinocytes and monocytes obtained from psoriatic and AD patients expressed null or low levels of IFN-kappa in response to IFN-gamma, which strongly upregulates IFN-kappa in normal keratinocytes. IFN-kappa accumulated in keratinocyte cytoplasm and plasma membrane, and only limited amounts were released extracellularly. Soluble IFN-kappa did not influence keratinocyte proliferation or chemokine and membrane molecule expression, and only its membrane-associated form activated IFN-stimulated response element (ISRE) signaling. Given the difference in IFN-kappa expression levels in the skin disorders examined, IFN-kappa presence or deficiency might have different pathogenetic consequences depending also on other disease-specific intrinsic alterations.

Adult↗

PubMed2006

Glutathione S-transferase and CYP1A1 gene polymorphisms and non-melanoma skin cancer risk in Italian transplanted patients.

Solid organ transplant recipients are at higher risk of non-melanoma skin cancer (NMSC), especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Genetic alterations in the production of detoxifying enzymes such as glutathione S-transferase (GST) and CYP1A1 may enhance this risk. We investigated the frequency of GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1) and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and 132 controls free from NMSC matched for type of transplanted organ, duration of transplantation, sex and age. Allele GSTP1*A was associated with a higher risk of NMSC [odds ratio (OR) 1.7 (1.1-2.5); P = 0.017]. Homozygosity for allele GSTP1 Val(105) was lower in cases [OR 0.3 (0.1-0.8); P = 0.012], especially in patients with SCC [OR 0.1 (0.0-0.7); P = 0.012]. A higher risk of BCC was found in patients with GSTM1 null/null [null/null versus A + B, OR 3.1 (1.4-6.8); P = 0.003]. Analysis of allelism and interaction between allelic variants showed significant association between combined GSTM1 and CYP1A1 Val(462) genotypes, where individuals homozygous for the risk allele GSTM1 null and carrying also the allele CYP1A1 Val(462), show a higher risk of developing NMSC [OR 4.5 (1.1-21.4); P = 0.03], especially SCC [OR 6.5 (1.4-34.4); P = 0.01]. GSTP1 polymorphisms are associated with both BCC and SCC risk. GSTM1 polymorphisms seem to be involved in BCC risk, while GSTM1 null/null genotype combined with CYP1A1 allele Val(462) are associated with a higher risk for SCC, indicating that allelism and/or interactions between allelic variants at other loci may also influence the risk of NMSC, particularly SCC.

Adult↗

PubMed2005

Videocapillaroscopic alterations in erythematotelangiectatic rosacea.

BACKGROUND: Rosacea is a common chronic dermatosis that involves the cutaneous microvasculature of the face. There are no objective measures for assessing the severity of erythematotelangiectatic rosacea. OBJECTIVE: Our purpose was to characterize and provide objective measures of vessel changes in erythematotelangiectatic rosacea by videocapillaroscopy. METHODS: We compared 30 patients with erythematotelangiectatic rosacea with 30 age- and sex-matched patients with facial seborrheic dermatitis and 30 healthy control subjects. Videocapillaroscopy was performed both on the cheeks and on the nailfold region. The analyzed parameters of the face were morphological (background color, vessel irregularities) and quantitative (polygonal net perimeter, telangiectasia, and vessel diameters). RESULTS: Characteristic alterations of skin vessels were observed in facial rosacea, with a pattern distinct from that of facial seborrheic dermatitis. In particular, rosacea showed neoangiogenesis and significantly larger polygons (13.21 +/- 3 vs 7.8 +/- 3 mm; mean +/- standard deviation, P < .001), more prominent telangiectases (267.8 +/- 108 vs 118.2 +/- 35 microm; P < .001) and larger mean vessel diameter (46.71 +/- 9 vs 24 +/- 10 microm; P < .001) compared with seborrheic dermatitis. Seborrheic dermatitis displayed more polygon irregularities and vessel tortuosity. In contrast, no differences were found in the nailfold region. LIMITATIONS: Vessel irregularities and overall erythema may be difficult to quantify. CONCLUSIONS: Videocapillaroscopy may represent a valid adjunctive method in the early diagnosis and measurement of erythematotelangiectatic rosacea.

Adult↗

PubMed2005

ERK1/2 regulates epidermal chemokine expression and skin inflammation.

Resident cell populations of the skin contribute to the inflammatory response by producing an array of chemokines, which attract leukocytes from the circulation. TNF-alpha is a major inducer of proinflammatory mediators in keratinocytes. We have recently observed that epidermal growth factor receptor (EGFR) signaling affects TNF-alpha-driven chemokine expression in epidermal keratinocytes, and its functional impairment increases the levels of crucial chemoattractants such as CCL2/MCP-1, CCL5/RANTES, and CXCL10/IFN-gamma-inducible protein-10. In this study, we report evidence that EGFR-dependent ERK1/2 activity is implicated in this mechanism. Abrogation of ERK1/2 activity with specific inhibitors increased chemokine expression in keratinocytes by enhancing mRNA stabilization. In mouse models, inflammatory response to irritants and T cell-mediated contact hypersensitivity were both aggravated when elicited in a skin area previously treated with an EGFR or a MAPK kinase 1/2 inhibitor. In contrast, impairment of p38alpha beta MAPK phosphorylation markedly attenuated these responses. Our data indicate that EGFR-dependent ERK1/2 activity in keratinocytes takes part to a homeostatic mechanism regulating inflammatory responses, and emphasize the distinct role of MAPKs as potential targets for manipulating inflammation in the skin.

Animals↗

PubMed2005

Severe impairment of quality of life in Hailey-Hailey disease.

Hailey-Hailey disease (a skin fragility disorder) runs a chronic course and may cause important disability. However, little has been formally investigated concerning the quality of life (QoL) of patients affected by this disorder. We studied the impact of Hailey-Hailey disease on the QoL of 22 consecutive patients seen at our dermatological clinic. Patients were examined by a dermatologist, and they were asked to complete two self-administered questionnaires: the Skindex-29, in order to determine their QoL, and the 12-item General Health Questionnaire, to evaluate psychological distress. Completed questionnaires were returned by 20 patients. Even in patients with few body sites involved, median overall QoL scores were much higher than those observed in other skin conditions in all three domains investigated by the Skindex-29 (i.e. symptoms, emotions and social functioning). This was true also for the levels of psychological distress. QoL impairment was substantial irrespective of the number of body sites involved. Our findings document a great impact of Hailey-Hailey disease on patients' QoL. Therefore, a more aggressive therapeutic approach may be warranted in all patients, including those with few lesions.

Adult↗

PubMed2005

Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis.

Recurrent skin infections in extrinsic atopic dermatitis (EAD) may be because of the suppression of anti-microbial peptide (AMP) expression by interleukin (IL)-4 and IL-13. Twenty to thirty percent of AD, however, are classified as intrinsic atopic dermatitis (IAD). They exhibit normal serum IgE levels, no allergen-specific sensitization, and lower levels of IL-4 and IL-13 than EAD. Both forms of AD have increased propensity to skin infection, suggesting a novel mechanism for infection in IAD. In this study, we observed significantly decreased human beta-defensin (HBD)-2 gene expression in the skin of both IAD (p = 0.010) and EAD (p = 0.004), as compared with psoriasis patients. Conversely, IAD (p = 0.019) and EAD (p = 0.002) skin lesions exhibited elevated IL-10 gene expression when compared with psoriasis. Using primary keratinocytes, we found that the deficiency in AMP expression is an acquired rather than a constitutive defect. Interestingly, neutralizing antibodies to IL-10 augmented the production of tumor necrosis factor-alpha and interferon-gamma by peripheral blood mononuclear cell from AD patients. Additionally, treatment of AD skin explants with anti-IL-10 augmented the expression of both HBD-2 and LL-37. Thus, increased levels of IL-10 may contribute to the AMP deficiency in both IAD and EAD by reducing cytokines that induce AMP.

Adult↗

PubMed2005

Pimecrolimus in dermatology: atopic dermatitis and beyond.

Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD). Pimecrolimus selectively targets T cells and mast cells. Pimecrolimus inhibits T-cell proliferation, as well as production and release of interleukin-2 (IL-2), IL-4, interferon-gamma and tumour necrosis factor-alpha. Moreover, pimecrolimus inhibits mast cell degranulation. In contrast to tacrolimus, pimecrolimus has no effects on the differentiation, maturation and functions of dendritic cells. In contrast to corticosteroids, pimecrolimus does not affect endothelial cells and fibroblasts and does not induce skin atrophy. Given the low capacity of pimecrolimus to permeate through the skin, it has a very low risk of systemic exposure and subsequent systemic side-effects. In different randomised controlled trials, topical pimecrolimus as cream 1% (Elidel) has been shown to be effective, well tolerated and safe in both adults and children with mild to moderate AD. In addition, pimecrolimus has been successfully used in inflammatory skin diseases other than AD, including seborrheic dermatitis, intertriginous psoriasis, lichen planus and cutaneous lupus erythematosus.

Dermatitis↗

PubMed2005

Keratinocytes in inflammatory skin diseases.

Although in the past, keratinocytes were considered simply as passive targets of immunological attack from infiltrating T lymphocytes, a number of studies have definitively demonstrated that keratinocytes actively participate in the cutaneous immune responses. Upon activation, keratinocytes express a plethora of cytokines, chemokines and accessory molecules, which can transmit both positive and negative signals to cells of innate and adaptive immunity. Dysregulation and abnormal expression of inflammatory mediators or their receptors in keratinocytes are relevant to the pathogenesis of chronic inflammatory skin diseases such as psoriasis, atopic dermatitis and allergic contact dermatitis.

Animals↗

PubMed2004

Inosine stimulates chemotaxis, Ca2+-transients and actin polymerization in immature human dendritic cells via a pertussis toxin-sensitive mechanism independent of adenosine receptors.

Inosine is an endogenous purine nucleoside, which is formed by adenosine deaminidase during adenosine breakdown and is released into the extracellular space from the sympathetic nervous system or injured cells. Here, we studied the biological activity of inosine on human dendritic cells (DC), which are specialized antigen presenting cells characterized by their ability to migrate from the blood to peripheral tissues, and then to secondary lymphoid organs where they initiate adaptive immune responses. In immature DC, inosine concentration-dependently stimulated Ca(2+)-transients, actin polymerization, and chemotaxis. Experiments with adenosine receptor antagonists and pertussis toxin (PTX) as well as desensitization studies suggested that the activity of inosine was mediated by a G protein-coupled receptor pathway independent of adenosine receptors. DC, induced to mature by lipopolysaccharide, lost their ability to respond towards inosine with these activities. Moreover, inosine did neither influence membrane expression of CD54, CD80, CD83, CD86, HLA-DR, and MHC class I molecules nor modulated secretion of interleukin (IL)-12, IL-10, and tumor necrosis factor alpha in immature and lipopolysaccharide-matured DC. In aggregate, our study indicates that inosine may be involved in the trafficking control system of immature DC, and mediates its chemotactic activity by a PTX-sensitive mechanism independent of adenosine receptors.

Actins↗

PubMed2004

Characterization of the biological activities of uridine diphosphate in human dendritic cells: Influence on chemotaxis and CXCL8 release.

Uridine nucleotides are endogenous nucleotides which are released into the extracellular space from mechanical stressed endothelial and epithelial cells as well as lipopolysaccharide (lps)-stimulated monocytes. Here, we studied the biological activity of the selective purinoreceptor P2Y6 (P2YR6) agonist Uridine 5'diphosphate (UDP) as well as the P2YR2- and P2YR4-activating uridine 5'triphosphate (UTP) on human dendritic cells (DC). These cells in their immature state have the ability to migrate from blood to peripheral target sites where they sense dangerous signals and capture potential antigens. Moreover, mature DC induce innate immune responses and migrate from peripheral tissues to secondary lymphoid organs in order to activate naive T cells and initiate adaptive immunity. Here, we were able to show that uridine nucleotides stimulated Ca(2+) transients, actin polymerization, and chemotaxis in immature DC. Experiments with pertussis toxin, the stable pyrimidine agonist uridine 5'-O-(2-thiodiphosphate) (UDPgammaS) and receptor antagonists, as well as desensitization studies suggested that these uridine nucleotides activities were mediated by different G(i) protein-coupled receptors. During lps-induced maturation, DC lost their ability to respond towards uridine nucleotides with these activities. Instead, UDP, but not UTP, stimulated the release of the CXC-chemokine 8 (CXCL8) from mature DC in a reactive blue sensitive manner. Moreover, our study indicates that UDP stimulates different signaling pathways in immature and mature DC in order to favor the accumulation of immature DC and to augment the capacity to secrete CXCL8 in mature DC.

Actins↗

PubMed2004

Treatment of recalcitrant scleromyxedema with thalidomide in 3 patients.

Scleromyxedema is a generalized, papular, and sclerodermoid form of lichen myxedematosus associated with monoclonal gammopathy and systemic changes. Despite anecdotal reports of success with various agents, no satisfactory treatments are currently available. We report 3 adult patients with recalcitrant scleromyxedema associated with paraproteinemia who were treated with thalidomide. All 3 patients had marked improvement of the skin lesions and joint mobility after the first 2 months of therapy, with further amelioration after 4 months, and reduction in paraprotein levels.

Aged↗