[Show abstract][Hide abstract] ABSTRACT: Aim: The aim of this paper to report the main clinical and immunopathological findings of our case series of 159 patients with dermatitis herpetiformis (DH). Methods: All DH patients that were diagnosed from 1995 to 2012 at the Section of Dermatology of the University of Florence were included in the study. Clinical data were collected for each patient. Moreover, histopathological examination on both the skin and the small bowel, direct immunofluorescence on perilesional skin as well as the search for anti-endomysium and anti-tissue transglutaminsase antibodies (tTG) were performed. Results: A total of 159 patients with a male predominance were enrolled. About 36% of the patients were below the age of 20. The most frequent clinical features seen in our DH patients were represented by figurate erythema, wheals, papules and scratching lesions, while the knees, elbows and buttocks were the most commonly involved sites. All the 22 patients that underwent a bowel biopsy showed the typical alterations found in celiac disease. Moreover, 100% of the patients showed granular IgA deposits at the papillary tips. Finally, anti-endomysium and anti-tTG antibodies were present in 90% and 96% of the patients, respectively. Conclusion: We reported one of the largest case series of patients with DH from a single center. Our study confirmed most of the data from the Literature, and in particular the association of DH to histologically proven CD in all the biopsied cases. Another interesting finding of our study is the high prevalence of DH within pediatric patients, that is usually underreported.
Giornale Italiano di Dermatologia e Venereologia 04/2013; 148(2):163-9. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To establish the possible sources and routes of transmission of a multidrug-resistant Acinetobacter baumannii outbreak involving 22 patients. STUDY DESIGN: Descriptive, retrospective study. METHODS: An environmental investigation was undertaken, monitoring surfaces, air and water. Reconstruction of the spread of the infection took several factors into account such as intrahospital movements of patients and healthcare personnel, hospitalization of patients in the same ward and in chronologically compatible periods, and length of stay. A. baumannii clinical samples were typed using the Multilocus Sequence Typing scheme. RESULTS: The outbreak originated from a patient admitted to the sub-intensive care unit, and the infection subsequently spread to other wards. The allelic profile proved to be the same for all the clinical isolates. Environmental monitoring yielded negative results for A. baumannii. CONCLUSIONS: The results suggest that this epidemic spread through cross-transmission involving healthcare workers.
[Show abstract][Hide abstract] ABSTRACT: Classification of the wide variety of autoimmune diseases that can occur before or after the onset of Sjögren's syndrome (SS) is currently debated within the conventional SS criteria or as primary SS (pSS) developing autoimmune disease or as 'associated-overlap' with other systemic autoimmune diseases. There is also debate on whether or not to consider annular polycyclic subacute cutaneous lupus erythematosus (SCLE) and annular erythema associated with Sjögren's syndrome (AESS) as a spectrum linked to Ro-SSA and/or La-SSB auto-antibodies (SSA/SSB auto-ab). We present the case of a 55-year-old female patient, with pSS positive for SSA and SSB auto-ab, who developed chronic relapsing polymyositis and atypical annular non-polycyclic SCLE lesions resembling AESS, which seemed to suggest a common spectrum. While a chronic-progressive polymyositis may be generally accepted as a relatively rare myositis complicating pSS, interpretation of annular lesions of non-systemic SCLE in SS patients might actually be underestimated as pSS skin manifestation likely related to SSA/SSB auto-ab.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Although regulatory T cells (Tregs) are affected in several autoimmune skin diseases, only two studies have been performed in patients with bullous pemphigoid (BP) with contrasting results. OBJECTIVE: To characterize Tregs and to determine the serum levels of regulatory cytokines in patients with BP. METHODS: In BP lesional skin, immunohistochemistry and confocal microscopy were performed for CD4(+) , CD25(+) , forkhead/winged helix transcription factor (FOXP3)(+) , transforming growth factor (TGF)-β(+) and interleukin (IL)-10(+) cells. In addition, the number of CD4(+) CD25(++) FOXP3(+) Tregs in peripheral blood was assessed by flow cytometry, and the levels of TGF-β and IL-10 were determined in serum samples by enzyme-linked immunosorbent assay before and after steroid therapy. Controls included patients with psoriasis, atopic dermatitis (AD) and healthy donors. RESULTS: The frequency of FOXP3(+) cells was significantly reduced in skin lesions from patients with BP (P < 0.001) compared with psoriasis and AD. Moreover, the number of IL-10(+) cells was lower in BP than in psoriasis (P < 0.001) and AD (P = 0.002), while no differences were observed in the number of TGF-β(+) cells. CD4(+) CD25(++) FOXP3(+) Treg in the peripheral blood of patients with BP was significantly reduced compared with healthy controls (P < 0.001), and augmented significantly after steroid therapy (P = 0.001). Finally, TGF-β and IL-10 serum levels were similar in patients with BP compared with healthy controls. However, after therapy, BP patients showed significantly higher IL-10 serum levels than before therapy (P = 0.01). CONCLUSIONS: These data suggest that the depletion of Tregs and of IL-10 in patients with BP may be an important factor in the pathogenesis of the disease.
Journal of the European Academy of Dermatology and Venereology 01/2013; · 2.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The deamidated gliadin peptides (DGP) cross linked to human tissue transglutaminase (tTg) comprises a novel neo-epitope structure (Neo-tTg) for serological screening of celiac disease (CD). Our aim is to verify anti-Neo-tTg IgA and IgG in adults with dermatitis herpetiformis (DH). METHODS: Multi-centric retrospective evaluation of the IgA/G autoantibodies in sera of DH patients on regular diet (n=40), gluten restricted diet (GRD, n=53) and control adults with autoimmune skin diseases (n=107) by ELISA. RESULTS: The sensitivities of Celicheck Neo IgA/G (76%, 95% CI 67-84%) and the Neo tTg-A (85%, 95% CI 70-97%) ELISA were significantly greater than that of tTg-A (56%, 95% CI 46-67%), eTg-A (62%, 95% CI 52-72%), DGP-A (55%, 95% CI 55-65%), DGP-G (61%, 95% CI 51- 71%), Glia-A (55%, 95% CI 45-65%) and Glia-G (56%, 95% CI 46-66%) ELISA. The specificities of all 8 ELISA were in the range 90-100%. The area under the curve (AUC) of receiver operator characteristics curve (ROC) for the two Neo-tTg ELISA (0.863 and 0.949) were higher than the AUCs for ROCs of tTg, DGP and eTG ELISA (range between 0.657 and 0.783). The autoantibody levels of DH patients on normal diet were significantly higher than those on GRD in the Celicheck Neo IgA/IgG, NeotTg- A; tTg- A and the eTg-A; ELISA (p< 0.01) and of no significance in the DGP and Gliadin ELISA. CONCLUSION: Neo-epitope IgA autoantibodies represent a new and sensitive serological marker of DH.
Clinica chimica acta; international journal of clinical chemistry 11/2012; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bullous pemphigoid (BP) is the most frequent autoimmune bullous skin disease, characterised by auto-antibodies against the hemidesmosome complex. Recently, regulatory T cells (Tregs) have been implicated in the development of several autoimmune diseases; few data are available in BP, failing to demonstrate a role of this subset in disease pathogenesis. The aim of this study was to investigate the expression and phenotypes of different Tregs (CD4+ CD25brightFOXP3+ and CD8+ CD28- cells) in BP to clarify whether the depletion of this subset constitutes one mechanism of tolerance loss. The CD4+ CD25brightFOXP3 and CD8+ CD28- circulating subsets were determined by flow-cytometry in 26 untreated BP patients and compared with a group of age- and sex-matched healthy controls (HC, n = 30). Absolute and percentage values of the CD4+ CD25brightFOXP3+ cells were significantly reduced in BP compared with HC (median CD25brightFOXP3+ expression within CD4+ cells: 1.8 vs. 3.5%, p = 0.002); conversely, BP patients were characterised by a significant expansion of the CD25brightFOXP3- "activated" T-cell subset. CCR4 and CD62L were expressed on the majority of CD4+ CD25brightFOXP3+ cells (75.2 and 82.3%, respectively). No differences in the CD8+ CD28- subset were found between BP and HC. This is the first report showing a significant reduction of circulating CD4+ CD25brightFOXP3+ Treg frequency in BP patients.
Archives for Dermatological Research 02/2012; 304(8):639-45. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To date, 71 patients having the so-called 'Rowell's syndrome' (RS) have been reported in the literature. However, most of them did not show all the clinical and serological features first described by Rowell and co-workers in 1963. Moreover, since then, subacute cutaneous lupus erythematosus (SCLE) has been identified and the diagnostic criteria as well as the clinical features of erythema multiforme (EM) defined. Accordingly several authors have questioned the existence of RS over the past years. In the present paper, the main clinical, histopathological and immunopathological features of both SCLE and EM are described and all of the cases of RS reported in the literature are also reviewed in depth. A real association between discoid LE and EM was present only in a minority of cases and could be considered a mere coincidence. As for other associations, e.g. those between CLE and lichen planus or psoriasis, the coexistence of CLE and EM does not justify the framing of a separate syndrome as suggested by Rowell et al.
[Show abstract][Hide abstract] ABSTRACT: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is a lupus variant with predominant skin involvement temporally related to drug exposure and resolving after drug discontinuation. It usually presents with annular polycyclic or papulosquamous eruptions on sun-exposed skin and shows serum anti-Ro/SSA antibodies.
To address the question whether DI-SCLE differs significantly from idiopathic SCLE by virtue of clinical features.
Ninety patients with SCLE seen in our departments from 2001 to 2010 were reviewed. Eleven of them diagnosed as having DI-SCLE were evaluated for type of skin lesions, systemic involvement, clinical course, and histopathological, direct immunofluorescence and laboratory findings. The cutaneous features were compared with those of the 79 patients with idiopathic SCLE.
The cutaneous picture was widespread in 82% of patients with DI-SCLE and in 6% of those with idiopathic SCLE [odds ratio (OR) 66·6, 95% confidence interval (CI) 11·2-394·9; P = 0·0001]. Bullous and erythema multiforme (EM)-like lesions were present in 45% of patients with DI-SCLE and in 1% of those with idiopathic SCLE (OR 65·0, 95% CI 6·5-649·6; P = 0·0001). Vasculitic lesions were observed in 45% of patients with DI-SCLE and in 3% of those with idiopathic SCLE (OR 32·1, 95% CI 5·1-201·7; P = 0·0001). Malar rash occurred in 45% of patients with DI-SCLE and in 6% of those with idiopathic SCLE (OR 12·3, 95% CI 2·8-54·9; P = 0·001). Visceral manifestations were excluded in all patients with DI-SCLE. Anti-Ro/SSA antibodies were found in all but one patient with DI-SCLE and disappeared after resolution in 73% of cases.
DI-SCLE differs from idiopathic SCLE by virtue of distinctive cutaneous features, particularly the widespread presentation and the frequent occurrence of malar rash and bullous, EM-like and vasculitic manifestations.
British Journal of Dermatology 05/2011; 165(2):335-41. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: T-lymphocytes are believed to play an important role in the pathogenesis of discoid lupus erythematosus (DLE). However, the reasons that lead to loss of tolerance and to development of autoimmunity in DLE remain unclear. In the present paper, we investigated serum levels of the regulatory cytokines transforming growth factor (TGF)-β and interleukin (IL)-10 in 25 newly diagnosed patients with DLE, 15 with systemic lupus erythematosus (SLE), 10 with psoriasis, 10 with atopic dermatitis (AD) and 20 healthy controls (HC). TGF-β serum levels were significantly lower in patients with DLE compared with patients with psoriasis and HC, while no differences were found between DLE, SLE and AD (medians: DLE: 28.49 ng/ml; psoriasis: 42.77 ng/ml; HC: 43.71 ng/ml; DLE vs. psoriasis: p < 0.05; DLE vs. HC: p < 0.05). IL-10 concentrations were reduced in DLE serum samples with respect to SLE, psoriasis, AD and HC (medians: DLE: 46.42 pg/ml; SLE: 127.64 pg/ml; psoriasis: 109.3 pg/ml; AD: 76.3 pg/ml; HC: 114.71 pg/ml; DLE vs. SLE: p < 0.05; DLE vs. psoriasis: p < 0.05; DLE vs. AD: p < 0.05; DLE vs. HC: p < 0.05). The downregulation of TGF-β and IL-10 in DLE may lead to defective immune suppression and thus to the generation of the tissue injury that is found in lupus patients.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to characterize regulatory T cells (T(reg)) in skin lesions and peripheral blood from patients with dermatomyositis (DM) and to determine the serum levels of regulatory cytokines in the disease. In skin biopsy specimens from patients with DM, immunohistochemistry was performed for CD4(+), CD25(+), forkhead/winged helix transcription factor (FoxP3)(+), transforming growth factor (TGF)-β(+) and interleukin (IL)-10(+) cells. Additionally, we defined the number of T(reg) subpopulations in peripheral blood by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RO, CD95, CCR4 and CLA. The levels of TGF-β and IL-10 were also determined in serum samples from patients with DM by enzyme-linked immunosorbent assays. Controls included patients with cutaneous lupus erythematosus, psoriasis and atopic dermatitis (AD) as well as healthy donors. The frequency of FoxP3(+) cells was significantly reduced in skin lesions from patients with DM (p < 0.001) compared to psoriasis and AD. Moreover, the number of cells positive for TGF-β was lower in DM than in psoriasis and AD, while IL-10(+) cells were significantly reduced only compared to psoriasis. The number of CD4(+)CD25(++)FoxP3(+) T(reg) in the peripheral blood of patients with DM was significantly reduced compared to healthy controls (p < 0.05), whereas other cell populations showed no significant differences. Finally, TGF-β and IL-10 serum levels were significantly lower in patients with DM compared to healthy controls (p < 0.05). These data suggest that the depletion of T(reg) and their main effector cytokines in the skin and the serum of patients with DM may be an important factor in the pathogenesis of the disease.
Journal of Autoimmunity 12/2010; 35(4):342-50. · 8.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alterations of Toll-like receptors (TLRs) seem to play a role in susceptibility to atopic dermatitis (AD).
To investigate the expression of TLRs in moderate to severe chronic AD in adults before and after a 3-week treatment with 0.1% tacrolimus ointment, compared with 0.1% topical hydrocortisone-17-butyrate.
In total, 21 adult patients with AD were enrolled: 11 were given tacrolimus ointment and 10 were given hydrocortisone butyrate; a further 6 healthy adults formed the control group. The clinical efficacy of the treatment was assessed using the SCORing Atopic Dermatis (SCORAD) index. Biopsies were taken from lesional skin before and after treatment, which were stained immunohistochemically with monoclonal antibodies to TLR-1, -2, -4 and -9.
Both 3-week topical treatments improved signs and symptoms in all 21 patients considered, with no significant difference between the two groups. In the skin of patients with AD, TLR-1 was overexpressed and TLR-2 underexpressed compared with healthy controls, whereas no differences were found for TLR-4 and TLR-9. Staining for TLR-1 was decreased in both groups after treatment. AD specimens had higher levels of TLR-2 expression after either treatment compared with baseline, and levels were higher after tacrolimus treatment than after hydrocortisone butyrate. Neither tacrolimus nor hydrocortisone butyrate affected expression of TLR-4 or TLR-9.
Short-term therapy with tacrolimus ointment reduced expression of TLR-1, which may inhibit the antimicrobial potential of TLR-2, and also reversed the impairment of TLR-2 in AD lesions. Expression of TLR-4 and TLR-9 was not affected by tacrolimus.
Clinical and Experimental Dermatology 11/2010; 36(3):235-41. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Systemic sclerosis (SSc) and morphoea are connective tissue diseases characterized by fibrosis of the skin. Although to date their pathogenesis has not been clearly defined, it is thought that autoimmunity may play a role in the development of the skin lesions observed in both these diseases. As regulatory T cells (Tregs) play a key role in the modulation of immune responses, it has recently been suggested that Treg impairment may lead to the development of autoimmune diseases.
To investigate the presence of Tregs and their immunomodulatory cytokines, transforming growth factor (TGF)-beta and interleukin (IL)-10, in patients with SSc and morphoea.
Fifteen patients with SSc and 15 with morphoea were enrolled. Immunohistochemistry was applied to identify FoxP3+ (forkhead/winged helix transcription factor) Tregs, TGF-beta+ cells and IL-10+ cells in the skin, cytofluorometry to detect CD4+CD25+FoxP3+ Tregs in the blood, and enzyme-linked immunosorbent assays to analyse TGF-beta and IL-10 serum levels.
Fewer FoxP3+ Tregs and TGF-beta+ and IL-10+ cells were found in the skin of patients with scleroderma than in controls. Similarly, there were reduced TGF-beta and IL-10 serum levels and fewer circulating CD4+CD25brightFoxP3+ cells in patients with SSc or morphoea, than in controls.
The quantitative reduction of Tregs, together with that of TGF-beta and IL-10 serum levels, may be responsible for the loss of tolerance observed in both SSc and morphoea.
British Journal of Dermatology 05/2010; 162(5):1056-63. · 3.76 Impact Factor