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PURPOSE: Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients. METHODS: This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype. RESULTS: A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07). CONCLUSION: These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment.
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Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.
Subject(s)
Breast Neoplasms , Carcinoma, Lobular , Humans , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Breast Neoplasms/prevention & control , Female , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/therapy , Carcinoma, Lobular/genetics , Carcinoma, Lobular/pathologySubject(s)
COVID-19 , Dermatomyositis , Female , Humans , Middle Aged , COVID-19/complications , Dermatomyositis/etiology , Dermatomyositis/complications , SARS-CoV-2ABSTRACT
Background: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. Methods: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. Findings: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and 65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Interpretation: Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Funding: Umberto Veronesi Foundation.
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INTRODUCTION: The objective of this study was to reclassify published germline CDH1 variants identified in gastric cancer (GC) in accordance with the latest ClinVar definition and to correlate their pathogenicity with the established international clinical criteria for genetic testing. METHODS: The relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations in accord with PRISMA guidelines. The collected variants were classified according to the latest ClinVar definition into the following classes: benign (B), likely benign (LB), pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS). The McNemar test was used to compare the adequacy of current versus previous International GC Linkage Consortium (IGCLC) criteria. RESULTS: We reclassified a total of 247 CDH1 variants, and we identified that about 70% of B/LB variant carriers were not fulfilling the defined clinical criteria. Instead, all P/LP variants (100%) were associated with the hereditary diffuse gastric cancer (HDGC) phenotype fulfilling the 2020 ILGCC criteria, with a significant improvement (p = 0.025) compared to previous version. CONCLUSIONS: We conclude that germline CDH1 genetic testing is indicated only in families meeting the clinical criteria for the HDGC syndrome. This observation suggests that clinical phenotypes that do not clearly fulfill these criteria should not be considered for CDH1 genetic testing.
Subject(s)
Adenocarcinoma , Stomach Neoplasms , Humans , Genetic Predisposition to Disease , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Pedigree , Genetic Testing , Germ-Line Mutation , Cadherins/genetics , Antigens, CD/geneticsABSTRACT
A breast unit is a multidisciplinary center specialized in the management of women with breast diseases, including breast cancer (BC). It represents a care path, passing from screening activities to diagnostic investigations, from surgery to the definition of the therapeutic strategy, from psychophysical rehabilitation to long-term checks (follow-up), and up to genetic counseling. Since 2006, following a resolution issued by the European Parliament to urge member states to activate multidisciplinary breast centers by 2016, work has been underway throughout Italy to improve the management of women with BC. In Italy, the State-Regions agreement was signed on 18 December 2014, sanctioning the establishment of breast units. These centers must adhere to specific quality criteria and requirements. In 2020, the experts of the EUSOMA group (European Society of Breast Cancer Specialists), in their latest document published, expanded the requirements of the breast units. Furthermore, Senonetwork was founded in 2012 with the aim of allowing BC to be treated in breast units that comply with European requirements to ensure equal treatment opportunities for all Italian women. Indeed, the available data indicate that the BC patient has a greater chance of better treatment in the breast units with a multidisciplinary team, thus increasing the survival rate with a better quality of life, compared to those managed in nonspecialized structures. The present review is a perspective on the current Italian reality of breast units, updated with the available literature and the most recent epidemiological data from Senonetwork and AgeNaS.
Subject(s)
Breast Neoplasms , Quality of Life , Female , Humans , Breast , Breast Neoplasms/diagnosis , Italy , Survival Rate , Multicenter Studies as TopicABSTRACT
PURPOSE: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome. METHODS: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant. RESULTS: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021). CONCLUSIONS: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC.
Subject(s)
Adenocarcinoma , Stomach Neoplasms , Humans , Male , Female , Infant , Stomach Neoplasms/diagnosis , Pedigree , Genetic Testing , Adenocarcinoma/genetics , Germ Cells , Cadherins/genetics , Germ-Line Mutation , Genetic Predisposition to Disease , Antigens, CD/geneticsABSTRACT
It is well known that viral infections play a relevant role in inducing or protecting from autoimmune diseases, thus representing a major environmental factor in the disruption of the immune system in genetically susceptible individuals. Since the beginning of the Covid-19 pandemic a great number of clinical and epidemiological studies have demonstrated that SARS-CoV-2 infection is no exception to the rule by interfering on many different levels in the normal functioning of our immune system. Even though a growing number of case series and case reports has been cited in the literature linking the infection to the new onset of autoimmune diseases, to date very little has been reported concerning a possible correlation between the virus and the clinical resolution of any kind of autoimmune pathology. Here we describe an interesting case of abrupt and unexpected resolution of Lichen planus pemphigoides mucocutaneous lesions in a fully vaccinated patient after a mildly symptomatic SARS-CoV-2 respiratory infection and we speculate on the possible underlying mechanisms correlating the two events.
Subject(s)
Autoimmune Diseases , COVID-19 , Lichen Planus , Humans , Pandemics , SARS-CoV-2ABSTRACT
Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from "pure" DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.
Subject(s)
Pemphigoid, Benign Mucous Membrane , Pemphigoid, Bullous , Humans , Autoantibodies , Retrospective Studies , Integrin beta4 , Italy , Mucous Membrane , AutoantigensSubject(s)
Pemphigus , Skin Diseases, Vesiculobullous , Blister , Humans , Immunoglobulin A , Pemphigus/diagnosisABSTRACT
The pandemic outbreak of Coronavirus Disease 2019 (COVID-19) led to the development of mRNA vaccines. With the extensive vaccination campaign performed worldwide, many adverse reactions to these drugs have been reported in the literature. Although most of them are mild and self-limiting, they may sometimes cause psychological stress and require efforts to make a differential diagnosis with other conditions. This is the case of lymphadenopathies and lymphedema in patients with a history of cancer. Herein we present a case of lymphedema of the arm developed ten days after a VAXZEVRIA COVID-19 vaccine shot in a patient who had concomitant signs and symptoms compatible with a diagnosis of dermatomyositis. It was later classified as paraneoplastic as instrumental investigation revealed a breast carcinoma contralateral to the site of vaccine injection. With this report we ponder an adverse reaction to COVID-19 vaccination with the aim of bringing new data for clinicians who face similar clinical presentations, particularly controversial for radiologists and oncologists.
ABSTRACT
Introduction: Pemphigus encompasses a group of muco-cutaneous autoimmune bullous diseases characterized by the loss of adhesion between keratinocytes. The disease is associated with increased morbidity and mortality. Materials and Methods: We characterized clinical patterns, survival, comorbidities, and drug prescriptions in patients with pemphigus referred to the Section of Dermatology of the University of Florence from January 2010 to December 2021. Results: A total of 149 patients were identified (female/male sex ratio = 2.0). Median age at diagnosis was 57.7 ± 17.2 years; 108 patients were diagnosed with pemphigus vulgaris (PV) (72.5%) and 35 (23.5%) with pemphigus foliaceus (PF). Paraneoplastic pemphigus (PNP) and IgA-pemphigus accounted for three patients each. The overall survival rate was 86.9%. Accordingly, 14 (9%) patients died during the study period. The average age at death was 77.8 ± 9.3. Age at diagnosis was a risk factor for death in patients with pemphigus. Average concentration of Dsg3-IgG and Dsg1-IgG was 85.6 ± 68.8 and 75.9 ± 68.4, respectively. The most serious comorbid diseases included cerebro- and cardiovascular accidents and malignancies. Regarding the treatment regimen, we found a substantially stable use of systemic steroids in the 2010-2018 period; the prevalence of use of mycophenolic acid increased, whereas that of azathioprine decreased. The use of rituximab showed the highest increase in the 2013-2018 period. Proton-pump inhibitors and antibiotics were the most frequently prescribed non-immunomodulating drugs. Conclusions: In this large series of the patients, patients with pemphigus showed a high incidence of serious comorbid diseases, highlighting the importance of a multidisciplinary approach for a proper management of the patients. Rituximab was the immunomodulating drug showing the highest increase in use over time, reflecting the growing evidence of its efficacy as a first-line treatment in pemphigus.
Subject(s)
Autoimmune Diseases , Pemphigus , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/diagnosis , Desmoglein 3 , Female , Hospitals , Humans , Immunoglobulin G , Male , Middle Aged , Pemphigus/diagnosis , Pemphigus/drug therapy , Pemphigus/epidemiology , RituximabABSTRACT
Recent studies have demonstrated that hereditary breast cancer (BC) has a prevalence of 5-10% among all BC diagnoses. Nowadays, significant technological advances in the identification of an increasingly broad spectrum of genetic mutations allow for the discovery of an ever-growing number of inherited pathogenic (P) or likely pathogenic (LP) variants of breast cancer susceptibility genes. As the management of BC patients carrying mutations in the BRCA1/2 genes or other high-penetrance genes is currently a challenge, extensive research is being carried out and a lively scientific debate has been taking place on what the most appropriate local therapy, especially surgical treatment, of patients with inherited BC should be. In many studies, BC outcomes in BRCA carriers and non-carriers have been compared. A number of them showed that, when compared with mastectomy, breast-conserving surgery in BRCA patients is oncologically safe in terms of overall survival, although an increased risk of ipsilateral recurrence was reported. In these patients, devising a specific therapeutic strategy is an inevitably complex process, as it must take into consideration a series of factors, require a multimodal approach, guarantee personalization, strictly adhere to scientific international guidelines, and consider all available evidence. The present narrative review purposes to identify and illustrate evidence from significant selected studies that discussed those issues, as well as to suggest useful tools to clinicians managing this specific clinical condition in daily clinical practice.
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INTRODUCTION: The combined use of 68gallium (68Ga)-DOTA-peptides and 18fluorine-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans in the workup of pancreatic neuroendocrine tumors (PanNETs) is controversial. This study aimed at assessing both tracers' capability to identify tumors and to assess its association with pathological predictors of recurrence. METHODS: Prospectively collected, preoperative, dual-tracer PET/CT scan data of G1-G2, nonmetastatic, PanNETs that underwent surgery between January 2013 and October 2019 were retrospectively analyzed. RESULTS: The final cohort consisted of 124 cases. There was an approximately equal distribution of males and females (50.8%/49.2%) and G1 and G2 tumors (49.2%/50.8%). The disease was detected in 122 (98.4%) and 64 (51.6%) cases by 68Ga-DOTATOC and by 18F-FDG PET/CT scans, respectively, with a combined sensitivity of 99.2%. 18F-FDG-positive examinations found G2 tumors more often than G1 (59.4 vs. 40.6%; p = 0.036), and 18F-FDG-positive PanNETs were larger than negative ones (median tumor size 32 mm, interquartile range [IQR] 21 vs. 26 mm, IQR 20; p = 0.019). The median Ki67 for 18F-FDG-positive and -negative examinations was 3 (IQR 4) and 2 (IQR 4), respectively (p = 0.029). At least 1 pathological predictor of recurrence was present in 74.6% of 18F-FDG-positive cases (vs. 56.7%; p = 0.039), whereas this was not found when dichotomizing the PanNETs by their dimensions (≤/>20 mm). None of the 2 tracers predicted nodal metastasis. The receiver operating characteristic curve analysis showed that 18F-FDG uptake higher than 4.2 had a sensitivity of 49.2% and specificity of 73.3% for differentiating G1 from G2 (AUC = 0.624, p = 0.009). CONCLUSION: The complementary adoption of 68Ga-DOTATOC and 18F-FDG tracers may be valuable in the diagnostic workup of PanNETs despite not being a game-changer for the management of PanNETs ≤20 mm.
Subject(s)
Fluorodeoxyglucose F18 , Octreotide/analogs & derivatives , Organometallic Compounds , Pancreatic Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Adult , Aged , Female , Humans , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pancreatic Neoplasms/surgery , Positron Emission Tomography Computed Tomography/standards , Retrospective StudiesABSTRACT
INTRODUCTION: The COVID-19 pandemic has severely limited the access to cancer surgery, but it is not known to what extent referral centers for pancreatic diseases were affected by its outbreak. The aim of this study is to describe the effect of COVID-19 pandemic on a third-level referral center for pancreatic surgery in Italy. METHODS: The 2020 activity of The Pancreas Institute of the University of Verona was reviewed, comparing different phases of the COVID-19 pandemic outbreaks using the pre-COVID era as a control. Endpoints were the overall caseload of pancreatic resections, surgical waiting list, administration of preoperative therapy, major morbidity and mortality, residents' training; number of inpatients beds, outpatient visits/procedures/diagnostics. RESULTS: In 2020, there was an overall significant reduction of pancreatic resections performed (394 vs. 506 in 2019), particularly during the first (March-May) and second (October-December) COVID-19 outbreaks, with an all-time-low of 16 resections/months in April (compared to 43 average resection/month in 2019). The rates of major morbidity (Clavien-Dindo ≥ 3) and mortality were similar to 2019 (16 vs 12%, p = 0.11 and 3 vs 2%, p = 0.29, respectively). During the first and second outbreaks resident's training, inpatient beds, outpatient visits, diagnostics, and procedures were severely impaired, while the waiting list for up-front cancer resections and the use of preoperative chemotherapy concomitantly raised. CONCLUSION: The COVID-19 pandemic has severely disrupted the activity of a third-level referral center for pancreatic surgery, affecting the access to cancer surgical procedures and raising concerns regarding the solidity of the current centralization model.
Subject(s)
COVID-19 , Neoplasms , Humans , Neoplasms/epidemiology , Pancreatectomy/methods , Pandemics , Referral and ConsultationABSTRACT
We describe an unusual case of myelodysplasia cutis in a patient with chronic myelomonocytic leukaemia.
Subject(s)
Leukemia, Myelomonocytic, Chronic , Leukemia, Myelomonocytic, Juvenile , Myelodysplastic Syndromes , Skin Neoplasms , Humans , Leukemia, Myelomonocytic, Chronic/complications , Leukemia, Myelomonocytic, Chronic/diagnosis , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/diagnosis , Skin , Skin Neoplasms/diagnosisABSTRACT
Pemphigus vulgaris is an intraepidermal autoimmune mucocutaneous blistering disease whose etiopathogenesis includes various trigger factors, i.e., drugs and malignancies. We present a case of malignancy-exacerbated pemphigus vulgaris which required a careful diagnostic process in order to rule out paraneoplastic pemphigus, along with the challenges posed by the need of treating both cutaneous and oncologic diseases. Possible post-operative complications post-poned the start of first-line immunosuppressive treatment of pemphigus. Moreover, the infective risks had to be minimized during the peak of the COVID-19 pandemic in Italy. Intravenous immunoglobulins were chosen as "bridge" therapy before the tumor surgical excision, followed by rituximab in post-operative phase.
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BACKGROUND: Existing postoperative pancreatic fistula risk scores rely on intraoperative parameters, which limits their value in the preoperative setting. A preoperative predictive model to stratify the risk of developing postoperative pancreatic fistula before pancreatoduodenectomy was built and externally validated. METHODS: A regression risk-tree model for preoperative postoperative pancreatic fistula risk stratification was developed in the Verona University Hospital training cohort using preoperative variables and then tested prospectively in a validation cohort of patients who underwent pancreatoduodenectomy at San Raffaele Hospital of Milan. RESULTS: In the study period 566 (training cohort) and 456 (validation cohort) patients underwent pancreatoduodenectomy. In the multivariable analysis body mass index, radiographic main pancreatic duct diameter and American Society of Anesthesiologists score ≥3 were independently associated with postoperative pancreatic fistula. The regression tree analysis allocated patients into 3 preoperative risk groups with an 8%, 21%, and 32% risk of postoperative pancreatic fistula (all P < .01) based on main pancreatic duct diameter (≥ or <5 mm) and body mass index (≥ or <25). The 3 groups were labeled low, intermediate, and high risk and consisted of 206 (37%), 188 (33%), and 172 (30%) patients, respectively. The risk-tree was applied to validation cohort, successfully reproducing 3 risk groups with significantly different postoperative pancreatic fistula risks (all P < .01). CONCLUSION: In candidates for pancreatoduodenectomy, the risk of postoperative pancreatic fistula can be quickly and accurately determined in the preoperative setting based on the body mass index and main pancreatic duct diameter at radiology. Preoperative risk stratification could potentially guide clinical decision-making, improve patient counseling and allow the establishment of personalized preoperative protocols.
Subject(s)
Pancreatic Fistula/epidemiology , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/epidemiology , Aged , Body Mass Index , Clinical Decision-Making/methods , Decision Trees , Female , Humans , Male , Middle Aged , Pancreatic Ducts/diagnostic imaging , Pancreatic Ducts/pathology , Pancreatic Ducts/surgery , Pancreatic Fistula/etiology , Postoperative Complications/etiology , Preoperative Period , Prospective Studies , Risk Assessment/methods , Risk FactorsABSTRACT
The reason why only few coeliac patients develop the cutaneous manifestation of the disease, named dermatitis herpetiformis (DH), is still unknown. Epidermal transglutaminase (TG3) has been described as the main autoantigen of humoral immunity in DH but the mechanisms leading to this autoimmune response remain obscure. Here we characterized T cells from skin, gut and peripheral blood of DH and coeliac disease (CD) patients, evaluated the impact of the gluten-free diet on circulating T lymphocytes' phenotype and investigated antigen specific T cell response toward epidermal and tissue transglutaminase (TG2). DH patients showed an increased frequency of skin-derived T cells producing TNFα when compared to CD patients. Moreover, circulating T cells producing TNFα and IL-17A positively correlated with clinical score of skin disease activity and decreased after gluten-free diet. Finally, TG2 and TG3-specific T cells resulted more reactive to antigens stimulation in DH patients and showed cross reactivity toward the two autoantigens in both the group of patients. Our data suggest a role of TNFα and IL-17A producing cells in the development of DH and, for the first time, show the existence of a crossed T cell response toward the two transglutaminases isoforms, thus suggesting new insights on T cells role in skin damage.