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1.
J Gastrointestin Liver Dis ; 33(2): 170-176, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38944862

RESUMO

BACKGROUND AND AIMS: The environmental factors, apart from gluten ingestion predisposing to coeliac disease are poorly known. Smoking is associated with many immune-mediated diseases, but research on coeliac disease is scarce. This study aims to investigate how smoking affects the clinical presentation, presence of comorbidities and response to gluten-free diet in coeliac disease. METHODS: Altogether 815 adults with coeliac disease participated in a nationwide cross-sectional study. Participants were interviewed and smoking habits (never, former, or current smoker), clinical presentation of coeliac disease and presence of comorbidities were elicited. Serology and severity of small bowel mucosal lesions at diagnosis were gathered from the participants' medical records and follow-up serology was measured. Gastrointestinal symptoms and psychological well-being were assessed using validated questionnaires. RESULTS: Current smokers were more often male and were diagnosed at younger ages than never or former smokers. There were no differences between the groups in clinical presentation, severity of symptoms or mucosal lesions at diagnosis or in dietary compliance and clinical, serological, and histological recovery. Musculoskeletal disorders, particularly osteoporosis and osteopenia, were more common in never smokers than in other groups (14.5% vs. 5.1% and 4.1%, p<0.001), and cardiovascular disorders were diagnosed more often in former smokers (36.2% vs. 23.5% and 21.9%, p=0.003). CONCLUSIONS: Smoking does not seem to have an impact on the clinical presentation, severity of symptoms or mucosal damage in coeliac disease. Histological and clinical recovery as well as seroconversion on gluten-free diet are not affected by smoking status.


Assuntos
Doença Celíaca , Dieta Livre de Glúten , Humanos , Doença Celíaca/dietoterapia , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Idoso , Resultado do Tratamento , Comorbidade , Fatores de Risco , Fumantes/estatística & dados numéricos , Ex-Fumantes/estatística & dados numéricos , Mucosa Intestinal/patologia
2.
Int Wound J ; 21(6): e14943, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899689

RESUMO

Vasculitic and pyoderma gangrenosum ulcers are traditionally treated with immunosuppressants, and the role of surgery in the treatment of these atypical ulcers remains unclear. This study aimed to investigate the need for surgical intervention as well as the outcome and safety of skin grafting in the treatment of 46 patients with vasculitic ulcers and 34 with pyoderma gangrenosum ulcers using data recorded in the validated Wound Registry. Of the 80 patients with atypical ulcers, 14% (n = 11) were treated surgically; these patients were older (p = 0.039), had lower mobility status (p = 0.002), and more often pulmonary diseases, rheumatoid arthritis, and previous arterial procedures (p = 0.007; p = 0.031; p = 0.031, respectively) than those treated conservatively. Of 181 ulcers, 15% (n = 27) were surgically treated, 78% once and 22% multiple times. During follow-up, 92.3% of both surgically and conservatively treated ulcers with available data healed. Of the surgically treated ulcers, median healing time after first surgical procedure was 96 days, and post-surgical complications were considered mild or unrelated to surgery. Our results suggest that if surgery is indicated, skin grafting is a safe and efficient treatment method provided that multidisciplinary approach is applied.


Assuntos
Pioderma Gangrenoso , Transplante de Pele , Cicatrização , Humanos , Pioderma Gangrenoso/cirurgia , Pioderma Gangrenoso/terapia , Masculino , Feminino , Transplante de Pele/métodos , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Úlcera Cutânea/cirurgia , Úlcera Cutânea/terapia , Vasculite/cirurgia , Vasculite/complicações
3.
Acta Derm Venereol ; 104: adv39891, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813742

RESUMO

Registers recording only 1 tumour per patient do not enable assessment of the real burden of cutaneous squamous cell carcinoma. To investigate recent changes in the incidence and characteristics of tumours, a retrospective 15-year patient cohort study was performed in Finland. Histopathological diagnoses of cutaneous squamous cell carcinomas diagnosed between 2016 and 2020 were obtained from the pathology database and clinical data from patient medical records and combined with previously collected data for the years 2006-2015. Altogether 1,472 patients with 2,056 tumours were identified. The crude incidence increased from 19/100,000 persons in 2006 to 42 in 2020 (p < 0.001), increasing most in people aged over 80 years. The percentage of tumours located on the trunk increased from 5.3% during the first 5-year period, 2006-2010, to 9.0% in 2016-2020. Also, the location of tumours was significantly different between men and women, as men had more tumours on the scalp and ears, and women on the lower limbs. A slight change in the tumours from poorly to well differentiated and a decrease in the invasion depth were noted between 2006 and 2020. As the burden of tumours continues to increase, more attention should be paid to their prevention.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Finlândia/epidemiologia , Estudos Retrospectivos , Masculino , Feminino , Incidência , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Adulto , Fatores de Tempo , Distribuição por Sexo , Distribuição por Idade , Adulto Jovem , Invasividade Neoplásica , Adolescente , Criança
4.
Ann Med ; 55(1): 2227423, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37378421

RESUMO

INTRODUCTION: Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed. METHODS: The study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR). RESULTS: The median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91-1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16-1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47-0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07-1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22-2.16) but not in DH. CONCLUSIONS: The risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation.


An increased risk for cardiovascular diseases was observed among patients with coeliac disease, but not among patients with dermatitis herpetiformis, a cutaneous manifestation of coeliac disease.The risk for cerebrovascular diseases was shown to be decreased in dermatitis herpetiformis patients, but conversely, an increased risk for cerebrovascular diseases was identified in coeliac disease patients.Coeliac disease, but not dermatitis herpetiformis, was shown to be associated with increased risk for venous thrombosis.


Assuntos
Doenças Cardiovasculares , Doença Celíaca , Dermatite Herpetiforme , Doenças Vasculares , Humanos , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Doença Celíaca/diagnóstico , Dermatite Herpetiforme/complicações , Dermatite Herpetiforme/epidemiologia , Dermatite Herpetiforme/diagnóstico , Estudos de Coortes , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Doenças Vasculares/complicações
5.
Dig Liver Dis ; 54(11): 1502-1507, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35589505

RESUMO

BACKGROUND: Celiac disease has been associated with increased mortality, but data on long-term mortality are scarce. AIMS: To determine long-term mortality in celiac disease. METHODS: The study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 - 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time. RESULTS: During the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85-1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38-4.24 and HR 2.14, 95% CI 1.05-4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09-1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortality CONCLUSIONS: Overall mortality was not increased in any celiac disease phenotype during a very long-term follow-up.


Assuntos
Doença Celíaca , Humanos , Doença Celíaca/complicações , Seguimentos , Causas de Morte , Estudos de Coortes , Fenótipo
6.
Front Immunol ; 11: 575805, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072118

RESUMO

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac disease (CD). Patients with DH have an elevated risk of development of another autoimmune blistering skin disease, bullous pemphigoid (BP). In this study we investigated whether patients with DH and CD (mean age for both 49 years) have circulating autoantibodies against BP180, the major BP autoantigen. ELISA tests showed that only a few DH (3/46) and CD (2/43) patients had BP180-NC16A IgG autoantibodies. Immunoblotting found that more than half of the DH samples contained IgG autoantibodies against full-length BP180. Epitope mapping with 13 fusion proteins covering the BP180 polypeptide revealed that in DH and CD patients, IgG autoantibodies did not target the NC16A or other epitopes typical of BP but recognized other intracellular and mid-extracellular regions of BP180. None of the analyzed DH and CD patients with either ELISA or immunoblotting positivity had IgG or IgA reactivity against the cutaneous basement membrane in indirect immunofluorescence analysis or skin symptoms characteristic of BP. Although only a minority of middle-aged DH patients had IgG autoantibodies against the immunodominant epitopes of BP180, our results do not exclude the possibility that intermolecular epitope spreading could explain the switch from DH to BP in elderly patients.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Autoimunidade , Doença Celíaca/imunologia , Dermatite Herpetiforme/imunologia , Epitopos Imunodominantes , Imunoglobulina G/sangue , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Dermatite Herpetiforme/sangue , Dermatite Herpetiforme/diagnóstico , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Feminino , Proteínas de Ligação ao GTP/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/diagnóstico , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/imunologia , Colágeno Tipo XVII
7.
J Invest Dermatol ; 139(10): 2108-2114, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30998982

RESUMO

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of celiac disease causing an itchy, blistering rash. Granular IgA deposits in the skin are pathognomonic for DH, and the treatment of choice is a lifelong gluten-free diet (GFD). Preliminary evidence suggests that there are patients with DH who redevelop gluten tolerance after adherence to a GFD treatment. To evaluate this, we performed a 12-month gluten challenge with skin and small-bowel mucosal biopsy samples in 19 patients with DH who had adhered to a GFD for a mean of 23 years. Prechallenge biopsy was negative for skin IgA and transglutaminase 3 deposits in 16 patients (84%) and indicated normal villous height-to-crypt depth ratios in the small bowel mucosa in all 19 patients. The gluten challenge caused a relapse of the rash in 15 patients (79%) in a mean of 5.6 months; of these 15 patients, 13 had skin IgA and transglutaminase 3 deposits, and 12 had small-bowel villous atrophy. In addition, three patients without rash or immune deposits in the skin developed villous atrophy, whereas one patient persisted without any signs of relapse. In conclusion, 95% of the patients with DH were unable to tolerate gluten even after long-term adherence to a GFD. Therefore, lifelong GFD treatment remains justified in all patients with DH.


Assuntos
Dermatite Herpetiforme/dietoterapia , Dermatite Herpetiforme/patologia , Dieta Livre de Glúten/métodos , Imunoglobulina A/metabolismo , Intestino Delgado/patologia , Adulto , Idoso , Biópsia por Agulha , Estudos de Coortes , Feminino , Finlândia , Seguimentos , Humanos , Imunoglobulina A/imunologia , Imuno-Histoquímica , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento
8.
Aliment Pharmacol Ther ; 49(3): 277-284, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30592070

RESUMO

BACKGROUND: The revised paediatric criteria for coeliac disease allow omission of duodenal biopsies in symptomatic children who have specific serology and coeliac disease-associated genetics. It remains unclear whether this approach is also applicable for adults with various clinical presentations. AIM: To evaluate the accuracy of serology-based criteria in adults with variable pre-test probabilities for coeliac disease. METHODS: Three study cohorts comprised adults with high-risk clinical coeliac disease suspicion (n = 421), moderate-risk family members of coeliac disease patients (n = 2357), and low-risk subjects from the general population (n = 2722). Serological and clinical data were collected, and "triple criteria" for coeliac disease comprised transglutaminase 2 antibodies >10× the upper limit of normal, positive endomysium antibodies, and appropriate genetics without requirement of symptoms. The diagnosis was based on intestinal biopsy. RESULTS: The diagnosis of coeliac disease was established in 274 subjects. Of these, 59 high-risk subjects, 17 moderate-risk subjects, and 14 low-risk subjects fulfilled the "triple criteria". All had histologically proven coeliac disease, giving the criteria a positive predictive value of 100%. Altogether, 90 (33%) of all 274 newly diagnosed patients could have avoided biopsy, including 37% among high-risk, 20% among moderate-risk, and 48% among low-risk patients. No histological findings other than coeliac disease were found in the biopsies of "triple positive" subjects. CONCLUSIONS: Coeliac disease can reliably and safely be diagnosed without biopsy in adults fulfilling the "triple criteria" regardless of the pre-test probability. Revised criteria would enable the number of endoscopies to be reduced by one-third.


Assuntos
Autoanticorpos/sangue , Doença Celíaca/diagnóstico , Proteínas de Ligação ao GTP/imunologia , Transglutaminases/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Doença Celíaca/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Proteína 2 Glutamina gama-Glutamiltransferase , Adulto Jovem
9.
Nutrients ; 10(5)2018 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-29757210

RESUMO

Dermatitis herpetiformis (DH) is a common extraintestinal manifestation of coeliac disease presenting with itchy papules and vesicles on the elbows, knees, and buttocks. Overt gastrointestinal symptoms are rare. Diagnosis of DH is easily confirmed by immunofluorescence biopsy showing pathognomonic granular immunoglobulin A (IgA) deposits in the papillary dermis. A valid hypothesis for the immunopathogenesis of DH is that it starts from latent or manifest coeliac disease in the gut and evolves into an immune complex deposition of high avidity IgA epidermal transglutaminase (TG3) antibodies, together with the TG3 enzyme, in the papillary dermis. The mean age at DH diagnosis has increased significantly in recent decades and presently is 40⁻50 years. The DH to coeliac disease prevalence ratio is 1:8 in Finland and the United Kingdom (U.K.). The annual DH incidence rate, currently 2.7 per 100,000 in Finland and 0.8 per 100,000 in the U.K., is decreasing, whereas the reverse is true for coeliac disease. The long-term prognosis of DH patients on a gluten-free diet is excellent, with the mortality rate being even lower than for the general population.


Assuntos
Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Dermatite Herpetiforme/diagnóstico , Dermatite Herpetiforme/etiologia , Biópsia , Doença Celíaca/dietoterapia , Dermatite Herpetiforme/dietoterapia , Dieta Livre de Glúten , Epiderme/enzimologia , Finlândia , Imunofluorescência , Trato Gastrointestinal/metabolismo , Humanos , Imunoglobulina A/metabolismo , Incidência , Prevalência , Transglutaminases/metabolismo , Reino Unido
10.
Nutrients ; 10(5)2018 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-29783727

RESUMO

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. At diagnosis, the majority of patients have villous atrophy in the small bowel mucosa. The objective of this study was to investigate whether the presence or absence of villous atrophy at diagnosis affects the long-term prognosis of DH. Data were gathered from the patient records of 352 DH and 248 coeliac disease patients, and follow-up data via questionnaires from 181 DH and 128 coeliac disease patients on a gluten-free diet (GFD). Of the DH patients, 72% had villous atrophy when DH was diagnosed, and these patients were significantly younger at diagnosis compared to those with normal small bowel mucosa (37 vs. 54 years, p < 0.001). Clinical recovery on a GFD did not differ significantly between the DH groups, nor did current adherence to a GFD, the presence of long-term illnesses, coeliac disease-related complications or gastrointestinal symptoms, or quality of life. By contrast, the coeliac disease controls had more often osteopenia/osteoporosis, thyroid diseases, malignancies and current gastrointestinal symptoms compared to the DH patients. In conclusion, villous atrophy at the time of DH diagnosis does not have an impact on the clinical recovery or long-term general health of DH patients.


Assuntos
Doença Celíaca/complicações , Dermatite Herpetiforme/etiologia , Intestino Delgado/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Estudos de Casos e Controles , Doença Celíaca/dietoterapia , Doença Celíaca/patologia , Criança , Pré-Escolar , Dermatite Herpetiforme/diagnóstico , Dieta Livre de Glúten , Feminino , Nível de Saúde , Humanos , Masculino , Microvilosidades/patologia , Pessoa de Meia-Idade , Prognóstico , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
11.
Acta Derm Venereol ; 98(3): 366-372, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29182792

RESUMO

Coeliac disease and dermatitis herpetiformis (DH) are characterized by autoantibodies targeting transglutaminase (TG)2 and TG3, respectively. Previous studies show that TG2 antibodies are produced in the gut and can be assessed in organ culture of small-intestinal biopsies from patients with coeliac disease. Thus far, no studies have investigated TG3 antibodies in organ culture of biopsies from patients with DH, or exploited the method in DH. The aim of this study was to investigate TG3 and TG2 antibody responses in serum and small-intestinal biopsies from patients with DH with active disease, and from those in remission. The majority of patients with DH were negative for both serum and organ culture medium TG2-targeting antibodies. Surprisingly, patients with active DH secreted TG3 antibodies into the culture medium despite seronegativity. In patients secreting high levels of TG3 antibodies into the culture medium, we also detected TG3-antibody-positive cells in the small-intestinal mucosa. These findings suggest that TG3 antibodies can be investigated in the organ culture system and that their secretion occurs in the small intestine, especially in active DH.


Assuntos
Autoanticorpos/biossíntese , Dermatite Herpetiforme/imunologia , Duodeno/imunologia , Mucosa Intestinal/imunologia , Transglutaminases/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores/sangue , Biópsia , Doença Celíaca/sangue , Doença Celíaca/enzimologia , Doença Celíaca/imunologia , Doença Celíaca/terapia , Dermatite Herpetiforme/sangue , Dermatite Herpetiforme/enzimologia , Dermatite Herpetiforme/terapia , Duodeno/enzimologia , Proteínas de Ligação ao GTP/imunologia , Humanos , Imunoglobulina A/sangue , Mucosa Intestinal/enzimologia , Proteína 2 Glutamina gama-Glutamiltransferase , Indução de Remissão , Técnicas de Cultura de Tecidos
12.
Acta Derm Venereol ; 98(2): 195-199, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29048096

RESUMO

Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease. The highest currently reported prevalence of DH is in Finland, but knowledge of diagnostic delay is limited. This study investigated the duration of rash prior to diagnosis in 446 patients with DH, analysing the results in 3 periods of 15 years. The diagnosis was considered delayed when the duration of rash before diagnosis was 2 years or longer. Factors associated with delayed diagnosis were analysed. Within the 45 years, the median duration of rash before diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000 were significantly associated with delayed diagnosis. In conclusion, the present study showed that one-quarter of patients currently have a diagnostic delay of 2 years or more, which is far from ideal.


Assuntos
Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Diagnóstico Tardio , Dermatite Herpetiforme/diagnóstico , Dermatite Herpetiforme/epidemiologia , Pele/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Biópsia , Doença Celíaca/patologia , Criança , Pré-Escolar , Dermatite Herpetiforme/patologia , Feminino , Finlândia/epidemiologia , Humanos , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
13.
Ann Med ; 49(1): 23-31, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27499257

RESUMO

Dermatitis herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in dermatitis herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in dermatitis herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.


Assuntos
Doença Celíaca/diagnóstico , Dermatite Herpetiforme/diagnóstico , Dermatite Herpetiforme/imunologia , Pele/patologia , Adulto , Autoanticorpos/sangue , Autoantígenos/imunologia , Doença Celíaca/epidemiologia , Doença Celíaca/imunologia , Dermatite Herpetiforme/dietoterapia , Dermatite Herpetiforme/patologia , Dieta Livre de Glúten , Linfoma de Células T Associado a Enteropatia/complicações , Feminino , Proteínas de Ligação ao GTP/sangue , Humanos , Imunoglobulina A/isolamento & purificação , Imunoglobulina A/metabolismo , Incidência , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Linfoma de Células B/complicações , Masculino , Pessoa de Meia-Idade , Proteína 2 Glutamina gama-Glutamiltransferase , Risco , Pele/imunologia , Transglutaminases/sangue
14.
Acta Derm Venereol ; 96(1): 82-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26084552

RESUMO

Dermatitis herpetiformis (DH) is a blistering skin disease, which is regarded as an extra-intestinal manifestation of coeliac disease. Refractory cases of coeliac disease, that do not respond to a gluten-free diet and which carry an increased risk of lymphoma, are well-known in coeliac disease. To determine whether refractory cases of DH with active rash and persistent small bowel atrophy occur we analysed our series of 403 patients with DH. Seven (1.7%) patients, who had been on a gluten-free diet for a mean of 16 years, but who still required dapsone to treat the symptoms of DH, were identified. Of these, one patient died from mucinous adenocarcinoma before re-examination. At re-examination skin immunoglobulin A (IgA) deposits were found in 5/6 refractory and 3/16 control DH patients with good dietary response. Small bowel mucosa was studied at re-examination from 5 refractory and 8 control DH patients and was normal in all 5 refractory and 7/8 control DH patients. One refractory DH patient died from adenocarcinoma, but no lymphoma developed in any of the patients. This study documents for the first time refractory DH, in which the rash is non-responsive to a gluten-free diet, but the small bowel mucosa heals. This differs from refractory coeliac disease, in which the small bowel mucosa does not heal on a gluten-free diet.


Assuntos
Doença Celíaca/dietoterapia , Dapsona/uso terapêutico , Dermatite Herpetiforme/terapia , Dieta Livre de Glúten , Pele/efeitos dos fármacos , Adolescente , Adulto , Atrofia , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Criança , Dermatite Herpetiforme/diagnóstico , Dermatite Herpetiforme/dietoterapia , Dermatite Herpetiforme/imunologia , Feminino , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/imunologia , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Cicatrização , Adulto Jovem
15.
Acta Derm Venereol ; 95(8): 917-22, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26059085

RESUMO

Dermatitis herpetiformis (DH) is an itchy, blistering skin disease with sites of predilection at the elbows, knees and buttocks. Although DH is mostly asymptomatic, all patients exhibit small bowel villous atrophy or at least coeliac-type inflammatory changes. Deposition of immunoglobulin A (IgA) in the papillary dermis is a key diagnostic feature of DH. Epidermal transglutaminase (TG3) is the antigen for IgA deposited in the skin, and tissue transglutaminase (TG2) is the antigen for IgA deposited in the small bowel mucosa. Clinically silent, but immunologically active coeliac disease in the gut appears to result in IgA TG3 antibody complexes aggregated into DH skin. The prevalence of DH in northern Europe is high (30-75/100,000), but its incidence is decreasing, possibly due to increased recognition of subclinical coeliac disease. The rash and small bowel heal on a gluten-free diet, which is a life-long treatment. The risk of non-Hodgkin's lymphoma is increased, but in patients with DH who adhere strictly to a gluten-free diet long-term prognosis is excellent.


Assuntos
Dermatite Herpetiforme/dietoterapia , Dermatite Herpetiforme/imunologia , Dieta Livre de Glúten , Imunoglobulina A/metabolismo , Transglutaminases/imunologia , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Ensaios Enzimáticos Clínicos , Dermatite Herpetiforme/diagnóstico , Proteínas de Ligação ao GTP/imunologia , Humanos , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Proteína 2 Glutamina gama-Glutamiltransferase
16.
Scand J Gastroenterol ; 50(4): 387-92, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25639558

RESUMO

OBJECTIVE: Dermatitis herpetiformis (DH) is a cutaneous form of celiac disease affecting ∼ 17% of celiac disease patients. The aim was to determine how often celiac disease precedes the development of DH, and what is the impact of gluten-free diet (GFD) in this phenotype change. MATERIAL AND METHODS: Our prospectively collected DH series from 1970 comprised 514 patients. We analyzed all DH patients who at least 2 years earlier had been diagnosed with celiac disease. DH diagnosis was confirmed by showing immunoglobulin A deposits in dermis. Serological and small bowel mucosal findings were analyzed, and the strictness of GFD treatment before and after the diagnosis of DH was evaluated. RESULTS: Twenty (4%) DH patients had a prior diagnosis of celiac disease. The median time interval between celiac disease and DH detection was 9.5 years. Before DH appeared 4 patients had been on a normal gluten-containing diet, 10 had dietary lapses on a GFD, and 6 were on a strict GFD. Celiac autoantibodies were positive in 7 out of 19 patients, and 5 out of 7 undergoing small bowel biopsy had partial villous atrophy. Following DH diagnosis the rash was controlled after a median of 6 months on a strict GFD. CONCLUSIONS: Patients with celiac disease may develop DH by time. This is most often an indicator of poor adherence to GFD, and a rigorous dietary intervention is necessary. In the majority of cases, DH will be detected without prior celiac disease diagnosis, but the physicians should recognize this phenotype alteration.


Assuntos
Doença Celíaca/dietoterapia , Dermatite Herpetiforme/dietoterapia , Dieta Livre de Glúten , Mucosa Intestinal/patologia , Fenótipo , Adolescente , Adulto , Idoso , Atrofia , Autoanticorpos/sangue , Doença Celíaca/complicações , Doença Celíaca/patologia , Criança , Pré-Escolar , Dermatite Herpetiforme/sangue , Dermatite Herpetiforme/complicações , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Fatores de Tempo , Adulto Jovem
17.
Clin Gastroenterol Hepatol ; 11(2): 166-71.e1, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23063678

RESUMO

BACKGROUND & AIMS: In patients with celiac disease, gluten-induced lesions of the small-bowel mucosa develop gradually. However, it is not clear whether clinical presentation correlates with the degree of mucosal damage based on histology analysis. We investigated whether the degree of mucosal damage to the small bowel correlates with clinical presentation and serum markers of celiac disease. METHODS: We collected results from serology tests and mucosal biopsy samples from 638 consecutive patients with celiac disease and compared them with reported gastrointestinal symptoms, health-related quality-of-life scores, results from laboratory tests, and bone mineral densities of patients. We assessed mucosal injury based on the ratio of villous height to crypt depth, numbers of intraepithelial CD3(+) cells, and semiquantitative Marsh classification criteria. Correlations were established based on the Pearson or Spearman coefficients. RESULTS: The ratio of the villous height to crypt depth correlated with the severity of gastrointestinal symptoms, quality-of-life scores, laboratory test results, numbers of intraepithelial CD3(+) cells, and serum levels of antibodies associated with celiac disease. There was no correlation between the ratio of villous height to crypt depth and bone mineral density. The number of intraepithelial CD3(+) cells was not associated with symptoms, whereas the Marsh classification and serum levels of antibodies associated with celiac disease correlated with gastrointestinal symptoms, laboratory test results, and numbers of intraepithelial CD3(+) cells. CONCLUSIONS: The ratio of small-bowel villous height to crypt depth and results from serology tests correlate with reported symptoms and quality of life of patients with celiac disease. Patient-reported outcomes are therefore of value, in addition to histology findings, in assessing patients with celiac disease.


Assuntos
Anticorpos/sangue , Doença Celíaca/imunologia , Doença Celíaca/patologia , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Soro/química , Adulto Jovem
18.
Clin Dev Immunol ; 2012: 640630, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22611420

RESUMO

BACKGROUND AND OBJECTIVE: Previous small studies suggest that chronic atrophic gastritis is common in dermatitis herpetiformis (DH). We here examined the frequency and topography of chronic gastritis in 93 untreated DH subjects and in 186 controls with dyspepsia. METHODS: Specimens were drawn from the gastric corpus and antrum and examined for atrophy, intestinal metaplasia, and Helicobacter pylori. Duodenal biopsies were taken. RESULTS: Atrophic corpus gastritis was more frequent in DH than in controls (16.0% and 2.7%, resp., P < 0.001); atrophy in the antrum was rare in both groups (3.2% and 1.1%, P = 0.34). Intestinal metaplasia was present in 13 (14.0%) DH and 12 (6.5%) control patients (P = 0.038) and H. pylori in 17 (18.3%) and 17 (9.3%) (P = 0.028), respectively. Small-bowel villous atrophy was seen in 76% of the DH patients, equally in patients with and without chronic gastritis. One DH patient with atrophic gastritis developed gastric cancer. CONCLUSION: In DH, chronic atrophic gastritis was common in the corpus, but not in the antrum. H. pylori will partly explain this, but corpus atrophy is suggestive of an autoimmune etiology. Atrophic gastritis may increase the risk of gastric cancer. We advocate performing upper endoscopy with sufficient histologic samples in DH.


Assuntos
Dermatite Herpetiforme/epidemiologia , Gastrite/epidemiologia , Trato Gastrointestinal/patologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Adolescente , Adulto , Idoso , Autoimunidade , Criança , Doença Crônica , Dermatite Herpetiforme/complicações , Dermatite Herpetiforme/patologia , Feminino , Finlândia , Gastrite/complicações , Gastrite/patologia , Trato Gastrointestinal/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
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