Risk of vascular diseases in patients with dermatitis herpetiformis and coeliac disease: a long-term cohort study.

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.

Mortality and causes of death in different celiac disease phenotypes during long-term follow-up.

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.

Gluten Challenge Induces Skin and Small Bowel Relapse in Long-Term Gluten-Free Diet-Treated Dermatitis Herpetiformis.

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.

Prognosis of Dermatitis Herpetiformis Patients with and without Villous Atrophy at Diagnosis.

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.

Dermatitis Herpetiformis: A Common Extraintestinal Manifestation of Coeliac Disease.

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.

Diagnostic Delay in Dermatitis Herpetiformis in a High-prevalence Area.

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.

Ex vivo Culture of Duodenal Biopsies from Patients with Dermatitis Herpetiformis Indicates that Transglutaminase 3 Antibody Production Occurs in the Gut.

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.

The effect of vernal solar UV radiation on serum 25-hydroxyvitamin D concentration depends on the baseline level: observations from a high latitude in Finland.

Humans obtain vitamin D from conversion of 7-dehydrocholesterol in the skin by ultraviolet B (UVB) radiation or from dietary sources. As the radiation level is insufficient in winter, vitamin D deficiency is common at higher latitudes. We assessed whether vernal solar UVB radiation at latitudes 61°N and 67°N in Finland has an impact on serum 25-hydroxyvitamin D [S-25(OH)D] concentrations. Twenty-seven healthy volunteers participated in outdoor activities in snow-covered terrain for 4-10 days in March or April, with their face and hands sun-exposed. The personal UVB doses and S-25(OH)D levels were monitored. A mean UVB dose of 11.8 standard erythema doses (SED) was received during an average of 12.3 outdoor hours. The mean S-25(OH)D concentration in subjects with a baseline concentration below 90.0 nmol/L (n=13) increased significantly, by 6.0 nmol/L from an initial mean of 62.4 nmol/L (p<0.001), whereas in those with a basal concentration above 90.0 nmol/L (n=12) it decreased significantly, by 6.7 nmol/L from a mean of 116.9 nmol/L (p<0.01). To conclude, only 7% of total body surface area was exposed to vernal sunlight and this was capable of increasing S-25(OH)D levels in subjects with a baseline level below 90 nmol/L but not in those with higher levels.

Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease.

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.

Dermatitis Herpetiformis Refractory to Gluten-free Dietary Treatment.

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.

Narrowband Ultraviolet B Exposures Maintain Vitamin D Levels During Winter: A Randomized Controlled Trial.

Exposure to solar ultraviolet B radiation during the summer months is the main source of vitamin D (VD) for people living in northern latitudes. The aim of this study was to determine whether artificial narrowband ultraviolet B (NB-UVB) whole-body exposures could maintain VD levels in winter. The intervention group received 2 standard erythema doses (SEDs) of NB-UVB exposures every second week from October 2013 to April 2014. In October 2013 serum 25-hydroxyvitamin D concentrations were 78.3 nmol/l in the intervention group (n = 16) and 76.8 nmol/l in the control group (n = 18). By April 2014 the concentrations had increased by 11.7 nmol/l (p = 0.029) in the intervention group and decreased by 11.1 nmol/l (p = 0.022) in the control group. The baseline VD concentration showed a negative correlation (p = 0.012) with body mass index (BMI). In conclusion, a suberythemal NB-UVB dose of 2 SED every second week maintains and even increases serum VD concentrations during the winter. A high BMI seems to predispose subjects to low levels of VD.

Dermatitis herpetiformis: pathognomonic transglutaminase IgA deposits in the skin and excellent prognosis on a gluten-free diet.

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.

Celiac disease evolving into dermatitis herpetiformis in patients adhering to normal or gluten-free diet.

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.

Narrow-band ultraviolet B treatment boosts serum 25-hydroxyvitamin D in patients with psoriasis on oral vitamin D supplementation.

A course of treatment with narrow-band ultraviolet B (NB-UVB) improves psoriasis and increases serum 25-hydroxyvitamin D (25(OH)D). In this study 12 patients with psoriasis who were supplemented with oral cholecalciferol, 20 µg daily, were given a course of NB-UVB and their response measured. At baseline, serum 25(OH)D was 74.14 ± 22.9 nmol/l. At the 9th exposure to NB-UVB 25(OH)D had increased by 13.2 nmol/l (95% confidence interval (95% CI) 7.2-18.4) and at the 18th exposure by 49.4 nmol/l (95% CI 35.9-64.6) above baseline. Psoriasis Area Severity Index score improved from 8.7 ± 3.5 to 4.5 ± 2.0 (p < 0.001). At baseline, psoriasis lesions showed low vitamin D metabolizing enzyme (CYP27A1, CYP27B1) and high human ß-defensin-2 mRNA expression levels compared with those of the healthy subjects. In conclusion, NB-UVB treatment significantly increases serum 25(OH)D in patients with psoriasis who are taking oral vitamin D supplementation, and the concentrations remain far from the toxicity level. Healing psoriasis lesions show similar mRNA expression of vitamin D metabolizing enzymes, but higher antimicrobial peptide levels than NB-UVB-treated skin in healthy subjects.

Chronic gastritis in dermatitis herpetiformis: a controlled study.

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.

IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors.

In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-α and IFN-γ, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.

Narrow-band ultraviolet B exposure increases serum vitamin D levels in haemodialysis patients.

BACKGROUND: Chronic kidney disease (CKD) patients are especially prone to vitamin D insufficiency. Narrow-band ultraviolet B (NB-UVB) treatment increases serum 25-hydroxyvitamin D [25(OH)D] in dermatological patients, and we studied whether it also improves vitamin D balance in CKD patients on haemodialysis. METHODS: Fifteen dialysis patients (mean age 48.3 years) and 12 healthy subjects (mean age 43.6 years) received nine NB-UVB exposures on the upper body. Serum 25(OH)D and 1,25(OH)(2)D were measured before and after the exposures. From skin biopsy specimen messenger RNA (mRNA) expression levels of CYP24A1 and CYP27B1, two enzymes needed for hydroxylation of vitamin D into its active metabolites, and of antimicrobial peptide cathelicidin, were examined. RESULTS: Before NB-UVB, mean serum 25(OH)D was 32.5 ± 10.2 nmol/L in the dialysis patients and 60.2 ± 18.0 nmol/L in the healthy subjects (P < 0.001). After eight NB-UVB exposures, serum 25(OH)D increased by 13.8 nmol/L (43%; P < 0.001) and serum 1,25(OH)(2)D by 3.3 pmol/L (27%; P = 0.002) in the dialysis patients. After NB-UVB exposures, CYP27B1 mRNA was increased (P = 0.04), whereas cathelicidin mRNA was decreased (P < 0.0001) compared to non-treated healthy subjects. One and 2 months after NB-UVB exposure, serum 25(OH)D was still 10% higher than initially in the dialysis patients. CONCLUSIONS: The present study shows that a short course of NB-UVB exposure increases significantly serum 25(OH)D and 1,25(OH)(2)D in dialysis patients. The effect is, however, short lasting suggesting that the patients need cyclic NB-UVB exposure to maintain their improved vitamin D concentration.

Spore film dosimeters are feasible for UV dose monitoring during heliotherapy.

The objective of the study was to compare Bacillus subtilis spore film dosimeters with a Robertson Berger UV meter (RB meter) and diary records for assessing personal UV-B doses during a 13-day heliotherapy (HT) for atopic dermatitis (AD). In addition, the relationship between the personal UV-B dose and change in serum 25-hydroxyvitamin D (25(OH)D) was studied. Altogether 21 adult patients with AD completed the study arranged in the Canary Islands, either in January or March 2005. The spore film dosimeters were used throughout the day during the HT. Serum 25(OH)D was analyzed using radioimmunoassay. The mean personal UV-B dose measured with the dosimeters was 75 SED in January and 131 SED in March. The respective results gained from the RB meter combined with diary records were 63 SED and 119 SED showing a close correlation with the dosimeter results. Serum 25(OH)D concentration increased by 9.7nmol L(-1) in January and by 26.0 7nmol L(-1) in March. The increase in serum 25(OH)D correlated with the UV-B dose received. The patients complied well to use the dosimeters. We conclude spore films to be a feasible and reliable personal UV dosimeter in vivo in field conditions.

The combination of etanercept and methotrexate increases the effectiveness of treatment in active psoriasis despite inadequate effect of methotrexate therapy.

Many patients with moderate-to-severe plaque psoriasis do not respond adequately to methotrexate monotherapy. This pilot study, with a small patient population, was performed to evaluate the effectiveness and safety of etanercept and methotrexate combination in patients with plaque psoriasis and inadequate response to methotrexate. Outpatients with plaque psoriasis (Psoriasis Area and Severity Index > or = 8 and/or body surface area > 10%), despite methotrexate treatment (> or = 3 months; > or = 7.5 mg/week) were randomized to either etanercept with metho nottrexate tapered and discontinued (n = 28) or etanercept with continuous methotrexate (n = 31). Significantly more patients had a Physicians' Global Assessment of "clear"/"almost clear" in the combination group compared with etanercept/methotrexate taper (66.7 vs. 37.0%, respectively; p = 0.025). Adverse events were similar for both groups, with no cases of tuberculosis, malignancies or opportunistic infections reported. Addition of etanercept to methotrexate achieved significant improvement in psoriasis after 24 weeks.