Reduced mortality in dermatitis herpetiformis: a population-based study of 476 patients.

BACKGROUND: Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease and most patients adhere to a life-long gluten free diet (GFD). Increased mortality rates have been reported in coeliac disease but knowledge in DH is scanty. OBJECTIVES: To survey the mortality rate and causes of death in a large cohort of patients with DH. MATERIAL AND METHODS: Patients with DH (n = 476 consecutive patients) diagnosed from 1970 onwards at the Tampere University Hospital were analysed for causes of death during 1971-2010. A questionnaire survey on key aspects of health behaviour was performed in patients with DH and comparisons were made with the Finnish population. RESULTS: The total number of deaths during 9079 person years followed up was 77 whereas 110 were expected. The standardized mortality rate (SMR) for all causes of death was significantly reduced, being 0·70 (95% CI 0·55-0·87), and similar in both sexes. The SMR was equal in the patients with DH with (0·73) and without (0·77) small bowel villous atrophy. The SMR was significantly reduced (0·38) for deaths due to cerebrovascular diseases. The SMR due to lymphoproliferative malignancies was significantly increased (6·86) in the first 5 years of follow-up but not thereafter. The questionnaire survey documented that 97·7% of the patients with DH adhered to a GFD. The patients reported significantly less hypercholesterolaemia and there were fewer current and past smokers compared with the age- and sex-matched control population. CONCLUSIONS: The present long-term follow-up study of DH documented significantly reduced all-cause and cerebrovascular disease mortality. Strict adherence to a GFD, less smoking and hypercholesterolaemia may play a role in the observed health benefit.

Rupatadine 10 mg in the treatment of immediate mosquito-bite allergy.

BACKGROUND: People frequently experience wealing and delayed papules from mosquito bites. Wealing is mediated by antisaliva IgE antibodies and histamine. Rupatadine is a new antihistamine effective in allergic rhinitis and urticaria, but the effect on mosquito-bite allergy is not known. OBJECTIVE: To determine the effectiveness of rupatadine in inmediate mosquito-bite allergy-confirmed adult patients. METHODS: A double-blind, placebo-controlled, cross-over study was performed with rupatadine 10 mg and matched placebo in 30 mosquito-bite-sensitive adults. The mean age was 37 years and the subjects had suffered from harmful mosquito bites for a mean of 15 years. Either rupatadine or placebo was taken at 08:00 am for 4 days, followed by a 5 day wash out period and then alternative treatment was given for 4 days. On day 3, in both drug periods the subjects received two Aedes aegypti mosquito-bites on the forearm. The size of lesions and intensity of pruritus [visual analogue scale (VAS)] were measured after 15 min bite reaction. RESULTS: Twenty-six subjects were analysed for efficacy. The size of the 15 min bite reaction under placebo was of 106 mm2 and under rupatadine, of 55 mm2. This is a significant decrease (48%; P=0.0003). The accompanying pruritus decreased from 60 (VAS; median) under placebo to 47.5 under rupatadine, which also is a significant (P=0.019) difference. There was no significant (P=0.263) difference in adverse events under rupatadine and placebo. CONCLUSION: The present placebo-controlled study in mosquito-bite-sensitive adults shows that rupatadine 10 mg prophylactically given is an effective treatment for the mosquito-bite wealing and skin pruritus.

Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration.

BACKGROUND: A short course of narrowband ultraviolet B (NB-UVB) exposures increases the serum 25-hydroxyvitamin D [25(OH)D] concentration in patients with psoriasis and healthy subjects. OBJECTIVES: To compare the effects of NB-UVB and oral vitamin D substitution in healthy subjects in winter. METHODS: Healthy adult hospital employees and medical students were screened for serum 25(OH)D concentration. Those with 25(OH)D below 75 nmol L(-1) were randomly given either 12 NB-UVB exposures or 20 µg of oral cholecalciferol daily for 4 weeks. The NB-UVB exposures were given with a Waldmann UV 7001 cabin and the mean cumulative dose was 48·4 standard erythema doses. Serum 25(OH)D was measured before and after the treatments by radioimmunoassay. RESULTS: The baseline serum 25(OH)D concentrations were 52·9 ± 10·4 (mean ± SD) in the 33 NB-UVB-treated and 53·5 ± 12·7 nmol L(-1) in the 30 oral cholecalciferol-treated subjects. The mean increase in serum 25(OH)D was 41·0 nmol L(-1) [95% confidence interval (CI) 34·8-47·2; P < 0·001] in the NB-UVB group and 20·2 nmol L(-1) (95% CI 14·6-26·0; P < 0·001) in the cholecalciferol group. The difference between the two treatments was significant at 2 weeks (P = 0·033) and at 4 weeks (P < 0·001). One month after the treatments the 25(OH)D concentrations had increased further. CONCLUSIONS: The present study shows that 12 NB-UVB exposures given during 4 weeks increase serum 25(OH)D concentration significantly more than 20 µg of oral cholecalciferol daily. A short NB-UVB course is an effective way to improve vitamin D balance in winter and the response is still evident 2 months after the course.

Prevalence and incidence of dermatitis herpetiformis: a 40-year prospective study from Finland.

BACKGROUND: Dermatitis herpetiformis (DH) is an external manifestation of coeliac disease presenting with blistering rash and pathognomonic cutaneous IgA deposits. Better knowledge of subclinical forms and serological testing has resulted in a sharp increase in the incidence and prevalence of coeliac disease. OBJECTIVES: To investigate the prevalence of DH and analyse whether the incidence of DH changed when the occurrence of coeliac disease increased. METHODS: All 477 patients with DH diagnosed from 1970 onwards at the Tampere University Hospital were analysed for prevalence in 2009. The incidence of DH was calculated in three 10-year periods from the year 1980. RESULTS: The prevalence of DH was 75·3 per 100,000 which is eight times lower than the prevalence of coeliac disease in our area. The annual incidence of DH in the whole period was 3·5 per 100,000, and in the three 10-year periods 5·2, 2·9 and 2·7 per 100,000, respectively. The decrease in incidence between the first and second 10-year period was significant (P<0·001). The male to female ratio of DH was 1·1:1. The mean age at diagnosis increased significantly during the study, in men from 35·3 to 51·1 years and in women from 36·3 to 45·8 years. CONCLUSIONS: The present study shows the highest prevalence of DH reported to date. Although the overall incidence of DH was also high, a significant decrease occurred in the 1990s, which is in contrast to the incidence of coeliac disease.

Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe.

BACKGROUND: Patient-oriented medicine is an emerging concept, encouraged by the World Health Organization, to greater involvement of the patient in the management of chronic diseases. The Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index is a self-assessment score allowing the patient to comprehensively evaluate the actual course of atopic dermatitis (AD), using subjective and objective criteria derived mainly from the SCORAD, a validated AD severity clinical assessment tool. OBJECTIVES: To validate the PO-SCORAD index in a large European population of patients exhibiting all forms of AD severity by assessing its correlation with the SCORAD index. PATIENTS/METHODS: Four hundred and seventy-one patients (185 adults, 286 children) consulting for AD in hospitals from 9 European countries were recruited. The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 ± 7 days later (D28). RESULTS: Patient-Oriented SCORing Atopic Dermatitis and SCORAD scores were significantly correlated at D0 [r = 0.67 (95% CI: 0.62; 0.72), P < 0.0001]. Consistency was confirmed at D28, with a stronger linear correlation between both scales [r = 0.79 (95% CI: 0.75; 0.83), P < 0.0001]. Absolute changes from baseline in SCORAD and PO-SCORAD scores were also significantly correlated [r= 0.71 (95% CI: 0.64; 0.76), P < 0.0001]. Although no specific intervention was investigated, AD improved over the study, with a decrease of PO-SCORAD and SCORAD scores from D0 to D28 by -19.19% and -24.39%, respectively. The consistency of the correlations was similar in the adult and children groups. CONCLUSIONS: This study validated the use of PO-SCORAD to self-assess AD severity and demonstrated its good correlation with SCORAD.

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. OBJECTIVES: To examine whether NB-UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB-UVB on antimicrobial peptide and cytokine expression in the skin. METHODS: Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB-UVB exposures on the whole body, given three times a week. Serum calcidiol (25-hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real-time quantitative polymerase chain reaction. RESULTS: At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L(-1)). NB-UVB treatment significantly increased (P < 0.001) serum calcidiol. The increase was 59.9 nmol L(-1) (95% confidence interval, CI 53.5-66.9) in psoriasis, 68.2 nmol L(-1) (95% CI 55.4-80.1) in AD and 90.7 nmol L(-1) (95% CI 63.8-123.4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0.001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human beta-defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB-UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB-UVB caused a marked but nonsignificant decrease of interleukin (IL)-1beta and IL-17 in psoriasis lesions. CONCLUSIONS: The present study shows that in addition to a significant improvement of psoriasis and AD, NB-UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.

Narrowband ultraviolet B course improves vitamin D balance in women in winter.

BACKGROUND: Vitamin D insufficiency is common in winter in the Nordic countries. OBJECTIVES: To examine whether a short course of narrowband ultraviolet B (NB-UVB) improves vitamin D balance. METHODS: Fifty-six healthy, white women (mean age 41 years) volunteered and 53 completed the study. NB-UVB exposures were given on seven consecutive days either on the whole body (n = 19), on the head and arms (n = 9) or on the abdomen (n = 14). Similarly, seven solar simulator exposures were given on the face and arms (n = 11). The cumulative UVB dose was 13 standard erythema doses in all regimens. Serum calcidiol (25-hydroxyvitamin D) concentration was measured by radioimmunoassay before and after the NB-UVB exposures. Follow-up samples were taken from the whole-body NB-UVB group at 2 months. RESULTS: At onset 41 women (77%) had vitamin D insufficiency (calcidiol < 50 nmol L(-1)) and six (11%) had vitamin D deficiency (calcidiol < 25 nmol L(-1)). Calcidiol concentration increased significantly, by a mean of 11.4 nmol L(-1) when NB-UVB was given on the whole body, by 11.0 nmol L(-1) when given on the head and arms and by 4.0 nmol L(-1) when given on the abdomen. Solar simulator exposures given on the face and arms increased calcidiol by 3.8 nmol L(-1). After 2 months serum calcidiol was still higher than initially in the group who received NB-UVB exposures on the whole body. CONCLUSIONS: NB-UVB exposures given on seven consecutive days on different skin areas of healthy women significantly improved serum calcidiol concentration. A short low-dose NB-UVB course can improve vitamin D balance in winter.

Diagnostic methods beyond conventional histology in coeliac disease diagnosis.

BACKGROUND: Coeliac disease diagnostic criteria currently require the detection of small bowel mucosal villous atrophy and crypt hyperplasia. AIMS: To compare conventional histological examination to the determination of small bowel mucosal intraepithelial lymphocytes (IELs) and to serum and intestinal coeliac autoantibodies in untreated coeliac disease with villous atrophy and in mild enteropathy coeliac disease. PATIENTS AND METHODS: Study comprised consecutive adult patients with coeliac disease suspicion; villous height-crypt depth ratio (Vh/CrD), the densities of CD3+, gammadelta+ and villous tip IELs and serum and intestinal transglutaminase 2 (TG2)-targeted autoantibodies were studied. Coeliac disease was diagnosed in 223 and excluded in 608 patients. Further, 66 patients were considered to suffer from mild enteropathy coeliac disease. Control group consisted of 138 patients. RESULTS: Vh/CrD determination detected 77% of untreated coeliac disease patients. Serum coeliac autoantibodies had 84% sensitivity for untreated coeliac disease with villous atrophy and 70% sensitivity for mild enteropathy coeliac disease; the specificity was 100%. Intestinal TG2-targeted autoantibodies had sensitivities of 100% and 93%, and 100% specificity, respectively. gammadelta+ and villous tip IELs proved more reliable than CD3+ IELs. CONCLUSIONS: Conventional histological examination as the golden standard in coeliac disease diagnosis is questionable. Serum and especially intestinal TG2-targeted autoantibodies seem promising in future coeliac disease diagnostics.

Decreased numbers of circulating plasmablasts and differences in IgA1-plasmablast homing to skin in coeliac disease and dermatitis herpetiformis.

The two clinical phenotypes of gluten enteropathy, coeliac disease (CD) and dermatitis herpetiformis (DH), were characterized for numbers and homing profiles of circulating final effector B cells, plasmablasts, identified as immunoglobulin (Ig)-secreting cells (ISC). In CD, the numbers of ISC were approximately 50% lower than in DH or controls. ISC expressed peripheral lymph node homing receptor (HR), L-selectin, less frequently in CD (54%) and DH (52%) patients than in controls (70%). The expression of gut mucosal HR, alpha(4)beta(7), was less frequent in CD (42%) than in DH (65%) or controls (60%). In DH, but not in CD or controls, a higher proportion of IgA1-ISC (40%) than IgA2-ISC (25%) expressed the skin HR, cutaneous lymphocyte-associated antigen. In gluten enteropathy circulating plasmablasts are more mature, but decreased in number, and have distorted homing profiles. Differential IgA1-plasmablast homing could be associated with the development of skin rash with IgA1-deposits in DH but not in CD.

Sensitization and allergy to turnip rape: a comparison between the Finnish and French children with atopic dermatitis.

AIM: Finnish children with atopic dermatitis (AD) are frequently sensitized and show positive food challenge to turnip rape. We examined whether French children are also allergic to this oilseed plant and whether mustard could be the cross-reacting allergen. METHODS: Turnip rape and mustard challenge was performed to 14 Finnish and 14 French children with atopic dermatitis and positive skin prick test to turnip rape. Specific IgE antibodies were measured by ImmunoCAP and enzyme-linked immunosorbent assay (ELISA). RESULTS: Open labial or oral challenge to turnip rape was positive in 14 (100%) Finnish and five (36%) French children and mustard challenge in five Finnish and five French children. IgE antibodies to oilseed rape and mustard were slightly more frequent in the Finnish (100% and 93%) than in the French (93% and 71%) children but rare (4%) in the 28 matched controls. The same findings were true for IgE antibodies to purified 2S albumin allergens, which showed similar cross-wise IgE inhibition patterns. CONCLUSION: French children with atopic dermatitis show IgE antibodies to turnip rape, oilseed rape and mustard similarly to the Finnish children. 2S albumin allergens in the seeds of these plants are highly cross-reactive and therefore, they all could be important sensitizers in children with atopic dermatitis.

Heliotherapy improves vitamin D balance and atopic dermatitis.

BACKGROUND: Vitamin D insufficiency during winter is common in the Nordic countries. Heliotherapy (HT) may heal atopic dermatitis (AD) but its effect on vitamin D balance has not been examined. OBJECTIVES: To study the effect of HT on serum calcidiol (25-hydroxyvitamin D) concentration and on healing of AD. METHODS: Twenty-three adult patients with AD received a 2-week course of HT in the Canary Islands in either January or March 2005. Daily solar ultraviolet (UV) radiation was measured and personal UV exposure calculated as standard erythema doses (SED). Blood samples were taken during HT and during a 1-2 month follow-up. Serum calcidiol concentration was measured by radioimmunoassay. Healing of AD was examined by SCORAD index. RESULTS: Before HT 17 (74%) AD patients had vitamin D insufficiency (calcidiol < 50 nmol L(-1)) and four patients high (> 80 nmol L(-1)) serum calcidiol values. The median personal UV dose during the 2-week HT course was 60 SED in the January group and 109 SED in the March group. Serum calcidiol concentration increased significantly in both groups, by 13.4 and 24.0 nmol/L(-1), respectively, and after HT only four (17%) patients had vitamin D insufficiency. SCORAD improved from 34 to 9 in the January HT group and from 30 to 9 in the March group. CONCLUSIONS: A 2-week course of HT significantly improved vitamin D balance by increasing serum calcidiol concentration, and caused a marked healing of AD. These parallel positive responses should be taken into account when the benefits of HT are considered.

Control of atopic eczema with pimecrolimus cream 1% under daily practice conditions: results of a > 2000 patient study.

BACKGROUND: Pimecrolimus cream 1% has been shown to effectively control atopic eczema (AE) when applied twice daily from the first signs or symptoms of AE until clearance. Moreover, pimecrolimus cream 1% has a favourable safety profile, lacking topical corticosteroid-related side-effects such as skin atrophy, making it particularly useful to treat delicate body regions (e.g. the face). OBJECTIVE: The objective of this naturalistic study was to monitor the safety, tolerability and efficacy of pimecrolimus when used in the long-term management of AE in a real-life setting. METHODS: A multicentre, open-label study was conducted in 2034 patients aged >or= 3 months with mild to moderate AE for up to 12 months' duration. Patients applied pimecrolimus cream twice daily, initiating treatment at first signs or symptoms of AE, continuing until clearance. RESULTS: Patients (n= 1847; 91%) completed 3 months of the study. Treatment success (clear or almost clear AE) after 3 months of treatment was observed on the whole body in 59% of patients and on the face in 81% of patients. Disease improvement of whole body and face was seen in 77% and 63% of patients, respectively. Pruritus was absent or mild in 79% of patients. Pimecrolimus cream was well tolerated throughout the study. CONCLUSION: In a daily practice setting, pimecrolimus cream 1% effectively and safely controls AE.

Latex allergy: low prevalence of immunoglobulin E to highly purified proteins Hev b 2 and Hev b 13.

BACKGROUND: Hevea brasiliensis (Hev b) 2 and Hev b 13 have recently been identified as major latex allergens by detecting specific IgE antibodies in >50% of sera from Hev b latex-allergic individuals. OBJECTIVE: We assessed the prevalence rates for sensitization to extensively purified latex allergens in patients from three diverse geographical areas. METHODS: Native Hev b 2, Hev b 5, Hev b 6.01 and Hev b 13 were purified by non-denaturating chromatography and were used in ELISAs to assess sera from 215 latex-allergic patients and 172 atopic non-sensitized controls from Finland, Spain and the United States to detect allergen-specific IgE antibodies. RESULTS: Unexpectedly, even highly purified Hev b 13 contained epitope(s) to which Hev b 6-specific human IgE antibodies bound effectively. Further purification, however, reduced the prevalence of IgE antibody reactivity to low levels: 15%, 5% and 11% for Hev b 2, and 18%, 30% and 27% for Hev b 13 among latex-allergic Finnish, Spanish and American patients, respectively. Interestingly, Finnish patients had a lower prevalence of Hev b 5-specific IgE antibody (28%) as compared with Spanish (49%) and American (71%) patients. The prevalence of Hev b 6.01-specific IgE reactivity was uniformly >50% in all three populations. CONCLUSION: Neither Hev b 2 nor Hev b 13 appear to be major latex allergens when evaluated in serological assays using highly purified allergens. The reason(s) for the observed differences in published sensitization rates in various geographic regions requires further study. The purity of the allergen preparations has a marked impact on the accuracy of latex-specific IgE antibody detection in epidemiological studies and in the serological diagnosis of latex allergy.

Latex allergy: the sum quantity of four major allergens shows the allergenic potential of medical gloves.

BACKGROUND: Assessment of allergenic potential of medical devices made of natural rubber latex (NRL) requires the measurement of concentrations of specific allergenic proteins or polypeptides eluting from rubber. METHODS: Four NRL allergens (Hev b 1, 3, 5, and 6.02) were quantified in all medical glove brands marketed in Finland in 1999, 2001, and 2003 (n = 208) by a capture enzyme immunoassay. The results were compared with those obtained from previous nationwide market surveys, using a skin prick test-validated human IgE-based ELISA-inhibition method. RESULTS: A high overall correlation (r = 0.87, 95% CI 0.83-0.90) emerged between the sum values of the four allergens(microg/g glove) and IgE-ELISA inhibition (allergen units, AU/ml, 1 : 5 diluted glove extract). The sum of four allergens when set at 0.15 microg/g discriminated 'low allergenic' (<10 AU/ml) from 'moderate- to high-allergenic' (>/=10 AU/ml) gloves at a sensitivity of 0.93 (95% CI 0.85-0.98) and specificity of 0.90 (95% CI 0.83-0.94). When the sum was below the detection limit (0.03 microg/g) all gloves belonged to the previously defined low-allergen category. CONCLUSIONS: By comparing the sum concentration of four selected NRL allergens with results obtained in human IgE-ELISA inhibition, it was possible set a cut-off level (0.15 microg/g) below which virtually all gloves contain low or insignificant amounts of allergens, and can be considered as low allergenic. At different cut-off-points, one could calculate the likelihood of a given glove to belong to the previously defined low, moderate or high allergen categories.