[How should the care of dermatological diseases be developed?].
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Attitude of Health Personnel↗
Biomedical subjects
Timo Reunala
Publications and source records attributed to Timo Reunala.
Napins, 2S albumins, are major allergens in oilseed rape and turnip rape.
BACKGROUND: Children with IgE-mediated allergy to foods frequently react to seeds of oilseed rape (Brassica napus ssp. oleifera) and turnip rape (Brassica rapa ssp. oleifera) in skin prick tests (SPTs). Sensitization pathways are not known. OBJECTIVE: We identified possible major allergens in oilseed rape and turnip rape using sera from 72 atopic children (mean age, 3.3 years) with positive SPT responses to oilseed rape and turnip rape. METHODS: Allergens from oilseed rape and turnip rape seed extracts were purified by using gel filtration and cation exchange chromatography and characterized by means of reversed-phase chromatography, N-terminal amino acid sequencing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. IgE binding of sera from 72 children with positive SPT reactions to oilseed rape and turnip rape and 72 age- and sex-matched atopic control subjects with negative SPT responses were analyzed by means of IgE ELISA and immunoblotting. In vivo reactivity of the purified allergens was tested with SPTs in 6 children. RESULTS: In IgE immunoblotting and IgE ELISA major reactivity was to a group of homologous, approximately 9.5- to 14.5-kd proteins. These allergens were identified as 2S albumins, also known as napins, by means of N-terminal amino acid sequencing. In ELISA approximately 80% of the patients had IgE to purified napins from both plants. In SPTs purified napins caused positive reactions in all 6 children tested. CONCLUSIONS: This study shows that 2S albumins in oilseed rape and turnip rape are new potential food allergens. Further studies are needed to clarify the routes of exposure and mechanisms of sensitization.
2S Albumins, Plant↗
Isolated hevein-like domains, but not 31-kd endochitinases, are responsible for IgE-mediated in vitro and in vivo reactions in latex-fruit syndrome.
BACKGROUND: Individuals with natural rubber latex allergy often have immediate reactions to plant-derived foods and fresh fruits, such as avocado and banana. IgE of these patients has been shown to bind endochitinases containing an N-terminal hevein-like domain (HLD). However, evidence on 31-kd endochitinase-induced reactions in vivo is lacking. OBJECTIVE: We sought to assess the clinical significance of 31-kd endochitinases and isolated HLDs in latex-fruit syndrome. METHODS: The 31-kd endochitinases and corresponding HLDs were purified or produced from avocado, banana, latex, and wheat germ. Skin prick test reactivities against purified proteins were examined in 15 patients with natural rubber latex allergy. The binding efficiency of IgE to purified proteins was studied by using an inhibition ELISA. Experimentally resolved or modeled structures of the proteins were compared to clarify the molecular basis of clinical reactions. RESULTS: Eleven (73%) patients had skin prick test reactions to isolated HLDs of avocado and banana, but only 1 (7%) patient reacted to their corresponding 31-kd endochitinases. HLDs from avocado and banana inhibited binding of IgE to prohevein (Hev b 6.01) in 59% and 38% of patients, respectively, whereas corresponding percentages for 31-kd endochitinases were 17% and 20%, respectively. Isolated HLDs of wheat germ agglutinin and 18-kd wheat germ agglutinin did not significantly inhibit IgE binding to hevein. CONCLUSION: The isolated HLD molecules alone, but not when linked to endochitinases, seem to be responsible for IgE-mediated clinical reactions in latex-fruit syndrome. Careful selection of relevant allergens in their proper molecular form is therefore crucial in forming a reliable diagnosis of latex-fruit syndrome.
Adult↗
Cutaneous, but not airway, latex exposure induces allergic lung inflammation and airway hyperreactivity in mice.
As respiratory symptoms are common in addition to skin reactions in natural rubber latex allergy, we investigated the significance of different allergen exposure routes in the development of lung inflammation and airway hyperreactivity (AHR). Both intracutaneous (IC) and intraperitoneal (IP) exposure followed by airway challenge with latex proteins induced an influx of mononuclear cells and eosinophils to the lungs. AHR and lung mucus production increased significantly after IC and IP but not after intranasal (IN) exposure. Infiltration of inflammatory cells was associated with the induction of T-helper type 2 (Th2) cytokines and several CC chemokines. Only a marginal induction of these mediators was found after IN exposure. On the contrary, increased levels of transforming growth factor-beta1 and forkhead box 3 mRNA, markers of regulatory activities, were found in the lungs after IN but not after IC exposure. Finally, IC and IP, but not IN, latex exposure induced a striking increase in specific immunoglobulin E (IgE) levels. Cutaneous latex exposure in the absence of adjuvant followed by airway challenge induces a local Th2-dominated lung inflammation and a systemic IgE response. Cutaneous exposure to proteins eluting from latex products may therefore profoundly contribute to the development of asthma in latex allergy.
Administration, Cutaneous↗
[Update on current care guidelines. Celiac disease].
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Antibodies, Anti-Idiotypic↗
Construction of hevein (Hev b 6.02) with reduced allergenicity for immunotherapy of latex allergy by comutation of six amino acid residues on the conformational IgE epitopes.
Recently we have established that IgE Abs bind to conformational epitopes in the N- and C-terminal regions of the major natural rubber latex allergen, hevein (Hev b 6.02). To identify the critical amino acid residues that interact with IgE, the hevein sequence was scanned by using site-specific mutations. Twenty-nine hevein mutants were designed and produced by a baculovirus expression system in insect cells and tested by IgE inhibition-ELISA using sera from 26 latex allergic patients. Six potential IgE-interacting residues of hevein (Arg(5), Lys(10), Glu(29), Tyr(30), His(35), and Gln(38)) were identified and characterized further in detail. Based on these six residues, two triple mutants (Hdelta3A, Hdelta3B) and hevein mutant where all six residues were mutated (Hdelta6), were designed, modeled, and produced. Structural and functional properties of these combinatory mutants were compared experimentally and in silico with those of recombinant hevein. The IgE-binding affinity of the mutants decreased by three to five orders of magnitude as compared with that of recombinant hevein. Skin prick test reactivity of the triple mutant HDelta3A was drastically reduced and that of the six-residue mutant Hdelta6 was completely abolished in all patients examined in this study. The approach presented in this paper offers tools for identification and modification of amino acid residues on conformational epitopes of allergens that interact with IgE. Hevein with a highly reduced ability to bind IgE should provide a valuable candidate molecule for immunotherapy of latex allergy and is anticipated to have a low risk of systemic side effects.
Adolescent↗
Latex allergy and skin.
PURPOSE OF REVIEW: In this review we address the prevalence and outcome of latex allergy in health care workers (HCWs). Recent findings in natural rubber latex (NRL) allergens and trials of specific immunotherapy (SIT) are also of interest. RECENT FINDINGS: A study involving skin prick test (SPT) screening in HCWs in Russia and adjacent countries found a prevalence of latex allergy of 1.9%. Questionnaire studies performed in Wales and in the USA identified prevalence rates of about 0.6%. An intervention undertaken at the Mayo Clinic, in which only gloves with low or undetectable allergen levels were allowed, reduced markedly the incidence of NRL allergy. Two studies, one from Finland and another from Ohio, showed that outcomes in latex-allergic HCWs are generally good. A study involving SPT screening showed that 6% of construction workers had latex allergy. A questionnaire study among allergists practicing in the USA showed that 62% performed latex SPT and 6% reported anaphylaxis, which mostly occurred while using a homemade SPT solution. Hev b 2, Hev b 5, Hev b 6.01 and Hev b 13 produced positive SPT reactions in over 60% of latex-allergic individuals. Topical application of NRL in a murine model of protein contact dermatitis caused a striking increase in prohevein-specific (Hev b 6.01) immunoglobulin E levels, together with a T-helper-2 type dermatitis. A placebo-controlled SIT trial with NRL extract alleviated cutaneous symptoms but caused some systemic reactions in latex-allergic patients. SUMMARY: Low prevalence rates suggest that the peak of the latex allergy epidemic has already passed in HCWs. Hospital-wide interventions requiring use of low-allergen gloves reduce sensitization and changing gloves to nonlatex ones, or even using low-allergen latex gloves, in the affected individuals appears to confer adequate secondary prevention. In the USA there is an urgent need for standardized latex SPT reagent. Hev b 5 and Hev b 6.01 are major in vivo NRL allergens. Findings in mice suggest that NRL proteins eluting from latex gloves may also cause hand eczema in humans. SIT with NRL extract must still be considered an experimental treatment.
Allergens↗
Epicutaneous natural rubber latex sensitization induces T helper 2-type dermatitis and strong prohevein-specific IgE response.
In addition to immediate type I allergy symptoms, natural rubber latex allergy may manifest as protein contact dermatitis on the hands of health-care workers and other natural rubber latex glove users. We examined whether repeated application of natural rubber latex on mouse skin causes sensitization to natural rubber latex and dermatitis. Epicutaneous sensitization with natural rubber latex produced a significant influx of mononuclear cells, CD4+ CD3+ cells, and eosinophils to the sensitized skin sites. The number of degranulated mast cells in natural rubber latex-sensitized skin sites was significantly higher compared with control sites treated with phosphate-buffered saline. The expression of interleukin-1beta and interleukin-4 mRNA was markedly increased in natural rubber latex-sensitized skin sites. Moreover, significant increases in the mRNA expression of chemokines CCL2 (monocyte chemoattractant protein-1), CCL11 (eotaxin-1), CCL3 (macrophage inflammatory protein-1alpha), and CCL4 (macrophage inflammatory protein-1beta) were found. In addition to the cutaneous inflammatory response, epicutaneous sensitization with natural rubber latex induced a striking increase in the total and specific immunoglobulin E levels but not in the immunoglobulin G2a levels. Intraperitoneal immunization with natural rubber latex induced a strong natural rubber latex-specific immunoglobulin G2a response, but only a weak immunoglobulin E response. We also studied the role of two major natural rubber latex allergens, the highly hydrophilic prohevein and the hydrophobic rubber elongation factor. Cutaneous application of natural rubber latex elicited a strong immunoglobulin E response against prohevein, but not against rubber elongation factor. On the contrary, intraperitoneal immunization with natural rubber latex elicited strong immunoglobulin G2a production to rubber elongation factor but not to prohevein. These results demonstrate that epicutaneous sensitization with natural rubber latex induces T helper 2-dominated dermal inflammation and strong immunoglobulin E response in this murine model of natural rubber latex induced protein contact dermatitis. Epicutaneous sensitization to natural rubber latex proteins eluting from latex gloves may therefore contribute to the development of hand dermatitis and also natural rubber latex-specific immunoglobulin E antibodies.
Allergens↗
Psoriasis susceptibility locus on 18p revealed by genome scan in Finnish families not associated with PSORS1.
The major susceptibility locus for psoriasis, PSORS1, resides on chromosome 6p and includes the candidate genes HLA-C, HCR, and CDSN. Based on a nationwide collection of psoriasis patients and genotyping for the PSORS1 susceptibility haplotype, we selected for a genome scan nine families who do not show association with PSORS1 to more easily detect minor loci for psoriasis susceptibility. In the genome scan, five loci gave initial evidence of linkage and were studied with a denser marker map. After fine mapping, only one locus on 18p11.23 showed suggestive evidence of linkage (nonparametric multipoint linkage analysis score, 3.58; p = 0.0038). The bootstrapping analysis showed that one large family contributed the majority of the linkage (p = 0.0039), but was supported by other families. Haplotype sharing between the linked families and haplotype association analysis gave additional support for the locus. Further, the 18p locus has shown nominal evidence of linkage with psoriasis in the British population. Taken together, these findings confirm the presence of a minor susceptibility locus for psoriasis on 18p11.
Adolescent↗
Transglutaminase-mediated cross-linking of a peptic fraction of omega-5 gliadin enhances IgE reactivity in wheat-dependent, exercise-induced anaphylaxis.
BACKGROUND: Patients with wheat-dependent, exercise-induced anaphylaxis (WDEIA) experience recurrent anaphylactic reactions when exercising after ingestion of wheat products. We have identified omega-5 gliadin (Tri a 19) as a major allergen in WDEIA, but the role of exercise in eliciting the symptoms remains obscure. OBJECTIVE: The aim was to examine whether tissue transglutaminase (tTG)-mediated cross-linking could be involved in modulating the IgE-binding ability and in vivo reactivity of digested omega-5 gliadin peptides in WDEIA. METHODS: Purified omega-5 gliadin was digested with pepsin or with pepsin and trypsin and treated with tTG. The binding of IgE antibodies in pooled sera from 10 patients with WDEIA was studied by means of immunoblotting before and after tTG treatment of the digested peptides. The peptides derived from pepsin digestion were separated by means of gel-filtration chromatography, and IgE reactivity of 4 different peptide fractions was studied by immunoblotting before and after tTG treatment. The fraction showing the greatest degree of cross-linking by tTG was further studied by means of IgE ELISA, ELISA inhibition, and skin prick testing. RESULTS: The IgE-binding ability of omega-5 gliadin was retained after pepsin and pepsin-trypsin digestion. tTG treatment of the whole peptic digest formed large peptide complexes, with molecular weights ranging from 40 to greater than 200 kd. These cross-linked aggregates bound IgE antibodies in immunoblotting more intensely than untreated, pepsin-digested, or pepsin-trypsin-digested omega-5 gliadin. A gel-filtration fraction of the whole peptic digest corresponding to the highest peak of the chromatogram and showing the greatest degree of tTG-mediated cross-linking showed an increase in serum IgE reactivity in ELISA after tTG treatment, as well as a shift of reactivity to cross-linked complexes. In the 20 patients with WDEIA, the mean skin prick test wheal elicited by this tTG-treated peptic fraction was 77% larger (P <.001) than that elicited by the untreated peptic fraction and 56% larger (P <.01) than that elicited by intact omega-5 gliadin. CONCLUSIONS: Omega-5 gliadin-derived peptides are cross-linked by tTG, which causes a marked increase in IgE binding both in vitro and in vivo. Activation of tTG during exercise in the intestinal mucosa of patients with WDEIA could lead to the formation of large allergen complexes capable of eliciting anaphylactic reactions.
Adult↗
Nationwide increase of Chlamydia trachomatis infection in Finland: highest rise among adolescent women and men.
BACKGROUND: Since 1995, the incidence of Chlamydia trachomatis infection has been increasing in Finland, although there have been no major changes in public sexually transmitted disease (STD) services or screening practice. OBJECTIVES: The objective was to study whether the change in C. trachomatis incidence is significant and to identify specific risk groups. METHODS: The incidence rates for all C. trachomatis cases notified by laboratories to the National Infectious Disease Register (NIDR) in Finland in 1995-2000 were calculated by gender, age, and domicile. Data from a sentinel STD surveillance network was used to analyze changes of risk-taking behavior in age groups with the highest C. trachomatis rates. RESULTS: During the 6-year study period, laboratory surveillance data documented an increase in the incidence rate from 23.4 per 10,000 to 29.2 per 10,000. The increase was most evident among people living in nonurban densely populated areas. Highest increase, 1.37-fold (95% confidence interval [CI], 1.29-1.46) in women and 1.69-fold (CI, 1.47-1.92) in men, occurred in the youngest age group (10-19 years old). In 2000, more women, but not men, in the age group of 10-29 years reported 5 or more annual sex partners (18.8%; CI, 16.3-21.6) than in 1995 (8.3%; CI, 5.7-11.5). CONCLUSION: National surveillance of C. trachomatis infection based on laboratory notification documented increasing incidence rates, especially among adolescents and young people. This risk group should be a target for screening and educational programs to control the epidemic of C. trachomatis infections.
Adolescent↗
Intraepithelial lymphocytes in celiac disease.
OBJECTIVE: The aim of this study was to investigate the value of immunohistochemical characterization of different intraepithelial lymphocytes (IELs) in the diagnostic workup of celiac disease (CD). METHODS: The study involved 928 consecutive adult patients undergoing endoscopy undertaken on suspicion of CD or to ascertain the dietary compliance; the control group consisted of 59 adults who underwent endoscopy because of indigestion. Small bowel mucosal morphology, CD3+, alphabeta+, and gammadelta+ IELs were determined. RESULTS: CD was detected in 138 and excluded in 545 adults. CD3+ and gammadelta+ IELs both showed a sensitivity of 93% for CD; specificity was 73% and 88%, respectively. For alphabeta+ cells, the sensitivity was 83% and specificity, 66%. The mucosal morphology recovered on a gluten-free diet and the densities of different IELs, even gammadelta+ cells, decreased. Only the density of gammadelta+ cells remained elevated compared with controls. CONCLUSIONS: Counting of IELs is recommended in borderline cases where the histology is difficult to interpret. An increase especially in gammadelta+ cells strengthens the probability of CD. However, IELs are not invariably increased in CD.
Adolescent↗
Recognition and management of the cutaneous manifestations of celiac disease: a guide for dermatologists.
In celiac disease, the ingestion of gluten-containing cereals, such as wheat, rye, and barley, results in small-bowel mucosal inflammation and villous atrophy with crypt hyperplasia. The prevalence of the condition may be as high as 1% in the adult population. The disease can also embrace various extraintestinal manifestations, of which dermatitis herpetiformis is the best known. Earlier, dermatitis herpetiformis was considered a skin disease occurring often concomitantly with celiac disease. At present, a body of evidence shows that dermatitis herpetiformis is a cutaneous manifestation of celiac disease, and affects approximately 25% of patients with celiac disease. Both conditions can appear in the same family and are closely linked to HLA class II locus in chromosome 6; 90% of patients have HLA DQ2 and, almost all the remainder, HLA DQ8. All patients with dermatitis herpetiformis have at least some-degree of mucosal inflammation or lesion consistent with celiac disease. The etiology of celiac disease in not fully understood, but tissue transglutaminase seems to be the predominant autoantigen both in the intestine and the skin. Serum antibodies against tissue transglutaminase can be used in the serologic screening and follow-up of dietary compliance of patients with celiac disease. Gluten-free diet is essential in the treatment of both conditions, and oral dapsone is usually needed in newly detected dermatitis herpetiformis in order to alleviate symptoms. Oral mucosal lesions, alopecia areata, and vitiligo probably occur more frequently in patients with dermatitis herpetiformis than in the general population. By contrast, the reported association of celiac disease with psoriasis seems to be coincidental.
Anti-Inflammatory Agents, Non-Steroidal↗
[Syphilis behind the mouth symptoms].
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Anti-Bacterial Agents↗
The major conformational IgE-binding epitopes of hevein (Hev b6.02) are identified by a novel chimera-based allergen epitope mapping strategy.
A novel approach to localize and reconstruct conformational IgE-binding epitope regions of hevein (Hev b6.02), a major natural rubber latex allergen, is described. An antimicrobial protein (AMP) from the amaranth Amaranthus caudatus was used as an immunologically non-IgE-binding adaptor molecule to which terminal or central parts of hevein were fused. Hevein and AMP share a structurally identical core region but have different N-terminal and C-terminal regions. Only 1 of 16 hevein-allergic patients showed weak IgE binding to purified native or recombinant AMP. Chimeric AMP with the hevein N terminus was recognized by IgE from 14 (88%) patients, and chimeric AMP with the hevein C terminus was recognized by IgE from 6 (38%) patients. In contrast, chimeric AMP containing the hevein core region was recognized by IgE from only two patients. When both the N-terminal and C-terminal regions of hevein were fused with the AMP core, IgE from all 16 patients bound to the chimera. This chimera was also able to significantly inhibit (>70%) IgE binding to the native hevein. On the contrary, linear synthetic peptides corresponding to hevein regions in the AMP chimeras showed no significant IgE binding capacity in either enzyme-linked immunosorbent assay or inhibition enzyme-linked immunosorbent assay. These results suggest that the IgE binding ability of hevein is essentially determined by its N-terminal and C-terminal regions and that major IgE-binding epitopes of hevein are conformational. The chimera-based epitope mapping strategy described here provides a valuable tool for defining structural epitopes and creating specific reagents for allergen immunotherapy.
Adenosine Monophosphate↗
Long-term outcome of 160 adult patients with natural rubber latex allergy.
Allergy to natural rubber latex is a major occupational problem in the health care sector and a problem even in other occupations in which protective gloves are used. There is little information available about the long-term outcome at work in large patient populations. To study the occupational outcome when all gloves in the working environment were changed either to low-allergen latex or non-latex gloves, in 1995 to 1996 we re-examined 160 of 174 adult subjects who were diagnosed with natural rubber latex allergy between 1982 and 1994 after a median of 3 years (range, 0.5 to 24 years) after the diagnosis. The outcome in daily work or as a patient in health care was investigated with the use of a questionnaire. Special attention was paid to the assessment of the occurrence of hand eczema. Glove selection policy as an intervention in the treatment of natural rubber latex allergy is described. Of 71 health care workers and 89 non-health care workers, 72% and 83% were atopic; 54% and 65% had hand eczema at the time of diagnosis, and 89% and 19% had work-related allergy to natural rubber latex, respectively. On re-examination, none of the health care workers had changed work because of natural rubber latex allergy, and only 38% had hand eczema (significant decrease). Ninety-eight percent of the non-health care workers, of which 58% had hand eczema, continued with their previous jobs. The use of low-allergen latex or non-latex gloves throughout the health care sector seems to be an adequate step for health care workers who have natural rubber latex allergy; nonhealth care workers get along with personal avoidance of latex gloves if they are not working directly with natural rubber latexcontaining materials in production.
Adult↗
Epidemics due to imported syphilis in Finland.
BACKGROUND: Russia and other states of the former Soviet Union experienced a huge increase in syphilis beginning in the early 1990s. At first these epidemics were not well known in neighboring countries such as Finland. STUDY DESIGN: In 1995 the incidence of syphilis in Finland doubled to 3.3/100,000 and a local cluster of 18 cases was detected in the city of Tampere. The reasons for this epidemic were analyzed and the occurrence of syphilis was carefully monitored up to 2001. RESULTS: The main reason for the increased incidence in Finland was the import of syphilis from Russia; only a few cases were acquired from Estonia or elsewhere. The source partners of Finnish men who contracted syphilis abroad were mostly sex workers or other casual partners. Mobile prostitution to Finland was not involved in the transmission. Most syphilis cases were found sporadically in southern Finland, in areas where foreign travel is frequent. Secondary transmission in Finland was usually limited to one or two partners. The only isolated cluster was further away and developed due to unawareness of the risk of syphilis by the cases and local healthcare providers. From 1995 onward, syphilis was carefully monitored by national reporting and a special sexually transmitted disease (STD) surveillance network, and the incidence remained at a constant level even though travel to and from Russia more than tripled. Nationwide serologic surveillance in STD and maternity clinics and among blood donors showed no major changes in the prevalence of syphilis. CONCLUSION: An epidemic of syphilis imported mainly by heterosexual men from Russia caused one sporadic cluster in Finland in 1995. Thereafter, general awareness by the public and healthcare providers about the risks of contracting syphilis from abroad, in addition to effective use of national surveillance and notification systems, was needed to protect the country from further spread of syphilis to an endemic infection.
Adult↗