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Biomedical subjects

C F Wahlgren

Publications and source records attributed to C F Wahlgren.

At least 19 recordsLinked to original sources

Genome-wide linkage analysis of allergic rhinoconjunctivitis in a Swedish population.

BACKGROUND: Allergic rhinoconjunctivitis is a common complex disorder characterized by itching and irritation in the nose, bouts of sneezing, watery rhinorrhoea, nasal congestion and itchy eyes with tears and swelling. Like other atopic disorders such as allergic asthma and atopic dermatitis, the development involves complex interactions of genes and environmental factors. OBJECTIVE: The purpose of this study was to identify susceptibility loci for allergic rhinoconjunctivitis. METHODS: We conducted a genome-wide linkage analysis using a non-parametric, affected-relative-pair method. The 250 families used were collected originally for an atopic dermatitis linkage study. RESULTS: Three regions showed favour in evidence of linkage to allergic rhinoconjunctivitis: 3q13 (D3S1278: logarithm of odds ratio (LOD)=1.64, P<0.003), 4q34-35 (D4S1652: LOD=1.49, P<0.005) and 18q12 (D18S535: LOD=1.94, P<0.002). In addition, four regions showed weaker evidence in favour of linkage: 6p22-24 (D6S1959: LOD=1.39, P<0.006), 9p11-q12 (D9S1118: LOD=1.15, P<0.02), 9q33.2-34.3 (D9S915: LOD=1.29, P<0.01) and 17q11.2 (D17S1294: LOD=1.13, P<0.02). In single-point analysis, one locus on chromosome 3 close to marker D3S1278 reaches the suggestive level (LOD=2.28, P<6 x 10(-4)) while one on chromosome 17 close to marker D17S921 almost reaches this level (LOD=2.17, P<8 x 10(-4), Table 3). CONCLUSION: Our results support the linkage to allergic rhinoconjunctivitis on 3q13, 6p23-p24 and 9q34.3 shown in previous investigations.

Chromosomes, Human, Pair 17↗

Susceptibility loci for atopic dermatitis on chromosome 21 in a Swedish population.

BACKGROUND: Atopic dermatitis (AD) is a hereditary, pruritic, chronic, relapsing, inflammatory skin disease resulting from multiplex interactions between genes and environmental factors. We have previously found several loci showing suggestive linkage on chromosomes 3q14, 13q14, 15q14-15 and 17q21, and weaker linkage to chromosomes 1p32, 4q24-26 and 21q21 in 109 Swedish families. METHODS: In order to confirm the linkage to chromosome 21, we carried out a replication linkage analysis with additional microsatellite markers on chromosome 21 in another set of 295 families. RESULTS: In the extended material, the Z-score was 2.40 (P < 7.4 x 10(-4)) in the region 21q21 for a semi-quantitative variable measurement; the severity of AD. When combining the two data sets into 404 families and stratifying according to asthma status, suggestive linkage was found only in the group of AD patients who also had asthma (Z-score 2.45, P < 7.4 x 10(-4) and 2.69, P < 7.4 x 10(-4)) in two different regions. CONCLUSIONS: Our results suggest that 21q21 could contain a susceptibility gene modulating the severity of AD especially in combination with asthma.

Biomarkers↗

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.

BACKGROUND: The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). OBJECTIVES: To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. METHODS: In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). RESULTS: Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. CONCLUSIONS: These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.

Adolescent↗

Family history and risk of atopic dermatitis in children up to 4 years.

BACKGROUND: The aetiology of atopic dermatitis (AD) is presumably multi-factorial, with interactions between genetic and environmental factors. OBJECTIVE: To investigate the relation between atopic family history and development of AD up to 4 years. METHODS: Using annual questionnaires, we studied the cumulative incidence of AD in 0-4-year-olds in a prospective birth cohort of 4089. Atopic diseases in parents and siblings were recorded at birth. The occurrence of serum immunoglobulin E (IgE) antibodies to inhalant and food allergens was analysed in 2614 4-year-olds, and AD was divided into non-IgE-associated and IgE-associated. RESULTS: Of the children without atopic parents, 27.1% developed AD; of those with single or double parental atopic history, 37.9% and 50.0%, respectively, did so. The effects of parental history of eczema and of atopic respiratory disease (ARD) did not differ significantly, nor did those of maternal and paternal history. Parental history of ARD increased the risk significantly more for IgE-associated AD than for non-IgE-associated AD (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.5-2.8 vs. OR 1.3; 95% CI 1.0-1.8), whereas the two forms lacked major differences in the effect of parental eczema. A history of eczema in older siblings was a risk indicator for both forms of AD (OR 2.1; 95% CI 1.4-3.3 vs. OR 1.8; 95% CI 1.2-2.6). CONCLUSIONS: We found no difference between the effects of maternal and paternal atopic history. Parental eczema was a risk factor for AD irrespective of its association with IgE, but parental history of ARD mainly increased the risk of IgE-associated AD.

Child, Preschool↗

Linkage and association to candidate regions in Swedish atopic dermatitis families.

We have studied, in 406 families with at least two siblings affected with atopic dermatitis (in total 1514 individuals) from the Swedish population, linkage and association to five chromosomal regions (2q35, 5q31-33, 6p21, 11q13 and 14q11) previously implicated in atopic diseases. The region on 14q11 gave evidence for linkage to atopic dermatitis (NPL-score: 2.36, P<0.009). In the 11q13 region, there was a clear association to an intragenic marker in the beta-subunit of the high-affinity IgE receptor for raised allergen-specific serum IgE levels (P<0.009). When a quantitative variable for the severity of atopic dermatitis was studied, evidence was found in favour of linkage to the 5q31-33 region, with the highest Z-score (2.06) close to the marker D5S458 (P<0.005).

Age of Onset↗

Split-skin grafting with lidocaine-prilocaine cream: A meta-analysis of efficacy and safety in geriatric versus nongeriatric patients.

Although the efficacy and safety of the topical anesthetic EMLA cream (lidocaine-prilocaine) have been studied extensively in children and adults, no published studies have focused on geriatric patients (>/=65 years of age). The objective of this study was to compare the efficacy and safety of EMLA in geriatric versus nongeriatric adults. A pooled analysis was made from original data of six studies of EMLA cream for split-skin grafting. The studies selected had a sufficient number of geriatric and nongeriatric adults and a uniform, standardized pain stimulus (split-skin grafting), pain rating (visual analogue scale, verbal rating scale) and adverse event recording. A total of 182 geriatric patients (82 aged 65 to 74 years; 100 aged 75 to 96 years) and 221 nongeriatric EMLA-treated patients were evaluated. There was no difference in the efficacy of EMLA between geriatric and nongeriatric adults who underwent similar onset and duration of anesthesia. EMLA cream 1.5 g/10 cm2 applied for 2 to 5 hours had a similar anesthetic effect in both age groups. A dose of 3 g/10 cm2 gave no further benefit. In a geriatric population, EMLA cream provided effective cutaneous anesthesia for the cutting of split-skin grafts to the same extent as did infiltrated lidocaine. Adverse event frequency and severity were similar in geriatric and nongeriatric patients. Transient application site pallor, redness, and edema were the most frequent adverse events. Topical anesthesia with EMLA cream for split-skin grafting is as safe and effective in geriatric as in nongeriatric adults.

Adult↗

Hanifin's and Rajka's minor criteria for atopic dermatitis: which do 2-year-olds exhibit?

BACKGROUND: In 1980 Hanifin and Rajka published major and minor criteria for atopic dermatitis (AD). Despite the early age at onset of AD, there are few prospective studies in young children of the prevalence of signs and symptoms meeting the minor criteria. OBJECTIVE: Our purpose was to identify those of Hanifin's and Rajka's minor criteria that are most frequent in 2-year-old children with AD and in controls. METHODS: Consecutive patients with AD (n = 221), 24 months of age or younger, were followed up to 2 years, when they were re-examined. The minor criteria were divided into 33 subcriteria, 29 of which were examined. Controls (n = 99), matched for age and sex, with no history of eczema at 2 years of age were examined in the same way. RESULTS: At the 2-year examination 157 of 221 had ongoing AD. Seven minor criteria were met in more than one fourth of these children, namely xerosis (100%), course influenced by environmental factors (87%), facial erythema (54%), skin reactions provoked by ingested food (39%), itch when sweating (34%), positive skin prick test (29%), and hand eczema (28%). In the control group, only xerosis (40%), facial erythema (25%), and skin reactions provoked by ingested food (9%) were present in 4% or more. CONCLUSION: Approximately half of the 29 criteria investigated were met in 3% or fewer of the cases, indicating that they may not be of much help to the clinician. Of the minor criteria of Hanifin and Rajka, only xerosis, course influenced by environmental factors, and facial erythema were seen in a majority of patients and would therefore be useful in the diagnosis of AD.

Age of Onset↗

Depth of cutaneous analgesia after application of a eutectic mixture of the local anesthetics lidocaine and prilocaine (EMLA cream).

BACKGROUND: EMLA cream, a eutectic mixture of lidocaine and prilocaine, is a topical anesthetic, frequently used to avoid pain during venipuncture and superficial surgery. However, the depth of analgesia needs further exploration. OBJECTIVE: Our purpose was to investigate the depth of cutaneous analgesia after application of EMLA cream. METHODS: In a single-blind crossover study, EMLA cream was applied under occlusion to the left thighs of 16 subjects. Eleven had application times of 60 and 120 minutes. Five subjects had application times of 3 to 4 hours. Approximately 10 minutes after removal of the EMLA cream, a skin biopsy punch (diameter 4 mm) was inserted to a depth of 1 mm into the skin and the subject rated the pain intensity on a visual analogue scale. If there was no pain or if pain was assessed as acceptable, a new biopsy punch was inserted at a new site to the depth of 2 mm. In this manner, the insertion depth was gradually increased in steps of 1 mm down to a maximum of 6 mm. No skin specimens were removed. RESULTS: After 60 and 120 minutes of EMLA application the mean insertion depths with acceptable pain were 2.9 and 4.5 mm (P <.01), respectively. After 3 to 4 hours of application, 6-mm deep insertions were made with acceptable pain in all 5 subjects. CONCLUSION: Skin biopsy punch insertions in steps of 1 mm appear adequate for assessing the depth of cutaneous analgesia. Biopsy punch insertions with acceptable pain can be made to depths of 1 to 2 mm after 60 minutes, to 2 to 3 mm after 120 minutes, and to 6 mm after 3 to 4 hours of EMLA cream application.

Adult↗

Localization of interleukin-13 gene-expressing cells in tuberculin reactions and lesional skin from patients with atopic dermatitis.

Interleukin (IL)-13 is a cytokine thought to play an important role in IgE-mediated allergic reactions. The aims of the present study were to localize IL-13 mRNA in positive tuberculin reactions and atopic dermatitis lesions using in situ hybridization and to study the possible influence of atopy on the cytokine gene expression in tuberculin reactions. Punch biopsy specimens were taken from tuberculin reactions in 17 nonatopic and 12 atopic (Phadiatop positive), but otherwise healthy, individuals 72h after injection of purified protein derivative, from chronic lichenified lesions and nonlesional skin in six patients with atopic dermatitis and from normal skin in 12 healthy individuals. IL-13-mRNA-producing cells were located mainly in the dermal-cell infiltrates, both in atopic dermatitis lesions and tuberculin reactions. In the atopic dermatitis lesions, IL-13-mRNA expression was found in close apposition to the epidermis. Higher numbers of IL-13-mRNA-producing cells were observed in the dermal-cell infiltrates of chronic lichenified skin lesions of patients with atopic dermatitis (13.3 cells/mm2, range 0.6-42.4 cells/mm2) than in the tuberculin reactions (1.1 cells/mm2, range 0-3.8 cells/mm2) (P<0.01) despite the larger cell infiltrates in the tuberculin reactions. No significant difference in IL-13 or interferon-gamma gene expression in the tuberculin reactions was seen between atopic and nonatopic individuals.

Adolescent↗

Itch and atopic dermatitis: an overview.

Itching is the hallmark of atopic dermatitis, and a vicious itch-scratch circle is easily established. Itching and scratching are important factors in the maintenance of symptoms and can have a significant impact on the sufferer's quality of life. The pathophysiology of itch in atopic dermatitis is still not understood. Unlike in urticaria, histamine is not considered to be a major pruritogen in atopic dermatitis. In fact, the peripheral pruritogens and their cellular origin(s) still remain to be identified in this disease. Various treatments are used to relieve the skin inflammation, itching, and scratching in patients with atopic dermatitis, but no specific antipruritic therapy is available. However, several nonspecific therapies can effectively break the vicious itch-scratch circle. The use of topical corticosteroids and emollients and the elimination of individual trigger factors are still first-line measures.

Anti-Inflammatory Agents↗

[Despite better knowledge of pathogenesis and treatment: atopic eczema--a disease with increasing incidence in Sweden].

The past twenty years have witnessed an increasing incidence of atopic dermatitis in Western Europe. The article consists in a discussion of the pathogenesis, clinical signs and treatment of this common skin disease. Both an IgE-mediated reaction on epidermal Langerhans cells, and a physiological/biochemical defect of the skin barrier structure may be crucial factors of the multifactorial pathogenesis. Local treatment with corticosteroids and moisturisers remains the basic approach, though the development of new more specific treatments is under way. Although much remains to be learned about atopic dermatitis, today all patients can be offered effective treatment resulting in improved quality of life.

Adult↗

IL-13 over-expression in skin is not confined to IgE-mediated skin inflammation.

IL-13 is produced by T cells and, like IL-4, it can induce the production of IgE and IgG4. In order to investigate if IL-13 is a specific marker for atopic dermatitis (AD), IL-13 gene expression was analysed in chronic lichenified lesions and non-lesional skin of patients with AD, in involved and non-involved skin of patients with psoriasis, in positive tuberculin reactions in non-atopics, and in the skin of healthy control subjects. Patients with AD (n = 9) showed sensitization to common air-borne allergens (positive Phadiatop) and had total serum IgE values in the range from 10 to 4800 kU/l (median 170 kU/l). Competitive reverse transcription-polymerase chain reaction (RT-PCR) was used to assess IL-13 gene expression in skin biopsy specimens. IL-13 gene expression was markedly higher in chronic lichenified lesions of patients with AD (P < 0.01), and in the positive tuberculin reactions (P < 0.01; n = 12) than in skin from healthy control subjects (n = 10). However, there was no significant difference in IL-13 gene expression in the skin of patients with psoriasis (n = 10) and that of healthy control subjects. The dermal cell infiltrates were larger and the relative amount of CD3+ and CD4+ cells in these infiltrates was higher in the skin of subjects with a positive tuberculin reaction than in lichenified AD skin. However, these differences were not reflected in differences in IL-13 gene expression. Different triggers of IL-13 gene expression may influence the diverse patterns of inflammation seen in different inflammatory skin disorders.

Adolescent↗

Lipoid proteinosis in three children.

We report on three children with lipoid proteinosis, an autosomal recessive disorder characterized by the deposition of hyaline-like material in the skin, mucous membranes and other tissues. All cases had characteristic hoarseness. Other symptoms observed were infiltrated whitish plaques and pock-like scars on the face, papules on the palpebral margins, and infiltrates in the mucous membranes of the lower lip and tongue. Two of the children were siblings whose parents were first cousins.

Child↗

Two-point discrimination of itch in patients with atopic dermatitis and healthy subjects.

The ability to perceive two pruritic stimuli as separate depending on the distance between them (two-point discrimination of itch) was determined in a single-blind study of 20 patients with atopic dermatitis and 20 healthy subjects. Itch was induced with pairs of histamine injections (0.1 micrograms each) given on the upper arm, either along its axis (longitudinally within a dermatome) or at right angles to it (transversally involving more than one dermatome). The interinjection distances were varied in 3-cm steps until the shortest distance at which the two itching stimuli could be perceived as separate was found. Pairs consisting of one injection of histamine (0.1 micrograms) and one of saline served as controls. The two-point discrimination of itch was significantly better in the atopic dermatitis patients than in the healthy controls, both longitudinally (atopic dermatitis: median 12 cm, range 3-21 cm; healthy controls: 15 cm, range 9-21; p < 0.01) and transversally (atopic dermatitis: median 6 cm, range 3-18; healthy controls: 12 cm, range 6-21; p < 0.001). The two-point discrimination of itch did not correlate with the subject's age, two-point discrimination of touch, or, for the atopic dermatitis patients, with their eczema scores or serum IgE levels. The quality, intensity or spatial summation of itch did not differ significantly between the two groups of subjects.

Adolescent↗

Sympathectomy does not influence experimental itch and cutaneous temperature perception thresholds.

The effect of endoscopic thoracic sympathectomy on experimentally histamine-induced itch was studied in seven patients, all of whom were suffering from palmar hyperhidrosis; cutaneous warm, cold, and heat pain perception thresholds were also studied in five of these seven patients. Surgery was effective in abolishing palmar sweating in all patients. No significant differences were seen in itch, flare, wheal, or thermal perception thresholds following sympathectomy as compared to the preoperative period. These findings suggest that the sympathetic system may be of limited importance for somatosensory perception in healthy humans during normal conditions.

Adult↗

Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects.

To explore the pruritogenic and inflammatory effects of cytokines, a single dose of 20 micrograms recombinant human interleukin-2 was injected intradermally into eight patients with atopic dermatitis and eight healthy controls. The study was double-blind and randomized with glucose as a negative control. The effects were evaluated by recording local itch and erythema over 72 h and by examining skin biopsies taken at 24 h and 72 h. In patients and controls, interleukin-2 provoked a low-intensity local itch with maximal intensity between 6 h and 48 h and erythema with maximal extension between 12 h and 72 h. In the atopic dermatitis patients, these reactions tended to appear earlier and were less pronounced than in the healthy controls. Interleukin-2 induced dermal mononuclear cell infiltrates consisting mainly of CD3+ cells. A majority of the T cells were CD4+. The number of dermal CD25+, HLA-DR+ and ICAM-1+ cells was also increased at the interleukin-2 induced spongiosis and exocytosis as well as HLA-DR+ and ICAM-1+ keratinocytes. The microscopic findings tended to be more prominent at 72 h than at 24 h in both groups, but with a somewhat slower onset in the atopic dermatitis patients. In conclusion, a single intradermal injection of interleukin-2 induced local itch, erythema, dermal T-cell infiltrates, spongiosis, exocytosis and activation of keratinocytes both in atopic dermatitis patients and in healthy controls.

Adult↗

Measurement of itch.

Measurement in its broadest sense can be defined as the assignment of numerals to objects or events according to rules. The rules settle the scale level, which in turn determines the mathematical and statistical operations permissible when handling the data. Itch is a subjective symptom that can be assessed only by the subject himself. No animal models are established for the investigation of itch. In contrast to pain research, a field with many similarities, rather few scientific attempts have been made to develop and evaluate methods for the quantitative analysis of itch. However, several investigators have recently addressed the challenge of itch measurement in both experimental and clinical situations. This is important, as valid quantitative techniques for the assessment of itch are of considerable value for studying the mechanisms of pruritus, and for the evaluation of antipruritic therapies.

Equipment Design↗