Health-related quality of life in adult dermatitis patients stratified by filaggrin genotype.

BACKGROUND: Information concerning health-related quality of life (HRQoL) and comorbidities of adult dermatitis patients stratified by loss-of-function mutations in the filaggrin gene (FLG) is limited. OBJECTIVE: To investigate HRQoL, skin symptoms and comorbidities in adult FLG mutation carriers. METHODS: This cross-sectional study included patients diagnosed with atopic dermatitis and/or hand eczema (n = 520). Patients completed questionnaires about dermatitis, skin symptoms, HRQoL, and comorbidities, including actinic keratosis, and atopic and mental disorders. RESULTS: FLG mutations (R501X, 2282del4, and R2447X) were identified in 16.9% of patients, and were significantly associated not only with atopic dermatitis, but also independently with skin fissures on the fingers and heels, and self-reported actinic keratosis. Although FLG mutations were significantly associated with reduced HRQoL, as measured by use of the Dermatology Life Quality Index (DLQI), no association with self-reported anxiety or depression was identified. Notably, the highest median DLQI score, reflecting greater impairment, was reported by patients with both FLG mutations and atopic dermatitis. Overall, 19.7% of patients with both atopic dermatitis and FLG mutations reported a 'large or extremely large' impact on their lives; this represents twice the prevalence seen in patients with atopic dermatitis and wild-type FLG (9.6%). CONCLUSION: Patients with both atopic dermatitis and common FLG mutations are more frequently affected by reduced HRQoL.

Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry-based study assessing risk of disability pension.

BACKGROUND: Atopic dermatitis and hand eczema often impair the ability of people to work. Only a few studies have investigated whether individuals with loss-of-function filaggrin gene (FLG) mutations, who often have severe and early onset of dermatitis, experience occupational consequences. OBJECTIVE: To investigate the personal consequences of having atopic dermatitis and/or hand eczema and FLG mutations. METHOD: Adult Danes from the general population (n = 3247) and patients with atopic dermatitis and/or hand eczema (n = 496) were genotyped for common FLG mutations, and completed a questionnaire about skin symptoms and hand eczema. Socioeconomic variables, including disability pension, and information on work in risk occupations were retrieved from national registries. The reasons for granting disability pension were unknown. RESULTS: Disability pension was associated with hand eczema in the general population, especially among individuals with a history of atopic dermatitis. Moreover, self-reported hand eczema and atopic dermatitis were associated with particularly high risk of disability pension among FLG mutation carriers [odds ratio (OR) 4.02 and 95% confidence interval (CI): 1.15-14.11; and OR 6.01 and 95%CI: 2.37-15.34, respectively]. Furthermore, 60% of the FLG mutation carriers with atopic dermatitis who developed hand eczema had experienced symptoms before adulthood. CONCLUSION: In the general population, self-reported hand eczema and atopic dermatitis, particularly in individuals with a genetically impaired skin barrier, were associated with disability pension, suggesting that FLG mutations carriers with a history of atopic dermatitis and hand eczema could benefit from early attention with respect to choice of occupation.

[Detection of HLA-B*13:01 gene by dual allele-specific real-time polymerase chain reaction in patients with trichlorethylene-induced dermatitis].

Objective: To investigate the detection of a human leukocyte antigen-B (HLA-B) allele HLA-B*13:01 by dual allele-specific real-time polymerase chain reaction (PCR) in patients with trichlorethylene-induced dermatitis. Methods: A total of 20 patients with trichlorethylene-induced dermatitis who were admitted and treated from January 2014 to October 2016 were enrolled as case group, and 20 persons who underwent physical examination from January to October, 2016 were enrolled as control group. Peripheral cubital venous blood samples were collected from all subjects, and dual allele-specific real-time PCR was used to detect the HLA-B*13:01 gene. The two groups were compared in terms of the proportion of subjects carrying HLA-B*13:01 gene. Results: There were no significant differences between the case group and the control group in median age (25.0 years vs 27.0 years, Z=0.30, P>0.05) and the proportion of male subjects (60.0% vs 70.0%, χ(2)=0.44, P>0.05) . The mean time of exposure to trichloroethylene was 30.8 days in the case group, while the subjects in the control group were not exposed to trichloroethylene. The case group had a significantly higher frequency of HLA-B*13:01 gene than the control group (80.0% vs 20.0%, χ(2)=14.40, P<0.01) with an odds ratio of 16.00. Conclusion: Dual allele-specific real-time PCR can be used for detection of the HLA-B*13:01 gene in patients with trichlorethylene-induced dermatitis.

Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations.

BACKGROUND: A high prevalence of contact dermatitis (CD) and respiratory symptoms has been observed in the construction industry, probably due to widespread exposure to irritants and allergens. It is unknown whether carriers of loss-of-function mutations in the gene encoding filaggrin (FLG), a known risk gene for eczema and asthma, are at increased risk. OBJECTIVES: To investigate associations of FLG mutations with CD and respiratory symptoms in Dutch construction workers. METHODS: A questionnaire including items on dermal and respiratory symptoms such as wheeze, shortness of breath and asthma was administered to construction workers. Total and specific serum IgE was analysed by enzyme immunoassays. Four FLG loss-of-function mutations were genotyped. CD was diagnosed by a team of a dermatologist and a clinical occupational medicine specialist using photographs of the subjects' hands and self-reported questionnaire data. RESULTS: Of the 506 participating workers, 6·3% carried at least one FLG mutation. Mild CD was diagnosed by the specialists in 34·0%, and severe CD in an additional 24·3%. CD was considered work related in 282 of 295 subjects (95·6%). Carriers of FLG variants had an increased risk of CD compared with subjects carrying wild-type alleles [mild CD: odds ratio (OR) 5·71, 95% confidence interval (CI) 1·63-20·06; severe CD: OR 8·26, 95% CI 2·32-29·39]. FLG variants and the presence of CD were not associated with respiratory symptoms and atopy. CONCLUSIONS: Contact dermatitis prevalence in construction workers is high. FLG loss-of-function mutations increase the risk of CD even further. FLG mutations were not associated with respiratory symptoms or atopy.

Filaggrin loss-of-function mutations and atopic dermatitis as risk factors for hand eczema in apprentice nurses: part II of a prospective cohort study.

BACKGROUND/OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene (FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. METHODS: Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. RESULTS: The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. CONCLUSION: A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships.

No remarkable differences in rates of sensitization to common type I and IV allergens between FLG loss-of-function mutation carriers and wild-type subjects.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) have been associated with reduced skin barrier function, possibly allowing increased penetration of irritants and allergens. OBJECTIVES: To study whether FLG loss-of-function mutation carriers show different rates of sensitization to common type I and IV allergens among patients referred for occupational contact dermatitis of the hands. MATERIALS AND METHODS: Four hundred and ninety-six Caucasian patients were genotyped for four FLG null mutations and patch tested with the European baseline series. In addition, 431 patients underwent prick testing with common type I allergens. RESULTS: Overall, 67 patients showed a heterozygous mutation in the FLG alleles R501X, R2447X, S3247X, and/or 2282del4. Sensitization rates for type I allergens from a European prick test series did not show significant differences between FLG loss-of-function mutation carriers and wild-type subjects. For type IV allergens, significantly more FLG loss-of-function carriers were found to be sensitized to lanolin and p-tert-butylphenol-formaldehyde resin. CONCLUSIONS: Probably a variety of immunological mechanisms other than that resulting from the filaggrin system have an impact on allergic sensitization to a greater degree. Larger cohorts may be necessary to increase the statistical power of the findings presented regarding type I and IV sensitization.

Psoriasis predisposition and occupational triggering factors in the appraisal of occupational medical expertises.

BACKGROUND: Psoriasis is an immune-mediated disease with a genetic background. Local psoriatic changes can be triggered by exogenous mechanical or irritant factors. Causative occupational factors have to be distinguished from the spontaneous course of psoriasis in occupational medical evaluations. The objective of this work is to demonstrate the medico-legal grounds for a homogenous assessment. PATIENTS AND METHODS: The presented recommendations were developed in a working group for Occupational and Environmental Dermatology (ABD) and the German contact dermatitis group (DKG) of the German Dermatologic Society (DDG) based on the German medico-legal framework. RESULTS: Causality between the insured activity and the appearance of psoriasis is a prerequisite for the recognition of the occupational nature of the disease. This is the case if the occupational activity is the exclusive or a legally essential contributing factor either for first manifestation or aggravation of the disease. A connection must be denied if everyday events are sufficient to trigger the psoriasis. From 1995 to 2010, 130 cases of psoriasis have been recognized as occupationally related by the German statutory accident insurance. CONCLUSIONS: The appraisal of psoriatic disease in the occupational medical evaluation is subject to the case assessment of the expert witness. In this position paper we present recommendations for a homologous basis for diagnosis, causality assessment, estimation of reduction in earning capacity and rehabilitation of occupational psoriasis.

Impact of atopic dermatitis and loss-of-function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis.

BACKGROUND: Atopic dermatitis (AD) and loss-of-function mutations in the filaggrin gene (FLG) are both associated with chronic irritant contact dermatitis (ICD). As FLG mutations also are a major risk factor for AD, it is not clear whether FLG mutations are an independent risk factor for ICD or whether the risk is mediated by AD. OBJECTIVES: To investigate the relative contribution and interaction of FLG mutations and AD in German patients with occupational ICD and controls (vocational school apprentices). METHODS: A total of 634 patients and 393 controls were genotyped for R501X, 2282del4, R2447X and S3247X. Current or past flexural eczema was used as an indicator of AD. RESULTS: FLG mutations were found in 15·9% of the patients with ICD and 8·3% of the controls, with a crude odds ratio (OR) of 2·09 [95% confidence interval (CI) 1·33-3·28] for the combined genotype. The adjusted OR for FLG mutations, corrected for AD, was 1·62 (95% CI 1·01-2·58). Subjects with AD were at approximately three times higher risk of developing ICD than controls (OR 2·89; 95% CI 2·09-3·99). There was no evidence of an interaction between these two risk factors. CONCLUSIONS: Our results indicate that both FLG mutations and AD increase the risk of ICD. Individuals with concurrent FLG mutations and AD are at the highest risk of developing ICD.

Occupational and non-occupational allergic contact dermatitis: a follow-up study.

BACKGROUND/AIMS: The aim of this study was to obtain insight into the clinical course and prognosis of allergic contact dermatitis (ACD), including potential effects of genetic and environmental factors. METHODS: Eighty-two patients with previously defined ACD acquired occupationally (OACD) or non-occupationally (NOACD) were patch retested and evaluated for the presence of persistent eczema, atopy and filaggrin mutations. RESULTS: The crude risk for the persistence of a positive patch test (PT) reaction was 6.3 times higher (95% CI 3.63-11.0) for PT reactions assessed as '+++' compared to '++' reactions at the first PT. Among the categories of OACD, NOACD, age, gender, atopy, and the number of positive PT reactions at the first and second PT, only OACD (OR 10.0, 95% CI 1.95-51.2) and number of positive PT reactions at retesting (OR 3.85, 95% CI 1.57-9.44) were found to be predictors of persistent eczema. CONCLUSIONS: Occupationally acquired contact allergy was emphasized as the most important factor in predicting poor prognosis of ACD.

Ethical issues of genetic susceptibility testing for occupational diseases: opinions of trainees in a high-risk job.

PURPOSE: Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are scarce. We investigated whether opinions of an intended stakeholder group, that is, student nurses, are sufficiently addressed by existing recommendations. METHODS: Attitudes and opinions of Dutch student nurses toward a genetic test for susceptibility to occupational contact eczema were studied in a qualitative setup using focus groups, interviews and electronic questionnaires. The results were compared with guidelines and recommendations extracted from the literature. RESULTS: Sixty-nine percent of the student nurses said they would partake in a genetic test for susceptibility to occupational contact eczema when available. Concerns were expressed regarding the difficulty of interpreting test results, the utility of the test result in practice and the necessity of genetic tests for non-severe diseases. For the issue of privacy and confidentiality, the students expressed few worries and much confidence. The existing guidelines largely covered the students' opinions. Still, the data emphasized the need for good individual risk communication both before and after testing, taking into account that the test concerns susceptibility. CONCLUSIONS: Comparing the students' statements with the issues addressed by the guidelines, we conclude that the guidelines should pay more attention to risk communication and practical advice accompanying the test results.

Genotype-phenotype associations in filaggrin loss-of-function mutation carriers.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) have been reported to be associated with specific phenotypic characteristics such as hyperlinearity and keratosis pilaris. OBJECTIVES: To study phenotypic features in patients with occupational irritant contact eczema of the hands in relation to FLG loss-of-function mutations. MATERIALS AND METHODS: In a prospective cohort study, genotype was determined for 459 study subjects for four FLG null alleles, and investigated for selected history, clinical and laboratory features. RESULTS: Overall, 68 patients showed a mutation in the FLG alleles R501X, R2447X, S3247X, and/or 2282del4. Flexural eczema, xerosis cutis, pityriasis alba, dirty neck, pulpitis sicca, hyperlinear palms, keratosis pilaris and family history of eczema were positively associated with FLG mutations (p < 0.05). Although we observed a statistically significant correlation with higher serum IgE in FLG mutation carriers, allergic rhinoconjunctivitis and allergic asthma were not over-represented in this group. CONCLUSION: This study shows further genotype-phenotype correlations in patients with occupational irritant contact eczema and FLG mutation carrier status. These features may help to identify those with FLG mutations on a specific phenotype basis.

Carriers of filaggrin gene (FLG) mutations avoid professional exposure to irritants in adulthood.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) are associated with xerosis, atopic dermatitis, and early onset of hand eczema. Irritant exposure is a risk factor for occupational hand eczema, and FLG mutations increase the risk of occupational irritant contact dermatitis on the hands in hospital cohorts. It is unknown whether FLG mutations affect the level of irritant exposure. OBJECTIVES: To evaluate whether exposure to occupational irritants was dependent on FLG mutations, atopic dermatitis, and age at hand eczema onset. METHODS: Randomly chosen Danish adults completed a questionnaire on general health and occupational exposures. Genotyping for FLG mutations (R501X, 2282del4, and R2447X) and patch testing were performed. RESULTS: Overall, 38.7% of subjects reported present or previous occupational exposure to irritants. Among individuals who reported hand eczema onset before entering their work life, 50.6% (45/89) of FLG non-mutation carriers became exposed to irritants, as compared with 28.6% (4/14) of heterozygous and 0% (0/6) of homozygous mutation carriers (p = 0.006). Avoidance was conspicuous among mutation carriers reporting childhood hand eczema and atopic dermatitis (odds ratio 0.08, 95% confidence interval 0.01-0.65). CONCLUSIONS: Carriers of FLG mutations who have had hand eczema onset in childhood avoid occupational exposure to irritants; the association is most marked with homozygous mutation status combined with atopic dermatitis.

Prevalence and risk factors for latex glove allergy among female clinical nurses: a multicenter questionnaire study in China.

BACKGROUND: Natural rubber latex glove use is widespread in mainland China, but the prevalence and risk factors for latex glove allergy among clinical nurses have previously been unreported. METHODS: A questionnaire was used to collect information on latex glove-related allergy among clinical nursing staff in 35 hospitals of eight provinces in the southern, central southern, and northern regions of China, and the risk factors were calculated with logistic regression analysis. Some subjects with glove dermatitis were patch tested with a modified European standard series of allergens. RESULTS: Among 8485 female nurses in eight provinces of China, overall prevalence of latex glove allergy was 8.8%. Of 743 symptomatic nurses, 573 (77.1%) and 475 (63.9%) reported symptoms suggestive of glove dermatitis and type I latex allergy, respectively. Of 69 randomly selected subjects with glove dermatitis, 18 (26.1%) had a positive patch to rubber additives. Employment seniority, positive family and personal history of allergic diseases, and longer extent of time spent in a single hospital room were associated with latex allergy, while using >5 pairs of gloves per working day may be a protective factor. CONCLUSION: Chinese nurses are at high risk for latex sensitization. Nurses who develop latex-related symptoms after exposure to latex gloves should undergo screening tests for latex allergy. Low-protein, powder-free natural rubber latex gloves, or latex-free gloves should be widely adopted in China, along with other preventive measures.

Clinical course of occupational irritant contact dermatitis of the hands in relation to filaggrin genotype status and atopy.

BACKGROUND: Filaggrin loss-of-function mutations and atopy may alter the clinical course of irritant contact dermatitis (ICD). OBJECTIVE: To investigate the clinical course of patients with occupational ICD according to loss-of-function mutations in the filaggrin gene (FLG) and atopy. METHODS: In a prospective cohort study, the clinical course, use of topical corticosteroids, sick leave, recovery rate and job continuation were investigated in 459 inpatients treated for occupational ICD of the hands. Patients were genotyped for four FLG mutations, examined for atopy and followed for up to 3 years after discharge. RESULTS: Our study included 327 (71·2%) atopic individuals and 132 nonatopic individuals. Overall, 68 patients showed a mutation in the FLG alleles R501X, R2447X, S3247X and 2282del4 (60 atopic and eight nonatopic). Nonatopic patients with ICD responded well to therapeutic approaches, while atopy status made subjects more resistant to therapy, resulting in lower rates of recovery and job continuation and higher use of topical corticosteroids. Carriage of FLG loss-of-function mutations in combination with atopy worsened the course. The risk of abandoning one's profession in this group was significantly increased when compared with 'pure' ICD (odds ratio 3·1) after 3 years. CONCLUSIONS: Patients with atopy are a special risk population for ICD. In the presence of atopy, FLG mutations seem to be a modifier of the severity of the clinical course in ICD. Early-stage identification of this subgroup may result in additional emphasis to these patients regarding the importance of adherence to specific therapeutic interventions.

Impact of tumour necrosis factor-α polymorphisms on irritant contact dermatitis.

BACKGROUND: Genetic variations in genes coding for cytokines involved in skin inflammation may alter their expression, thus changing the susceptibility to irritant contact dermatitis (ICD). OBJECTIVES: To determine the prevalence of polymorphisms in the cytokine genes TNFA-238 and TNFA-308 in patients with occupational ICD, and to compare it with that in controls. METHODS: In a case-control study, 478 patients with occupational ICD of the hands were genotyped for TNFA-238 and TNFA-308 polymorphisms. The results were compared with those for 393 apprentices from the same high-risk occupations (controls). RESULTS: For a carrier of a variant TNFA-238A allele, the odds ratio (OR) of acquiring ICD was 0.57 [95% confidence interval (CI) 0.34-0.97], suggesting a protective effect of the A allele. The genotype distributions were 94.4% wild type (G/G), 5.6% heterozygous (G/A) and 0% homozygous for variant allele (A/A) in patients, and 90.9%, 8.5%, and 0.6%, respectively in controls. In contrast, carriers of the variant TNFA-308A allele had an increased risk of ICD [OR 1.33; 95% CI 1.05-1.74; G/G 66.4%, G/A 31.2%, and A/A 2.4% (patients) versus 73.5%, 24.6%, 1.9% in controls]. CONCLUSIONS: Individuals with a TNFA-238 polymorphism are less prone and those with a TNFA-308 polymorphism are more prone to develop ICD of the hands, suggesting a protective versus a detrimental effect of the A allele respectively.

[Polymorphism of genes of the system of biotransformation of xenobiotics in patients with occupational allergic dermatoses].

Evaluation of genes polymorphic system of xenobiotics biotransformation in patients with occupational allergodermatoses showed significantly higher percentage of incidence of polymorphic variants of genes CYP 1A1 *2C and EPHX1 AND-415G compared with population control. A combination of 3 or more adverse hetero--and homozygous gene alleles CYP 1A1, CYP3A4, EPHX1 and deletions of genes GSTM1 and GSTT1, is characterized by earlier (with the experience of work in harmful conditions up to 5 years) development, severe and unfavorable prognosis of occupational pathology of the skin.

Genetic susceptibility to occupational contact dermatitis.

Contact dermatitis (CD) is one of the most prevalent work-related diseases, often resulting in an impaired quality of life and a loss of work ability. CD can be divided into allergic (ACD) and irritant contact dermatitis (ICD). Although skin exposure is a prerequisite for the development of CD, there is substantial evidence that under similar exposure conditions some individuals are more prone to acquiring CD than others. Recently, a number of studies have investigated the link between individual susceptibility to CD and variations in the genes that are involved in the maintenance of the skin barrier, inflammatory response and biotransformation. The most important development has been the discovery that loss-of-function mutations in the gene encoding the epidermal protein filaggrin increase the risk for ICD and for nickel sensitization and nickel ACD, emphasizing the importance of the skin barrier in the pathophysiology of CD. Among the inflammatory genes, a TNFA-308 G/A polymorphism has been shown to associate with susceptibility to both ICD and ACD. In studies specifically for ACD, polymorphisms in genes encoding N-acetyltransferases were shown to modify the risk for sensitization to p-phenylenediamine. Although recent studies have identified a number of biologically plausible susceptibility genes, the predictive value of these genetic markers is too low for the reasonable selection of susceptible individuals in occupational health practice. Additional studies in larger cohorts with well-defined disease phenotypes and appropriate control population are needed to confirm and extend our knowledge of the impact of genetic variations on the susceptibility to occupational CD.

[Study on mRNA expression of immune-related genes in patients with allergic dermatitis induced by trichloroethylene].

OBJECTIVE: To study mRNA expression of immune-related genes (Foxp3, GATA3, CTLA4 and T-bet) in peripheral blood of the patients with allergic dermatitis induced by trichloroethylene (TCE). METHODS: The peripheral blood samples were collected from 8 healthy workers (control group) and 8 patients with allergic dermatitis induced by TCE (case group). Real-time quantitative PCR was applied to detect mRNA expression of immune-related genes (Foxp3, GATA3, CTLA4, T-bet). RESULTS: The mRNA expression levels of Foxp3, GATA3 and CTLA4 genes increased by 115%, 97% and 241% in case group, as compared with control group (P < 0.01). The mRNA expression level of T-bet gene decreased by 47% in case group, as compared with control group (P < 0.01). CONCLUSION: The mRNA expression levels of some immune-related genes changed in patients with allergic dermatitis induced by TCE, those genes may play an important role in TCE-induced allergy.

[Role of polymorphous genes of xenobiotic biotransformation system in pathogenesis of occupational allergic dermatoses].

Studying genetic polymorphism of xenogiotics biotransformation system genes in patients with occupational allergic dermatoses, the authors revealed reliably higher percentage of polymorphous variants of CYP 1A1 *2C and EPHX1 A-415G genes, if compared with reference population. Combination of 3 polymorphous variants of xenobiotics biotransformation system genes (CYP 1A1, CYP3A4, EPHX1, GSTM1 and GSTT1) is characterized by earlier development, severe course and unfavorable prognosis of occupational skin condition.

[Molecular genetic studies in occupational medicine].

DNA diagnostic techniques aimed at elaborating informative criteria for assessment of the risk for occupational, occupationally induced diseases are extensively used to study the molecular mechanisms involved in the development of occupational diseases in labor medicine. Patients with different forms of occupational bronchopulmonary diseases have been found to have matrix metalloproteinase-1 (MMP-1) gene mutations. In some individuals, a combination of polymorphic variants of MMP-1 and alpha1-proteinase inhibitor genes is characterized by the presence of clinical complications and the concurrence of bronchopulmonary and skin diseases. GSTM1 gene mutation is noted for the earlier onset (up to 5 years), severity, and poor prognosis of allergic dermatoses.