Clinical examination for hyperlinear palms to determine filaggrin genotype: A diagnostic test accuracy study

Bradshaw, Lucy; Haines, Rachel H; Kim, Thomas; Chalmers, Joanne R; Irvine, Alan D.; Williams, Hywel C; Brown, Sara J.

doi:10.1111/cea.14025

Cited by 7 publications

(10 citation statements)

References 41 publications

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“…There were more severe AD patients with hand dermatitis (82.1%), palmar hyperlinearity (41.8%) and contact allergies (25.7%), which seem to be linked to a more severe disease in Finnish patients. Palmar hyperlinearity has been linked to FLG mutations and possible markers of AD severity 40 . Hand dermatitis and contact allergy has been linked to epidermal barrier dysfunction and FLG mutations but not with AD severity 41 .…”

Section: Discussionmentioning

confidence: 99%

Factors associated with severity of atopic dermatitis – a Finnish cross‐sectional study

Salava

Salo

Leppänen

et al. 2022

Acad Dermatol Venereol

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Background Severity‐associated factors in atopic dermatitis (AD) have focussed on early onset, concomitant atopic diseases, markers of Th2‐shifted inflammation and filaggrin mutations. Objectives To investigate factors associated with severe AD in Finnish patients. Methods We conducted a single‐centre, cross‐sectional observational study with 502 AD patients aged 4.79 to 79.90 years (mean 32.08 years). Disease severity was assessed with the Rajka–Langeland severity score and EASI and associated clinical signs were evaluated. Data regarding onset, relatives, atopic and other comorbidities was gathered retrospectively. We investigated total serum IgE‐levels, a panel of filaggrin null mutations and functional variants of genes associated with skin barrier defects. Results Factors more frequent in severe AD included early onset (P = 0.004, 95%CI 0.000–0.024), male sex (P = 0.002, 95%CI 0.000–0.11), history of smoking (P = 0.012, 95%CI 0.000–0.024), concomitant asthma (P = 0.001, 95%CI 0.000–0.011), palmar hyperlinearity (P = 0.013, 95%CI 0.014–0.059), hand dermatitis (P = 0.020, 95%CI 0.000–0.029) and history of contact allergy (P = 0.042, 95%CI 0.037–0.096). Body mass indices (P < 0.000, 95%CI 0.000–0.011) and total serum IgE‐levels (P < 0.000, 95%CI 0.000–0.011) were higher in severe AD. No differences were observed for allergic rhinitis, allergic conjunctivitis, food allergy, peanut allergy, prick positivity, keratosis pilaris, history of herpes simplex infections, filaggrin null mutations and other gene variants. Conclusions Severity determinants in Finnish patients seem to be early‐onset, male sex, smoking, overweight, concomitant asthma, palmar hyperlinearity, hand dermatitis and high IgE‐levels. A sub‐typing of patients in relation to confirmed severity determinants may be useful for course prediction, prognosis and targeted AD management.

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Section: Discussionmentioning

confidence: 99%

Factors associated with severity of atopic dermatitis – a Finnish cross‐sectional study

Salava

Salo

Leppänen

et al. 2022

Acad Dermatol Venereol

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“…The study shows that KP in Finnish AD patients may be associated with the FLG LoF mutation 2282del4 and the clinical sign of palmar hyperlinearity 5 . There have been observations that link KP with asthma, atopic sensitization, hand dermatitis and contact allergies based on mechanistic studies and increased epicutaneous penetration of allergens 6–8 .…”

Section: Discussionmentioning

confidence: 86%

“…Although genetic sequencing from different countries have shown links to FLG‐mutations, especially R501X and 2282del4, they do not account for the complete KP phenotype or explain the wide clinical spectrum 1,2 . For example, clinical studies and genetic sequencing data from Croatia, 11 the United States, 12 the United Kingdom, 5 Austria 13 and Singapore 14 have underlined geographical differences regarding FLG‐mutations, comorbidity with atopic dermatitis and associated clinical signs. To our knowledge there are no former studies on clinical KP characteristics or genetic testing in Finnish patients with concomitant AD.…”

Section: Discussionmentioning

confidence: 99%

“…The study shows that KP in Finnish AD patients may be associated with the FLG LoF mutation 2282del4 and the clinical sign palmar hyperlinearity. 5 There have been observations that link KP with asthma, atopic sensitization, hand dermatitis and contact allergies based on mechanistic studies and increased epicutaneous penetration of allergens. [6][7][8] We did not observe similar effects in our cohort although the prevalence of atopic comorbidities (e.g., asthma) was relatively high in the studied Finnish AD patients.…”

Section: Discussionmentioning

confidence: 99%

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Keratosis pilaris and filaggrin loss‐of‐function mutations in patients with atopic dermatitis – Results of a Finnish cross‐sectional study

Salava

Salo

Remitz

2022

The Journal of Dermatology

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Keratosis pilaris (KP) associates with epidermal barrier defects in atopic dermatitis (AD) but its role in disease severity and concomitant atopic diseases seems to vary between populations. We performed a cross‐sectional observational study with 502 randomly selected AD patients of a Finnish tertiary health care center. At a single clinical examination, disease severity (Rajka Langeland severity score and EASI), clinical signs and patient history were evaluated and total IgE levels and frequent filaggrin (FLG) loss‐of‐function mutations were investigated. There was no link with disease severity (p = 0.649, 95% CI 0.569–0.654), asthma (p = 0.230, 95% CI 0.206–0.281) or atopic sensitization (p = 0.351, 95% CI 0.309–0.392). Keratosis pilaris was significantly associated with palmar hyperlinearity (p < 0.000, 95% CI 0.000–0.006, OR 4.664, 95% CI 2.072–10.496) and the filaggrin loss‐of‐function mutation 2282del4 (p < 0.000, 95% CI 0.000–0.009, OR 4.917, 95%CI 1.961–12.330). The prevalence of KP in the cohort was generally low and KP seems to be infrequent in Finnish AD patients. This may be explained by the fact that the tested FLG loss‐of‐function mutations are rarer in the Finnish population compared for example, with central Europe or Asia. Mutations in other locations of the FLG gene or other genes of the epidermal barrier may play a more important role.

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“…This is consistent with the report that palmar hyperlinearity is inversely correlated with intrinsic subtype. 26 Certainly, FLG mutation is not the single factor for the disrupted barrier as several reports demonstrate that the levels of loricrin, involucrin, and keratin in some AD patients without FLG mutations were significantly down-regulated compared to those in healthy controls.…”

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confidence: 99%

Intrinsic Atopic Dermatitis and Extrinsic Atopic Dermatitis: Similarities and Differences

Liu¹,

Song²,

Song³

2022

CCID

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In atopic dermatitis (AD), recent research advances have portrayed a complex disease profile based on different subtypes/ phenotypes and underlying molecular mechanisms/endotypes. Extrinsic and intrinsic subdivision is one of the most common types, defined in terms of total serum immune globulin E (IgE) and/or specific IgE to food and environmental allergens. Extrinsic AD is the most common type (80%), with high IgE, impaired skin barrier, as well as high incidence of comorbid atopic diseases, whereas intrinsic AD accounted for 20% of AD, with normal IgE and intact barrier function. Clinical studies have shown that extrinsic AD was a classic Th2-based inflammatory dermatitis, while the intrinsic subtype presented increased Th1/Th17/Th22 but normal Th2 cytokines. Protein sensitization, a classic Th2 response, has been clearly characterized in extrinsic AD, while metal hapten induces intrinsic AD's sensitization, which may be associated with suprabasin deficiency. In this review, we aimed to further expand our knowledge about similarities and differences between these two subtypes, which will expand our capability to further dissect pathophysiology of AD and enable us to develop personalized medicine approaches.

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Clinical examination for hyperlinear palms to determine filaggrin genotype: A diagnostic test accuracy study

Cited by 7 publications

References 41 publications

Factors associated with severity of atopic dermatitis – a Finnish cross‐sectional study

Factors associated with severity of atopic dermatitis – a Finnish cross‐sectional study

Keratosis pilaris and filaggrin loss‐of‐function mutations in patients with atopic dermatitis – Results of a Finnish cross‐sectional study

Intrinsic Atopic Dermatitis and Extrinsic Atopic Dermatitis: Similarities and Differences

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