Filaggrin Null-mutations May be Associated with a Distinct Subtype of Atopic Hand Eczema

Abstract

Null-mutations in the profilaggrin gene are associated with atopic dermatitis (AD) and palmar hyperlinearity (1). Before the filaggrin era, there were several attempts to identify the phenotype of atopic hand eczema (2-5). In 1944 Nexmand observed 100 patients with AD over a mean period of 6 months and found that 24%, 9% and 34% had dermatitis on the volar aspect ofthe wrists, and the dorsal aspects ofthe fingers and hands, respectively, whereas no patients had palmar hand eczema (3). These findings were confirmed in more recent studies: Fartasch et al. showed that palmar hyperlinearity was a phenotypic marker of atopic dermatitis in 17 (34%) of 49 patients (4), and Simpson et al. showed that among 777 consecutive patients with AD, hand dermatitis mainly affected the dorsal hand surfaces and the volar wrists, whereas vesicular lesions ofthe palms and sides of fingers were found in only 4.3% (5). Taken together, in a subgroup of patients with AD, hand eczema is characterized by dermatitis on the dorsal aspects of the fingers and hands, palmar hyperlinearity and, rarely, by palmar vesicles.Most patients who have attended our tertiary referral contact dermatitis and AD clinic within the past 3 months have been genotyped for the two most prevalent filaggrin null-mutations, R501X and 2282del4. So far, approximately 200 patients have been tested. In this relatively small patient series, a striking phenotype of atopic hand eczema was observed in 8 patients. All had severe generalized AD and asthma. Their atopic hand eczema was characterized by dermatitis on the dorsal aspects ofthe hands and sometimes on the volar aspects ofthe wrists as well as palmar hyperlinearity (Fig. 1). In two patients, there were signs of mild palmar dermatitis with a few vesicular lesions. Light palmar scaling was observed in one patient. Two ofthe patients were related (father and son) and had identical distribution of their hand eczema. Of note, we found that all 8 patients with this specific phenotype had null-mutations in the filaggrin gene (of which 5 were heterozygotic for either mutation, and 3 were compound heterozygotic), whereas no patients with wildtype filaggrin status had a similar clinical expression. Thus, we speculate that the special phenotype of atopic hand eczema identified in previous reports may be explained consistently by null-mutations in the profilaggrin gene.Prospective studies are clearly warranted to confirm our clinical observations. If they are confirmed, atopic hand eczema in patients with null-mutations in the profilaggrin gene represents a distinct clinical subtype that may be easy to diagnose. It is possible that patients Acta Derm Venereol 90 Fig. /. Patients with the atopic hand eczema subtype defined by mandatory null-mutations in the profilaggrin gene typically had asthma, generalized atopic dermatitis, hand eczema on the dorsal aspects ofthe hands and fingers, palmar hyperlinearity. and absence of palmar hand eczema.with filaggrin null-mutations and atopic hand eczema should be treated differently than, fo...

Clinical Presentation of Atopic Dermatitis by Filaggrin Gene Mutation Status during the First 7 Years of Life in a Prospective Cohort Study

“…Furthermore, the clinical observation was recently made, that adult patients with the FLG null genotype had a distinct phenotype of hand dermatitis characterized by fissured eruptions on the back of the hands and wrists with only sparse involvement of the palmar aspects, similar to the clinical description of hand dermatitis among atopic individuals previously described by other groups [28], [29]. It is interesting that we could partly confirm this finding in our cohort of children, as FLG null carriers mainly had chronic markers of dermatitis on the back of their hands, whereas acute markers were upregulated in the palms as well as the back of the hands.…”

Association between filaggrin null mutations and concomitant atopic dermatitis and contact allergy

“…The phenotypic traits of patients with AD and the FLG mutation genotype are still not clear. To date, the mutations have been associated with persistence of AD into adulthood, 10 increased disease severity and early onset, 11 hyperlinearity of the palms, keratosis pilaris, 12 and perhaps a particular subtype of hand eczema 13 …”

Hand Eczema

“…In a case series by Thyssen et al, eight FLG mutation carriers with generalized AD were presented who suffered from a distinct type of hand eczema characterized by hyperkeratosis and dermatitis on the dorsal aspects of the hands and fi ngers, whereas the palmar involvement was sparse or not present at all [ 58 ]. Genotyping 128 patients in a pilot study for R501X and 2282del4, Thyssen et al demonstrated that hand eczema in FLG mutation carriers was mainly located on the dorsal aspects of the hands.…”