Nail Involvement in Epidermolysis Bullosa

Nail abnormalities are a common feature in most subtypes of epidermolysis bullosa (EB), and they recently have been included among the criteria for scoring EB severity. Trauma undoubtedly contributes to the development of nail dystrophy, and for this reason the great toenails often are affected more severely. The nail abnormalities may be the first or the only symptom of EB. Nail abnormalities observed in EB are not specific or pathognomonic, as they result from nail bed and matrix scarring. The spectrum of clinical severity is large, and nail abnormalities may cause severe disability or just be a mild cosmetic problem. This article reviews the nail abnormalities observed in EB.

Although the anatomy of the nail apparatus is different from that of the skin, the antigenic expression of basement membrane zone (BMZ) components in the normal matrix, nail bed, proximal nail fold, and hyponychium is similar to that of normal skin. In addition, there are no differences in the antigenic composition of the BMZ between the different portions of the nail matrix. Nail expression of all the target antigens found in the normal nonappendage basement membrane explains why nail involvement is a feature of most epidermolysis bullosa (EB) subtypes.

Even though the absence or presence of nail changes at birth should not be used as absolute criteria for differential diagnosis between different subtypes of EB, nail involvement recently has been included among the criteria for scoring EB severity, as early nail dystrophy and loss are correlated with disease severity and progression, particularly in junctional epidermolysis bullosa (JEB) and recessive dystrophic epidermolysis bullosa (RDEB).

Trauma undoubtedly contributes to the development of nail dystrophy, and for this reason, the great toenails more often are affected severely.

The nail abnormalities may be the first or the only symptom of EB. In fact they may precede the development of skin blistering as in the late-onset JEB ( Fig. 1 ) and pretibial DEB, or be an isolated finding as reported in some families with dominant dystrophic EB (DDEB) ( Figs. 2 and 3 ).

Nail involvement is uncommon in localized EB simplex (EBS) and is not a feature of EBS migratory circinate or EBS with pyloric atresia ( Table 1 ).

Table 1

Classification of EB and the nail involvement in the different subtypes of EB

Major Type of EB	Subtypes	Frequency of Nail Involvement	Nail Signs
EBS (simplex)	EBS superficialis AD	70%	Dystrophic nails
	Lethal acantholytic EBS AR	100%	Nail loss
	Plakophilin deficiency AR	100%	Thickened dystrophic nail
	EBS localized AD	Uncommon	Blistering may cause onycholysis and onychomadesis, with normal regrowth or thickened dystrophic nails
	Dowling-Meara AD	>75%	Onychomadesis, pachyonychia, onychogryphosis, pincer nails or absent nails
	EBS other generalized AD (previously called Koebner)	14%	Onychomadesis with normal regrowth, pachyonychia, thickened great toenail
	AR EBS		Hyperkeratotic nails, horizontal ridging, anonychia
	EBS-Ogna AD		Onychogryphosis
	EBS migratory circinate	Absent	None
	EBS with mottled pigmentation	Uncommon	Dystrophic nails, small toenail
	EBS with muscular dystrophy	50%	Onychomadesis, pachyonychia, onychogryphosis, pincer nails, anonychia
	EBS with pyloric atresia	Absent	None
JEB	Herlitz AR	>75%	Pachyonychia, exuberant granulation tissue, nail erosion, anonychia
	Non-Herlitz AR (generalized and localized)	>75%	Anonychia, dystrophic nails
	With pyloric atresia AR		Nail thinning and atrophy or absent nails
	Inversa JEB	>50%	Dystrophic or absent nails
	Late-onset JEB		Onycholysis, nail loss, Beau’s lines
	LOC syndrome	100%	Nail thickening, nail erosions with granulation tissue, anonychia
DEB (dystrophic EB)	DDEB generalized	>75%	Nail thickening, onychogryphosis, anonychia, pseudosyndactyly
	RDEB severe generalized	>75%	Anonychia, pseudosyndactyly
	RDEB generalized other	>75%	Dystrophic or absent nails
	Acral DDEB and RDEB	>75%	Nail thickening anonychia
	Pretibial DDEB and RDEB,	>75%	Nail thickening
	Pruriginous DEB, AD or AR	>75%	Nail thickening, anonychia
	DDEB nails only	100%	Pachyonychia, thickened dystrophic nails anonychia
	DEB-BDN	25 – 50%	Nail thickening, anonychia pseudosyndactyly
	RDEB inversa	>75%	Nail thickening
	RDEB centripetalis	>75%	Dystrophic or absent nails
Kindler syndrome	AR		Nail dystrophy, parrot beak nail deformity, absent nails