Diagnostic pitfalls in newborns and babies with blisters and erosions

Abstract

Establishing the correct diagnosis in newborns presenting with blisters and erosions is not always a straightforward process. Many different disease entities including acquired (i.e., infectious, immunobullous, traumatic) and inherited disorders have to be taken into consideration. Similarities in clinical appearance, colonization and/or superinfections of preexisting skin lesions, as well as the absence of late changes in the neonate often pose significant diagnostic challenges. In this paper we discuss by giving examples the process of making an accurate diagnosis of blistering skin diseases in the neonatal period on the basis of a diagnostic algorithm. In addition, we provide an overview of the rational use and the limitations of laboratory procedures such as microbial testing, routine light microscopy, immunofluorescence antigen mapping, transmission electron microscopy, and molecular genetic analysis.

Figure 1

Diagnostic algorithm of blisters and erosions in newborns. DIF: direct immunofluorescence; IB: immunoblot; IIF: indirect immunofluorescence; IP: immunoprecipitation; KOH: potassium hydroxide fungal test; PCR: polymerase chain reaction: TEM: transmission electron microscopy.

Figure 2

(a) Extensive denuded area enclosing the heel, ankle, joint, and dorsum of the left foot shortly after birth. (b) The same region at the age of 2 years showing an atrophic scar. (c) Dystrophy of toenails.

Figure 3

Segregation of the mutation 7120G > A: G2374R and its phenotypic features are shown in the pedigree of the family. The index patient (IV-1) and his grandmother (II-3) show blisters and nail dystrophy. His mother (III-4) presented with blisters solely in childhood and appears with nail dystrophy. All other family members carrying this mutation present with nail dystrophy without blisters.

Figure 4

Detection of mutation 7120G > A; G2374R in COL7A1 by sequence analysis in selected family members, except sample III-3, which is wildtype for this locus.

Figure 5

Detection of SNP 7006G > A; G2336W in COL7A1 by sequence analysis in selected family members, except sample III-3, which is wildtype for this locus.

Figure 6

(a) and (b) patient 2: Partially ruptured pustules, resulting in large circumscribed erosions on the right hand and left foot.

Figure 7

(a) Patient 3: haemorrhagic blister on the left little toe. (b) Histology of perilesional skin shows basal cell cytolysis (arrows) (Hematoxylin-eosin stain; original magnification: X100).

Figure 8

Sequence analysis of 374G > A; R125H in KRT14. The patient is a heterozygous carrier for this de novo mutation, whereas the parental alleles reflect wildtype status.

Figure 9

(a) Patient 4: shortly after birth, a large denuded area was found on the left leg. (b) The same leg four weeks later showing healing and scar formation. (c)-(d) IF antigen mapping of perilesional skin: absence of BPAG2 (c) and collagen type VII (d). (e)-(f) IF antigen mapping of clinically unaffected skin (inner aspect upper arm): positive staining for collagen type XVII (e) and collagen type VII (f) ((c)–(f) original magnification: X400).

Figure 10

Sequence analysis of 3760-1G > A in COL7A1. The patient is homozygous for this mutation, and parental heterozygous alleles confirm the genetic transmission.