We report on a 2-year-old boy with a 2-month history of widespread skin blisters and erosions with involvement of the oral mucosa (Fig. 1a). Dental examination revealed profound and extensive carious lesions, partially complicated with periapical lesions of all deciduous teeth and upper permanent incisors (Fig. 2). Histopathological examination revealed a subepidermal blister with a dense inflammatory dermal infiltrate. Direct immunofluorescence (IF) microscopy showed linear staining for immunoglobulin (Ig)G and C3 at the dermoepidermal junction. By indirect IF microscopy on salt-split skin, circulating IgG autoantibodies binding on the dermal side were detected (Fig. 1b). IgG autoantibodies reacted with a recombinant form of collagen VII by enzyme-linked immunoassay. The digital dental radiographs revealed the presence of all permanent tooth buds intramaxillary with no evidence for dysplastic disorders of the hard dental tissues.
Based on clinical, histopathological and immunological findings, the diagnosis of epidermolysis bullosa acquisita (EBA) was established. Initial treatment with prednisone 1 mg/kg daily and topical corticosteroids led to partial improvement. However, 1 week later, further generalized blistering re-occurred. High-dose i.v. Ig, 400 mg/kg daily for 4 days and dapsone 1 mg/kg daily were then added to the corticosteroid regimen. This combined treatment controlled formation of new blisters, while the majority of lesions cleared. The doses of prednisone and dapsone were tapered to 0.5 mg/kg daily and 25 mg daily, respectively. To date, the patient has been followed up for 5 years. Several flare-ups of cutaneous blisters occurred in response to skin trauma.
Dental caries have a complex pathogenesis and may be influenced by a variety of genetic and environmental factors. Childhood EBA is a very rare disease and none of the previously described patients had dental abnormalities as a clinical manifestation of this disease. Interestingly, defects in enamel maturation and/or mineralization have been reported in dystrophic and junctional epidermolysis bullosa. The Col17−/− mice, a model to study non-Herlitz junctional epidermolysis bullosa enamel hypoplasia, exhibit imperfect amelogenesis demonstrated by malformed enamel rods and irregular enamel matrix. Similar changes are observed in some cases of epidermolysis bullosa caused by mutations in laminin 5, α6β4 integrin or collagen VII. The tooth abnormalities due to type VII collagen deficiency investigated in Col7a1−/− and COL7-rescued humanized mice may be attributed to poorly differentiated ameloblasts. Defective enamel structure may provide a flourishing local environment for cariogenic bacteria by providing more adhesive and colonization potential and being more acid soluble. Hence, defective enamel appears to be a favoring factor for dental caries of childhood.
We have followed the patient closely for 5 years and could exclude a spectrum of factors, which are known to affect the development of hard tissue, including nutrition, fluoride exposure, salivary flow, infectious, genetic diseases and malignancies. Thus, the pathogenesis of his dental abnormalities is unclear. We can only speculate that local inflammation may have facilitated extensive dental caries compounded by low patient compliance with oral hygiene procedures and inability of the dental surgeon to perform dental treatment. Nevertheless, we cannot exclude a direct effect of collagen VII-specific autoantibodies on enamel formation. In adult EBA, gingival and enamel abnormalities were reported in one patient with long-standing disease.
In conclusion, our patient presented a severe inflammatory variant of EBA associated with caries of the whole dentition. Early and severe onset of EBA could have an impact on the development of dental caries by several mechanisms. Thus, as facilitating factors for the extensive dental caries, autoantibodies against collagen VII triggered a chronic inflammatory reaction and might have also interfered with the ligand function of collagen VII, compounding the patient's inability to perform oral hygiene.