Conflicts of interest: None declared.
Cutis laxa in hereditary gelsolin amyloidosis
Article first published online: 3 FEB 2005
British Journal of Dermatology
Volume 152, Issue 2, pages 250–257, February 2005
How to Cite
Kiuru-Enari, S., Keski-Oja, J. and Haltia, M. (2005), Cutis laxa in hereditary gelsolin amyloidosis. British Journal of Dermatology, 152: 250–257. doi: 10.1111/j.1365-2133.2004.06276.x
- Issue published online: 23 FEB 2005
- Article first published online: 3 FEB 2005
- Accepted for publication 16 June 2004
- cutis laxa;
- elastic fibres;
- hereditary amyloidosis
Background Hereditary gelsolin amyloidosis (AGel amyloidosis) is an age-associated systemic disease with global distribution, caused by a G654A or G654T gelsolin gene mutation. Cutis laxa is a principal clinical manifestation of this disease. However, only few data on the dermatological involvement are available, and the pathogenesis of this amyloidosis-associated form of cutis laxa has remained unknown.
Objectives To elucidate the pathomechanism of this less well-known genodermatosis.
Methods We performed systematic clinical, histological, immunohistochemical and ultrastructural skin biopsy studies in 12 patients with a G654A gelsolin gene mutation. For comparison, skin specimens from 10 control subjects were analysed.
Results All patients had clinically characteristic cutis laxa, and frequently other signs of symptomatic skin disease such as increased fragility and risk for intracutaneous bleeding. All patients showed cutaneous deposition of gelsolin amyloid (AGel), mainly attached to basement membranes or basal laminae of various cutaneous structures, dermal nerves and blood vessel walls, and elastic fibres, particularly in the lower reticular dermis. AGel often encircled the elastic fibres, and colocalized with amyloid P component (AP), an elastic fibre microfibrillar sheath-associated protein. Fragmentation and loss of elastic fibres, epidermal atrophy, and reduction of dermal appendages were also common. Antibodies to wild-type gelsolin bound to S-100-positive epidermal dendritic cells, a previously unrecognized immunoreaction. Patients had fewer gelsolin-positive dendritic cells than controls.
Conclusions Widespread skin involvement with AGel deposition and elastic fibre involvement are essential pathological features in AGel amyloidosis, and contribute to the characteristic cutis laxa, dramatic in old age. Codistribution of AGel and AP, with demonstrated specific binding affinity for amyloid fibrils, suggests that elastic fibre-associated AP acts as a matrix for cutaneous amyloid deposition in AGel amyloidosis.