Advertisement

Virchows Archiv A

, Volume 417, Issue 4, pp 325–331 | Cite as

Skin deposits in hereditary cystatin C amyloidosis

  • Eiríkur Benedikz
  • Hannes Blöndal
  • Gunnar Gudmundsson
Article

Summary

Clinically normal skin from 47 individuals aged 9–70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17–46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker. Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use in following progression of the disease.

Key words

Hereditary disease Amyloidosis Skin Cysteine proteinase inhibitor Immunohistochemistry 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abrahamson M (1988) Human cysteine proteinase inhibitors. Isolation, physiological importance, inhibitory mechanism, gene structure and relation to hereditary cerebral hemorrhage. Scand J Clin Lab Invest 48 [Suppl 191]:21–31Google Scholar
  2. Árnason Á (1935) Apoplexie und ihre Vererbung. Acta Psychiatr Neurol Suppl VIII 7:1–180Google Scholar
  3. Blöndal H, Gudmundsson G, Benedikz E, Jóhannesson G (1989) Dementia in hereditary cystatin C amyloidosis. In: Iqbal K, Wisniewski HM, Winblad B (eds) Alzheimer's disease and related disorders. Liss, New York, pp 157–164Google Scholar
  4. Breathnach SM (1985) The cutaneous amyloidoses. Arch Dermatol 121:470–475Google Scholar
  5. Breathnach SM, Bhogal B, Dyck RF, De Beer FC, Black MM, Pepys MB (1981) Immunohistochemical demonstration of amyloid P component in skin of normal subjects and patients with cutaneous amyloidosis. Br J Dermatol 105:115–124Google Scholar
  6. Brownstein MH, Helwig EB (1970) The cutaneous amyloidosis. II. Systemic forms. Arch Dermatol 102:20–28Google Scholar
  7. Coria F, Castano E, Prelli F, Larrondo-Lillo M, Duinen S van, Shelanski ML, Frangione B (1988) Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis. Lab Invest 58:454–457Google Scholar
  8. Ghiso J, Pons-Estel B, Frangione B (1986) Hereditary cerebral amyloid angiopathy: the amyloid fibrils contain a protein which is a variant of cystatin C, an inhibitor of lysosomal cysteine proteases. Biochem Biophys Res Commun 136:548–554Google Scholar
  9. Glenner GG (1980) Amyloid deposits and amyloidosis. N Engl J Med 302:1283–1292Google Scholar
  10. Grubb A, Jensson Ó, Gudmundsson G, Árnason A, Löfberg H, Malm J (1984) Abnormal metabolism of gamma trace alkaline microprotein: the basic defect in hereditary cerebral hemorrhage with amyloidosis. N Engl J Med 311:1547–1549Google Scholar
  11. Gudmundsson G, Hallgrimsson J, Jónasson TA, Bjarnason Ó (1972) Hereditary cerebral haemorrhage with amyloidosis. Brain 95:387–404Google Scholar
  12. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody PAP procedures. J Histochem Cytochem 29:577–580Google Scholar
  13. Khan AM, Walker F (1984) Age related detection of tissue amyloid P in the skin. J Pathol 143:183–186Google Scholar
  14. Kitamoto T, Ogomori K, Tateishi J, Prusiner SB (1987) Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab Invest 57:230–236Google Scholar
  15. Lever WF, Schaumburg-Lever G (1975) Histopathology of the skin. Lippincott, PhiladelphiaGoogle Scholar
  16. Levy E, Lopez-Otin C, Ghiso J, Geltner D, Frangione B (1989) Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteinases. J Exp Med 169:1771–1778Google Scholar
  17. Löfberg H, Grubb A (1979) Quantitation of γ-trace in human biological fluids: indications for production in the central nervous system. Scand J Clin Lab Invest 39:619–626Google Scholar
  18. Löfberg H, Grubb A, Nilsson E, Jensson Ó, Gudmundsson G, Blöndal H, Árnason A, Thorsteinson L (1987) Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis. Stroke 18:431–440Google Scholar
  19. Masu S, Hosokawa M, Seiji M (1981) Amyloid in localized cutaneous amyloidosis: immunofluorescence studies with anti-keratin antiserum especially concerning the difference between systemic and localized cutaneous amyloidosis. Acta Dermveneredol (Stockh) 61:381–384Google Scholar
  20. Pálsdóttir Á, Abrahamson M, Thorsteinsson L, Árnason A, Ólafsson Í, Grubb A, Jensson Ó (1988) Mutation in cystatin C gene causes hereditary brain hemorrhage. Lancet II 603–604Google Scholar
  21. Pepys MB (1988) Amyloidosis: some recent developments. Q J Med 252:283–298Google Scholar
  22. Rubinow A, Cohen A (1978) Skin involvement in generalized amyloidosis. Ann Intern Med 88:781–785Google Scholar
  23. Rubinow A, Cohen A (1981) Skin involvement in familial amyloidotic polyneuropathy. Neurology 31:1341–1345Google Scholar
  24. Wong CK (1987) Cutaneous amyloidoses. Int J Dermatol 26:273–277Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Eiríkur Benedikz
    • 1
  • Hannes Blöndal
    • 1
  • Gunnar Gudmundsson
    • 2
  1. 1.Departments of Anatomy and PathologyUniversity of Iceland Medical SchoolReykjavíkIceland
  2. 2.Department of NeurologyUniversity HospitalReykjavíkIceland

Personalised recommendations