Amyloidosis (overview) E85.9/L99.0

Virchow, 1854; Lubarsch, 1929; Gutmann, 1928; Freudenthal, 1930; Gottron, 1950;

Heterogeneous group of diseases whose common feature is the mostly extracellular deposition (in some localized amyloidoses also intracellular deposition) of a misfolded protein complex that is not degradable for the organism. Usually, the formed proteins are present in solute form and are proteolytically degradable. Disorders of protein folding(beta-fold conformation) lead to the formation of now insoluble fibrillar complexes (amyloid fibrils). These fibrils cannot be phagocytized because they cannot be attacked by the macrophage system due to their conformational peculiarities. Thus, amyloid accumulates in various organs (kidney, liver, spleen, adrenal glands, gastrointestinal tract), including the skin (see cutaneous amyloidoses below) with characteristic clinical and histological changes. To date, > 30 amyloidogenic proteins are known. Remark: Amyloid biding is comparable to the pathogenic protein deposits in beta-sheet structure that characterize prion diseases.

Systemic (generalized) amyloidoses

• Non-hereditary systemic amyloidoses (95%)
  • AA-type amyloidoses (most common form of amyloidosis)
  • AL-type amyloidoses (immunngloulin-associated amyloidoses)
  • ß2-microgobulin-associated amyloidosis (hemodialysis patients)

Hereditary (systemic/localized) amyloidoses (=familial amyloidoses/ transthyretin amyloid; AFib; AAPoA1/2; Alys; Agel; Aß; ACys; ABri/ADan; Familial primary localized cutaneous amyloidosis) (5%)

Localized amyloidoses (symptoms at the site of amyloid synthesis).

• Non-cutaneous localized amyloidoses
  • Diabetes mellitus type 2: deposition of islet amyloid polypeptide (IAPP)in dn beta cells of islets of Langerhans; amyloid in tumors, metastases and environment; senile cardiac amyloid (native TTR in myocardium in elderly); Alzheimer's disease (Alzheimer's plaques in brain = aggregated Abeta peptide, cleavage product of amyloid praecursor protein-APP)
• Cutaneous (primary) localized amyloidosis
  • Macular cutaneous amyloidosis
  • Papular cutaneous amyloidosis (lichen amyloidosus)
  • Biphasic cutaneous amyloidosis
  • Nodular cutaneous amyloidosis(amyloidosis cutis nodularis atrophicans)
  • Cutaneous amyloidosis /special forms
• Cutaneous (secondary) localized amyloidosis
  • Amyloidoses in actinic (permanent) lesions (also after PUVA therapy/Amyloid K)
  • Amyloid deposits (amyloid K) in benign and malignant tumors (basal cell carcinoma/50%; spinocellular carcinoma, seborrheic keratoses, actinic keratoses)
  • "Friction amyloidosis": Cutaneous amyloidosis due to constant scratching and scrubbing of certain skin areas with hard brushes or other objects (nylon brush macular amyloidosis)/amyloid K. There are pathogenetic relationships to notalgia paraesthetica.
  • X-linked reticular pigment disorder (rare syndrome characterized by recurrent infections and sterile multiorgan inflammation (mutation in POLA1 gene encoding the catalytic subunit of DNA polymerase-alpha (Pol-α) (Starokadomskyy Pet al. 2019).

1. Breathnach SM (1988) Amyloid and amyloidosis. J Am Acad Dermatol 18: 1-16
2. Cohen AS, Jones LA (1993) Advances in Amyloidosis. Curr Opin Rheumatol 5: 62-76
3. Dubrey S et al (2014) The transthyretin amyloidoses: advances in therapy. Postgraduate Med J doi: 10.1136/postgradmedj-2014-133224.
4. Hung CC et al (2003) Unusual skin manifestation of cutaneous amyloidosis. Dermatology 207: 65-67
5. Lubarsch O (1899) Hyaline and amyloid degeneration. Erg allg Path 4: 449-460
6. Moon AO et al (2003) Nodular amyloidosis: review and long-term f-up of 16 cases. Arch Dermatol 139: 1157-1159
7. Santos-Juanes J et al (2004) Nodular primary localized cutaneous amyloidosis. J Eur Acad Dermatol Venereol 18: 224-226
8. Virchow R (1854) On the course of amyloid degeneration. Virch Arch 8: 364-368
9. Woollons A et al (2001) Nodular localized primary cutaneous amyloidosis: a long-term follow-up study. Br J Dermatol 145: 105-109