Skin nontumor

Dermal collagen and elastic tissue alterations, and cutaneous deposits

Lipoid proteinosis

Last author update: 1 August 2017
Last staff update: 4 August 2020

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PubMed Search: Lipoid proteinosis [title] skin

Hillary Zalaznick, M.D.
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Cite this page: Zalaznick H. Lipoid proteinosis. website. Accessed October 4th, 2023.
Definition / general
  • Autosomal recessive condition caused by mutations in the ECM1 gene, which leads to deposits of hyaline material in the skin and mucosal surfaces
Essential features
  • Deposits of PAS and PASD positive homogenous, eosinophilic material in the dermis and lamina propria corresponding clinically to waxy yellowish white lesions
  • Variable clinical presentation (see clinical features below)
  • Autosomal recessive inheritance
  • Also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease
  • Men and women are equally affected
  • Typically occurs in consanguineous families
  • Rare, only a few hundred known patients
  • Increased incidence in South Africa (likely due to founder mutation, Mol Syndromol 2016;7:26)
  • Uncertain
  • ECM1 (extracellular matrix protein 1) is a component of the extracellular matrix and patients with LP lack functional ECM1 - this leads to hyaline deposits through an unknown mechanism
  • Autosomal recessive disease
Clinical features
  • Clinical features are variable but include (Vahidnezhad: GeneReviews - Lipoid Proteinosis, 2016):
    • Hoarse cry as an infant, hoarse voice
    • Moniliform blepharosis (papules on the eyelid margins)
    • Vesicles with hemorrhagic crust on skin and oral mucosa in early lesions
    • Lesions evolve into waxy yellowish white papules, nodules or plaques
    • Poor wound healing
    • Calcifications in the brain, particularly a "bean shaped" calcification above the pituitary fossa
    • Seizures
    • Behavioral issues such as memory impairment, paranoia, aggressive behavior, hallucinations and lack of fear (involvement of the amygdala)
    • Parotitis and poor dental hygiene
    • Upper respiratory infections
    • Shortened tongue, difficulty in protruding tongue
    • Patchy alopecia
  • Clinical suspicion followed by sequencing of the ECM1 gene
  • Biopsy may be helpful but is not required for the diagnosis
  • There are no specific laboratory findings
Radiology description
  • Brain CT can identify calcifications but is not needed for diagnosis
Prognostic factors
  • Patients with lipoid proteinosis have a normal life expectancy
  • However, deposits in the larynx can lead to airway obstruction and may need to be ablated
Case reports
  • Lesions can be excised or ablated but there is no curative treatment
Clinical images

Case #433

Beaded papules over bilateral eyelids

Waxy papules over back of forearm

Gross description
  • Skin or mucosa with waxy yellowish white nodules
Microscopic (histologic) description
  • Amorphous, eosinophilic mostly acellular hyaline material in the papillary dermis and extending around sweat glands and blood vessels
  • In mucosal biopsies can be seen surrounding salivary gland acini
Microscopic (histologic) images

Case #433

Eosinophilic homogenous material in the papillary dermis

PAS positive

Positive stains
Negative stains
Differential diagnosis
  • Amyloidosis
    • Deposits are similar on H&E but special stains for amyloid will be positive
  • Porphyria
    • Histologic appearance of early lesions in lipoid proteinosis can be similar to those of porphyria
    • Both show hyaline deposits involving blood vessels
    • Lesions in porphyria are limited to sun exposed areas, which is not true of lipoid proteinosis
  • Smokeless tobacco keratosis (Arch Pathol Lab Med 2004;128:e17)
    • Similar deposits of amorphous, eosinophilic PAS and PASD+ material in the lamina propria around vessels and salivary glands
    • More focal than lipoid proteinosis and limited to oral cavity
    • Lesions of smokeless tobacco keratosis are reversible when use of smokeless tobacco products is discontinued
Additional references
Board review style question #1
The deposits seen in lipoid proteinosis are:

  1. Known to be made of amyloid AA
  2. Negative for PASD
  3. Positive for Congo red
  4. Positive for PAS
Board review style answer #1
D. The deposits in lipoid proteinosis are positive for PAS, positive for PASD, negative for Congo red and are of unknown composition (but are not amyloid)

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Reference: Lipoid proteinosis
Board review style question #2
The histologic appearance of lipoid proteinosis is best described as:

  1. An infiltrate of histiocytes and foreign body giant cells engulfing elastotic fibers
  2. Dense, band-like lymphocytic infiltrate in dermis that obscures the dermoepidermal junction
  3. Hyaline deposits in the dermis, particularly around blood vessels and sweat glands
  4. Marked fatty infiltration of the dermis
  5. Orthokeratotic hyperkeratosis and papillomatosis of stratum spinosum
Board review style answer #2
C. Hyaline deposits in the dermis, particularly around blood vessels and sweat glands

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Reference: Lipoid proteinosis
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