What is lipoid proteinosis?
Lipoid proteinosis is a rare genetic skin disease in which an amorphous hyaline material is deposited in the skin, mucosa, and internal organs.[1,2] It often presents as hoarseness in early childhood, associated with thickening of skin and mucosae.
It is also called hyalinosis cutis et mucosae, and Urbach-Wiethe disease.
Who gets lipoid proteinosis?
Lipoid proteinosis is inherited as an autosomal recessive disorder. This means that both parents of an affected individual carry an abnormal gene. The parents are often related to each other by birth, and there may be a family history of the disease.
Lipoid proteinosis affects males and females equally.
- To date, about 300 cases have been reported [2,3].
- Lipoid proteinosis is more prevalent than elsewhere in the Namaqualand area of Northern Cape province in South Africa (1 in 300). All affected patients carry the same mutation (Q276X), which is likely due to a founder effect.
- Most reported cases are of European ancestry (Dutch or German), but Indian and Chinese cases have also occurred [4,5].
What causes lipoid proteinosis?
Lipoid proteinosis is due to loss of function mutations in a gene encoding extracellular matrix protein 1 (ECM1) on band 1q21. This encodes an important structural protein in the basement membrane and extracellular matrix [6,7].
What are the clinical features of lipoid proteinosis?
Lipoid proteinosis often presents in early childhood, but may rarely present at birth or in adulthood if cutaneous manifestations are subtle.[1,2]
It has variable phenotype, ie, clinical features differ between affected individuals, even within families. Although skin and mucous membranes of mouth, pharynx, and larynx are commonly affected, hyaline material may infiltrate any part of the body .
The characteristic skin changes of lipoid proteinosis tend to occur in overlapping stages.[1,3] They are due to dermal infiltration with hyaline.
- Recurrent blistering most commonly seen on face and extremities, predominantly on sites of trauma. This heals slowly with haemorrhagic crusting and scarring.
- Waxy yellow skin thickening
- Beaded eyelid papules (moniliform blepharosis)
- Generalized skin thickening, most obvious on face, axilla and scrotum
- Warty papules and plaques at sites of friction (eg elbows and extensor forearms)
Other common cutaneous features include:
- Thickened oral mucosa (cobblestone lips, tongue or gingiva)
- Scarring and premature photoaging of sun-exposed skin
- Mild alopecia (localised or diffuse hair loss)
Hyaline infiltration of the respiratory tract can lead to:
- Difficulty swallowing
- Dry mouth and dental decay
- Swelling of salivary glands
- Recurrent upper respiratory tract infections
- Impaired tongue mobility
- Missing teeth
Central nervous system
Lipoid proteinosis may affect the nervous system. Features may include:
- Amygdala dysfunction leading to mood disturbance and inappropriate social and behavioural changes
- Mild mental retardation
- Complex partial seizures
- Memory loss
- Severe generalized dystonia (muscle spasms and abnormal posture).
When lipoid proteinosis affects the eye, it can lead to:
- Drusen-like fundal lesions (drusen are yellow deposits under the retina)
- Corneal ulcers
- Loss of eyebrows and eyelashes.
How is lipoid proteinosis diagnosed?
The 2 most reliable signs of lipoid proteinosis are :
- Hoarse voice, classically presenting as an infant with a faint or hoarse cry
- Thickened sublingual frenulum (a band of tissue), which prevents patients from protruding the tongue
Further testing should be performed in patients with suggestive clinical features.
- Skin biopsy shows PAS-positive deposition of amorphous hyaline material in the papillary dermis. Immunohistochemical staining may show absence or attenuation of ECM1.
- Electron microscopy shows dermal deposits, excess basement membrane material around blood vessels, and irregular duplication of the lamina densa at the dermal-epidermal junction.
- Head CT/MRI may reveal bilateral bean-shaped calcifications within the hippocampal region of the temporal lobes in up to 75%; this is pathognomonic.
- Polymerase chain amplification (PCR) and direct nucleotide sequencing of the ECM1 gene may detect mutations.
Differential diagnosis of lipoid proteinosis
Depending on clinical presentation, other diagnoses to consider may include [2,3,9]:
- Hydroa vacciniforme
- Erythryopoietic protoporphyria
- Lichen amyloidosis
- Papular mucinosis (scleromyxoedema)
- Congenital dysphonia
- Congenital hypothyroidism.
What is the treatment for lipoid proteinosis?
There is no known effective treatment for lipoid proteinosis. The following have been trialed with variable success [2,3,10].
- Laser ablation/ dermabrasion of papules
- Acitretin for voice hoarseness
- Topical and oral corticosteroids
- Oral dimethyl sulfoxide
There may be potential for development of effective treatments for lipoid proteinosis in the future, such as recombinant ECM1 gene therapy .
Patients with lipoid proteinosis are often under the care of multiple specialists, including:
- Otolaryngologist (ear, nose, throat specialist)
What is the outcome for patients with lipoid proteinosis?
Lipoid proteinosis is a chronic disease with a generally favourable prognosis that runs a slowly progressive, benign course [1,2,11]. Lifespan is normal for most patients, with the exception of those with central nervous system and/or respiratory tract involvement .
However, progressive thickening of the skin and scarring, along with abnormal voice, can have a significant psychosocial impact, leading to difficulties at work, low self-esteem and overall poor quality of life .