Lipoid Proteinosis Clinical Presentation

Updated: Apr 17, 2017
  • Author: Dirk M Elston, MD; Chief Editor: William D James, MD  more...
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Presentation

History

A weak or hoarse cry from birth or starting in early infancy is typical and remains throughout life. Cutaneous manifestations usually arise during the first 2 years of life.

Skin findings manifest in sequential but overlapping stages, as follows:

  1. Initially, an inflammatory, vesicular, and crusted eruption appears on the face and extremities and may resemble impetigo or acne. The lesions are self-limited, occur predominantly in sites of trauma, and ultimately heal with scarring. [7]

  2. The second stage is characterized by dermal deposits of amorphous hyaline material, creating a diffuse, waxy, thickened appearance that is most apparent on the skin of the face, eyelids, axillae, and scrotum, although any cutaneous site is vulnerable.

  3. Verrucous papules and plaques then arise on surfaces subject to friction, such as the elbows, knees, and hands.

Children may have seizures, behavioral changes, learning difficulties, and rage attacks resulting from characteristic temporal lobe calcifications. A case of striatal calcifications associated with generalized dystonia has been reported. [8]

A positive family history may be elicited because the disease is inherited in an autosomal recessive pattern. [9, 10]

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Physical Examination

Characteristic physical findings are thought to result from the deposition of hyaline material in the skin and mucous membranes.

Skin

Early findings include recurrent, variably sized vesicles, pustules, bullae, and hemorrhagic crusts that arise on the skin and in the mouth and throat. The face and distal extremities are the most common sites. Resolution of the lesions occurs with permanent, poxlike atrophic scarring.

Late findings are noted as the child ages; the skin develops a waxy, thickened, yellowish appearance due to dermal infiltration. Papules, plaques, and nodules arise on the face, axillae, and scrotum. A pathognomonic sign is a row of beaded papules along the eyelid margins, resembling a string of pearls; this is termed moniliform blepharosis. [10, 11]

Hyperkeratotic, verrucous plaques may arise in sites of trauma, particularly the elbows, knees, and dorsum of the hands. A generalized hyperkeratosis and widespread scale may occur.

See the images below.

Waxy skin with atrophic, depressed scars on the fo Waxy skin with atrophic, depressed scars on the forehead. Courtesy of Kenneth E. Greer, MD.
Infiltrated, thickened skin with atrophic and hype Infiltrated, thickened skin with atrophic and hyperpigmented scarring in 2 brothers with lipoid proteinosis. Note the tongues, which are firm and woody, ulcerated, and unable to be completely protruded because of infiltration of the frenulum. Courtesy of Kenneth E. Greer, MD.

Scalp

Involvement manifests as patchy or diffuse hair loss.

Oral cavity

All sites within the oral mucosa may be involved. The tongue is the most commonly affected oral site, and tongue involvement is associated with a history of more affected family members. The palate and gingiva are the least involved mucosal sites. [12]  Pebbling of the lip mucosa imparts a cobblestone appearance, which may also involve the tongue and gingiva. Infiltration of the tongue and frenulum results in a woody firmness and impaired mobility. Patients may not be able to fully protrude the tongue, and this may be associated with impaired speech and gustation. Transient swelling and ulceration of the lips and tongue may occur. Hypoplasia or aplasia of the teeth, particularly the lateral incisors and premolars, may occur. Recurrent parotitis may occur as a consequence of infiltration of the Stensen duct.

See the images below.

Beaded papules on the upper labial mucosa. Courtes Beaded papules on the upper labial mucosa. Courtesy of Kenneth E. Greer, MD.
Woody induration and depression of the tongue. Cou Woody induration and depression of the tongue. Courtesy of Kenneth E. Greer, MD.

Upper airway

Infiltration of the larynx, vocal cords, and surrounding structures may produce hoarseness, dysphagia, and airway obstruction. [10]

Central nervous system

A classic and pathognomonic radiographic finding is bilateral, intracranial, bean-shaped suprasellar calcifications in the temporal lobe.

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Causes

Loss of function mutations in the gene encoding extracellular matrix protein 1 (ECM1) on band 1q21 has been identified as the cause of lipoid proteinosis. [1, 2, 13]

The exact mechanistic correlation between the genetic mutations described and the clinical manifestations of the disease remains unclear.

The Medscape Genomic Medicine Resource Center may be of interest.

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Complications

Laryngeal involvement may lead to airway obstruction. Vocal cord involvement may lead to impaired speech.

Intracranial calcifications may result in seizures, behavioral changes, rage attacks, and dystonia.

The deposition of hyaline in the small bowel is reported to cause gastrointestinal bleeding.

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