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Lipoid Proteinosis Clinical Presentation

  • Author: Ivan D Camacho, MD; Chief Editor: Dirk M Elston, MD  more...
Updated: Mar 22, 2016


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.[6]
  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.[7]

A positive family history may be elicited because the disease is inherited in an autosomal recessive pattern.[8, 9]



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


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.[9, 10]

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.


Involvement manifests as patchy or diffuse hair loss.

Oral cavity

All sites within the oral mucosa may be involved. 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.

Upper airway

Infiltration of the larynx, vocal cords, and surrounding structures may produce hoarseness, dysphagia, and airway obstruction.[9]

Central nervous system

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



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] 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.

Contributor Information and Disclosures

Ivan D Camacho, MD Dermatologist, Private Practice; Voluntary Assistant Professor of Dermatology, Department of Dermatology and Cutaneous Surgery, University of Miami, Leonard M Miller School of Medicine

Ivan D Camacho, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Florida Medical Association, International Society of Dermatology, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.


Kelly M Cordoro, MD Assistant Professor of Clinical Dermatology and Pediatrics, Department of Dermatology, University of California, San Francisco School of Medicine

Kelly M Cordoro, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Association of Professors of Dermatology, Dermatology Foundation, Medical Society of Virginia, National Psoriasis Foundation, Society for Pediatric Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Vincent A De Leo, MD Clinical Professor of Dermatology, Department of Dermatology, College of Physicians and Surgeons of Columbia University; Chairman, Department of Dermatology, Director of Dermatology Residency Training Program, St Luke's-Roosevelt Hospital Center; Chairman, Department of Dermatology, Beth Israel Medical Center

Vincent A De Leo, MD is a member of the following medical societies: American Academy of Dermatology, American College of Occupational and Environmental Medicine, American Contact Dermatitis Society, American Dermatological Association, American Medical Association, American Society for Photobiology, Dermatology Foundation, New York Academy of Medicine, New York County Medical Society, Photomedicine Society, Society for Investigative Dermatology,Society of Toxicology, and Women's Dermatologic Society

Disclosure: estee lauder Consulting fee Consulting; laroche posay Consulting fee Consulting; schering plough Consulting fee Consulting; pfizer Consulting fee Consulting; orfagen Grant/research funds study - clinical

Michael F Osleber University of Virginia School of Medicine

Disclosure: Nothing to disclose.

Joseph J Shaffer, MBBS Fellow, Dermatologic Surgery, Department of Cutaneous Surgery, Fairview University Medical Center

Disclosure: Nothing to disclose.

  1. Hamada T, McLean WH, Ramsay M, et al. Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). Hum Mol Genet. 2002 Apr 1. 11(7):833-40. [Medline].

  2. Hamada T, Wessagowit V, South AP, Ashton GH, Chan I, Oyama N, et al. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation. J Invest Dermatol. 2003 Mar. 120(3):345-50. [Medline].

  3. Izadi F, Mahjoubi F, Farhadi M, Tavakoli MM, Samanian S. A novel missense mutation in exon 7 of the ECM1 gene in an Iranian lipoid proteinosis patient. Genet Mol Res. 2012 Nov 14. 11(4):3955-60. [Medline].

  4. Nasir M, Latif A, Ajmal M, Qamar R, Naeem M, Hameed A. Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family. Diagn Pathol. 2011 Jul 26. 6:69. [Medline]. [Full Text].

  5. Kabre V, Rani S, Pai KM, Kamra S. Lipoid proteinosis: A review with two case reports. Contemp Clin Dent. 2015 Apr-Jun. 6 (2):233-6. [Medline].

  6. Gutte R, Sanghvi S, Tamhankar P, Khopkar U. Lipoid proteinosis: Histopathological characterization of early papulovesicular lesions. Indian Dermatol Online J. 2012 May. 3(2):148-9. [Medline]. [Full Text].

  7. Arkadir D, Lerer I, Klapholz L, Halpert M, Newman JP, Gomori JM, et al. Lipoid proteinosis with bilateral amygdalae calcifications, headache, and cognitive impairments. Neurology. 2013 Jul 16. 81(3):303-4. [Medline].

  8. Salih MA, Abu-Amero KK, Alrasheed S, Alorainy IA, Liu L, McGrath JA, et al. Molecular and neurological characterizations of three Saudi families with lipoid proteinosis. BMC Med Genet. 2011 Feb 24. 12:31. [Medline]. [Full Text].

  9. Xu W, Wang L, Zhang L, Han D, Zhang L. Otolaryngological manifestations and genetic characteristics of lipoid proteinosis. Ann Otol Rhinol Laryngol. 2010 Nov. 119(11):767-71. [Medline].

  10. Callizo M, Ibáñez-Flores N, Laue J, Cuadrado V, Graell X, Sancho JM. Eyelid lesions in lipoid proteinosis or Urbach-Wiethe disease: case report and review of the literature. Orbit. 2011 Oct. 30(5):242-4. [Medline].

  11. Chan I, South AP, McGrath JA, Oyama N, Bhogal BS, Black MM, et al. Rapid diagnosis of lipoid proteinosis using an anti-extracellular matrix protein 1 (ECM1) antibody. J Dermatol Sci. 2004 Aug. 35(2):151-3. [Medline].

  12. Kaya TI, Kokturk A, Tursen U, Ikizoglu G, Polat A. D-penicillamine treatment for lipoid proteinosis. Pediatr Dermatol. 2002 Jul-Aug. 19(4):359-62. [Medline].

  13. Wong CK, Lin CS. Remarkable response of lipoid proteinosis to oral dimethyl sulphoxide. Br J Dermatol. 1988 Oct. 119(4):541-4. [Medline].

  14. Dertlioglu SB, Calik M, Ciçek D. Demographic, clinical, and radiologic signs and treatment responses of lipoid proteinosis patients: a 10-case series from Sanliurfa. Int J Dermatol. 2013 Dec 10. [Medline].

  15. Akoglu G, Karaduman A, Ergin S, Erkin G, Gokoz O, Unal OF. Clinical and histopathological response to acitretin therapy in lipoid proteinosis. J Dermatolog Treat. 2011 Jun. 22(3):178-83. [Medline].

  16. Kroukamp G, Lehmann K. Treatment of laryngeal lipoid proteinosis using CO2 laser. S Afr Med J. 2007 Feb. 97(2):90, 92. [Medline].

Characteristic beaded papules on the eyelid (moniliform blepharosis). Courtesy of Kenneth E. Greer, MD.
Waxy, yellow skin thickening and atrophic scarring. Courtesy of Kenneth E. Greer, MD.
Beaded papules on the upper labial mucosa. Courtesy of Kenneth E. Greer, MD.
Woody induration and depression of the tongue. Courtesy of Kenneth E. Greer, MD.
Waxy, infiltrated, yellowish skin with depressed, atrophic scarring. Courtesy of Kenneth E. Greer, MD.
Waxy skin with atrophic, depressed scars on the forehead. Courtesy of Kenneth E. Greer, MD.
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.
Adult male with lipoid proteinosis. His leonine facies appearance is a result of diffuse skin infiltration. Courtesy of Kenneth E. Greer, MD.
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