International Journal of Pediatric Otorhinolaryngology Extra
Volume 1, Issue 1 , Pages 1-4, March 2006

Urbach–Wiethe disease

  • Efstathios Rallis

      Affiliations

    • Department of Dermatology of 401 General Military Hospital of Athens, 1 Kanelopoulou Street–Papagos, GR-11525 Athens, Greece
    • 11 Pafsaniou Street–Pagrati, GR-11635 Athens, Greece. Tel.: +30 210 7244008; fax: +30 210 7244008.
    • ,
  • Dimitrios G. Balatsouras

      Affiliations

    • ENT Department of Tzanion General Hospital, 11 Zani & Afentouli Street, GR-18536 Piraeus, Greece
    • Corresponding Author InformationCorresponding author. 23 Achaion Street–Ag. Paraskevi, GR-15343 Athens, Greece. Tel.: +30 210 600 4683; fax: +30 210 4592 671.
    • ,
  • Pavlos Papadakis

      Affiliations

    • Department of Dermatology of 401 General Military Hospital of Athens, 1 Kanelopoulou Street–Papagos, GR-11525 Athens, Greece
    • 7 Eantos Street, GR-11631 Athens, Greece. Tel.: +30 210 7494000; fax: +30 210 7494095.
    • ,
  • Nicolas C. Economou

      Affiliations

    • ENT Department of Tzanion General Hospital, 11 Zani & Afentouli Street, GR-18536 Piraeus, Greece
    • 32 Dimitrakopoulou Street–Voula, GR-16673 Athens, Greece. Tel.: +30 210 9658 226; fax: +30 210 4592 671.
    • ,
  • Antonis Kaberos

      Affiliations

    • ENT Department of Tzanion General Hospital, 11 Zani & Afentouli Street, GR-18536 Piraeus, Greece
    • 6 Arifronos Street–Kypseli, GR-11364 Athens, Greece. Tel.: +30 210 8677 935; fax: +30 210 4592 671.
    • ,
  • Stavros Korres

      Affiliations

    • ENT Department of Athens National University, Hippokration Hospital, 114 Vas. Sofias Av., GR-11528 Athens, Greece
    • 47-49 Promitheos Street–Ekali, GR-14576 Athens, Greece. Tel.: +30 210 724 1249; fax: +30 210 8136 971.

Received 24 March 2005; received in revised form 10 October 2005; accepted 18 October 2005.

Article Outline

Summary 

Objective: Urbach–Wiethe disease (lipoid proteinosis) is a rare, recessively inherited disorder, characterized by infiltration of a hyalin-like material in skin, mucous membranes, brain and other internal organs. We present a case of a child with this rare disease. Case report: A 15-year-old boy was referred to our clinic because of a 10-year history of hoarseness. On clinical examination, waxy papules were seen on the face. The cutaneous lesions appeared early in childhood soon after the development of hoarseness and were located along the margin of both eyelids and on the upper lip on a beaded arrangement. Hyperkeratotic plaques were also found on the elbows and white–yellow infiltrates on the mucosae of the pharynx and the tongue. Full laboratory investigation was unremarkable. A biopsy from oral mucosae confirmed the diagnosis of lipoid proteinosis. Conclusion: Lipoid proteinosis is thought to be a multisystemic disorder due to deposition of hyaline material around the blood vessels in internal organs. Usual manifestations of the disease include recurrent parotitis related to the occlusion of the salivary duct, epilepsy owed to intracranial suprasellar calcification, malfunction of the eyelashes causing corneal ulceration or alopecia of the eyelashes and eyebrows. The most serious manifestation of lipoid proteinosis is the possible respiratory obstruction in infancy because of the enlargement of the tongue and the presence of hyaline infiltrates in pharynx. Otherwise, the disease is compatible with a normal life span. The disfiguring lesions and the permanent hoarseness can seriously impair quality of life. There is no effective therapy at the present time.

Keywords: Urbach–Wiethe disease, Lipoid proteinosis, Hoarseness

 

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1. Introduction 

Urbach–Wiethe disease (UWD), known also as lipoid proteinosis and hyalinosis cutis et mucosae [1] is a very rare, recessively inherited disorder, characterized by yellowish white infiltrative deposits on the skin, the mucous membranes and other internal organs. Hoarseness is usually the first clinical manifestation of the disease, caused by infiltration of the vocal cords [2]. In most cases this develops soon after birth or during the first year of life or, rarely, after a few years [3]. The pathogenesis of lipoid proteinosis still remains obscure. We present a case of a child with this uncommon disease.

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2. Case report 

A 15-year-old boy was referred to our clinic because of a 10-year history of hoarseness. No medical advice had been asked during this time. On clinical examination, waxy, papular and nodular infiltrates over the entire face were noticed, as well as lesions resembling pitted, atrophic, acneiform scars located in acneogenic and non-acneogenic regions of the skin. A beaded arrangement of small pearly nodules and papules was also seen on the upper lip and along the margin of both eyelids without loss of eyelashes, in symmetrical distribution (Fig. 1).

Hyperkeratotic plaques were also found on the elbows and on the dorsal aspects of the hands. The tongue was enlarged, firm in palpation and movable only with difficulty, making the patient unable to protrude it beyond the margins of the lips. White yellowish infiltrates were located on the oral mucosa, from where a first biopsy specimen was taken, and on the mucosa of the pharynx and the tongue. The tonsils were covered with a waxy mass and fiber-optic endoscopy of the larynx revealed severe involvement of the larynx with nodular deposits on the epiglottis and the vocal cords (Fig. 2), from where a second biopsy specimen was taken.

According to patient's history, the cutaneous lesions appeared early in childhood, soon after the development of hoarseness. His parents were in good health and none of the family members showed familial features. The patient could not confirm the appearance of new lesions in the skin or the mucous membranes, after trauma.

Routine laboratory tests were within normal range. Electroencephalogram, electromyogram, electrocardiogram, computed tomography scanning of the head and colonoscopy revealed no abnormalities. Ophthalmologic, neurologic, endocrinologic and phychiatric examinations were normal. Histological examination showed dilation of the blood vessels, thickening of their walls and infiltration of the dermis with amorphous, extracellular, eosinophilic, hyaline deposits and a small amount of lipids (Fig. 3). Stains for amyloid were negative. These findings were consistent with lipoid proteinosis.

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3. Discussion 

UWD or lipoid proteinosis was initially described as hyalinosis cutis et mucosae by the dermatologist E. Urbach and the otolaryngologist C. Wiethe, in 1929 [1], [2]. This rare disturbance was characterized by deposition of hyaline material into the skin, oral cavity and larynx. In order to avoid possible confusion with other lipoidoses, the first name was later modified to lipoid proteinosis [2].

UWD is a rare, autosomal recessive disorder that affects both sexes equally and presents in infancy with failure to cry and a hoarse, gravelly voice [3]. Skin lesions, consisting of waxy papules or nodules and acneiform or pox-like scars, usually appear during the first few years of life or develop later. The classic and most easily recognizable sign is the beaded eyelid papules [4], as in our patient. Hyperkeratotic plaques may be present in sites exposed to mechanical friction, such as the elbows, knees, and buttocks.

The mucosae of the pharynx, tongue, soft palate and lips soon develop firm yellow-white infiltrates. The larynx may be involved to a severe degree with nodules on the epiglottis and the vocal cords. Rarely, this may cause obstruction of the upper respiratory tract, requiring tracheostomy [5]. In our patient, although severe involvement of the larynx was evident, respiratory function was normal.

Involvement of the scalp leads to loss of hair but alopecia is an uncommon finding in most cases of UWD. Recurrent parotitis related to the occlusion of the salivary duct, poor dental hygiene and short tongue with a thickened frenulum have also been reported in association with UWD [3], [6], [7], [8]. Other extracutaneous features include epilepsy, neuropsychiatric abnormalities, a bilateral intracranial sickle-shaped para-sellar calcification (seen in 50% of the patients), dental abnormalities, cardiac, endocrine and urogenital disorders [2], [3]. Widespread visceral involvement described as deposition of hyaline material around the blood vessels has been seen by microscopy to be present in internal organs [2], [9].

The pathogenetic mechanism of the disease is not clear. Harper et al. [10] suggested that lipoid proteinosis may involve a primary perturbation of collagen metabolism. Histological and ultrastructural examination reveals widespread deposition of hyaline material and disruption or reduplication of basement membrane around blood vessels and at the dermal–epidermal junction [3]. Recently, lipoid proteinosis was mapped to 1q21 and pathogenetic loss of function mutations were identified in the extracellular matrix protein 1 gene (ECM1) [11].

The diagnosis is easily made by the combination of hoarseness in early childhood, thickening of the tongue and presence of the characteristic yellow–white papules and nodules. The disease should be differentiated from erythropoietic protoporphyria (light sensitivity and deposition of PAS-positive material in sun-exposed areas), xanthomatosis (xanthoma cells in histological examination), amyloidosis (amyloid deposition in histological examination), tuberous sclerosis (histological examination shows sebaceous adenoma) and lichen myxoedematosus.

UWD is progressive until early adult life but in general the prognosis is good [9]. However, the quality of life can be seriously impaired by the disfiguring lesions and the permanent hoarseness [2]. There is no sufficient therapy for the disease. The use of plastic surgery and dermabrasion is questionable because it appears that trauma provokes deposition of hyaline material [2]. However, a remarkable clearance of skin and laryngeal lesions has been reported in a single case of UWD after 3 years of continuous oral dimethylsulphoxide therapy [12]. A good clinical response has also been seen after 3 months treatment with etretinate and almost complete clearance of hyaline material from the dermis was noticed after one year [13]. Carbon dioxide laser surgery of thickened vocal cords and beaded eyelid papules has proved to be helpful in some studies [14], [15]. Hamada [3] supports that identification of mutations in ECM1 in UWD now provides a basis for the development of more rational forms of treatment, including trials of recombinant ECM1 protein and the development of somatic gene therapy for skin or respiratory mucosa.

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References 

  1. Urbach E, Wiethe C. Lipoidosis cutis et mucosae. Virchows Arch. Path. Anat. 1929;273:285–319
  2. Lapiere CM. Lipoid proteinosis. In:  Fitzpatrick TB,  Eisen AZ,  Wolff K,  Freedberg IM,  Austen KF editor. Dermatology in General Medicine. vol. II:New York: McGraw Hill; 1993;p. 1937–1940
  3. Hamada T. Lipoid proteinosis. Clin. Exp. Dermatol. 2002;27:624–629
  4. Bozdag KE, Gul Y, Araman A. Lipoid proteinosis. Int. J. Dermatol. 2000;39:203–204
  5. Ramsay ML, Tschen JA, Wolf JE. Lipoid proteinosis. Int. J. Dermatol. 1985;24:230–232
  6. Hofer PA. Urbach–Wiethe disease (lipoglycoproteinosis; lipoid proteinosis; hyalinosis cutis et mucosae). A review. Acta Derm. Venereol. Suppl. (Stockh.). 1973;53:1–52
  7. Disdier P, Harle JR, Andrac L, Swiader L, Weiller PJ. Specific xerostomia during Urbach–Wiethe disease. Dermatology. 1994;188:50–51
  8. Aroni K, Lazaris AC, Papadimitriou K, Paraskevakou H, Davaris PS. Lipoid proteinosis of the oral mucosa: case report and review of the literature. Pathol. Res. Pract. 1998;194:855–859
  9. Caplan RM. Visceral involvement in lipoid proteinosis. Arch. Dermatol. 1967;95:149–155
  10. Harper JI, Duguid KP, Staughton RC, Moffat DA. Oropharyngeal and laryngeal lesions in lipoid proteinosis. J. Laryngol. Otol. 1983;97:877–880
  11. Hamada T, McLean WH, Ramsay M, Ashton GH, Nanda A, Jenkins T, et al. Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). Hum. Mol. Genet. 2002;11:833–840
  12. Wong CK, Lin CS. Remarkable response of lipoid proteinosis to oral dimethyl sulphoxide. Br. J. Dermatol. 1988;119:541–544
  13. Dowlati A, Dowlati Y, Mausauri P, et al. Lipoid proteinosis and its response to etretinate therapy. In:  Pierard GE,  Pierard-Franchimont C editor. The Dermis: From Biology to Diseases. Paris: Monographies Dermatopathologiques Liegoises; 1989;p. 135–142
  14. Rosenthal G, Lifshitz T, Monos T, Kachco L, Argov S. Carbon dioxide laser treatment for lipoid proteinosis (Urbach–Wiethe syndrome) involving the eyelids. Br. J. Ophthalmol. 1997;81:253–254
  15. Haneke E, Hornstein OP, Meisel-Stosiek M, Steiner W. Hyalinosis cutis et mucosae in siblings. Hum. Genet. 1984;68:342–345

PII: S1871-4048(05)00002-X

doi:10.1016/j.pedex.2005.10.001

International Journal of Pediatric Otorhinolaryngology Extra
Volume 1, Issue 1 , Pages 1-4, March 2006

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