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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.78 no.6 Rio de Janeiro Nov./Dec. 2003
Lipoid proteinosis - a report of two cases*
Letícia Rathlew de LimaI; Fabiane Andrade Mulinari-BrennerII; Luciana Cristina ManfrinatoII; Ana Sílvia Dal PizolII; Sérgio Zuñeda SerafiniIII; José Fillus NetoIV
IIIAssistant Professor, Dermatology Service
IVAdjunct Professor, Anatomical Pathology Service
Lipoid proteinosis (Urbach-Wiethe disease) is a rare disorder with autosomal recessive inheritance, characterized by progressive deposition of hyaline substance in the skin, mucous membranes and internal organs. Clinically, there are papular and nodular lesions on the face, with areas of infiltration in the elbows, knees and hands; the tongue is firm and hoarseness may be present at birth. We describe two cases of this disease in the same family (brother and sister).
Lipoid proteinosis, also denominated Urbach-Wiethe disease, mucocutaneous hyalinosis, lipoidosis cutis et mucosae, lipoproteinosis and lipoglycoproteinosis, was described for the first time in 1908 by Seibenmann,1,2 but the first detailed report was made by Urbach and Wiethe in 1929.1,2,3 It is a rare recessive autosomal dermatosis, which can be congenital or precocious with onset in infancy, characterized by the progressive deposition of an amorphous hyaline substance with a glycoproteic constitution in the skin and mucous membranes (mouth, pharynx and larynx). Generalized visceral involvement has also been reported.4,5 It is characterized clinically by papular lesions, that can aggregate forming plaques with a yellowish coloration, located mainly in the face, neck and in areas subject to attrition, there is also hoarseness caused by the mucous involvement. The course of the disease is usually benign and chronic, the pathogenesis is not fully understood and treatment somewhat ineffective.1,4,5
The objective of the present work was to describe two cases of this rare entity, which has been infrequently reported, with approximately 250 cases found in the medical literature.5,6
Patient, 31 year-old man, white, married, agricultural worker, born and resident in Pitanga - Parana State.
Ever since infancy he presented hoarseness and "fragile skin", with formation of ulcers following minor traumas, which healed with difficulty. Twenty years ago papular lesions appeared in the hands, fists and elbows, with slow but progressive worsening. To date the picture is stable, though there is worsening of the lesions in the summer and with solar exposure.
He referred to several hospitalizations during childhood due to the onset of a bullous picture in the skin and oral mucous membrane. Four years previously he had developed a peptic ulcer and is taking cimetidine at a daily dose of 400mg.
Paternal great-grandfather and sister with similar skin lesions. There is no history of consanguinity.
Dermatological exam showed small coalescing hyperkeratose papules, located in the back of the hands and in the lateral faces of the fists; verrucose lesions in the elbows (Figure 1) and xerotic skin in inferior members.
Histopathological study demonstrated epidermis with compact hyperkeratose focuses, regular acanthosis and focal spongiosis. Dermis with superficial, perivascular and periannexal deposition of PAS-positive and diastase-resistant material (Figures 2 and 3).
Videolaryngoscopy, revealed a rigid, infiltrated tongue with an amyloid aspect; wall of the pharynx with irregular and granulated infiltration; body of the larynx with presence of granulations.
A slight improvement was observed following the use of 20% urea cream, twice daily.
Patient, 35 year-old woman, white, separated, works doing general services, born in Pitanga - PR and resident in Curitiba - PR.
Since birth, the parents noticed "redness in the skin". During infancy, papular and pruriginous lesions appeared in the face, neck and elbows, as well as ulcerated lesions in the oral mucous membrane. She had been using topical neomycin and oral tetracycline, without medical prescription and there had been no significant improvement of the picture.
She had suffered episodes of convulsions 23 years previously, diagnosed as epilepsy. At the time of publication she was taking 100mg/day phenobarbital.
Dermatological exam, showed multiple papular lesions, which were small and yellowish, in forehead, inferior palpebral borders (Figure 4) and, to a lesser extent, papular lesions in the neck and back of the hands.
Anatomicopathological exam of the skin showed dermis with superficial, perivascular and periannexal deposition of a PAS-positive and diastase-resistant material. Videolaryngoscopy revealed a rigid and infiltrated tongue, as well as infiltration in the body of the larynx. Computed tomography of the skull detected bilateral, gross calcifications in the paraselar area (Figure 5).
The patient was referred to the Service of Neurology for treatment of epilepsy. The cutaneous picture remains clinically stable.
Lipoid proteinosis is a rare disease with autosomal recessive inheritance, approximately 250 cases have been described in the literature, with a higher prevalence in South Africa and Sweden.5,6 It is characterized by the deposition of an amorphous hyaline material with a glycoproteic constitution in the skin, mucous membranes and internal organs. The etiopathogenesis of the lipoid proteinosis is not still completely clarified, but it seems to be related to an alteration in the synthesis and metabolism of the collagen, leading to an increase in the production of collagen types IV and V by the endothelial cells of the blood vessels, a decrease in the production of collagen types I and II, and an increase in the synthesis of a glycoproteic substance by the fibroblasts.5,7,8
Clinically, it is characterized by papular, nodular and keratose lesions with a yellowish coloration, located mainly in the face, neck and in areas submitted to mechanical trauma, such as the elbows and knees. Verrucose lesions can appear in places suffering attrition. Small lesions frequently appear in the margins of the eyelids (moniliform blepharosis); this distribution can be useful in the diagnosis.1,4,5 Usually, the initial clinical manifestation is hoarseness, due to infiltration of the larynx, which can be present from birth. In familial cases, the mother can recognize the child with this disease by its hoarse cry.6,7 The cases described here present characteristic lesions, firstly in the hands, fists and elbows, and then in the face, neck and palpebral margins; both presented hoarseness since infancy.
Other clinical manifestations are alopecia, hypohidrosis, slow ungual growth and dental abnormalities,3,5 however these alterations were not found in the presented cases.
The central nervous system can also be involved. Bilateral intracerebral calcifications are frequently found in the lipoid proteinosis and these are sometimes responsible for behavioral disturbances and epilepsy.3,9,10 In addition, generalized visceral involvement has been reported, however, since this is asymptomatic it is usually only found in the necropsy.1,4,5 In the second case, the patient presented convulsive tonicoclonic crises, computed tomography of the skull showed bilateral gross calcifications in the paraselar region.
In relation to the histopathological study, there is extensive deposition of an amorphous eosinophilic substance around the capillaries, sudoriparous glands and papillary dermis; focal deposition can be found in the profound dermis. This hyaline substance is PAS-positive and diastase-resistant. Both cases described here presented dermis with superficial, perivascular and periannexal deposition of PAS-positive and diastase-resistant material, which is characteristic of the disease.1,2,5,8
Under electron microscopy, three main alterations can be observed in the dermis: considerable thinning of the basal layer; extensive deposition of an amorphous hyaline material, predominantly in the superficial dermis and around the blood vessels, together with a significant reduction in the number and size of the collagen fibers.1,2
The differential diagnosis of this pathological entity should consider erythropoietic protoporphyria, the lesions of which are restricted to solar exposed areas and there is involvement of the mucous membranes. Other differential diagnoses are papular mucinosis, leprosy, amyloidosis and cutaneous xanthomatosis.4,11
The clinical course of lipoid proteinosis is usually benign and chronic.1,4 Regarding treatment, dermabrasion, chemical peeling and etretinate have been attempted for the cutaneous lesions but without satisfactory results.10,11 There is a report of a case in which the lesions improved following oral dimethyl sulfoxide,2 and another with long-term satisfactory results in facial lesions using a combination of surgical methods, such as dermabrasion, chemical exfoliation, blepharoplasty and brow transplant.13 Specific and effective treatments are not still available.10,11,14 The objective of this work was to underscore the importance of lipoid proteinosis as a cause of cutaneous and mucous alterations in infancy, this being of particular relevance to dermatologists, otorhinolaryngologists and pediatricians.
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Letícia Rathlew de Lima
Rua Professora Zélia Dulce de Campos Maia, 411/4
Vila Florinda Sorocaba SP 18040-580
Tel.: (15) 232-3524 / (41) 243-0562
Received in September,
22nd of 2000
Approved by the Consultive Council and accepted for publication in January, 24th of 2003
* Work done at the Dermatology Service of the Hospital de Clinicas, Federal University of Parana.