Ultrastructural aspects of the skin in lipoid proteinosis (Urbach-Wiethe disease)

Abstract Lipoid proteinosis is a rare autosomal recessive disease, characterized by hyaline deposits of PAS-positive material in tissues due to mutations in the ECM1 gene. This study evaluated the ultrastructure of the skin of a 6-year-old child affected by this condition. The light microscopy identified PAS-positive hyaline deposits, which were more intense in the papillary dermis. Scanning electron microscopy of the dermis showed a compact papillary dermis and fibrillar deposits in the middle dermis. Transmission electron microscopy clearly showed the deposition of fibrillar material in the dermis, forming clusters adherent to elastic fibers, between the collagen bundles and the collagen fibers, and also filling up the cytoplasm of dermal fibroblasts.

Lipoid proteinosis: a rare disease in pediatric dentistry

Abstract This report describes the diagnostic process of a rare disorder in a Brazilian female child. The patient presented initially as a 7-year-old with multiple whitish submucosal nodules of a fibrous consistency in the lower lip, but with an inconclusive pathology report. When she turned 9 years of age, she presented with exacerbation of the original clinical findings, which then involved the upper lip, buccal mucosa, tongue and lingual frenulum. In addition, dermatological lesions were noted on the child's limbs and face, as well as a hoarse voice. Histopathological examination of the buccal mucosa revealed dense connective tissue with hyaline foci, which were positive with periodic acid-Schiff (PAS) staining and resistant to diastase digestion. Clinical and histopathological findings led to the diagnosis of a rare genetic disease with fewer than 300 reported cases - lipoid proteinosis. Magnetic resonance imaging revealed calcium deposits in her amygdaloid region of the brain, and nasopharyngolaryngoscopy revealed lesions in her vocal cords. The patient currently is stable and under multidisciplinary follow-up, but no treatment has been recommended to date.

Resumo Este relato descreve o processo diagnóstico de uma doença rara em uma criança brasileira do sexo feminino. A paciente, inicialmente com 7 anos de idade, apresentava múltiplos nódulos submucosos esbranquiçados, de consistência fibrosa, no lábio inferior, mas com um laudo patológico inconclusivo. Quando completou 9 anos de idade, ela apresentou exacerbação dos achados clínicos originais, que envolveram o lábio superior, mucosa bucal, língua e frênulo lingual. Além disso, lesões dermatológicas foram observadas nos membros e no rosto da criança, assim como rouquidão. O exame histopatológico da mucosa bucal revelou tecido conjuntivo denso com focos hialinos, que foram positivos com coloração periódica com ácido-Schiff (PAS) e resistente à digestão da diástase. Os achados clínicos e histopatológicos levaram ao diagnóstico de uma doença genética rara com menos de 300 casos relatados - proteinose lipoide. A ressonância magnética revelou depósitos de cálcio em amígdala cerebral e a nasofaringolaringoscopia revelou lesões em cordas vocais. Atualmente, a paciente está estável e em acompanhamento multidisciplinar, mas nenhum tratamento foi recomendado até o momento.

Is it always blepharitis? Urbach-Wiethe syndrome (lipoid proteinosis) / É sempre blefarite? Síndrome de Urbach-Wiethe (proteinose lipóide)

ABSTRACT A 12-year-old girl presented with recurrent crusty debris and dandruff at the base of both eyelashes despite having completed different medical treatments. She had had a hoarse voice since her early childhood. Upon anterior segment examination of the eyes, we found yellow-white, bead-like papules on the margins of the eyelids. An otolaryngologist detected multiple nodules on the vocal cords and buccal mucosa. Ultrasonography revealed salivary stones in the main parotid ducts. And a dermatological examination revealed thickened skin lesions on the elbows and knees with a biopsy showing histopathological findings of lipoid proteinosis. We diagnosed the patients as having Urbach-Wiethe syndrome or lipoid proteinosis, a rare autosomal recessive multisystem disorder with variable manifestations vary that difficult the diagnosis. The ocular manifestations are not well known among ophthalmologists, but the typical lid lesions are pathognomonic and ophthalmologists should be aware of this presentation to identify patients with Urbach-Wiethe syndrome.

RESUMO Uma menina de 12 anos apresentava restos crostosos e caspa recorrente na base de ambos os cílios, apesar de ter completado diferentes tratamentos médicos. Ela tinha uma voz rouca desde a infância. No exame do segmento anterior dos olhos, encontramos pápulas amarelo-esbranquiçadas nas margens das pálpebras. Um otorrinolaringologista detectou múltiplos nódulos nas cordas vocais e na mucosa bucal. A ultrassonografia revelou cálculos salivares nos principais ductos parotídeos. Um exame dermatológico revelou lesões cutâneas espessas nos cotovelos e joelhos com uma biópsia mostrando os achados histopatológicos de proteinose lipoide. Diagnosticamos os pacientes da síndrome de Urbach-Wiethe ou proteinose lipoide, um distúrbio multissistêmico autossômico recessivo raro, com manifestações variáveis, que dificultam o diagnóstico. Manifestações oculares não são bem conhecidas entre oftalmologistas, mas as lesões típicas da pálpebra são patognomônicas e os oftalmologistas devem estar atentos a essa apresentação para identificar pacientes com síndrome de Urbach-Wiethe.

Clinical, dermoscopy and histopathological findings in a case of lipoid proteinosis

Introduction@#Lipoid proteinosis is a rare autosomal recessive genodermatosis with only approximately 300 cases reported worldwide. This condition is due to the loss of function mutation of the ECM1 gene which encodes for extracellular matrix protein 1 (ECM1), a secretory protein that promotes angiogenesis and is a negative regulator of endochondral bone formation.@*Case summary@#We report a case of a 23-year-old male who presented with chronic recurrent verrucous and waxy lesions on the face and body, diffuse alopecia of the scalp, and hoarseness of voice. Lesions heal leaving scars. Dermoscopy of the eyelid margins show white to yellowish clods with accentuated brownish halo. Lesions on the nape show multiple follicular symmetric whitish-yellow clods with brownish halo and well-defined borders. Lesions on the elbows show a reticular pattern with white clods and diffusely distributed brown dots. Histopathology shows basket-woven stratum corneum, spongiosis of the epidermis with vacuolar alteration, and formation of clefts in the basal cell layer. The papillary dermis shows hyaline material which also surrounds the blood vessel and the adnexal structures. There is mild superficial and mid dermal perivascular inflammatory infiltrate of lymphocytes. PAS highlights eosinophilic material in the papillary dermis which also surrounds the blood vessels and the adnexal structures. Alcian blue staining reveals positive staining for hyaline deposits.@*Conclusion@#This report highlights the importance to recognize the clinical, dermoscopic and histopathological findings of lipoid proteinosis.

Esophageal aperistalsis in a patient with lipoid proteinosis

Lipoid proteinosis is a rare disorder with autosomal recessive inheritance, characterized by progressive deposition of hyaline material in the skin, mucous membrane, and different organs of the body, resulting in a multitude of clinical manifestations. A 34-year-old woman presented with hoarseness, dysphagia, eyelid beeding, and acneiform scars on the facial skin and extremities. The patient was diagnosed clinically as having lipoid proteinosis, which was confirmed by laryngeal biopsy. The objective of the present report is to describe this rare entity. This case report also illustrates that lipoid proteinosis may show protean clinical features and yet may remain undiagnosed for many years

Pentoxifilina como tratamiento efectivo de la lipoidoproteinosis / Pentoxifylline as an effective treatment of lipoidoproteinosis

La lipoido proteinosis es una enfermedad rara, que ocurre por un defecto en el gen que codifica la proteína de la matriz extracelular 1 (ECM1). Estogenera un aumento del colágeno tipo IV, que resulta en depósitos de material hialino anómalo en la dermis y otros tejidos. Actualmente no hay terapias curativas y los múltiples tratamientos utilizados han tenido resultados variables y efectos adversos relevantes.La pentoxifilina es un fármaco que inhibe al factor de crecimiento transformante beta (TGF-beta) y así, regula la producción de colágeno por los fibroblastos. Se ha empleado con éxito en casos de fibrosis renal, hepática y pulmonar y luego de la radioterapia. Se presenta este caso que constituye la primera comunicación de lipoidoproteinosis tratada con pentoxifilina, en el que se evidenció una mejoría clínica, ecográfica y laringoscópica.

Lipoid proteinosisis a rare disease, causedby a defect in the gene encoding the extracellular matrix protein 1 (ECM1), that leads to an increased of collagen type IV, resulting in abnormal deposits of hyaline material in the dermis and other tissues. Currently, there are no curative therapies; several ones have been used with varied results and adverse effects. Pentoxifylline is a drug with inhibitory effect on TGF-beta, thus regulates collagen production by fibroblasts. It has been successfully used in renal, liver and lung transplant and after radiotherapy fibrosis. We present this case because it is the first report of lipoid proteinosis treated with pentoxifylline; with demonstrated clinical, sonographic and laryngoscopic improvement.

Lipoid proteinosis in two Indian brothers - a case report from South Bengal

Lipoid proteinosis is a rare autosomal recessive disorder with variable phenotype, caused by defect in extracellular matrix protein-1 and is characterized by deposition of periodic acid-Schiff-positive, diastase resistant material in skin, mucous membrane and internal organs. There are only few reports regarding lipoid proteinosis in literature and in this part of the world. Here, we report a case of lipoid proteinosis in a 29-year-old male with positive family history and widespread distribution involving skin and internal organs. Histopathological finding was consistent with clinical diagnosis of lipoid proteinosis

Lipoidoproteinosis: relato de un caso / Lipoidoproteinosis: case report

La lipoidoproteinosis, es una enfermedad hereditaria autosómica recesiva, de presentación infrecuente, con manifestaciones clínicas características desde etapas tempranas de la vida y hallazgos histopatológicosdados por un depósito de lípidos y proteínas anormales de tipo hialino en diferentes tejidos.Presentamos el caso de una mujer de 18 años, valorada en nuestra consulta por la aparición de llanto y habla disfónica, asociados a lesiones cutáneas y mucosas, con diagnóstico clínico e histopatológico de lipoidoproteinosis, con buena respuesta terapéutica al dimetil-sulfóxido.Resaltamos que se trata de un caso de infrecuente presentación, cuyo enfoque temprano y multidisciplinario son esenciales para su pronóstico...

Lipoidoproteinosis is a rare autosomal recessive hereditary disease, with typical clinical features since first years of life and histopathological findings of deposits of lipids and abnormal hyaline-like proteins in different tissues. We report the case of an 18 year-old woman, examined at our clinic for the presence of dysphonic weeping and speech, associated with cutaneous and mucosal lesions with clinical and histopathological diagnosis of lipoidoproteinosis, that presented a good therapeutic response to dimethyl sulfoxide. We emphasize that this is a case of rare presentation, whose early and multidisciplinary approach is essential for prognosis...

Lipoproteinoses e otorrinolaringologia / Lipoid proteinosis and otolaryngology

A lipoproteinose é uma doença de herança autossômica recessiva que se caracteriza pela deposição de material hialino difuso em pele, mucosas, parede de vasos sanguíneos, entre outros órgãos. É decorrente de mutações em um gene que codifica a glicoproteína 1 da matriz extracelular (ECM1), sendo que diferentes mutações podem cursar com alterações epiteliais distintas. A doença tem um curso crônico e benigno, sendo as principais alterações observadas: lesões na pele de apresentação precoce e aspectos variados, blefarose moniliforme, calcificações intracranianas com manifestações neuropsiquiátricas, sintomas de pirose e empachamento associados a nodulações em todo TGI. Dentre as manifestações otorrinolaringológicas a principal é a disfonia, que geralmente se inicia nos primeiros anos de vida, podendo apresentar irregularidades na superfície das pregas vocais e espessamento da região interaritenoidea. O diagnóstico é feito pela clínica associada aos achados clássicos da biópsia ou mapeamento do gene ECM1. O tratamento é direcionado para os sinais e sintomas dos órgãos acometidos e o principal impacto da doença é na qualidade de vida, por seus prejuízos estéticos e funcionais. Este artigo propõe uma revisão da literatura, apoiada na descrição detalhada de quatro casos clínicos, com enfoque nas manifestações otorrinolaringológicas.

Oral manifestations of lipoid proteinosis: a case report and literature review

Lipoid proteinosis is an uncommon autosomal recessive metabolic disorder that presents in early life with hoarseness and pox-like acneiform scars involving the skin and mucous membranes. Previous studies have attributed the prevalence of lipoid proteinosis to consanguineous parents. This paper reports a classical case of lipoid proteinosis with oral manifestations but without a history of consanguinity

Enfermedades hereditarias de la dermis: revisión de la literatura / Hereditary diseases of the dermis: literature review

Nuestra piel tiene propiedades de elasticidad y firmeza, dada por las fibras del tejido conectivo ubicadas en la dermis. La elasticidad está dada principalmente por pequeñas fibraselásticas compuestas de elastina, mientras que la firmeza se explica por las redes de fibrillas de colágeno tipo I, III y V. La relevancia de estos componentes de la matriz extracelular, junto con otras fibras, como fibrilina y fibulina, se ha reflejado en el reconocimiento de diferentes enfermedades hereditarias causadas por mutaciones en estas proteínas. Muchas de éstas pueden tener características comunes, constituyendo un espectro de alteraciones, dependiendo de la proteína alterada, dando un pronóstico particular tanto en morbilidad y mortalidad. En esta revisión se desarrollarán las principales patologías de la dermis de importancia en dermatología.

Our skin is flexible and firm due to the fibers of the connective tissue in the dermis. Flexibility is mainly given by little elastic elastine fibers, meanwhile firmness is expressed by fibers networks made of collagen type I, III and V. The importance given to these components, including other fibers like fibrillin and fibulin in the extracellular matrix has been displayed in the recognition of different hereditary diseases caused by mutations in these proteins. Many of them have common characteristics, that build a wide spectrum of disorders depending on the altered protein, and give a particular prognostic in morbidity as well as in mortality. The main pathologies of the dermis with an importance in dermatology will be considered in this review.

Urbach-Wiethe disease (lipoid proteinosis).

Lipoid proteinosis is a rare autosomal recessive disorder of variable severity that may involve the skin, mucous membranes of the upper respiratory tract and internal organs that may display different clinical manifestations based on the site of involvement. A 34-year-old male patient was admitted to our hospital with a complaint of hoarseness present since childhood but had worsened in recent years. A dermatological examination revealed light brown papillomatous skin lesions on the dorsum of both hands and elbows present for a long duration. Endoscopic examination of the larynx revealed widespread mucosal thickening and irregularity. Microscopic examination revealed acid Schiff (PAS) positive, Congo red negative eosinophilic hyaline material deposits in the dermis and submucosal regions. The final diagnosis was lipoid proteinosis with skin and larynx involvement. This typical case has been reported to draw attention to the fact that lipoid proteinosis should be included in the differential diagnosis of patients presenting with hoarseness in childhood.

Lipoidoproteinosis en otorrinolaringología: presentación de un caso / Lipoidoproteinosis in otolaryngology: case report

La lipoidoproteinosis es una enfermedad de muy baja frecuencia de aparición y con pocos casos reportados en la literatura, con manifestaciones otorrinolaringológicas de importancia para la especialidad. A continuación se presenta el reporte de un caso con sus manifestaciones otorrinolaringológicas …

The lipoid proteinosis is a disease of very low frequency of occurrence with few cases reported in the literature and ENT manifestations of importance to the specialty. Below is the report of a case with otolaryngological manifestations. The following is the report of a case with ENT manifestations …

Lipoid proteinosis in two Iranian sisters: a case report and review of literature

Lipoid proteinosis is a rare autosomal recessive disorder which may be seen within a family very occasionally. Herein, we report lipoid proteinosis in two sisters characterized by verrucous lesions and hoarseness of voice, dysphagia and multiple beaded papules along the margins of their eyelids, fissured lips and thick ferenulum

Manifestation and treatment of lipoid proteinosis in larynx / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the manifestation, characteristics and treatment of lipoid proteinosis (LP) in larynx.</p><p><b>METHODS</b>Sixteen cases of LP with hoarseness as the first sign were reported. The onset was in the newborn period in 10 cases. The upper eyelids were infiltrated in all cases, 13 of them reported an age of onset older than 6 - 8 years. The laryngeal behaviors and its treatment, multisystem manifestations, and characteristics of histopathology were evaluated.</p><p><b>RESULTS</b>One patient had moderate hoarseness, and the others had severe hoarseness. Videolaryngoscopy revealed thickening of the interarytenoid region and irregularities along the rims and the surface of the vocal folds due to yellowish papules. Oral tissues showed yellow-white infiltrates in 13 cases (81.3%). Whitish moniliform papules on the upper eyelids were found in all cases. Pock-like or acneiform scars were particularly evident on the face and the limbs in 14 cases (87.5%). Histologically, it was characterized by deposition of hyaline material in the submucosa and dermis of the eyelid or larynx with periodic acid-Schiff-positive and Congo red stain-negative. Eight patients underwent microlaryngosurgery for the excision of deposits in the vocal folds. The vocal function was significantly improved after surgery.</p><p><b>CONCLUSIONS</b>One of the most common features of lipoid proteinosis is hoarseness since infancy with laryngeal involvement. LP patients also display skin or mucosa infiltration of multiple systems. Microlaryngosurgical excision of the deposits in the vocal fold could improve the voice.</p>

Lipoidoproteinose: relato de caso / Lipoidproteinosis: case report

JUSTIFICATIVA E OBJETIVOS: Trata-se de uma doençarara com envolvimento multissistêmico. O objetivo desteestudo foi apresentar um caso de lipoidoproteinose com achados clínicos típicos e exuberantes. RELATO DO CASO: Paciente do sexo masculino, 27 anos, branco, com rouquidão desde o início da fala e surgimento de lesões orais infiltradas durante a infância. Relata aparecimento de lesões bolhosas difusas pelo tegumento até os 15 anos de idade, que regrediram deixando cicatrizes. Histórico de crises convulsivas. O exame demonstrou pele de coloração amarelada e infiltrada na face e regiões de dobras, pápulas amareladas nas bordas palpebrais, hiperceratose palmar transgressiva, lesões ictiosiformes nos membros inferiores, lesões hipocrômicas varioliformes no tronco, placas hiperceratóticas nos joelhos e cavidade oral infiltrada. O estudo histopatológico da pele foi compatível com lipoidoproteinose. CONCLUSÃO: A lipoidoproteinose é uma doença genética rara, cujas lesões clássicas envolvem pele, mucosa oral, faringe, laringe, mas que pode também apresentar amplo comprometimento sistêmico, com infiltração de órgãos internos por material hialino, sendo de interesse para várias especialidades médicas.

Lipoidoproteinose / Lipoid proteinosis

OBJETIVO: Apresentar as características clínicas, tratamento cirúrgico e achado histológico de um caso de lipoidoproteinose. DESCRIÇÃO DO CASO: Criança do sexo masculino, cinco anos de idade, branco, que procurou atendimento odontológico na Universidade. A mãe da criança relatou presença de intensa halitose e dificuldade na alimentação e higienização bucal, decorrentes de crescimento gengival generalizado nos arcos dentários superior e inferior. No exame clínico, verificaram-se comprometimento funcional e estético generalizado (rouquidão, artralgia bilateral no joelho e tornozelo, lesões tumorais nas orelhas, entre outros), além de extensa hiperplasia gengival em ambos os arcos dentários. Optou-se pelo tratamento cirúrgico, com remoção do tecido hiperplásico e exodontia de todos os dentes decíduos e de dois permanentes. O exame histopatológico da peça cirúrgica confirmou o diagnóstico de lipoidoproteinose. COMENTÁRIOS: A lipoidoproteinose é uma doença rara caracterizada pela deposição da substância hialina na pele, membranas mucosas e nos órgãos internos. Os sinais que podem surgir após o nascimento, são: rouquidão; lesões pápulo-nodulares na cabeça, pescoço e membros; lesões papulares amareladas nas margens das pálpebras. O curso desta doença é benigno e crônico.

OBJECTIVE: Report clinical characteristics, histological findings and treatment of a patient with lipoid proteinosis. CASE DESCRIPTION: Five year-old male patient was assisted in the university clinic for dental treatment. The mother reported the presence of intense halitosis and difficulties for feeding and oral hygiene due to extensive gingival hyperplasia on the maxillary and mandibular arches. Clinical examination revealed generalized functional and esthetic involvement, including hoarseness; bilateral knee and ankle arthralgia; tumoral lesions on the ears and gingival hyperplasia throughout the extent of both dental arches. The surgical treatment removed the hyperplastic tissue and all deciduous teeth, as well as two permanents teeth. Histopathological examination of the specimen confirmed the diagnosis of lipoid proteinosis. COMMENTS: Lipoid proteinosis is a rare disorder characterized by progressive deposition of hyaline material in the skin, mucous membranes and organs. Clinical signs appear after birth and are characterized by hoarseness, papulonodular lesions on the head, neck and limbs and yellowish papules on the eyelid margins, among others. The disease has a benign and chronic evolution.