|Year : 2017 | Volume
| Issue : 3 | Page : 166-168
Lipoid proteinosis: A rare congenital genodermatosis
Mitali Madhumita Rath, Pranita Mohanty
Department of Pathology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
|Date of Web Publication||25-Sep-2017|
Mitali Madhumita Rath
Department of Pathology, IMS and SUM Hospital, Bhubaneswar, Odisha
Source of Support: None, Conflict of Interest: None
Lipoid proteinosis or Urbach–Wiethe disease is a very rare autosomal recessive disease. The term was first coined by Urbach. This disorder is characterized by intercellular deposition of periodic-acid Schiff-positive amorphous hyaline material in the skin, mucosa, and viscera. Fewer than 300 cases have been reported in the literature till date. Characteristic skin lesions include multiple brown atrophic scars over the face and distal extremities, beaded papules over the margins of the eyelids, and verrucous nodules over the friction bearing areas such as elbows, knees, and buttocks. The overall prognosis is good. There is no definitive treatment. We present a case of this rare disorder with relevant review of the literature.
Keywords: Autosomal recessive disease, genodermatois, lipoid proteinosis, periodic-acid Schiff
|How to cite this article:|
Rath MM, Mohanty P. Lipoid proteinosis: A rare congenital genodermatosis. J NTR Univ Health Sci 2017;6:166-8
| Introduction|| |
Lipoid proteinosis is a rare congenital genodermatosis with autosomal recessive inheritance usually presenting with mucocutaneous lesions starting since birth. It is also known as hyalinosis cutis et mucosae or Urbach–Wiethe disease. The term lipoid proteinosis was first coined by Urbach. Fewer than 300 cases of lipoid proteinosis have been reported in the literature till date. Hence, the actual data about incidence and prevalence is not built up. No definitive age, sex, or race predilections exist. This disorder is characterized by intercellular deposition of periodic-acid Schiff (PAS)-positive amorphous hyaline material in the skin, mucosa, and viscera. Recently, it has been shown that it is caused by mutations in the extracellular matrix protein 1 gene (ECM1 gene).
Here, we report a case of lipoid proteinosis in a 28-year-old male patient with hoarseness of voice, beaded papules over the palpebral margins of the eyelids, and hyperkeratosis of the elbows and knees, which was diagnosed clinically and was confirmed by histopatholgy.
| Case Report|| |
A 28-year-old male reported to the outpatient department of dermatology, STD, and leprosy of our institute with chief complaints of progressive skin and mucous membrane changes since childhood. The patient had developed hoarseness of voice since 2 years of age. He also had restricted tongue movements and was unable to protrude his tongue beyond the lip margin. Since the past 8 years, his eyelids had become thickened, beaded, and irregular. The patient also complained of yellowish waxy scarring of the skin over the face and trunk since he was 7 years old. There was no history of convulsions or any neuropsychiatric disturbances or visual impairment.
On physical examination, multiple, hyperpigmented, and verrucous plaques were present on both elbows and knees. Frenulum of the tongue was thickened causing reduced movement and an inability to protrude. He had waxy beaded papules around the eyelid margins. There was presence of acneiform scarring over his face and trunk. Systemic examination of the patient did not reveal any abnormal finding. Routine laboratory investigations including complete hemogram, urine examination, stool examination, liver function tests, kidney function tests, and thyroid function were all within normal limits.
A skin biopsy from one of the verrucous plaques on elbows was performed and the histopathological examination of the specimen revealed keratinized stratified squamous epithelium with papillomatosis, elongation of rete ridges [Figure 1], and underlying dermis showed amorphous eosinophilic deposits arranged in fascicles perpendicular to the epidermis [Figure 2], around the sweat glands, and blood vessels [Figure 3]. This material was PAS-positive and diastase resistant. It also stained positive for Alcian blue.
|Figure 1: Low power view of epidermis showing keratinized stratified squamous epithelium with papillomatosis and elongation of rete ridges, (H and E, ×100)|
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|Figure 3: Periodic-acid Schiff-positive amorphous material deposited around the sweat glands and blood vessels, ×400|
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| Discussion|| |
Lipoid proteinosis also known as Urbach–Wiethe syndrome or hyalinosis cutis et mucosae is a sporadic autosomal recessive metabolic disorder which was first described by Viennese E. Urbach and C. Wiethe in 1929. The term lipoid proteinosis was first coined by Urbach.
Till date, about 300 cases have been reported in literature. Although lipoid proteinosis has a worldwide distribution, most of the cases reported so far have been from South Africa and Central Europe., Mutations in the ECM1 gene on chromosome 1q21 resulting in dysfunctional ECM1 was introduced as the cause of lipoid proteinosis. However, the exact mechanistic correlation between genetic mutations and clinical manifestations of the disease remains unclear.
The clinical manifestations of lipoid proteinosis (LP) are protean and may vary considerably between affected individuals. The diagnosis can be established on the basis of characteristic clinical symptoms, confirmed by histopathology. The most common presentation of lipoid proteinosis is progressive hoarseness of voice which may be present at birth or early childhood due to diffuse infiltration of hyaline material in the mucous membrane of the vocal cords. Skin lesions follow hoarseness, including waxy yellow papules with generalized skin thickening on the face, trunk, flexures, and extremities. Acneiform scarring may occur predominantly on the face and trunk. Hyperkeratosis may appear in the regions exposed to mechanical friction, such as, hands, elbows, knees, buttocks, and axillae, and our patient presented with similar features. Beaded papules over the palpebral margins of the eyelids identified as “moniliform blepharosis” are pathognomonic for this disease. Eye papules were characterized in the present patient and further strengthened our suspicion of lipoid proteinosis. Hyaline deposits are seen in the cornea, conjunctiva, and retina and may even be found in the small bowel leading to intestinal bleeding. Other clinical features include epilepsy, memory loss, and neuropsychiatric abnormalities. Our patient did not have any visual or neurological manifestations of the disease.
LP is rarely a life-threatening condition in clinical practice. Infiltration of oral mucosa may lead to xerostomia and dysphagia and involvement of the pharynx and larynx may even cause respiratory distress.
Histologically lipoid proteinosis is characterized by extensive mucocutaneous deposition of amorphous eosinophilic material surrounding capillaries, sweat coils, and in the thickened papillary dermis. Focal deposits are also found in the deeper dermis. In verrucous lesions, the homogenous bundles often are oriented perpendicular to the epidermis. This hyaline material is PAS positive and diastase resistant. Staining with Alcian blue at pH 2.5 is slightly positive and is sensitive to hyaluronidase digestion. The presence of lipid is variable and likely results from adherence of lipids to glycoproteins, rather than abnormal lipid production. Ultrastructurally, there are multiple concentric rings of basement membrane around the blood vessels and irregular reduplications of lamina densa at the dermoepidermal junction. Demonstration of pathogenetic mutations in the ECM1 gene in lipoid proteinosis provides a definite means of establishing diagnosis. Mutations have been detected in all the exons of ECM1, but more than half of the mutations have occurred in exon 6 or the alternatively spliced exon 7.
The prognosis of LP patients is generally good despite the progressive nature of the disease until early adulthood. However, there is currently no effective therapy. Microlaryngoscopy and dissection of the vocal cords with excision of deposits may be performed to preserve or improve the voice. Therapeutic approaches reported in the literature include oral steroids, dimethyl sulfoxide, intralesional heparin, and Etretinate.
Hoarseness of voice since infancy, beaded papules along the margin of eyelids, inability to protrude tongue, hyperkeratotic plques on elbows, and knees along with PAS-positive diastase resistant material deposited around the blood vessels and sweat coils, revealed histologically, clinched the diagnosis of lipoid proteinosis in our case. This report will hopefully spawn further studies that will lead to early diagnosis.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]