Advances in treatment for lipoid proteinosis (Urbach-Wiethe disease): a case report and systematic review.

BACKGROUND: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis, caused by mutations in the ECM1 gene. This results in the deposition of periodic acid-Schiff (PAS)-positive, hyaline-like material on the skin, mucosae and internal organs. OBJECTIVES: To present a case report of LP and a systematic review to synthesize the scientific literature on the management of this uncommon and frequently missed diagnosis. METHODS: We present a case report of a 48-year-old man with LP who exhibited significant improvement after oral acitretin therapy. To address the lack of large case-control studies on LP treatment, we performed a systematic review of the literature following the PRISMA 2020 criteria. The search was conducted in PubMed, Web of Science, Cochrane and Scopus databases from inception until June 2023. To assess the methodological quality of case reports and case series, we used the Joanna Briggs Collaboration critical appraisal tool. RESULTS: We included 25 studies that met eligibility criteria. Data from 44 patients with a histopathologically confirmed diagnosis were analysed. Treatment ranged from systemic therapies (acitretin, etretinate, dimethyl sulfoxide, corticosteroids, penicillamine) to surgical or laser procedures. Regarding methodological quality, the main discrepancies arose in the reporting of participant characteristics and treatment interventions. CONCLUSIONS: Low-dose oral acitretin could have potential in managing LP, exhibiting fewer side-effects compared with other therapeutic agents. Further research is needed to establish more comprehensive and evidence-based treatment guidelines.

Treatment of lipoid proteinosis with acitretin in two patients from two unrelated Chinese families with novel nonsense mutations of the ECM1 gene.

Lipoid proteinosis is a rare recessive genetic disorder caused by loss-of-function mutations to chromosome 1 at 1q21, the extracellular matrix protein 1 (ECM1) gene. Two children with lipoid proteinosis were reported from two unrelated Chinese families, both manifesting with a typical hoarse voice, white acne-like atrophic lesions and scarring on the skin, and beaded papules around the eyelids. The diagnosis had been confirmed by laboratory tests, skin biopsy and laryngoscope examination. Genomic DNA sequencing was performed for both children and their family members. The two children were treated with acitretin for 6 months and followed up for 1 year. Genomic DNA sequencing of the ECM1 gene showed a novel homozygous nonsense mutation of C1522>T (p.R508X) at exon 10 in one patient, and a novel compound heterozygote for a nonsense/frame-shift combination of mutations of R281X/1596delG at exons 7 and 10 in the other patient. The symptom of hoarse voice was improved by 6-month treatment with acitretin, while there was no improvement in the skin lesions. These results demonstrated that acitretin treatment may have efficacy for some of patients with lipoid proteinosis, with superior effect on laryngeal symptoms than skin lesions. However, the conclusive therapeutic effect and underlying mechanisms remain to be further investigated.

Ocular manifestations in lipoid proteinosis: A rare clinical entity.

Lipoid proteinosis is a rare autosomal recessive genodermatosis with abnormal lipid protein complexes deposition in different parts of the body, especially in the skin and mucus membranes of the upper aerodigestive tract. Though ocular involvement in lipoid proteinosis is rare, ophthalmologists may encounter diverse ocular complications accompanying this syndrome in clinical practice. We describe a case of lipoid proteinosis involving bilateral eyelids with pathognomonic moniliform blepharosis in a 33-year-old gentleman who presented with the complaints of itching of eye lids on and off since 10 years.

Demographic, clinical, and radiologic signs and treatment responses of lipoid proteinosis patients: a 10-case series from Sanliurfa.

OBJECTIVES: Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis characterized by mucocutaneous lesions and hoarseness that develop in early childhood. This paper presents the clinical and radiologic characteristics and treatment responses of 10 LP patients from five different families. METHODS: Ten LP patients followed in our university clinic in Sanliurfa, Turkey, were evaluated. Clinical features, as well as histopathologic and radiologic findings, were analyzed. Diagnoses were established based on clinical features, with histopathologic confirmation in nine cases. The patients were started on acitretin at a dose of 0.5 mg/kg/day for six months. RESULTS: Typical cutaneous signs of LP and hoarseness of the voice were observed in all patients. No side effects associated with the drug were found during treatment. At the end of the sixth month, the cutaneous papules and plaques were diminished in seven patients. Hoarseness receded in seven patients (particularly in three), vesiculobullous lesions were reduced in three patients, and the frequency of oral ulcers decreased in three patients. In a patient with palmoplantar hyperkeratosis, lesions were found to disappear completely. CONCLUSIONS: We believe acitretin is quite effective and reliable in the treatment of cutaneous lesions and hoarseness in patients with LP.

[Hyalinosis cutis et mucosae : 5 cases from Tabarka (Tunisia)]. / La hyalinose cutanéo-muqueuse : 5 cas originaires de Tabarka (Tunisie)

BACKGROUND: Hyalinosis cutis et mucosae (HCM), is a rare autosomal recessive genodermatosis. Cutaneous features are characteristic and allow to suspect diagnosis. AIM: To report a series of HCM. METHODS: A retrospective study of all cases of HCM, diagnosed in a dermatology department over a period of 25 years (1983-2007). RESULTS: Over the considered period, 5 new cases of HCM were diagnosed. Patients were aged between 14 and 41 years. They were 3 females and 2 males. All patients were native of Tabarka (northwestern Tunisia). The age of the onset of the disease varied from neonatal period to 5 years. Hoarseness was the first clinical manifestation in all cases. Skin lesions developed between the ages of 3 and 8 years. Vesiculobullous lesions were observed in 2 patients. Moniliform blepharosis was seen in all patients. Warty and hyperkeratotic papules were observed in 3 patients. Diffuse thickening of the skin was seen in 3 patients. Lesions were primarily distributed on the face. All patients presented diffuse scars. Linear palmoplantar keratoderma was seen in one patient. Asymptomatic endocranial calcifications were noted in 4 patients. A pituitary adenoma was noted in one patient. Histopathological examination of a skin lesion revealed a typical pattern of HCM. Two patients were treated with systemic retinoids without improvement. CONCLUSION: We reported five new cases of HCM. All patients were native from Tabarka. We report also one case of linear palmar keratoderma associated with HCM. This association was not reported in the literature. Finally, the association HCM-pituitary adenoma, seen in one patient, may be fortuitous.

Clinical and histopathological response to acitretin therapy in lipoid proteinosis.

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis associated with deposition of periodic acid-Shiff (PAS)-positive hyaline material in skin, mucosa, and other tissues. LP is caused by loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1). No curative therapy is available. In this report, we describe the clinicopathological and genetic features of a Turkish LP family with four cases, and evaluate the response of acitretin therapy. Patients were presented with hoarseness and beaded eyelid papules, thickened frenulum, hyperkeratotic plaques and infiltrated warty papules and nodules. Skin biopsies revealed deposition of PAS-positive hyaline material in dermis. A homozygous nonsense mutation in exon 3 of the ECM1 gene, R53X, was detected in the family. Acitretin therapy was administered in two patients, in whom some regression and softening of skin lesions were achieved. However, no histopathological change in PAS-positive deposition could be detected. Although there is no current effective treatment for LP, acitretin may be helpful for patients, especially those who complain about hyperkeratosis.

Enfermedad de Urbach-Wiethe / Urbach-Wiethe disease

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D-penicillamine treatment for lipoid proteinosis.

Lipoid proteinosis, a rare disorder inherited in an autosomal recessive fashion, is characterized by the deposition of hyaline-like material in the skin, mucous membranes, and other tissues. Perturbation of collagen metabolism has been suggested to play an important role in the pathogenesis. No effective therapy is available for the disease. The chelating agent D-penicillamine has long been used to treat several diseases. In addition to its immunosuppressive and anti-inflammatory effects, it also impairs fibroblast proliferation and inhibits the formation of the cross-links in collagen and elastin fibers. A 13-year-old girl was clinically and histologically diagnosed with lipoid proteinosis. We treated her with 600 mg/day of D-penicillamine for 2 years. The patient had improved clinically and histopathologically by the end of this treatment. We suggest D-penicillamine as a promising agent, even in low doses, for the treatment of lipoid proteinosis.

Hemorheology and tissue oxygenation in hypertensives with lipoidoproteinosis and peripheral occlusive arterial disease (POAD) treated with sulodexide and pravastatine and evaluated with laser assisted optical rotational red cell analyzer (LORCA) and transcutaneous oxymetry.

BACKGROUND: During arterial hypertension it is often possible to find other factors like lipoidoproteinosis and peripheral arterial disease (POAD), which can accentuate blood rheological abnormalities in hypertensive subjects. A group of hypertensives with lipoidoproteinosis (LP) and POAD were therefore examined to evaluate the relationship between these factors and blood rheological disorders and, if possible, to correct it. METHODS: We studied a group of 27 hypertensives with LP and POAD (15 males and 12 females in menopause for at least 1 year, aged 48 +/- 4 years), with WHO stage I hypertension, obesity (BMI = 30 +/- 2), stage II type "a" POAD, class 2 type "b" lipoidoproteinosis (acc. to Fredrick-son's classification) and hyperfibrinogenemia. All patients received oral medication with 500 lipidic units (ULS) sulodexide a day, 20 mg pravastatin o.d. orally, and were put on a low-salt and low-calorie diet (1400 kcal/day) during a follow-up of 60 days. Blood rheology status was evaluated before and after treatment (red blood cell--RBC--deformability and aggregability) using a new computerized instrument, which uses laser rays: the laser assisted optical rotational red cell analyzer (LORCA) (acc. to Hardeman) and RBC deformability using optical microscopy under immersion (acc. to Zipursky and Forconi). Transcutaneous oxymetry was also used to evaluate tissue oxygenation. RESULTS AND CONCLUSIONS: At the end of the study a significant improvement (p < 0.01) was noted in the blood rheological patterns of peripheral perfusion and tissue oxygenation. This underlined the positive influence of sulodexide with pravastatin in improving hemorheological patterns and modulating hypercholesterolemia and hyperfibrogenemia in hypertensives with POAD II "a" and LP 2 "b" and blood rheology disorders.

Lipoid proteinosis of the oral mucosa: case report and review of the literature.

We describe a 37-year-old woman who presented with progressive mouth dryness. Physical examination revealed long-standing plaques on the face and upper limbs, papular lesions of the oral cavity and tongue firmness. A lower lip biopsy was performed. Light microscopy demonstrated accumulation of PAS-positive material around blood vessels, capillaries and salivary gland canaliculi as well as focally massive hyaline deposits in the submucosa. Immunohistochemistry revealed widespread presence of type IV collagen in the hyaline material and around thickened blood vessels. Laminin immunoreactivity was particularly strong at thickened basement membranes. The above findings were compatible with lipoid proteinosis, which is likely to involve primary perturbation of collagen metabolism and production of glycoproteins.

[Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]. / Orale DMSO-Therapie bei 3 Patienten mit Lipoidproteinose. Ergebnisse einer Langzeittherapie.

Lipoid proteinosis is a rare autosomal recessive disorder with a chronic, benign course. There is no generally accepted systemic therapy apart from the experimental oral use of dimethyl sulphoxide (DMSO) and etretinate in two single cases. We treated two sisters and an unrelated man with lipoid proteinosis with longterm oral DMSO (60 mg/kg/d). At the end of an average treatment time of 3 years, DMSO was withdrawn because it produced no beneficial effects with regard to their skin, mucosal lesions or hoarseness. Additionally, one patient showed progression of her disease with worsening hoarseness and onset of dyspnea, requiring surgical removal of vocal cord infiltrates. Three patients with lipoid proteinosis failed to show any beneficial response to long term treatment with DMSO.

Remarkable response of lipoid proteinosis to oral dimethyl sulphoxide.

We report the successful treatment of lipoid proteinosis in a 41-year-old man using oral dimethyl sulphoxide. The initial dosage was 40 mg/kg/day, which was then increased progressively to 60 mg/kg/day. After 3 years of treatment, the patient's skin lesions, hoarseness of voice and abnormal oesophageal function improved remarkably. No side-effects were noted except for a garlic-like smell on the patient's breath.