Successful Use of Acitretin in an Indian Child with Lipoid Proteinosis : Indian Journal of Paediatric Dermatology

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Case Report

Successful Use of Acitretin in an Indian Child with Lipoid Proteinosis

Kote, Shraddha P.; Chopkar, Apoorva Dhananjay; Supekar, Bhagyashree Babanrao; Mukhi, Jayesh Ishwardas

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Indian Journal of Paediatric Dermatology 23(3):p 238-241, Jul–Sep 2022. | DOI: 10.4103/ijpd.ijpd_95_21
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Lipoid proteinosis, also known as “Urbach[FIGURE DASH]Wiethe” disease and hyalinosis cutis et mucosae, is a rare disorder resulting in a multitude of clinical manifestations. It is due to mutation of the ECM1 gene that encodes a glycoprotein known as extracellular matrix protein 1.[1] More than 300 cases are published worldwide, but very few cases have been confirmed genetically, especially from the Indian subcontinent.[2]

Case Report

A 7-year-old boy, born of nonconsanguineous marriage, presented to us with recurrent spontaneous blistering and raw areas over both elbows, upper and lower back, and anterior trunk from 4 years of age. He also complained of recurrent oral ulceration and reduced mouth opening for 3 years. On inquiry, the mother told about hoarseness of voice in the child from 8 months of age; however, she denied a history of hoarse cry at birth. There was no history of any allergies, medical or surgical illness, or any treatment taken in the past. The child had no history of seizures, cognitive or behavioral impairment, stridor, respiratory difficulties, and dysphagia. There was no history of photosensitivity and the lesions did not have a predilection for sun-exposed areas or trauma-prone sites. None of the family members were affected. The immunization schedule was fully completed till date for his age. He was moderately nourished. Cutaneous examination revealed waxy appearance of facial skin [Figure 1a], multiple residual atrophic hypopigmented and hyperpigmented patches over the lower back [Figure 1b], and bilateral shoulders secondary to blistering [Figure 1c]. Most of the erosions healed with a combination of hypo or hyperpigmentation and atrophy. Hyperpigmented verrucous plaques were present over bilateral elbows [Figure 1d] and knees. On mucosal examination, skin-colored papules were present over bilateral angles of mouth associated with reduced mouth opening [Figure 2a]. Multiple hyperpigmented patches (healed ulcers) were present over hard palate [Figure 2b]. The dorsum of the tongue was studded with multiple white-colored papules [Figure 2c]. It was enlarged, firm in consistency with restriction in protrusion [Figure 2d]. There was no xerostomia. Multiple white beaded papules (moniliform blepharosis) were present over bilateral eyelid margins [Figure 3a]. The scalp examination showed multiple patches of scarring alopecia [Figure 3b]. Ophthalmological examination revealed myopia in both eyes. Direct laryngoscopy depicted bulky arytenoids and fleshy deposits over vocal cords with restricted movement. Based on the clinical examination, lipoid proteinosis, erythropoietic protoporphyria, and epidermolysis bullosa (EB) were considered as diagnostic possibilities. Routine laboratory investigations including lipid profile were within normal limits. Computed tomography scan of the head was normal. Biopsy taken from the raised plaque over buccal mucosa showed irregular acanthosis, mild spongiosis, and Periodic Acid[FIGURE DASH]Schiff-positive hyaline material deposition around proliferating blood vessels in dermis suggestive of lipoid proteinosis [Figure 4a-d]. Based on the aforementioned findings, a diagnosis of lipoid proteinosis was reached. Electron microscopy and genetic mutation analysis were not done due to financial constraints. He was started on acitretin at a dose of 25 mg alternate day and an emollient-containing urea and lactic acid on the verrucous plaques over the elbows. There was moderate resolution in hyperkeratotic plaques over elbows [Figure 5a] and knees and papules over the dorsum of the tongue as well as improvement in mouth restriction (from two fingers to three fingers) [Figure 5b] after 4 months of therapy with acitretin. There was a mild resolution in beaded papules over bilateral eyelid margins [Figure 5c and d] after 4 months of acitretin and mild improvement in hoarseness of voice after 7 months of acitretin therapy. No new skin and mucosal lesions were observed during the course of treatment. There were no hematological and cutaneous side effects during treatment. The patient was managed with maintenance dose of acitretin, 25 mg alternate day for 9 months, and regular use of emollient containing urea and lactic acid, during which no relapse was observed. The patient was counseled regarding the prognosis and regular monthly follow-up thereafter, but unfortunately, he was lost to follow-up.

Figure 1:
Waxy appearance of facial skin (a). Atrophic hypopigmented and hyperpigmented patches over the lower back (b). left shoulder (c). Hyperpigmented verrucous plaques over bilateral Elbows (d)
Figure 2:
Skin-colored papules over bilateral angles of mouth with reduced mouth opening (a). Hyperpigmented patches (healed ulcers) over hard palate (b). The dorsum of the tongue showed multiple white papules (c). Firm, enlarged tongue with restriction in protrusion (d)
Figure 3:
Bilateral eyelid margins showed white beaded papules (moniliform blepharosis) (a). Scarring alopecia present over the scalp (b)
Figure 4:
Histopathology from oral ulcers revealed acanthotic epidermis (yellow arrow) and eosinophilic pink extracellular material in dermis (black arrow) (H and E, ×4:a and ×40:b). Deposition of Periodic Acid[FIGURE DASH]Schiff-positive hyaline material around blood vessels (black arrow) (Periodic Acid[FIGURE DASH]Schiff stain, ×10:c and ×40:d)
Figure 5:
Moderate resolution in hyperkeratotic plaques over elbows (a) and papules over the dorsum of the tongue and improvement in mouth restriction (two fingers to three fingers) (b). Mild resolution of beaded papules over bilateral eyelid margin before (c). And after (d) acitretin therapy


Lipoid proteinosis (Urbach[FIGURE DASH]Wiethe disease, hyalinosis cutis et mucosae) is a rare autosomal recessive disorder first described in 1929 by Urbach and Wiethe.[2] It is characterized by deposition of amorphous hyaline material with a glycoprotein constitution in the skin, mucous membranes, and internal organs. It usually presents in early infancy with hoarseness of voice due to infiltration of vocal cords, as was seen in our patient. It is followed by the appearance of recurrent blood or pus-filled vesicles, bullae, macules, papules, and skin-colored nodules, which may coalesce resulting in diffuse thickening of the skin and mucous membrane.[3] Our patient also had history of bullae formations which resolved with diffuse skin thickening. Scalp infiltration gives rise to patchy or diffuse alopecia. Oral ulcers have also been reported.[4] Bead-like pearly papules over the upper and lower eyelid margins (moniliform blepharosis) are the characteristic sign of lipoid proteinosis.[5] Our patient had myopia in addition to other findings of lipoid proteinosis. Erythropoietic protoporphyria, EB should be considered in the closest differential diagnosis of lipoid proteinosis. Erythropoietic protoporphyria patients may show similar skin symptoms, but they lack oral lesions and the skin lesions are distributed over sun-exposed parts. EB is characterized by skin fragility, resulting in blister formation predominantly over trauma-prone sites following mechanical trauma or friction. No curative therapy is available for lipoid proteinosis as of now. However, several treatment modalities have been tried with variable outcomes, including oral dimethyl sulfoxide, steroids, d-penicillamine, retinoids, intralesional heparin, chemical peeling, dermabrasion, and resurfacing with fractional CO2 laser for cutaneous lesions and CO2 laser ablation of the eyelid and vocal cord lesions.[6] Oral acitretin has also been tried with favorable results in the literature in the dose ranging from 0.3 to 0.5 mg/kg/day, as depicted in Table 1. From the various studies, it is evident that acitretin has much more favorable effect on hoarseness of voice as compared to skin lesions. The rationale for using acitretin in the treatment of lipoid proteinosis underlies its inhibitory effects on collagen production and thereby decreasing the hyaline material deposition in dermis and restoring the basement membrane.[8] In our case, excellent response was observed after 7 months of therapy in the form of decrease in hyperkeratotic plaques over elbows and knees and improvement in hoarseness of voice. Our report demonstrated the possible role of acitretin in the treatment of both mucosal and cutaneous lesions of lipoid proteinosis. There is paucity of literature on lipoid proteinosis and its management from India. Thus, we report the case of lipoid proteinosis in a 7 year old boy treated favorably with oral acitretin.

Table 1:
Literature review describing response of acitretin in lipoid proteinosis

Declaration of consent

The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s)/guardian(s) of the patient. In the form, the parent(s)/guardian(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


I express my thanks for providing histopathology images to Dr. Dharitri Bhat, Associate Professor, Department of Pathology, Government Medical College Nagpur.[12]


1. Chan I, Liu L, Hamada T, Sethuraman G, McGrath JA. The molecular basis of lipoid proteinosis: Mutations in extracellular matrix protein 1 Exp Dermatol. 2007;16:881–90
2. Srinivas SM, Maganthi M, Chandrasekaran PJ, Gowdra A, Palany R. Clinical and molecular characterization of lipoid proteinosis in three Indian families Indian J of Paediatr Dermatol. 2020;21:167–73
3. 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;11:833–40
4. Sabater-Abad J, Matellanes-Palacios M, Pont-Sanjuan V, Miquel-Miquel J, Navarro-Conde P, Gimeno-Carpio E. Oral ulcer – A disabling manifestation in a patient with lipoid proteinosis JAMA Dermatol. 2019;155:977–9
5. Di Giandomenico S, Masi R, Cassandrini D, El-Hachem M, De Vito R, Bruno C, et al Lipoid proteinosis: Case report and review of the literature Acta Otorhinolaryngol Ital. 2006;26:162–7
6. Gündüz O, Sahiner N, Atasoy P, Senyücel C. Acitretin treatment for lipoid proteinosis Case Rep Dermatol Med. 2012;2012:324506
7. Desmet S, Devos SA, Chan I, Hamada T, Dhooge I, McGrath JA, et al Clinical and molecular abnormalities in lipoid proteinosis Eur J Dermatol. 2005;15:344–6
8. Toosi S, Ehsani AH. Treatment of lipoid proteinosis with acitretin: A case report J Eur Acad Dermatol Venereol. 2009;23:482–3
9. Akoglu G, Karaduman A, Ergin S, Erkin G, Gokoz O, Unal OF, et al Clinical and histopathological response to acitretin therapy in lipoid proteinosis J Dermatolog Treat. 2011;22:178–83
10. Bakry OA, Samaka RM, Houla NS, Basha MA. Two Egyptian cases of lipoid proteinosis successfully treated with acitretin J Dermatol Case Rep. 2014;8:29–34
11. Luo XY, Li Q, Tan Q, Yang H, Xiang J, Miao JK, et al Treatment of lipoid proteinosis with acitretin in two patients from two unrelated Chinese families with novel nonsense mutations of the ECM1 gene J Dermatol. 2016;43:804–7
12. Carnevale C, Castiglia D, Diociaiuti A, Proto V, Giancristoforo S, Boldrini R, et al Lipoid proteinosis: A previously unrecognized mutation and therapeutic response to acitretin Acta Derm Venereol. 2017;97:1249–51

Acitretin; ECM1; hyaline material; lipoid proteinosis; moniliform blepharosis

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