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Year : 2019  |  Volume : 3  |  Issue : 1  |  Page : 49-53

Utility of acitretin in improving quality of life in lipoid proteinosis

1 Department of Dermatology, Sion Hospital, Mumbai, Maharashtra, India
2 Department of Dermatology, Dr. Zakir Hussain Hospital, Nashik, Maharashtra, India
3 Department of ENT, Sion Hospital, Mumbai, Maharashtra, India

Date of Web Publication22-Aug-2019

Correspondence Address:
Dr. Tejas Vishwanath
OPD 16 (Department of Dermatology), New OPD Building, Sion Hospital, Mumbai - 400 022, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aiao.aiao_4_19

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Lipoid proteinosis is a rare autosomal recessive disorder, the exact incidence of which is unknown. It initially manifests as hoarseness followed by cutaneous findings, including blisters on trauma-prone sites, waxy papules, and pock-like atrophic scarring. Major morbidity in this disease is persistent hoarseness due to hyaline deposition on the vocal cords. Acitretin has recently been discovered to have a prominent role in the improvement of cutaneous manifestations and hoarseness of voice caused by this disease. We report one such case with documented improvement in voice with voice samples and direct laryngoscopic findings before and after treatment with acitretin.

Keywords: Acitretin, direct laryngoscopic, hoarseness, lipoid proteinosis

How to cite this article:
Vishwanath T, Dhurat R, Borawake S, Joshi A, Agrawal S, Ghate S. Utility of acitretin in improving quality of life in lipoid proteinosis. Ann Indian Acad Otorhinolaryngol Head Neck Surg 2019;3:49-53

How to cite this URL:
Vishwanath T, Dhurat R, Borawake S, Joshi A, Agrawal S, Ghate S. Utility of acitretin in improving quality of life in lipoid proteinosis. Ann Indian Acad Otorhinolaryngol Head Neck Surg [serial online] 2019 [cited 2020 May 29];3:49-53. Available from: http://www.aiaohns.in/text.asp?2019/3/1/49/265139

  Introduction Top

Lipoid proteinosis is an autosomal recessive genodermatosis caused by mutations in extracellular matrix protein 1 (ECM1). The first and most striking manifestation is a hoarse cry either after birth or during infancy owing to vocal cord infiltration.[1],[2]

Cutaneous manifestations occur in the 1st year of life or later in the form of skin-colored waxy papules and bullae on trauma-prone sites. Bullae resolve with characteristic disfiguring pock-like scars.[3]

Persistent hoarseness of voice (dysphonia) is major morbidity causing considerable academic and psychological morbidity. Hence, early treatment of dysphonia is essential. Many treatments have been tried for this disease, including D-penicillamine, dimethyl sulfoxide, etretinate, and carbon dioxide lasers.[3] There are a few reports on the use of acitretin for hoarseness in lipoid proteinosis with variable results. We present one such case.

  Case Report Top

A 12-year-old boy born of a nonconsanguineous marriage presented with hoarseness since birth and facial papules, plaques, and atrophic scars on the trunk and extremities. He had a history of trauma-induced vesicles and blisters on the elbows and knees before 5 years of age.

Dermatologic examination revealed yellow-tinged waxy papules [Figure 1] and [Figure 2], atrophic scars on the chin [Figure 3] and trunk and buttocks [Figure 4], and beaded papules on the upper eyelid margin-moniliform blepharitis [Figure 5]. Pock-like scars were noted on the face, trunk, and limbs. The tongue showed woody induration with reduced protrusability [Figure 6]. Direct laryngoscopic examination revealed bulky vocal cords [Figure 7] and nodules of hyaline deposition on the pharyngeal walls [Figure 8]. Histopathological examination of a 4-mm punch biopsy sample from one of the cutaneous papules revealed extensive deposition of amorphous eosinophilic material in the upper dermis [Figure 9] and surrounding the eccrine coils and capillaries [Figure 10]. This was periodic acid–Schiff positive. Grade, roughness, breathiness, asthenia, strain (GRBAS) score was calculated to be 15 (complete aphonia). Complete blood count and biochemical profile were within normal limits.
Figure 1: Yellow tinged waxy papules on the nape of the neck

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Figure 2: Waxy papules on the forehead

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Figure 3: Atrophic scars on the chin

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Figure 4: Atrophic scars on the buttocks

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Figure 5: Beaded papules on the eyelid margin.moniliform blepharitis

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Figure 6: Tongue with woody induration with reduced protrusability (a characteristic feature of lipoid proteinosis)

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Figure 7: Bulky, opaque vocal cords on direct laryngoscopy (red*)

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Figure 8: Nodules of hyaline deposits on the pharyngeal walls (black*)

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Figure 9: Amorphous eosinophilic material in the upper dermis (marked with black star) (H and E, ×20)

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Figure 10: Amorphous eosinophilic material surrounding the eccrine coils and capillaries (marked with black star) (PAS stain, ×40)

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Magnetic resonance imaging and computerized tomography of the brain were normal. The ophthalmic evaluation was within normal limits.

A diagnosis of lipoid proteinosis was made. He was treated with 0.3 mg/kg/day (10 mg) acitretin and emollients. Therapeutic response was assessed after 6 months.

Although improvement in cutaneous features was minimal, we noted dramatic improvement in voice quality (as recorded in voice samples). GRBAS score dropped from 15 (at presentation) to 10. The patient also noticed improved quality of life and was able to improve his scholastic performance at school. To objectively corroborate the finding of improved voice quality, direct laryngoscopy was repeated which revealed reduced bulkiness of vocal cords [Figure 11] and reduction in the hyaline nodular deposits on the pharyngeal walls [Figure 12]. “Voice samples (videos) recorded before and after 6 months of Acitretin are available on www.aiaohns.in [Videos 1 and 2].
Figure 11: Reduced bulkiness and increased translucency of vocal cords after 6 months of acitretin therapy (red* – compared with Figure 7)

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Figure 12: Reduced hyaline nodular deposits on the pharyngeal walls on repeat direct laryngoscopy after 6 months of acitretin (compared with Figure 8 – both images taken at approximately same height above vocal cords and notice the reduced number of pharyngeal wall nodules)

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  Discussion Top

Lipoid proteinosis (also known as Urbach–Wiethe disease)[4] is a rare autosomal recessive genodermatosis with unknown prevalence. This disease is caused by mutations in ECM1 gene located on chromosome 1q21.[4] ECM1 may be a “biological glue” in the dermis binding various dermal matrix components.[4] Loss of ECM1 has been postulated to lead to infiltration with hyaline material in the skin and submucosa chiefly collagen 3 and 4 as detected by immunohistochemistry[5] and scarring.[4] Clinical features of this disease include a characteristic hoarse cry at birth[1],[2] followed by bullae on the face and limbs, which resolve with atrophic pock-like scarring along with the development of waxy yellow papules on the skin.[3] Persistent dysphonia due to vocal cord infiltration is a major morbidity in this disease. Various treatment modalities for the treatment of dysphonia include dimethyl sulfoxide, D-penicillamine, retinoids, carbon dioxide laser, and surgical procedures. Limited success in the treatment of dysphonia has been achieved with these treatment modalities.

Retinoids, e.g., etretinate and isotretinoin, have been shown to tackle the disease at the site of pathogenesis, i.e., they reduce synthesis of Type III and IV collagenin vitro along with reduced proliferation and activity of fibroblasts.[6],[7] Acitretin may be superior to etretinate in this respect.[4]

In the largest case series by Dertlioǧlu et al.,[8] ten patients of lipoid proteinosis were treated with acitretin for 6 months. They reported marked softening of skin lesions and improvement in hoarseness in seven patients.

Other authors[1],[2],[4],[9] also administered acitretin for durations ranging from 6 to 16 months with varied improvement in skin lesions. Improvement in hoarseness, however, was not quantified or studied extensively.

Methods of assessing and grading dysphonia clinically include perceptual-auditory analysis (the oldest and most widely used method) and GRBAS (grade of dysphonia, roughness, breathiness, asthenia, and strength perceptual scale), which is an accepted method in international studies,[10] owing to its convenience and reproducibility in assessing improvement in voice quality.

In the present case, we studied improvement in voice quality after acitretin administration by GRBAS score and corroborated this improvement with laryngoscopic findings.

Our patient had dramatic improvement in voice quality after 6 months of acitretin therapy, with reduction of GRBAS score from 15 (maximum possible score) to 10. This was correlated with reduced deposition of hyaline nodules on pharyngeal walls and reduced bulkiness of vocal cords. To our knowledge, this is the first case report documenting clinical and laryngoscopic improvement with the utilization of GRBAS scoring.

  Conclusion Top

Lipoid proteinosis has considerable morbidity right from birth in the form of dysphonia and skin lesions. Various treatment modalities are available in the literature with varying degrees of success with respect to improvement in cutaneous and vocal manifestations of this disease. Among these, oral acitretin has shown considerable promise in various case reports and series. The present case is the first in our knowledge, which uses GRBAS score to assess voice quality and corroborates improvement in dysphonia with direct laryngoscopic findings.

Declaration of patient consent

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


Late (Dr.) Yogendra Rathod for his contribution in eliciting voice samples.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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.  Back to cited text no. 1
Toosi S, Ehsani AH. Treatment of lipoid proteinosis with acitretin: A case report. J Eur Acad Dermatol Venereol 2009;23:482-3.  Back to cited text no. 2
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.  Back to cited text no. 3
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.  Back to cited text no. 4
Newton JA, Rasbridge S, Temple A, Pope FM, Black MM, McKee P. Lipoid proteinosis – New immunopathological observations. Clin Exp Dermatol 1991;16:350-4.  Back to cited text no. 5
Xiao R, Kanekura T, Yoshida N, Higashi Y, Yan KL, Fukushige T, et al. 9-cis-retinoic acid exhibits antifibrotic activity via the induction of cyclooxygenase-2 expression and prostaglandin E2 production in scleroderma fibroblasts. Clin Exp Dermatol 2008;33:484-90.  Back to cited text no. 6
Oikarinen A. Comparison of the effects of retinoids and glucocorticosteroid on protein and type IV collagen synthesis in HT-1080 (human basement membrane forming fibrosarcoma) cells. Dermatologica 1989;179:14-7.  Back to cited text no. 7
Dertlioǧlu SB, Çalık M, Çiçek D. Demographic, clinical, and radiologic signs and treatment responses of lipoid proteinosis patients: A 10-case series from Şanlıurfa. Int J Dermatol 2014;53:516-23.  Back to cited text no. 8
Gündüz O, Sahiner N, Atasoy P, Senyücel C. Acitretin treatment for lipoid proteinosis. Case Rep Dermatol Med 2012;2012:324506.  Back to cited text no. 9
Spina AL, Crespo AN. Assessment of grade of dysphonia and correlation with quality of life protocol. J Voice 2017;31:243.e21-8.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]


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