INTRODUCTION

Lipoid proteinosis is a rare genodermatosis, originally termed as hyalinosis cutis et mucosae. It manifests with myriad features: hoarseness of voice, acneiform scarring, warty papules, and eyelid beading. Although the disease is benign, it has a chronic course. Herein, we present a series of four patients diagnosed with lipoid proteinosis.

CASE REPORT

Case 1

A thirteen-year-old female born of second-degree consanguineous marriage presented with a history of recurrent erosions healing with scarring on the face and body, recurrent oral ulcers since seven months of age, moniliform blepharosis, and hoarseness of voice since two years of age. The child was normal at birth with normal developmental milestones. A history of similar complaints was present in the younger sibling.

An examination revealed multiple pox-like scars on the face, trunk, and limbs and hyperpigmented verrucous plaques on the elbows and natal cleft (Figs. 1a and 1b). Thickening and infiltration of the tongue and uvula were noted along with loss of teeth (Fig. 2). Video laryngoscopy revealed an irregularity in the arytenoid fold.

	Figure 1: (a) Multiple scars and crusted erosions on the face and body (case 1). (b) Scars on the trunk (case 1).
	Figure 2: Infiltration of the tongue (case 1).

Histopathology of a skin biopsy showed perivascular lymphohistiocytic inflammatory cell infiltrate and thick perivascular and periadenexal periodic acid–Schiff (PAS) positive hyaline deposits in a concentric fashion with immunoglobulin G (IgG) positivity in the basement membrane. A final diagnosis of lipoid proteinosis was established based on the classic clinic-pathological findings. The patient was put on acitretin 10 mg and oral zinc along with speech therapy.

Case 3

A male patient presented at seven years of age with moniliform blepharosis and hoarseness of voice (Fig. 3). A diagnosis of lipoid proteinosis was made based on classic clinical features. He was put on oral isotretinoin for four months, after which no improvement was noted, and the patient was lost to follow-up. The patient revisited after fifteen years and reported a spontaneous improvement in voice without treatment.

Figure 3: Moniliform blepharosis (case 3).

Case 4

The fourth and last case was a five-year-old female who presented with complaints of hoarse voice, moniliform blepharosis, and hypopigmented scars on the upper limbs and trunk. She was born of a second-degree consanguineous marriage, and similar complaints of voice change were present in the younger sibling aged three years. Laryngoscopy revealed vocal nodules. As the attenders did not give consent for a skin biopsy, the diagnosis was established based on the classic cutaneous, ocular, and laryngoscopic findings. The patient was planned for retinoids.

Table 1 list the clinical features of the above cases.

Table 1: Clinical features of cases 1–4.

DISCUSSION

Lipoid proteinosis, also known as Urbach–Wiethe disease, is an autosomal recessive genodermatosis caused by ECM-1 gene mutation, which is located on chromosome 1q21 [1].

The main pathology is due to the deposition of hyaline-like material in skin, mucosae, and other visceral organs, which results in the clinical features.

The initial presentation is a weak cry at birth or hoarseness of voice, which develops later in life due to the infiltration of vocal cords [2]. Skin lesions appear within the first two years of life. It presents in two stages, the first being characterized by vesiculobullous lesions and hemorrhagic crusts healing with pox-like scars, followed by the stage characterized by diffuse thickening of the facial skin and flat, yellowish papules and plaques on the body. Verrucous lesions may develop at sites of friction, particularly, on the hands, elbows, knees, buttocks, and axilla as seen in case 1 [3]. The involvement of the scalp may lead to alopecia, as seen in case 2.

Moniliform blepharosis manifested by yellowish-white beaded papules on the eye lid margin is pathognomonic of lipoid proteinosis, as was seen in all of our cases. Other ocular manifestations reported are trichiasis, madarosis, distichiasis, focal degeneration of macula, and drusen formation in Bruch’s membrane [4].

Oral mucosal involvement may manifest as the thickening of the frenulum and tongue resulting in limited tongue protrusion, which was seen in the first case. Pharyngeal and laryngeal infiltration may lead to speech impairment and occasionally respiratory difficulties [5].

The neurologic abnormalities include epilepsy and neuropsychiatric abnormalities, as seen in case 2 [6].

The common findings in our cases were hoarseness of voice, moniliform blepharosis, consanguinity, and the onset of the symptoms in early childhood.

The differential diagnoses include epidermolysis bullosa simplex, erythropoietic protoporphyria, and hydroa vacciniformae.

Histopathology shows PAS-positive and diastase-resistant deposits of hyaline material at the dermo-epidermal junction, blood vessels, and adnexal structures [3].

Diagnosis is established in a patient with classic clinical findings and either characteristic histopathology or biallelic ECM1 pathogenic variants identified by genetic testing.

The disease runs a benign course with a normal life expectancy. Respiratory obstruction and neuropsychiatric involvement may result in significant morbidity [5,6]. There is no increased risk of malignancy.

Early diagnosis and treatment are aimed at symptomatic and cosmetic relief, thereby enhancing the quality of life for the patient.

The management of a patient with lipoid proteinosis entails a multidisciplinary approach toward systemic involvement and genetic counseling. The limited therapeutic modalities include oral steroids, oral dimethyl sulfoxide, oral retinoids, and D- penicillamine.

The hoarseness of voice and cutaneous lesions have been reported to respond to systemic retinoids, such as acitretin at the dose of 0.5 mg/kg/day. Retinoids have been postulated to regulate connective tissue matrix metabolism, reduce dermal hyaline material, and inhibit collagen production [7].

Other modalities, such as ablative laser therapy and cryosurgery, have been employed in the management of cutaneous, laryngeal, and ocular lesions, albeit with limited success.

CONCLUSION

This case series on lipoid proteinosis highlighted the clinical variability and diagnostic challenges of this rare genodermatosis. Early recognition of characteristic hoarse voice, moniliform blepharosis, and cutaneous lesions is crucial for timely diagnosis. Although there is no definitive treatment, multidisciplinary management may help to mitigate the symptoms and enhance the quality of life for the affected individuals. Our findings underscore the importance of increased awareness and the need for further research into newer therapeutic modalities for lipoid proteinosis.

REFERENCES

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2. Savage MM, Crockett DM, McCabe BF. Lipoid proteinosis of the larynx:A cause of voice change in the infant and young child. Int J Pediatr Otorhinolaryngol. 1988;15:33-8.

3. Hamada T. Lipoid proteinosis. Clin Exp Dermatol. 2002;27:624-9.

4. Kamath SJ, Marthala H, Manapragada B. Ocular manifestations in lipoid proteinosis:A rare clinical entity. Indian J Ophthalmol. 2015;63:793-5.

5. Xu W, Wang L, Zhang L, Han D, Zhang L. Otolaryngological manifestations and genetic characteristics of lipoid proteinosis. Ann Otol Rhinol Laryngol. 2010;119:767-71.

6. Hurlemann R, Wagner M, Hawellek B, Reich H, Pieperhoff P, Amunts K, et al. Amygdala control of emotion-induced forgetting and remembering:Evidence from Urbach–Wiethe disease. Neuropsychologia. 2007;45:877-84.

7. Hein R, Mensing H, Müller PK, Braun-Falco O, Krieg T. Effect of vitamin A and its derivatives on collagen production and chemotactic response of fibroblasts. Br J Dermatol. 1984;111:37-44.