Hyperkeratosis lenticularis perstans (Flegel disease)

What is hyperkeratosis lenticularis perstans?

Hyperkeratosis lenticularis perstans (HLP), also known as  Flegel disease, is a rare heritable disorder of keratinisation that was first described by Flegel in 1958. It is characterised by red-brown  papules  with irregular horny  scales  located mainly on the dorsal aspect of the feet and lower legs. It has been regarded as a variant of Kyrle disease, however its clinical and  pathological  features are sufficiently distinct to establish it as a separate disease entity.

Red 3-4 mm scaly papules, typical of Flegel's disease, on the hand (HLP-patient1)

Scaly papules on the ears, typical of Flegel's disease (HLP-patient1)

Multiple red scaly papules over the legs due to Flegel's disease 

Close-up of the scaly papules typical of Flegel's disease 

3-4 mm scaly papules over the feet in Flegel's disease 

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Who gets hyperkeratosis lenticularis perstans?

This condition:

• Typically presents in the fourth or fifth decade of life, however it has been reported in individuals as young as 13 years of age
• Is more common in women than men
• Is considered a rare skin condition, and no data exist on the prevalence of this disease.

What causes hyperkeratosis lenticularis perstans?

Hyperkeratosis  lenticularis perstans is an autosomal-dominant genodermatosis, although sporadic cases are commonly reported.

The underlying cause of this disease is due to heterozygous pathogenic variants in the SPTLC1 gene, which encodes serine palmitoytransferase (SPT), specifically the long chain base subunit -1 (SPTLC1). SPTLC1 is the key enzyme in sphingolipid biosynthesis.

Frameshift or splicing variants in this gene lead to nonsense-mediated mRNA decay, hence reducing SPTLC1 protein levels. This reduction leads to the development of HLP.

As for the sporadic cases, there is no clear understanding of the specific triggers for HLP. It has been associated with several systemic conditions, including adult-onset diabetes, hyperaldosteronism, and hyperthyroidism.

What are the clinical features of hyperkeratosis lenticularis perstans? 

Lesions  are small, red-brown, 1–5 mm  scaly  papules distributed symmetrically on the dorsal aspect of the feet and lower legs. Removal of the  scale  reveals a bright red base, often with pinpoint bleeding. The papules are asymptomatic, except for rare episodes of mild pruritus or burning sensation.

Less typical sites of occurrence have been reported such as axillae, eyes, palms and soles, single leg involvement, trunk, upper extremities, buttocks, forehead, outer ear lobes, and oral mucosa.

Dermoscopic features

• White scaling structureless areas on the surface due to hyperkeratosis.
• Brownish structureless areas at the centre of the lesions because of reactive activation of melanocytes produced by the lichenoid infiltrate and also due to pigment incontinence.
• Brown/grey structureless areas could correspond to pigment dropout as a result of the lichenoid damage to the basal layer.

What are the complications of hyperkeratosis lenticularis perstans?

HLP is asymptomatic and has no serious complications. Hence, it is considered mostly an aesthetic issue.

• Koebner reaction may occur if lesions are removed by scratching.
• Curettage of the hyperkeratotic papules may cause depression and pinpoint bleeding.

How is hyperkeratosis lenticularis perstans diagnosed?

Hyperkeratosis  lenticularis perstans can usually be diagnosed clinically, especially if there is a family history of HLP, and confirmed on a skin  biopsy with histological features of focal compact hyperkeratosis, thinned stratum Malpighii, epidermal atrophy, and a dense, band-like lymphocytic infiltrate in the papillary dermis.

Figure 1 

The histopathology of HLP - marked hyperkeratosis, thinned stratum malpighi, epidermal atrophy and a lichenoid dermal infiltrate

What is the differential diagnosis for hyperkeratosis lenticularis perstans?

• Kyrle disease (which has clinically larger papules and is histologically distinct due to the presence of keratin plug and inflammatory material perforating through the epidermis).
• Disseminated superficial actinic porokeratosis.
• Stucco keratosis.
• Keratosis pilaris.
• Lichen planus.
• Lichenoid drug eruption.

What is the treatment for hyperkeratosis lenticularis perstans?

General measures

• It is important to educate patients on the disease and its chronicity.
• Lesions are  benign  and are mainly treated for cosmetic reasons.
• General measures include emollient and avoiding scratching the lesions.

Specific measures

• Topical corticosteroids such as betamethasone diproprionate 0.05%.
• Topical 5-fluorouracil 5% cream.
• Topical imiquimod
• Topical or systemic retinoids: systemic retinoids such as acitretin or isotretinoin are considered to have better results than topical retinoids.
• Topical Vitamin D (calcipotriene 0.05%)
• PUVA (photochemotherapy)
• Ablative treatments such as dermabrasion, cryotherapy, local excision, carbon dioxide laser and curettage.

What is the outcome for hyperkeratosis lenticularis perstans?

Lesions are largely asymptomatic. The overall disease course is chronic and stable with no serious complications. The primary concern of the disease is often cosmetic. Treatment is often challenging and not satisfactory, and therefore patients usually refuse aggressive therapies. With the genetic basis of the disorder now known, novel therapies enhancing sphingolipid synthesis may be on the horizon.

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