Hyperkeratosis Lenticularis perstans (Flegel’s Disease) Report of a case 高雄長庚紀念醫院皮膚科 病理科* 黃仁杰 黃柏翰 何宜承 黃昭誠*

Chief Complain Multiple asymptomatic 2-3mm reddish-brown papules with thick horny scale over 4 extremities

Present Illness This 66 y/o male patient came to our OPD due to multiple red-brownish hyperkeratotic small papules(2-3mm in size), first noted over his bil. doral feet since about 30 yrs ago with slow extension to lower legs, thighs and bil. forearms in recent yrs. Palms and soles are spared. No mucosal lesion or other skin manifestation was noted.

Past History Diabetes mellitus and H/T for yrs without regular control Ischemic heart disease with angina Hx about 4 yrs ago No known drug or food allergy Hx

Familial History   Patient Affected family members Normal family members The same identical lesions appeared in all affected ones around their 4~5th decades over dorsal feet with upward progression

Clinical Impression Hyperkeratosis lenticularis perstans (Flegel’s Disease) Skin biopsy was arranged and histopathologic exam was performed

Treatment Oral acitretin 25mg/day was given and partial response was noted, but local swelling and erythematous change over bil. lower legs made patient discontinued medication. Emollients use was suggested

DISCUSION

Hyperkeratosis Lenticularis Perstans First described by Flegel in 1958 A rare, probably autosomal dominant inherited keratinization disorder with distinct clinical picture Typical lesion appeared between 4rd ~ 5th decade with slow progression No gender predilection ever reported

Clinical Manifestation(1) 1. Multiple discrete small red-brown papules with horny scales ( 1-5mm in diameter, < 1mm in thickness) 2. Removal of the scale shows a reddish base with bleeding point 3. Usually symptomless, occasionally itching was complained during the early phase

Clinical Manifestation(2) 4.Dorsal feet and legs are the most severe and earliest sites of involvement. 5.More widespread involvement of upper extremities may occurred but mostly spare palm and sole. 6.Few cases of mucosa involve ever reported 7.No obvious associated disease was noted

Histopathologic Findings(1) Compact hyperkeratotic stratum corneum, mostly are orthokeratotic horny layer with occasional parakeratotic areas Thinning of underlying epidermis, including granular and malpighian layers Effacement of rete ridge and flattening of papllary dermis

Histopathology Findings(2) Lower epidermis intercellular edema with occasionally basal cell degeneration Dense lymphohistiocytes infiltration over upper dermis with sharply demarcated lower margin Capillary proliferation within inflammatory area

Electron Microscopy Study Lack of Odland bodies in the epidermis underlying the keratotic papule Reduced Keratohyalin granules and tonofilaments in the flatten epidermis Persistence of the desomsomal discs through the whole stratum corneum

Treatment Emollients or urea provide some benefit Topical retinoid is not effective with SE of irritation Oral retinoid bring partial response but SE often over-weight benefits Topical 5-FU is reported to be effective agent with minimal SE

Differential Diagnosis 1. Arsenic keratosis 2. Stuccokeratoses 3. Porokeratosis of Mibelli 4. Actinic porokeratosis 5. Kyrle’s disease 6. Darier’s disease 7. Acrokeratosis verruciformis

Association with Skin Tumors Familial cases with associated high incidence of cutaneous carcinoma ever reported, but not arising in the keratosis