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Int J Dermatol 2020 May 13. Epub 2020 May 13.

Dermatology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Hyperkeratosis lenticularis perstans (HLP), or Flegel's disease (FD), is a rare disorder of keratinization first described in 1958 by Flegel. HLP is characterized by asymptomatic small papules distributed symmetrically on the dorsal feet and lower part of the legs. It typically presents in the fourth or fifth decade of life. Read More

Cutis 2019 Aug;104(2):E37-E38

Department of Dermatology, University of Texas Medical Branch at Galveston, USA.

JAMA Dermatol 2019 Jun;155(6):739-740

Department of Pathology, Hospital General Universitario de Elche, Elche, Spain.

Eur J Dermatol 2019 Feb;29(1):106-107

Department of Dermatology, Hospital General Universitario Gregorio Marañón, Madrid.

J Dermatol 2019 08 25;46(8):e298-e299. Epub 2019 Feb 25.

Institute of Dermatology, "Santa Maria della Misericordia" University Hospital, Udine, Italy.

J Dtsch Dermatol Ges 2018 Jan;16(1):72-74

Department of Dermatology and Venereology, China-Japan Friendship Hospital, Beijing, China.

J Dtsch Dermatol Ges 2018 Jan 12;16(1):72-73. Epub 2017 Dec 12.

Department of Dermatology and Venereology, China-Japan Friendship Hospital, Beijing, China.

J Am Acad Dermatol 2016 Dec;75(6):e211-e213

Guangdong Provincial Dermatology Hospital, Guangzhou, China. Electronic address:

J Dtsch Dermatol Ges 2016 Apr;14(4):416-8

Servicio de Anatomía Patológica, Hospital San Juan de Dios, Santiago de Chile.

Folia Microbiol (Praha) 2016 Sep 15;61(5):359-63. Epub 2016 Jan 15.

Biology Center, Institute of Parasitology CAS, České Budějovice, Czech Republic.

Determination of the causative agent of erythema-like skin lesions in case of nonspecific superficial perivascular dermatitis was supported by histological examination and led to the latter diagnosis of Hyperkeratosis lenticularis perstans (Flegel disease) in patient. The presence of antibodies against Borrelia burgdorferi in patient serum was confirmed by a routine ELISA method and verified by Western blot technique. Skin biopsy and blood specimens were analyzed by PCR and multilocus sequence analysis (MLSA). Read More

Cutis 2015 Dec;96(6):E5-7

Department of Dermatology, University of Virginia, Charlottesville, USA.

J Clin Pathol 2015 Dec 20;68(12):1011. Epub 2015 Nov 20.

St Johns' Institute of Dermatology, UK.

J Am Acad Dermatol 2015 Aug;73(2):346-8

Hershey, Pennsylvania.

Indian J Dermatol 2013 Mar;58(2):161

Department of Dermatology, Venereology and Leprology, GMERS Medical College, Sola, Ahmedabad, Gujarat, India. E-mail:

J Dermatol Case Rep 2012 Sep;6(3):93-5

Department of Dermatology, Venereology & Leprosy, Mahatma Gandhi Institute of Medical Sciences (MGIMS), Sewagram, Wardha, Maharashtra, India - 442102.

Hyperkeratosis lenticularis perstans also known as Flegel's disease is a keratinisation disorder characterized by small keratotic papules with horny scales. Most cases have been reported in Europe with age of presentation between 35 and 60 years. We report a case of a 25-year-old man, who presented with 1-5 mm multiple asymptomatic hyperkeratotic papules of 15 years duration on both legs and hand along with lichenified plaques with Koebner phenomenon in the axillary folds, anticubital and popliteal fossae. Read More

An Bras Dermatol 2011 Jul-Aug;86(4 Suppl 1):S76-7

UNOESC, University of Western Santa Catarina, Joacaba, SC, Brazil.

Flegel's disease, also known as hyperkeratosis lenticularis perstans, is a rare skin disease characterized by small reddish-brown asymptomatic hyperkeratotic papules usually located on the lower extremities. The histopathological features are hyperorthokeratosis, epidermal atrophy and band-like inflammatory infiltrate in the superficial dermis. Treatment is generally ineffective. Read More

Actas Dermosifiliogr 2009 Mar;100(2):157-9

Acta Dermatovenerol Croat 2009 ;17(1):16-9

Department of Anatomic Pathology, Hospital El Bierzo, Spain.

We present a case of hyperkeratosis lenticularis perstans (Flegel's disease) in a 71-year-old-woman. Apart from all the typical morphological features of the disease, we evidenced mounds of parakeratosis that contained neutrophils, alternating with other strata of the horny layers in which no infiltrate was seen. Such a pattern has been described in association with diseases that show a periodic clinical pattern of presentation with periods of exacerbations and remissions. Read More

Arch Dermatol 2008 Nov;144(11):1509-14

University of British Columbia and St Paul's Hospital, Vancouver, British Columbia, Canada.

Int J Dermatol 2008 Nov;47 Suppl 1:38-41

Department of Dermatology, and Maastricht University Center for Molecular Dermatology, University Medical Center Maastricht, The Netherlands.

Flegel's disease, also known as hyperkeratosis lenticularis perstans, is a rare skin disease characterized by small, red-brown, hyperkeratotic, papules that are usually located on the lower extremities. The diagnosis is based on the clinical appearance in association with the typical histologic features of orthohyperkeratosis and a subepidermal band-like infiltrate. Treatment is difficult and rarely fully effective. Read More

Am J Dermatopathol 2006 Apr;28(2):122-6

Department of Dermatology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.

A case of hyperkeratosis lenticularis perstans (Flegel's disease) was studied histopathologically comparing early and old lesions. The age of the lesions were judged by both the patient's history and direct observation. The histopathologic and immunophenotypic features of a new lesion were essentially in accordance with previous findings. Read More

Wien Klin Wochenschr 2004 ;116 Suppl 2:78-80

Department of Dermatology, Maribor Teaching Hospital, Maribor, Slovenia.

An 82-year-old female presented with an 11-year history of multiple, symmetrically disseminated hyperkeratotic red-brown papules 3-5 mm in diameter on the dorsal aspects of the upper and lower extremities. The eruption first appeared on the dorsa of the feet and on the lower parts of the legs. During the last few years, the lesions extended gradually to the upper part of the legs and thighs, also disseminating over the trunk. Read More

Clin Exp Dermatol 2003 May;28(3):339-40

Department of Dermatology, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, UK.

Med Trop (Mars) 2002 ;62(1):85-8

Service de Dermatologie, Hôpital d'Instruction des Armées Alphonse Laveran, BP 50, 13998 Marseille Armées, France.

This report describes the case of a 33-year-old black woman who presented atypical hyperkeratosis. Atypical features included location on the dorsum of the foot and presence of punctate pits. The lesion was classified as intermediate between keratosis punctata of the palmar creases and focal acral hyperkeratosis. Read More

Dermatology 2001 ;202(3):255-8

Department of Dermatology, Eberhard Karl University, Tübingen, Germany.

Hyperkeratosis lenticularis perstans (HLP) or Flegel's disease is a rare dermatosis characterized by asymptomatic hyperkeratotic papules predominantly located on the lower extremities. Lesional and non-lesional epidermis samples were studied by light- and electron-microscopic examination. The main ultrastructural finding was the presence of structurally altered Odland bodies/membrane-coating granules. Read More

Hautarzt 2001 Mar;52(3):231-5

Klinik und Poliklinik für Dermatologie und Venerologie der Universität Rostock, Augustenstrasse 80, 18055 Rostock.

A case report of hyperkeratosis lenticularis perstans (Flegel) is presented. The disease is characterized clinically, histologically and with electron microscope. The evolution of the disease since Flegel described it 40 years ago is considered, with emphasis on etiology, pathogenesis and unanswered questions. Read More

Hautarzt 2000 Jan;51(1):31-5

Univ.-Hautklinik Münster.

Hyperkeratosis lenticularis perstans (Flegel's disease) is a rare but clinically and histologically highly characteristic genodermatosis. We report on new immunohistochemical and ultrastructural findings suggesting a complex disorder of epidermal differentiation. In this context, a good response to calcipotriol, a synthetic vitamin D3 derivative is of particular interest. Read More

Am J Dermatopathol 1999 Aug;21(4):395-8

J Am Acad Dermatol 1998 Oct;39(4 Pt 1):655-7

Department of Dermatology, Medical University of Valladolid, Hospital Clínico Universitario, Spain.

Arch Dermatol 1997 Jul;133(7):910-1, 913-4

National Taiwan University Hospital, Taipei.

J Am Acad Dermatol 1992 Nov;27(5 Pt 2):812-6

Department of Dermatology I, University of Vienna Medical School, Austria.

Lesional and perilesional skin samples from a 57-year-old man who had hyperkeratosis lenticularis perstans (HLP) (Flegel's disease) were studied by light and electron microscopic examination. Keratohyalin granules were diminished at the center of a fully-developed lesion. In contrast, keratohyalin appeared normal and membrane-coating granules were found in reduced numbers at the edges of the HLP lesion and were easily detected in normal numbers in clinically normal, perilesional skin. Read More

Cutis 1991 Sep;48(3):201-4

Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.

A case of hyperkeratosis lenticularis perstans involving only the back of a thirty-nine-year-old woman is reported. Histologic examination showed foci of compact and eosinophilic hyperkeratosis overlying a thinned stratum malpighii. In the underlying papillary dermis there was no evidence of inflammatory infiltrate. Read More

G Ital Dermatol Venereol 1990 Jun;125(6):281-4

Divisione di Dermatologia, E.O. Ospedali Galliera, Genova.

A case of a woman of 55-years-old with verrucous lesions localized on the dorsa of her feet and hands is reported. The light microecopy reveals marked hyperkeratosis with some degree of parakeratosis, epidermal atrophy and light lympho-histiocytic infiltrate in the papillary dermis. A diagnosis of hyperkeratosis lenticularis perstans is made on the basis of the physical examination and histologic findings. Read More

Med Cutan Ibero Lat Am 1989 ;17(5):321-5

Hospital Universitario de Valladolid.

The case of a female patient, 67 years old, with hyperkeratotic papules in the lower extremities which are characteristic of hyperkeratosis lenticularis perstans is reported. The clinical, histological and ultrastructural findings are shown. We have recorded the absence of Odland bodies in the area of the lesion, the persistence of desmosomes in the stratum corneum and lymphocytes with cerebriform nuclei within the inflammatory cell infiltrate. Read More

Int J Dermatol 1988 Mar;27(2):120-1

Department of Dermatology, Hamad General Hospital, Doha, Qatar.

Acta Derm Venereol 1988 ;68(4):341-5

Department of Dermatology, University of Basle, Switzerland.

We report a patient with hyperkeratosis lenticularis perstans (HLP) manifesting as multiple reddish-brown hyperkeratotic papules on the lower extremities. Typical histologic features of HLP include hyperkeratosis, thinning or absence of the granular layer and a band-like infiltrate in the upper dermis underlying an atrophic epidermis. In order to determine the cellular composition of the infiltrate, skin biopsy specimens were studied immunohistochemically using a series of commercially available monoclonal antibodies. Read More

J Cutan Pathol 1987 Aug;14(4):207-11

An ultrastructural study of lesional skin from 4 subjects with hyperkeratosis lenticularis perstans (Flegel's disease) demonstrated variable numbers of lamellar bodies of normal size and architecture within cells of the stratum granulosum and the upper stratum spinosum. Their characteristic lamellate inclusions were frequently observed within the intercellular spaces. These observations suggest that the lamellar bodies are qualitatively normal in Flegel's disease. Read More

Br J Dermatol 1987 May;116(5):681-91

The clinical and histopathological features of 12 female patients with Flegel's disease were studied. The onset of this dermatosis was delayed until adulthood. The eruption consisted of scaly papules 1-5 mm in diameter which developed principally on the lower legs, upper arms and pinnae. Read More

J Am Acad Dermatol 1987 Jan;16(1 Pt 2):190-5

A case of Flegel's disease, or hyperkeratosis lenticularis perstans, is reported. This rare chronic disorder is characterized by asymptomatic hyperkeratotic papules, usually located on the lower extremities. Most reported cases have been from Europe. Read More

Dermatologica 1987 ;174(2):96-101

Lesional as well as uninvolved skin were studied by light and electron microscopy in 1 case of hyperkeratosis lenticularis perstans (Flegel's disease). The main ultrastructural finding was a morphological alteration of lamellar (Odland) bodies. A review of the literature on the ultrastructure of Flegel's disease is made, and the significance of the ultrastructural findings is briefly discussed. Read More

Int J Dermatol 1986 Dec;25(10):642-5

Typical papules obtained from a patient with hyperkeratosis lenticularis perstans (HLP) were examined by light and electron microscopy. Dense cellular infiltrate, which consisted mainly of mononuclear cells, was observed in the dermis underlying the lesion. Electron microscopic studies revealed that these cells were mostly lymphocytic cells. Read More

Z Hautkr 1986 Feb;61(4):214-7

A case of hyperkeratosis lenticularis perstans was successfully treated with etretinate. Following a short period of aggravation of the condition, an almost total clearing of the lesions was observed after 10 weeks of treatment. Read More

Hautarzt 1985 May;36(5):299-301

Hyperkeratosis lenticularis perstans (Flegel's disease) is a rare form of dermatosis, which can only be diagnosed microscopically. A typical case is reported; histological differential diagnosis and treatment with systemic retinoids are discussed. Read More

Acta Derm Venereol 1985 ;65(6):562-4

Three women with hyperkeratosis lenticularis perstans (HLP) are described. The lesions developed after the age of 45 and there was no family history of this disease. The possible role of UV-light in the pathogenesis of this disease is discussed. Read More

J Dermatol 1984 Aug;11(4):407-9

Nihon Hifuka Gakkai Zasshi 1984 Jun;94(7):849-53

G Ital Dermatol Venereol 1983 Jul-Aug;118(4):223-6

Acta Derm Venereol 1983 ;63(4):357-60

A 62-year-old female with a 20-year history of small horny papules on the skin of the legs is described. Light microscopy revealed a hyperkeratotic papule with atrophic epidermis and a dense dermal inflammatory cell infiltrate with many cerebriform lymphocytes not earlier described in connection with hyperkeratosis lenticularis perstans (HLP). The electron-microscopic picture showed membrane-coating granules (MCG) and keratohyalin located in different cells, indicating that the disorder of keratinization in HLP is possibly caused by reduced co-operation between these cells and that the keratinization process occurs in the absence of MCG. Read More

J Dermatol 1982 Dec;9(6):473-9

Dermatologica 1982 Jun;164(6):379-85

The dyskeratotic changes in the lesions of hyperkeratosis lenticularis perstans were examined electron microscopically and histochemically. Under electron microscopy, the formation of keratohyalin granules was reduced and there was a lack of lamellar granule formation. In addition, the catabolic processes were disturbed, and ribosomal and mitochondrial structures remained, and lipid crystal-like structures were seen in the stratum corneum. Read More