Hyperkeratosis Lenticularis Perstans (Flegel Disease)

Hyperkeratosis Lenticularis Perstans (Flegel Disease)

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Flegel originally described hyperkeratosis lenticularis perstans (HLP) in 1958 as red-brown papules with horny scales of irregular outline measuring 1-5 mm in diameter and up to 1 mm in depth. [1] Lesions are located primarily on the dorsal feet and lower legs, with a decreasing likelihood of manifestation proximally. Most cases have been reported in Europe.

No instigating factor has been identified clearly; some investigators have implicated UV light. However, in one case report, evidence of Borrelia infection (Borrelia burgdorferi and Borrelia garinii) was found using DNA sequencing in fresh tissue and blood from a patient with hyperkeratosis lenticularis perstans, without clinical evidence of Lyme borreliosis. [2] Ultrastructurally, a loss or decreased number of membrane-coating granules (also termed Odland bodies) has been reported. Membrane-coating granules are influential in the normal process of desquamation. A decrease, malformation, or absence of these membrane-coating granules may result in decreased desquamation of the stratum corneum, retention hyperkeratosis, and clinically keratotic hyperkeratosis lenticularis perstans lesions. Some authors have suggested that a cell-mediated cytotoxicity against epithelial cells may be involved in the pathogenesis of hyperkeratosis lenticularis perstans.

United States

No data exist on incidence or prevalence of this disease. Hyperkeratosis lenticularis perstans (Flegel disease) likely has both a familial and nonfamilial variant, since several reports have postulated both an autosomal dominant and a sporadic mode of inheritance. [3]


Most cases have been reported in Europe. International incidence is similar to that seen in the United States.

Hyperkeratosis lenticularis perstans does not have a race predilection, although it has mostly been reported in the white population.

No sex predilection is apparent.

Hyperkeratosis lenticularis perstans reportedly occurs most commonly in mid-to-older age groups; however, reports exist of hyperkeratosis lenticularis perstans occurring in patients as young as 13 years.

Except for the possibility that lesions may progress slowly and involve more proximal sites, prognosis for hyperkeratosis lenticularis perstans (Flegel disease) is excellent. No mortality has been reported.

Flegel H. [Hyperkeratosis lenticularis perstans.]. Hautarzt. 1958 Aug. 9(8):363-4. [Medline].

Schwarzova K, Kozub P, Szep Z, Golovchenko M, Rudenko N. Detection of Borrelia burgdorferi sensu stricto and Borrelia garinii DNAs in patient with Hyperkeratosis lenticularis perstans (Flegel disease). Folia Microbiol (Praha). 2016 Sep. 61 (5):359-63. [Medline].

Bean SF. The genetics of hyperkeratosis lenticularis perstans. Arch Dermatol. 1972 Jul. 106(1):72. [Medline].

Humphrey S, Crawford RI, Au S. Long-standing spiny papules on the lower extremities. Flegel disease, or hyperkeratosis lenticularis perstans (HLP). Arch Dermatol. 2008 Nov. 144(11):1509-14. [Medline].

Li TH, Hsu CK, Chiu HC, Chang CH. Multiple asymptomatic hyperkeratotic papules on the lower part of the legs. Hyperkeratosis lenticularis perstans (HLP) (Flegel disease). Arch Dermatol. 1997 Jul. 133(7):910-1, 913-4. [Medline].

Miljkovic J. An unusual generalized form of hyperkeratosis lenticularis perstans (Flegel’s disease). Wien Klin Wochenschr. 2004. 116 Suppl 2:78-80. [Medline].

Krishnan A, Kar S. Photoletter to the editor: Hyperkeratosis lenticularis perstans (Flegel’s disease) with unusual clinical presentation. Response to isotretinoin therapy. J Dermatol Case Rep. 2012 Sep 28. 6(3):93-5. [Medline]. [Full Text].

Valdebran M, Terrero D, Xue R. Dermoscopic findings in hyperkeratosis lenticularis perstans. J Am Acad Dermatol. 2016 Dec. 75 (6):e211-e213. [Medline].

Miranda-Romero A, Sanchez Sambucety P, Bajo del Pozo C, Martinez Fermandez M, Esquivias Gomez JI, Garcia Munoz M. Unilateral hyperkeratosis lenticularis perstans (Flegel’s disease). J Am Acad Dermatol. 1998 Oct. 39(4 Pt 1):655-7. [Medline].

Urbina F, Sudy E, Misad C. A case of localized, unilateral hyperkeratosis lenticularis perstans on a woman’s breast. J Dtsch Dermatol Ges. 2016 Apr. 14 (4):416-8. [Medline].

Ando K, Hattori H, Yamauchi Y. Histopathological differences between early and old lesions of hyperkeratosis Lenticularis Perstans (Flegel’s disease). Am J Dermatopathol. 2006 Apr. 28(2):122-6. [Medline].

Jang KA, Choi JH, Sung KJ, Moon KC, Koh JK. Hyperkeratosis lenticularis perstans (Flegel’s disease): histologic, immunohistochemical, and ultrastructural features in a case. Am J Dermatopathol. 1999 Aug. 21(4):395-8. [Medline].

Blaheta HJ, Metzler G, Rassner G, Garbe C. Hyperkeratosis lenticularis perstans (Flegel’s disease)–lack of response to treatment with tacalcitol and calcipotriol. Dermatology. 2001. 202(3):255-8. [Medline].

Metze D, Lubke D, Luger T. [Hyperkeratosis lenticularis perstans (Flegel’s disease) – a complex disorder of epidermal differentiation with good response to a synthetic vitamin D3 derivate]. Hautarzt. 2000 Jan. 51(1):31-5. [Medline].

Pearson LH, Smith JG Jr, Chalker DK. Hyperkeratosis lenticularis perstans (Flegel’s disease). Case report and literature review. J Am Acad Dermatol. 1987 Jan. 16(1 Pt 2):190-5. [Medline].

Wilson PD, Ive FA. Treatment of hyperkeratosis lenticularis perstans (Flegel) with topical fluorouracil. Dermatologica. 1980. 160(5):337-40. [Medline].

Gabrielsen TO. [Tigason in hyperkeratosis lenticularis perstans (HLP)–a case report]. Z Hautkr. 1986 Feb 15. 61(4):214-7. [Medline].

Cooper SM, George S. Flegel’s disease treated with psoralen ultraviolet A. Br J Dermatol. 2000 Feb. 142(2):340-2. [Medline].

Langer K, Zonzits E, Konrad K. Hyperkeratosis lenticularis perstans (Flegel’s disease). Ultrastructural study of lesional and perilesional skin and therapeutic trial of topical tretinoin versus 5-fluorouracil. J Am Acad Dermatol. 1992 Nov. 27(5 Pt 2):812-6. [Medline].

Lindsay E. Zinc paste bandages and the treatment of Flegel’s disease. Br J Community Nurs. 2005 Mar. 10(3):S14-9. [Medline].

Sterneberg-Vos H, van Marion AM, Frank J, Poblete-Gutierrez P. Hyperkeratosis lenticularis perstans (Flegel’s disease) – successful treatment with topical corticosteroids. Int J Dermatol. 2008 Nov. 47 Suppl 1:38-41. [Medline].

Daniel Roling, MD Associate Clinical Professor, Department of Dermatology, Hospital of the University of Pennsylvania

Daniel Roling, MD is a member of the following medical societies: American Academy of Dermatology, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Jacqueline M Junkins-Hopkins, MD Associate Professor, Director, Division of Dermatopathology and Oral Pathology, Department of Dermatology, Johns Hopkins Medical Institutions

Jacqueline M Junkins-Hopkins, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Dermatopathology

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke’s Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Hyperkeratosis Lenticularis Perstans (Flegel Disease)

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