CLINICAL HISTORY:

Signs and symptoms:  Patient reports a persistent eruption for 4 years that originally started on his lower extremities which progressed to his arm, palms, and low back (Fig 1 and Fig 2). He also reported occasional pruritus of the lesions which was not severe. The patient and his wife both denied any suspected precipitating factors. He also denied constitutional symptoms such as fever, chills, weight loss, myalgia, or arthralgia.

Previous Treatment:  The lesions were previously treated with topical triamcinolone 0.1% cream with no clinical improvement.

Other information:  Past medical history was significant only for Parkinson’s disease. There was no known history of other major medical disorders, such as metabolic diseases or malignancies. He also denied recent travel or history of any sexually transmitted diseases, including syphilis. No other family members or close personal contacts were afflicted with similar lesions.

PHYSICAL EXAM:

Examination revealed numerous symmetric 1-5mm red-brown scaly, focally keratotic papules on his lower legs and feet. Other anatomic regions of involvement included the arms, palms, abdomen, and back. Importantly, the lesions were monomorphic in appearance overall. No excoriations, vesicles, pustules or burrows were noted. The face, neck, and scalp were spared, and no lesions were noted on his genitalia. Removal of the scales resulted in pinpoint bleeding. Oral mucosa, hair and nails were not affected. There was no cervical, axillary, or inguinal lymphadenopathy.


Figure 1 Diffuse scaly pink papules distributed symmetrically on bilateral legs


Figure 2 Lesions present on bilateral palms

LABORATORY TESTS:

A 4mm punch biopsy was obtained from one of the lesions and sent for histological analysis.

DERMATOHISTOPATHOLOGY:

Histopathologic examination revealed a band-like infiltrate of lymphocytes and histiocytes. There was also exocytosis of lymphocytes into the overlying epidermis, with mild spongiosis with focal vacuolar alteration of the basal layer keratinocytes. In addition, there was an absence of the granular layer with overlying compact orthokeratosis and focal parakeratosis. Epidermal thinning with flattened rete ridges were also observed. The adjacent epidermis revealed preservation of granular layer with overlying basket-weave orthokeratosis (Fig 3 and Fig 4).

Figure 3 Basket-weave orthokeratosis and an adjacent area showing thicker epidermis with a preserved granular layer. Hematoxylin-eosin stained and 10x magnification


Figure 4 Slight compact orthokeratosis, absence of granular layer, and band-like infiltrate of lymphocytes with spongiosis. There is epidermal thinning and flattened rete ridges. Hematoxylin-exosin stained and 10x magnification

DIFFERENTIAL DIAGNOSIS:

1.   Acrokeratosis verruciformis of Hopf
2.   Actinic keratosis
3.   Hyperkeratosis lenticularis perstans (Flegel’s disease)
4.   Hyperkeratosis follicularis et parafollicularis in cutem penetrans (Kyrle’s disease)
5.   Keratosis follicularis (Darier’s disease)

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Hyperkeratosis lenticularis perstans (Flegel’s Disease)

DISCUSSION:

In 1958, Flegel first described a rare keratinization disorder with a predilection for the distal extremities of adults named hyperkeratosis lenticularis perstans or Flegel’s disease.1 The name hyperkeratosis lenticularis perstans (HLP) refers to the disc or lens shape (lenticularis) of the papules and their persistent nature (perstans).1 To date, all reports of HLP have been in Caucasian patients with no apparent gender predilection.2 Most cases have been reported in Europe, with the international incidence similar to that seen in the United States.2 Onset is during adulthood with red brown keratotic lesions that are symmetrically distributed, and usually symptomatic and chronic.3 HLP is occasionally associated with endocrine diseases and neoplasias. Some authors have implicated exposure to ultraviolet (UV) light as a precipitating factor.2 Others have suggested that a cell-mediated cytotoxicity against epithelial cells may be involved.2 Lesions are not evident until mid-to-late adulthood, but have been described in individuals as young as 13 year of age.4,5 Thus far, there is no clear understanding of the pathogenesis of HLP.2
HLP presents clinically with red-brown papules, most often covered by focal horny scale. Individual papules of HLP measure between 1-5 mm in diameter and generally are up to 1 mm in depth (height).6 Papules of HLP are primarily located on the dorsal feet and lower legs, and are less likely to manifest proximally. This disorder has also been known to involve the thighs, hands, forearms, trunk, ears, and oral mucosa.3,7 Lesions of HLP are typically distributed symmetrically, however, unilateral cases have been reported.3 Involvement of the trunk has been reported as an unusual variant.8 The ear pinna, arms, palms, plantar surfaces, and oral mucosa have also been reported, with such areas of involvement considered to be rare.2 Removal of the scales commonly reveals a bright red base with pinpoint bleeding.2
Ultrastructurally, a decrease, malformation, or absence of membrane-coating granules (Odland bodies) can be observed.2 Structurally altered Odland bodies, which contain hydrolytic enzymes results in decreased desquamation of the stratum corneum and retention hyperkeratosis.9 A lymphoid infiltrate with occasional histiocytes in a band-like pattern in the papillary dermis is typically seen.2 Although the most characteristic feature is an absence or reduction in Odland bodies, this is not always the case.10 Depending on the stage of the disease, the histopathologic findings can be quite non-specific with older lesions displaying mild hyperkeratosis with little or no inflammatory infiltrate.1 Studies reveal the presence of many normal appearing, Odland bodies in the keratinocytes of older HLP lesions, which is not observed in earlier hyperkeratotic lesions.9
Clinically, the differential diagnosis may also include disseminated superficial actinic porokeratosis (DSAP). However, this possibility can be ruled out by histopathological examination of the lesion revealing a cornoid lamella at the hyperkeratotic edge of a DSAP lesion. HLP is a diagnosis that requires a high index of clinical suspicion and appropriate histopathologic correlation. Skin biopsy is helpful in excluding other disorders considered in the differential diagnosis.

TREATMENT:

HLP can be problematic to treat due to its persistent nature. It is characteristically resistant to topical corticosteroids and keratolytic agents.2 Destructive therapies, such as dermal abrasion and shave-excision, have been noted to be more effective.1,3 Topical 5-fluorouracil has been shown to be moderately effective in some cases.3 However, some patients may not tolerate this treatment due to its irritant side effects.1 Oral retinoids, (etretinate, isotretinoin) have also been shown to be effective, but relapse occurs after treatment is discontinued.3 Topical retinoids are not as effective.11,12,13 However, isotretinoin 0.05% gel has been reported to produce good results.3 Other options include psoralen ultraviolet A (PUVA)14 and topical calcipotriol.15 Currently no standard therapy exists and many cases of HLP are refractory to therapy.
In our case of HLP described above, the patient was refractory to multiple treatment regimens including topical corticosteroids and topical 5-fluorouracil. He was subsequently lost to follow up.

ACKNOWLEDGEMENT:
Thank you to Narciss Mobini MD who provided dermatopathology services in this case and assistance with obtaining photomicrographs of histologic findings.

REFERENCES:

1. Bolognia JL, Jorizzo JL, Rapini RP, et al. Dermatology. Spain, Mosby.
2. Roling H, Junkins-Hopkins JM. Hyperkeratosis lenticularis perstans (Flegel disease). www.emedicine.medscape.com
3. Miranda-Romero A, Sambucety PS, Bajo del Pozo C, et al. Unilateral hyperkeratosis lenticularis perstans (Flegel’s disease). J Am Acad of Dermatol 1998; 39(4):655-657.
4. Knipper JE, Hud JA, Cockerell CJ. Disseminated epidermolytic acanthoma. Am J Dermatopathol. 1993;15:70-2.
5. Bean S. Hyperkeratosis lenticularis perstans: a clinical,histopathologic, and genetic study. Arch Dermatol. 1969;99:705-9.
6. Flegel H. Hyperkeratosis lenticularis perstans. Hautarzt. 1958;9(8):363-4.
7. Ando K, Hattori H, Yamauchi Y. Histopathological differences between early and old lesions of hyperkeratosis lenticularis perstans (Flegel’s disease). Am J Dermatopathol. 2006;28(2):122-6.
8. Miljkovic J. An unusual generalized form of hyperkeratosis lenticularis perstans (Flegel’s disease). Wien Klin Wocheschr. 2004;116 Suppl 2:78-80.
9. Jang K, Choi J, Sung K, et al. Hyperkeratosis lenticularis perstans (Flegel’s disease): histologic immunohistochemical, and ultrastructural features in a case. Am J Dermatopathol. 1999;21:395-8.
10. Pearson LH, Smith JG, Chalker DK. Hyperkeratosis lenticularis perstans (Flegel’s disease): case report and literature review. J Am Acad Dermatol 1987;16:190-5.
11. De Argila D, Revenga F, Rodriguez JL, et al. Hiperqueratosis lenticularis perstans (enfermedad de Flegel): studio clinic-patologico de 10 casos. Actas Dermosifilogr 1994;85:309-15.
12. 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;27:812-6.
13. Crespo A,m Crespo V, Sanz A, et al. Hiperqueratosis lenticular persistent. Actas Dermosifiliogr 1990;81:153-5.
14. Cooper SM, George S. Flegel’s disease treated with psoralen ultraviolet A. Br J Dermatol 2000;142:340-42.
15. Bayramgurler D, Apaydin R, Dokmeci S, et al. Flegel’s disease: treatment with topical calcipotriol. Clin Exp Dermatol 2002;2:161-2.

Additional Comment:

ACKNOWLEDGEMENT:

Thank you to Narciss Mobini MD who provided dermatopathology services in this case and assistance with obtaining photomicrographs of histologic findings.

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