Man Presents with Growing Lesions on Upper and Lower Extremities

A 49-year-old white male presented with well-circumscribed lesions on both the upper and lower extremities of 10 years duration. The lesions were slowly increasing in size and number, without any associated symptoms. He was a construction worker and spent most of his time outdoors. His past health was unremarkable and he was not on any medications. He believed that his father, now passed away, may have had similar skin lesions.

PHYSICAL EXAMINATION

The patient had multiple, well-demarcated, brown macules on both upper and lower extremities. The majority of lesions were oval and only slightly asymmetrical in shape. The peripheral ridge was slightly raised compared to an atrophic center. 

What's Your Diagnosis?

A. Porokeratosis
B. Psoriasis
C. Actinic keratosis
D. Seborrheic keratosis
E. Solar lentigo

(Answer and discussion on next page)

Answer: Porokeratosis

Porokeratosis is a disorder of keratinization, characterized clinically by centifugally enlarging macules or patches with central atrophy, raised hyperkeratotic borders, and histologically, by a distinctive hyperkeratotic ridge-like border (cornoid lamella).¹ The disorder was first described by Vittorio Mibelli in 1893 and now bears his name.² Different variants of porokeratosis have subsequently been described.

Epidemiology 

Porokeratosis is an uncommon disorder, although the exact prevalence is not known. In one study, 94 patients with porokeratosis were seen at the National Skin Centre in Singapore between 2000 and 2010.³ The disorder is most prevalent in Caucasians, particularly Italians, and is rarely observed in dark-skinned people. The peak age of onset and the sex ratio vary with different variants of porokeratosis (vide infra). 

Etiopathogenesis

The condition has an autosomal dominant mode of inheritance with incomplete penetrance.⁴ Focal forms of parakeratosis, such as porokeratosis of Mibelli and linear porokeratosis, may occur as a consequence of mosaicism.^1,4 Several susceptible loci have been identified, such as disseminated superficial actinic porokeratosis (DSAP)1 (12q23.2-24.1), DSAP2 (15p25.1-26.1), DSAP3 (1p31.3-p31.1), and DSAP4 (16q24.1.1-24.3).¹ Predisposing factors include irradiation, mechanical trauma, immunosuppression, medications (eg, thiazide), liver disease, and Crohn’s disease.^1,4 

Histopathology

Histological findings include compact columns of parakeratotic cells (cornoid lamella) overlying an area of invagination, absence of a granular layer in the base of invagination, and often a thin epidermis.⁵ A mild perivascular mononuclear cell infiltrate may be seen in the dermis.⁴ The cornoid lamella is often very prominent in porokeratosis of Mibelli.¹

Clinical Manifestation

According to the number, size, and distribution, the following main clinical variants of porokeratosis have been recognized. These include DSAP, disseminated superficial porokeratosis, porokeratosis of Mibelli, punctate porokeratosis, porokeratosis palmaris et plantaris disseminata, and linear porokeratosis.^1,4 Rarer variants, which will not be discussed, include genitogluteal porokeratosis, porokeratosis ptychotropica, follicular porokeratosis, and eruptive pruritic papular porokeratosis.¹

DSAP is the most common type of porokeratosis.⁵ The term was coined by Andrew in 1937 as a clinical variant of porokeratosis of Mibelli.⁶ The condition is characterized by multiple skin-colored, erythematous, or hyperpigmented macules on sun-exposed areas as is illustrated in the present case.⁵ The lesions have atrophic centers and hyperkeratotic rims (typically “double-edged”). They are typically less than 1 cm in diameter and are slowly progressive.⁴ Pruritus and/or stinging occur in 33% to 50% of patients.^1,5 Sites of predilection include the extensor surfaces of the limbs, shoulders, and back.^1,4 There is often a history of extensive exposure to natural or artificial ultraviolet radiation.¹ Approximately 50% of patients have exacerbation during the summer months.⁴ The condition usually occurs during the third or fourth decades of life.^1,4 The female to male ratio is 1.8:1.^1,4 

Disseminated superficial porokeratosis is clinically similar to DSAP except that ultraviolet light does not act as an eliciting factor.⁴ The lesions occur both in the sun-exposed areas and non sun-exposed areas.^1,4 Disseminated superficial porokeratosis typically presents between 5 and 10 years of age.^1,4 

Porokeratosis of Mibelli is the second most common type of porokeratosis.¹ Typically, it presents with a single or multiple plaques of variable size, predominately on an extremity. The border is usually greater than 1 mm high and a thin furrow is seen in the center of the ridge.¹ The lesion may be asymptomatic or slightly pruritic. Rarely, the lesion is giant sized. The disorder usually presents in childhood or adolescence. The male to female ratio is 2 to 3:1.⁷

Punctate porokeratosis is characterized by multiple, seed-like, keratotic lesions with thin, raised margins and/or pits on the palms and soles.¹

Porokeratosis palmaris et plantaris disseminata is characterized by relatively small, uniform macules on the palms and soles.¹ The peripheral ridge is minimally raised with an atrophic center. The lesion may be asymptomatic or pruritic.¹

Linear porokeratosis can be localized or generalized. The more common localized form is characterized by single or multiple plaques with hyperkeratotic peripheral rims linearly and unilaterally distributed on one extremity.^1,4,8 The hyperkeratotic border is often prominent. In the rare generalized form, lesions are multiple, and found on more than one extremity or on the trunk following the lines of Blaschko.^1,4,8 Linear porokeratosis typically presents during infancy or early childhood.¹ There is a slight female predominance.^1,4

Diagnosis

The diagnosis is mainly clinical. If necessary, marker ink or iodine and fake suntan can be used to make the distinctive outer rim of the lesion more obvious.^1,9 The use of dermoscopy and confocal microscopy facilitate visualization of the cornoid lamella. Dermoscopy and confocal microscopy of the lesion reveal a peripheral white rim (corresponding to the cornoid lamella) in conjunction with multiple dotted and linear irregular vessels.¹⁰ A skin biopsy or referral to a dermatologist should be considered if the diagnosis is in doubt.

Differential Diagnosis 

Differential diagnosis includes psoriasis, actinic keratosis, seborrheic keratosis, solar lentigo, pityriasis rosea, psoriasis, nummular eczema, tinea corporis, granuloma annulare, Bowen’s disease, squamous cell carcinoma, melanoma, Darier’s disease, lichen nitidus, nevoid basal cell nevus syndrome, porokeratotic eccrine ostial and dermal duct nevus, benign hamartoma of the eccrine sweat glands, and hereditary punctate keratoderma.^4,5,7

Complications 

Malignant transformation, with the exception of punctate keratosis, occurs in approximately 7% to 11% of patients with porokeratosis.^1,7 Linear porokeratosis and the rare giant porokeratosis (a manifestation of porokeratosis of Mibelli) have a higher incidence of malignant transformation.^1,4 On the other hand, patients with DSAP have an extremely low risk of malignant transformation.¹ Squamous cell carcinoma is the most common malignancy, followed by Bowen’s disease and basal cell carcinoma.^1,7 

Prognosis

Without treatment, the lesions tend to persist. Spontaneous regression is rare.¹

Management 

The importance of sun protection and periodic screening for malignancy cannot be overemphasized. Treatment is not required for the majority of patients with porokeratosis, but may be considered for cosmetic reasons and for symptomatic lesions. Treatment should be individualized and the patient’s preferences should be taken into consideration. In general, for patients with a few small lesions, treatment is most commonly with cryotherapy and, less commonly, using electrodessication and curettage or surgical excision.¹ For patients with large and multiple lesions, treatment options include topical imiquimod, topical 5-flurouracil, topical keratolytics (eg, salicyclic acid), topical retinoids and, less commonly, topical vitamin D analogs.^1,11 Additional choices for destruction of the lesion include dermabrasion, chemical peels, laser therapy, and photodynamic therapy with methyl aminolevulinate.^1,4,7 Systemic retinoids should be reserved for severe cases. 

Alexander K.C. Leung, MD, is clinical professor of pediatrics at the University of Calgary and pediatric consultant at the Alberta Children’s Hospital in Calgary, Alberta, Canada.

Benjamin Barankin, MD, is a dermatologist, medical director, and founder of the Toronto Dermatology Centre in Toronto, Ontario, Canada.

References:

1. Spencer LV. Porokeratosis. Medscape. http://emedicine.medscape.com/article/1059123-overview#a0101. Updated September 9, 2014. Accessed May 20, 2015.

2. Mibelli V. Contribute allo studio della ipercheratosi dei canali sudoriferi (porokeratosis). G Ital Mal Ven. 1893;28:313-355.

3. Tan LS, Chong WS. Porokeratosis in Singapore: an Asian perspective. Australas J Dermatol. 2012;53(2):e40-e44.

4. Sertzing P, von Felbert V, Megahed M. Porokeratosis: present concepts. J Eur Acad Dermatol Venereol. 2012;26(4):404-412.

5. Rouhani P, Fischer M, Meehan S, et al. Disseminated superficial actinic porokeratosis. Dermatol Online J. 2012;18(12):24.

6. Andrew GC. Porokeratosis (Mibelli) disseminated and superficial type. Arch Dermatol Syphilol. 1937;36:1111.

7. Ferreira FG, Santos N, Tagliarini FA, Lira ML. Porokeratosis of Mibelli—literature review and a case report. An Bras Dermatol. 2013;88(6 Suppl 1):179-182.

8. Curkova AK, Hegyi J, et al. A case of linear porokeratosis treated with photodynamic therapy with confocal microscopy surveillance. Dermatol Ther. 2014;27(3):144-147.

9. Katugampola RP, Finlay AY. Fake sun tan diagnosis of porokeratosis. J Eur Acad Dermatol Venereol. 2000;20(2):224-226.

10. Moscarella E, Longo C, Zalaudek I, et al. Dermoscopy and confocal microscopy clues in the diagnosis of psoriasis and porokeratosis. J Am Acad Dermatol. 2013;69(5):e231-e233.

11. Gajic B, Tang K, Whitfeld M. Porokeratosis of Mibelli: involution and resolution with 5% imiquimod cream. Australas J Dermatol. 2011;52(4):301-303.