What is Causing The Pain and Pruritus in This Man’s Penile Area?

A 48-year-old man presented with pain and pruritus in the penile area of approximately 15 months’ duration. The pain was worse with penile erection and he had difficulties with sexual intercourse. He had Hashimoto’s thyroiditis and was treated with thyroxine replacement. His past health was otherwise unremarkable. In particular, he was not circumcised and there was no history of trauma. 

PHYSICAL EXAMINATION

Physical examination revealed multiple, sclerotic, ivory-white plaques on the glans penis. The inner surface of the prepuce was sclerotic with areas of erosions and ulcerations. The prepuce was tight, inelastic, and nonretractile. He did not have skin lesions elsewhere. 

What's Your Diagnosis?

A. Lichen planus
B. Psoriasis
C. Leukoplakia
D. Lichen sclerosus

(Answer and discussion on next page)

Answer: Genital lichen sclerosus 

Lichen sclerosus (also called lichen sclerosus et atrophicus) is an autoimmune, chronic, progressive, inflammatory dermatosis that presents with sclerosis, atrophy, and pruritus predominately affecting the anogenital area. Approximately 6% to 15% of patients present with extragenital lesions.^1,2 The lesions typically begin as polygonal papules that coalesce into porcelain white plaques. The disorder was first described clinically by Hallopeau³ in 1887 and histologically by Darier⁴ in 1892.

EPIDEMIOLOGY 

The exact prevalence is not known. It is estimated lichen sclerosus accounts for 1 in 300 to 1000 patients who are referred to dermatologists.⁵ The female to male ratio is 6 to 10:1.⁶ White people are more commonly affected.^6,7

In females, it has bimodal age peaks of onset, in the prepubertal and postmenopausal years.⁸ In males, it also has a bimodal onset, with age peaks in young boys and men between 30 and 49 years of age.^6,8 

ETIOPATHOGENESIS

Lichen sclerosus is a chronic, inflammatory, lymphocyte-mediated dermatosis that is believed to be autoimmune in nature. Other autoimmune diseases such as Hashimoto’s thyroiditis, alopecia areata, diabetes mellitus type 1, celiac disease, and pernicious anemia occur with increased frequency in patients with lichen sclerosus.^1,5 Detection of autoantibodies to extracellular matrix 1 protein and basement membrane zone in approximately 75% of affected patients suggests that autoimmunity to these components might contribute to the pathogenesis.^1,5

There is a genetic predisposition as evidenced by the occurrence of familial cases and its significant association with HLA-DQ7 and DRB1*12.9. 

Lichen sclerosus is more common in uncircumcised males. The occlusive, moist environment under the prepuce may play a role in its development. Chronic exposure of a susceptible epithelium to urine may also be responsible.⁹ 

Genital lichen sclerosus has been reported following genital jewelery, trauma, and instrumentation.¹ Koebner phenomenon has been postulated as a causative factor as well. Lichen sclerosus occurs with increased frequency in patients with atopy or morphea.

Several infective agents—such as Borrelia burgdorferi, Epstein-Barr virus, human papillomavirus, and acid fast bacilli—have been incriminated.¹ However, such a relationship has not been unequivocally established.⁵

In females, lack of estrogen has been suggested as a causative factor as the condition is most commonly observed in low estrogen states, such as prepubertal girls and postmenopausal women.^5,6 However, there is no association of lichen sclerosus and pregnancy, contraceptive use or hormonal replacement, or hysterectomy.^5,6

HISTOPATHOLOGY

Characteristic histopathologic findings include epidermal atrophy with hyperkeratosis, follicular plugging, loss of rete ridges, degeneration of the basal cells, and homogenization of the collagen in the upper dermis with an underlying lymphocytic infiltrate.^1,6,9

CLINICAL MANIFESTATIONS

The classic symptoms are pain and intense pruritus.^8,9 The latter is often worse at night. The lesions typically begin as polygonal papules that coalesce over time into porcelain-white, atrophic, fragile patches and/or plaques with epidermal wrinkling. 

In adult males, lichen sclerosus usually affects the prepuce, glans penis, coronal sulcus and, less commonly, the penile shaft. Rarely, the perianal region may also be affected.^6,8 In the early stage, there are grayish- or bluish-white discolorations on the glans and/or the inner surface of the prepuce.¹ As the disease progresses, atrophy of the skin and sclerotic plaques ensue. The prepuce may become tightened and nonretractile.¹ The affected inelastic skin is prone to erosions, ulcerations, and fissuring, especially with sexual intercourse.¹ Ecchymosis, purpura, and bullae may also be seen. In boys, phimosis as a result of scarring of the prepuce is the most common presenting symptom. Other symptoms include dysuria, deviation of the urinary stream, and ballooning of the prepuce during voiding. Physical examination typically shows a white, porcelain-like, circumferential, sclerotic plaque on the distal prepuce, appearing as a whitish ring.⁷

In adult females, the characteristic sites involved are the interlabial sulci, labia majora, labia minora, clitoris, clitoral hood, perineum, and perianal area, giving rise to the characteristic “figure-of-eight” or “hourglass” shape.^1,8 The genital mucosa is usually not affected. Typically, the affected skin has an ivory-white, parchment-like or cellophane paper-like (often called “cigarette paper wrinkling”) appearance. Fragility and wrinkled skin are hallmarks of lichen sclerosus.^1,9 Over time, the epidermis becomes atrophic, dry, and hypopigmented and the dermis becomes sclerotic. Excoriations, ulcerations, fissuring, ecchymosis, purpura, and lichenification may be seen as a result of repeated scratching. Affected females may have vulvar pruritus, pruritus ani, dyspareunia, and dysuria.^5,9 Prepubertal girls show the same skin changes seen in adult females. They often present with irritation, itchiness, and soreness in the affected area. Perianal involvement is a frequent finding in young girls and affected girls may present with painful defecation, constipation, fecal soiling, and anal fissures.⁸ 

DIAGNOSIS 

The diagnosis is mainly clinical and can be aided by dermoscopy. Skin biopsy or referral to a dermatologist is warranted if the diagnosis is in doubt.

LABORATORY STUDIES

Because of the associations with autoimmune diseases, screening with a thyroid-stimulating hormone, antithyroglobulin antibody, antithyroid peroxidase antibody, complete blood count, fasting blood glucose/hemoglobin A1c, and antinuclear antibody should be considered.⁸ A potassium hydroxide wet-mount examination of skin scrapings should be performed if a coexisting fungal infection is suspected. Likewise, a bacterial culture should be performed if secondary bacterial infection is suspected.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis includes lichen planus, lichen simplex chronicus, allergic or irritant dermatitis, seborrheic dermatitis, leukoplakia, vitiligo, psoriasis, cicatricial pemphigoid, and morphea.

Complications

Lichen sclerosus can lead to scarring and destruction of the genital structure.⁹ In males, this may result in phimosis, erectile dysfunction, and painful erection. In females, this may result in burying of the clitoris, fusion of the labia minora, and narrowing of the vaginal introitus. Dyspareunia and sexual dysfunction are not uncommon. Urethral involvement may result in meatal or urethral stenosis and obstruction.¹ Lichen sclerosus has tremendous negative impact on the patient’s quality of life as a result of pruritus, pain, poor self-image, marked distress, and anxiety. Genital lichen sclerosus is associated with an increased risk of squamous cell carcinoma and verrucous carcinoma.²

PROGNOSIS

The disease tends to run a chronic, progressive, protracted course with exacerbations and remissions.⁶ Spontaneous remissions are possible.

TREATMENT

Ultrapotent topical corticosteroids are the mainstay of therapy.^8-10 Topical immunomodulators, such as tacrolimus and pimecrolimus, are not as fast-acting or effective as ultrapotent topical corticosteroids in the treatment of this skin condition, although they can be considered in the maintenance phase of treatment.¹ Emollients should also be used to help repair the skin barrier. Other less commonly used treatment options include topical and systemic vitamin A and D analogues, systemic corticosteroids, systemic hydroxychloroquine, topical and systemic cyclosporine, phototherapy, photodynamic therapy, and surgery.^1,5 The latter should be considered for patients who need correction of functionally incapacitating, scarring processes such as urethral stricture, meatal stenosis, and narrowed vaginal introitus that interferes with sexual intercourse. ■

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

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

References:

1. Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol. 2013;14(1):27-47.
2. Rosenthal IM, Taube JM, Nelson DL, Erdag G. A case of infraorbital lichen sclerosus. Dermatol Online J. 2013;19(10):20021.
3. Hallopeau H. Lecons Clinique sur les maladies cutanees et syphilitique. L’Union Medicale. 1887;43:742-747.
4. Darier J. Lichen plan sclereux. Ann Dermatol Syph. 1892;2:833-837.
5. Cooper SM, Arnold SJ. Vulvar lichen sclerosus. In: Post TW, ed. UpToDate. Waltham, MA. Accessed November 10, 2014.
6. Pugliese JM, Morey AF, Petwerson AC. Lichen sclerosus: review of the literature and current recommendations for management. J Urol. 2007;178(6):2268-2276.
7. Christman MS, Chen JT, Holmes NM. Obstructive complications of lichen sclerosus. J Pediatr Urol. 2009;5(3):165-169.
8. Neill SM, Lewis FM, Tatnall FM, et al. British Association of Dermatologists’ guidelines for the management of lichen sclerosus 2010. Br J Dermatol. 2010;163(4):672-682.
9. Murphy R. Lichen sclerosus. Dermatol Clin. 2010;28(4):707-715
10. Chi CC, Kirtschig G, Baldo M, et al. Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus. J Am Acad Dermatol. 2012;67(2):305-312.