Enlarging white patches

CASE #1: Vitiligo Vitiligo was first described in 1500 B.C. and may have been derived from the Latin word vitium, meaning "blemish" or vitelilus, meaning the "white, glistening flesh of calves."1 Throughout history, confusion with such disorders as leprosy continually...

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CASE #1: Vitiligo

Vitiligo was first described in 1500 B.C. and may have been derived from the Latin word vitium, meaning “blemish” or vitelilus, meaning the “white, glistening flesh of calves.”¹ Throughout history, confusion with such disorders as leprosy continually provoked discrimination and segregation for vitiligo sufferers. Unfortunately, it was not until the late 19th century that significant progress was made in the understanding of vitiligo and the melanocyte was discovered as the causative factor.

Vitiligo affects approximately 0.5% to 2% of the population worldwide.² It may appear at any age throughout life, with the average age of onset being approximately 20 years.

The pathogenesis of vitiligo is largely unknown but is thought to be multifactorial. Many believe that vitiligo results in the destruction and loss of histochemically recognizable melanocytes. However, others have proposed that melanocytes may still be present in very small numbers or in an undifferentiated state without melanogenic activity.

The importance of genetics in the development of vitiligo has been demonstrated in various twin and family studies. Interestingly, these genetic associations seem to be strongest in families with various vitiligo-associated autoimmune diseases rather than in those with only localized or generalized vitiligo.

Many hypotheses surrounding the destruction of melanocytes exist. These include such theories as an autoimmune destruction, an intrinsic defect of melanocytes, a defective free-radical defense, reduced melanocyte survival, destruction by autocytotoxic metabolites, membrane lipid alterations, a deficiency of unidentified melanocyte growth factors, destruction by neurochemical substances, and a viral cause.

A convergence theory has also been proposed, in which several of these factors are thought to contribute in some way to the phenomenon of vitiligo.

Vitiligo most commonly presents as an amelanotic macule or patch that is surrounded by normal-appearing skin. Lesions of vitiligo expand centrifugally and the borders are usually convex, making it appear as if the depigmented areas are invading the normal skin. The macules and patches of vitiligo usually have well-defined borders and range from a few millimeters to several centimeters in size. Lesions may be round, oval, or linear in shape.

Vitiligo may also display the Koebner phenomenon, which is defined as the development of vitiligo at the sites of trauma.

Patients are usually asymptomatic; however, pruritus may occasionally be present. In individuals with fair skin, the lesions of vitiligo may be difficult to appreciate. However, visualization may become more apparent with the help of a Wood’s lamp or after tanning of uninvolved skin.

Vitiligo can be classified into localized, generalized, and universal types. The localized type includes such variants as focal, segmental, and mucosal. Focal vitiligo affects one nondermatomal site (e.g., the glans penis). Segmental, or unilateral, vitiligo presents with one or more macules involving a unilateral segment of the body.

Segmental vitiligo tends to appear at an earlier age and is resistant to treatment. In mucosal vitiligo, only mucosal-membrane lesions exist. The generalized pattern is the most common and includes such variants as vulgaris, acrofacial, and mixed. Vitiligo vulgaris features scattered patches of vitiligo that are widely distributed. In acrofacial vitiligo, patients present with lesions that are limited to the distal extremities and face. Mixed vitiligo may present as several combinations of the above subtypes. Universal vitiligo results in complete or nearly complete depigmentation.

Most patients with vitiligo are otherwise healthy. However, there has been an association with various autoimmune endocrinopathies, in particular thyroid dysfunction. Most studies on the subject point to an increased risk in individuals with increasing age.³ However, these studies are controversial, and most recommend that clinicians be aware of the increased risk and be attentive to symptoms of thyroid disease.

On histopathology of well-established lesions, a complete absence of melanocytes will be noted. Although most lesions do not demonstrate an inflammatory infiltrate, early lesions may show a superficial perivascular and occasionally lichenoid mononuclear cell infiltrate at the border.

The differential diagnosis for vitiligo includes chemical leukoderma, postinflammatory hypopigmentation, halo nevi, tinea versicolor, leprosy, leukoderma associated with scleroderma, late stages of treponematosis or onchocerciasis (river blindness), hypopigmentation associated with topical corticosteroid use and lichen sclerosus.

Treatment of vitiligo is aimed at stabilizing the depigmenting process and gaining repigmentation. There are a number of treatment options (many of which are off-label); however, there is no single therapeutic approach that works in all patients.

The areas that tend to have the highest degree of repigmentation are the face, mid-extremities, and trunk. The treatment of choice for generalized vitiligo is narrowband UVB. Excimer laser phototherapy can also be effective on limited areas. Potent or superpotent topical corticosteroids may be useful for localized areas, but patients should be advised to discontinue treatment after two months if there is no visible improvement and should be warned about the possibility of atrophy.

Systemic corticosteroids can halt rapidly progressing vitiligo but cannot be used long-term due to their toxicity. Topical 0.1% tacrolimus (Protopic) ointment has also resulted in repigmentation of vitiligo and is often used on the face and genitals. For recalcitrant stable vitiligo, such surgical therapies as autologous transplantation may be performed. If more than 50% to 80% of the body surface area is affected, consider depigmentation with monobenzone (Benoquin) 20%.

The course of the disease is very unpredictable. Every individual is different, and while some degree of spontaneous repigmentation is not uncommon, complete and stable repigmentation is rare.

The boy in this case was treated with tacrolimus 0.1% ointment. Some repigmentation was noted at a follow-up appointment two months later.

CASE #2: Lichen sclerosus

Ferdinand Jean Darier made the first histologic description of lichen sclerosus in 1882.⁴ In 1887, Francois Henri Hallopeau reported the first clinical description and named the entity lichen plan atrophique. Other terms that have been used include lichen sclerosus et atrophicus, kraurosis vulvae, and balanitis xerotica obliterans. As proposed by the International Society for the Study of Vulvar Disease, today the entity is now most commonly known as lichen sclerosus.

Lichen sclerosus is relatively uncommon, and the prevalence in the female population is thought to be approximately 1.7%. All ages may be affected by the disorder; whites tend to be preferentially affected, and females predominate at all ages. Females also tend to have a bimodal age distribution, with peaks occurring in prepubertal girls and postmenopausal women. In both sexes, the anogenital area is affected in approximately 85% of cases.

The pathogenesis of lichen sclerosus is poorly understood. Inflammation seems fundamental for the initiation of lichen sclerosus; however, the mechanisms leading to subsequent sclerosis remain unknown.

A genetic predisposition is thought to contribute to the development of lichen sclerosus, and an association with MHC class II antigen HLA-DQ7 has been observed.⁵ Interestingly, this same region is also associated with an increased risk of autoimmune diseases. Immunoglobulin G autoantibodies to extracellular matrix protein 1 have been found in approximately 80% of individuals with lichen sclerosus.⁶

Although detection of the antibody may be helpful in diagnosing the disorder, it has no role in quantifying the extent of the disease. Other proposed causal factors include oxidative stress, infections, and hormonal influences.

Lichen sclerosus can affect both anogenital and extragenital skin. In women, anogenital involvement is most commonly observed on the vulva and the perianal region. The lesion will often encircle both the genitalia and the perianal region, forming a figure-eight configuration. Lesions in women begin as areas of sharply demarcated and slightly raised erythema. Areas may then become eroded and eventually evolve into a dry and hypopigmented sclerotic patch.

Early lesions may occasionally appear bruised, hemorrhagic, or eroded. Girls and women who present for treatment of this complaint may be misdiagnosed as victims of sexual abuse. Patients frequently complain of severe pruritus and pain. Due to the fissuring and erosions, patients may also complain of dysuria, dyspareunia and/or pain with defecation. Constipation is a common complaint in children with lichen sclerosus. If left untreated, the atrophy may become so severe that it leads to shrinkage or obliteration of the labia major, labia minora and/or clitoris.

In males, lesions usually only involve the glans penis; however, they can extend onto the penile shaft and scrotum. The lesions are atrophic and markedly hypopigmented or depigmented. Phimosis and paraphimosis are common complications. Most men with lichen sclerosus are uncircumcised. However, circumcision in these patients does not universally “cure” the disease. If left untreated, urethral meatal stenosis may occur.

Extragenital lichen sclerosus is more common in older age groups and is often asymptomatic. Patients may occasionally complain of dryness or pruritus. The extragenital lesions occur most commonly on the neck, flexural surfaces of the wrists, and sites of physical trauma or continuous pressure such as the shoulder or hip. The tongue and oral mucosa are rarely involved.

Lesions begin as bluish-white shiny papules that may coalesce into plaques or patches and eventually develop into a scarlike atrophy with an ivory color. Telangiectasias and follicular plugging may be seen in advanced stages, and lesions may occasionally develop hemorrhagic bullae.

Histologically, lesions of lichen sclerosus show a trilayered appearance, often described as the “red, white, and blue” sign. The first zone is the compact hyperorthokeratotic scale and atrophic epidermis (red) with vacuolar degeneration.

The second, deeper zone is the pale edematous dermis (white) and subjacent is a variably dense interstitial lymphocytic inflammatory infiltrate (blue). Established lesions demonstrate hyperkeratosis with an atrophic epidermis, pale superficial dermal stroma, and rare inflammatory cells. A cleftlike space often separates the atrophic epidermis from the pale dermis.

Extragenital lichen sclerosus must be differentiated from vitiligo, morphea, anetoderma, discoid lupus erythematosus, idiopathic guttate hypomelanosis, post-inflammatory hypopigmention, and chemical leukoderma.

Genital lichen sclerosus may mimic lichen planus, lichen simplex chronicus, vulvar intraepithelial neoplasia, erythroplasia of Queyrat, vitiligo, and extramammary Paget disease.

Early aggressive treatment with such superpotent topical steroids as clobetasol has been shown to prevent disease progression.⁷ In most relevant studies, clobetasol propionate 0.05% cream was applied for 12 to 24 weeks.⁸ The majority of patients undergoing this treatment showed a significant improvement in pruritus and burning, but the visible white and atrophic skin is often only minimally improved. Long-term side effects have not been seen, even with long-term and maintenance use of clobetasol.

Topical tacrolimus 0.1% and 0.03% ointments, along with pimecrolimus (Elidel) 1% cream, have also been proven effective, but should only be used when topical steroids are not effective or are not tolerated.

In refractory cases, such off-label treatments as hydroxychloroquine (Plaquenil), topical calcitriol (Vectical), topical calcipotriol, cyclosporine (Gengraf, Neoral, Sandimmune), topical tretinoin, acitretin (Soriatane), and hydroxyurea (Droxia, Hydrea) may be tried. Phototherapy and surgery are other options. Circumcision is the treatment of choice for genital lichen sclerosus in males.

Persons with lichen sclerosus have a lifetime risk of approximately ≤5% of developing squamous cell carcinoma. Patients should be educated on this risk and monitored on a regular basis for progression.

As for the woman in this case, biopsy confirmed the diagnosis of lichen sclerosus, and the patient was treated with clobetasol 0.05% ointment daily for three months. On follow-up, the patient reported no pruritus, but the lesion had only improved minimally.

Kerri Robbins, MD, is an instructor in the Department of Dermatology at Baylor College of Medicine in Houston.

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TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read White facial papules and sparse, brittle hair and Painful, nonbleeding lesion on the ear.

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