A man, aged 38 years, presented with an asymptomatic, colorless, 3-cm lesion on his thigh. The lesion has been present since birth and has remained unchanged in size and appearance. The man was concerned because a friend had recently been diagnosed with amelanotic melanoma. The patient was otherwise in good health with no similar lesions elsewhere and no personal or family history of diseases manifesting on the skin. Punch biopsy of the lesion was performed and read as normal with no pathologic changes.
Asymptomatic skin changes began almost one year before this 53-year-old woman sought evaluation in dermatology. Her lesions, located on her upper shoulder, had also grown appreciably, adding to her concern. The woman’s primary-care provider had diagnosed the lesions as a fungal infection, but the oxiconazole (Oxistat) cream she applied to the lesions twice a day had provided no relief. OTC hydrocortisone 0.5% cream was ineffective as well. The patient was in good health otherwise and reported no difficulty swallowing, or breathing.
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Case #1: Nevus amenicus
A diagnosis of melanoma can have a ripple effect among friends and family, generating concern over a wide range of lesions, even ones present for many years. Fortunately, the appearance and congenital nature of the lesion in this case narrow the differential considerably, making the diagnosis of nevus anemicus (NA) all but certain.
First described in 1906, NA has since been investigated thoroughly. The condition appears to represent a localized vascular anomaly in which the defect is an increased sensitivity to catecholamines. For this reason, NA is perhaps best termed a “pharmacologic nevus,” a conclusion also supported by donor-site dominance in autograft exchange transplantation studies.1
In addition to being quite pale, NA macules are predictably cooler than surrounding skin; tend to vary in size and shape; and cannot be turned red by trauma, cold, heat, or even with injection of such vasodilatory agents as bradykinin, serotonin, histamine, acetylcholine, or nicotine.2 However, a sympathetic block or local intradermal injection of the potent alpha-adrenergic blocking agent pilocarpine (Salagen) allows the normal triple response of Lewis, strongly supporting the pharmacologic basis for what is seen with NA.3
NA is unusual but not rare. The condition is usually congenital, often presenting in early childhood with characteristic asymptomatic depigmented macules with irregular margins. The macules can measure up to 10 cm and can involve the presence of satellite lesions as well.
Typically an incidental finding on routine physical examination, NA is slightly more common in women but does not appear to have any racial predilection. The lesions can be solitary or multiple, linear or rounded, and are easily overlooked. They can be found on every part of the body, including the lips, but are most commonly seen on the upper trunk.
In certain cultures, especially in India, any loss of pigment in a child is viewed with alarm. This reaction is partly due to concern about possible Hansen disease (one type of which can present in such a manner), and partly because the darker skin of these people makes such lesions stand out so starkly, thus representing a “defect” for the entire world to see, including the parents of a potential spouse in an arranged marriage.
The finding of such a depigmented patch suggests several possible diagnoses, particularly vitiligo. Several useful techniques to separate NA from its lookalikes have evolved. For example, Wood’s lamp examination accentuates vitiligo and other truly depigmenting conditions but makes NA lesions all but disappear. Diascopy (i.e., viewing the lesion through a transparent glass slide or clear plastic convex instrument pressed to the skin) causes NA to merge with surrounding skin, while the margins of a vitiligo lesion remain distinguishable.
Unlike vitiligo, biopsy of NA lesions shows a normal amount of melanin and, remarkably, normal vasculature, even under electron microscopy. Biopsy is seldom necessary for diagnosis.
Nevus depigmentosus (ND) is another type of lesion in the differential for NA, but this condition is often dermatomal, is accentuated with Wood’s lamp examination, and turns red with vigorous stroking. ND is thought to represent a developmental defect of fetal melanocytes. Unlike the depigmented lesions of a type of Hansen disease, none of the other items in the differential for NA demonstrate a loss of sensation in the surface of the lesions.
As mentioned above, NA lesions are unique in their lack of an erythematous response to a linear scratch across the lesion, while surrounding normal skin reacts as expected. This sets NA lesions apart from such other items in the differential as the depigmented macules seen with tuberous sclerosis, neurofibromatosis, or as one component of phakomatosis pigmentovascularis.
A form of Hansen disease can also involve acquired areas of depigmentation, as can a large number of such other conditions as cutaneous T-cell lymphoma, tinea versicolor, nevus depigmentosus, lupus, and sarcoidosis.4,5
NA lesions are devoid of such epidermal change as atrophy, scaling, or other textural defects. This characteristic sets them apart from such other depigmenting conditions as lichen sclerosus et atrophicus and morphea.6 Along with the other methods of differentiation, the lack of surface detail of NA also helps to set it apart from other items in the differential.
Treatment of NA lesions is neither necessary nor possible, except as a means of camouflage or other cover-up. Again, biopsy is seldom necessary since a clinical diagnosis is usually apparent. The diagnosis of NA has no pathologic implication but does occasionally require definitive diagnosis with biopsy and copious patient and/or family reassurance.
In this case, the congenital nature of the lesion and its history of stability allowed ready differentiation from amelanotic melanoma,6-8 and no treatment was required.
Case #2: Lichen scherosus et atrophicus
The majority of cases of lichen sclerosus et atrophicus (LS&A) involve the genitals, but as this case illustrates, the condition can occur on nongenital skin as well. A chronic inflammatory condition, LS&A manifests with porcelain-white papules and plaques demonstrating epidermal atrophy.
Genital cases outnumber nongenital by 5:1, with the vast preponderance (6:1) of cases appearing in women. Oral involvement has also been described but is thought to be rare.9
LS&A is also seen on the penile glans, where it is termed balanitis xerotica obliterans (BXO). This skin disease presents most often in uncirmcumcised individuals, first as atrophy and whiteness of focal areas of the glans. BXO may then move proximally to result in a phimotic balanitis of the foreskin and, in the extreme, meatal stenosis. Also seen with vaginal LS&A, meatal stenosis is thought to be responsible for cases that present with dysuria.10
LS&A represents infiltration of the papillary dermis with altered fibroblastic function, leading to fibrosis and ultimately to atrophy of the upper dermis and epidermis.
The more common genital involvement with LS&A is usually symptomatic (in women more so than in men), predominantly with burning and itching. The symptoms frequently progress in severity in women (e.g., bleeding, obliteration of the labia minora, and stenosis of the introitus with resulting dyspareunia). Occasionally, the perivaginal inflammation becomes so severe that it results in the formation of bullae.9
In a fully developed case of LS&A, sharply demarcated hypopigmentation and atrophy outline the perivaginal and perianal areas, sparing the perineum, resulting in an hourglass or figure-eight appearance. This manifestation can be difficult to appreciate unless specifically sought on inspection of the area.10
Early on in extragenital LS&A, white polygonal papules and plaques marked by evenly spaced comedolike plugs correspond to obliterated appendiceal ostia. These plugs disappear over time, giving way to a smooth, porcelainlike, and shiny atrophic surface on which focal telangiectasias and purpura can be seen. The sizes of the lesions vary from multiple tiny guttate papules to confluent lesions involving large areas of the upper trunk.
LS&A is thought to result from autoantibodies to the glycoprotein extracellular matrix protein 1, which may be associated with histological evidence of vasculitis. The role of hypoxia and ischemia in the initial cellular and vascular damage is supported by the relative lack of vascular endothelial growth factor expressed in affected skin.11
Because LS&A and morphea can coexist and have similar histology, some authors posit that they are essentially the same condition.
Reports have long surfaced in Europe of the association of LS&A with Borrelia burgdorferi, but polymerase chain reaction-based studies in this country have failed to corroborate this theory. Although no definite cause is known, several authors have mentioned the possibility of an autoimmune basis.12
Under the microscope, the histologic picture of LS&A shows an interface dermatitis with vacuolar alteration of the keratinocytes early on. With maturation, the epidermis thins, and rete ridges are effaced. At the outset, the upper dermis is remarkably edematous, but this is transformed by dense homogenous fibrosis as the lesions mature.
The differential diagnosis for LS&A includes vitiligo, lichen planus, discoid lupus, atrophoderma of Pasini and Pierini, and morphea. When found on the genitals especially, the differential also includes extramammary Paget disease, Bowen disease, and erythroplasia of Queyrat, among others.10
The appearance of the patient’s lesion in this case was characteristic enough to allow visual identification, and treatment with clobetasol 0.05% cream every other day was instituted. While this strategy should at least stop the progression of the condition, the asymptomatic nature of extragenital LS&A often obviates treatment.
The use of such powerful topical steroids as clobetasol cream has proven so successful that it has drastically changed the therapeutic picture. Nevertheless, control is still a more likely outcome than is cure. Mild cases in young girls may clear on their own.
BXO is also treated with class 1 or 2 steroid creams or ointments but frequently requires circumcision to control the phimotic process. Pathologic examination of the removed tissue also serves to rule out focal cancerous transformation, which can also be seen in vaginal involvement, where it manifests as focal ulceration.12-14
Referral to urology may be necessary in cases of associated meatal stenosis. In cases of significant introital stenosis, a gynecologic consult is advised. LS&A in young girls can mimic sexual abuse; refer to pediatrics for evaluation if necessary.15
Joe Monroe, PA-C, specializes in dermatology at Dawkins Dermatology in Oklahoma City.
- Greaves MW, Birkett D, Johnson C. Nevus anemicus: a unique catecholamine-dependent nevus. Arch Dermatol. 1970;102:172-176.
- James WD, Berger TG, Elston DM. Dermal and subcutaneous tumors. In: Andrews’ Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, Pa.: Saunders-Elsevier; 2006:582.
- Ahkami RN, Schwartz RA. Nevus anemicus. Dermatology. 1999;198:327-329.
- Castori M, Rinaldi R, Angelo C, et al. Phacomatosis cesioflammea with unilateral lipohypoplasia. Am J Med Genet A. 2008;146A:492-495.
- Mountcastle EA, Diestelmeier MR, Lupton GP. Nevus anemicus. J Am Acad Dermatol. 1986;14:628-632.
- Alagheband M, Engineer L. Nevus anemicus. Skin and Aging. 1998;11:60.
- Requena L, Sangueza OP. Cutaneous vascular anomalies. Part I. Hamartomas, malformations, and dilation of preexisting vessels. J Am Acad Dermatol. 1997;37:523-549.
- Medscape Reference. Nevus anemicus.
- Medscape Reference. Lichen sclerosus et atrophicus.
- James WD, Berger TG, Elston DM. Lichen planus and related conditions. In: Andrews’ Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, Pa.: Saunders-Elsevier; 2006:227-229.
- Chan I, Oyama N, Neill SM, et al. Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Clin Exp Dermatol. 2004;29:499-504.
- De Vito JR, Merogi AJ, Vo T, et al. Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases. J Cutan Pathol. 1996;23:350-358.
- Bjekic´ M, Šipetic´ S, Marinkovic´ J. Risk factors for genital lichen sclerosus in men. Br J Dermatol. 2011;164:325-329.
- Jones RW, Sadler L, Grant S, et al. Clinically identifying women with vulvar lichen sclerosus at increased risk of squamous cell carcinoma: a case-control study. J Reprod Med. 2004;49:808-811.
- Meffert JJ, Davis BM, Grimwood RE. Lichen sclerosus. J Am Acad Dermatol. 1995;32:393-416.
All electronic documents accessed August 15, 2012.