Are You Confident of the Diagnosis?

What you should be alert for in the history

Nevus anemicus (NA) may be present at birth or early childhood and is not hereditary. The lesion should not elicit symptoms.

Characteristic findings on physical examination

NA is characterized by well-defined, hypopigmented macules often forming a patch of varying size and shape (Figure 1). The margins are usually irregular and there may or may not be islands of normal skin scattered throughout the nevus with surrounding smaller satellite macules. NA occurs predominantly on the trunk, although lesions on the head, neck, and extremities have been reported. It is slightly paler than the surrounding skin and thus can be easily overlooked on physical examination. It is an asymptomatic lesion.

Figure 1.

A newborn infant with a nevus anemicus on the left lateral neck.

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Expected results of diagnostic studies

Histological examination demonstrates a normal epidermis and melanocytes in the basal layer as well as a normal-appearing dermis, dermal appendages, and blood vessels. A sparse mononuclear cell infiltrate around superficial blood vessels in the dermis can be seen. Few reports have described abnormal superficial blood vessels with narrow and slit-like lumina and tightly apposed endothelial cells lining the blood vessel walls.

Electron microscopy (EM) findings have mirrored those found on light microscopy. Under Wood’s light examination, NA is not accentuated and becomes indistinguishable from the surrounding normal skin. Diascopy with a glass microscope slide obliterates the border between the NA and normal skin, making the lesion inapparent. Gross sensory response is unaffected with the hypopigmented macule. Friction or heat application fails to induce erythema in the lesion compared to the surrounding normal skin and enhances the nevus.

Firm stroking through lesional and nonlesional skin will elicit the triple response of Lewis in normal skin with an abrupt lack of response in the NA. Only the wheal without a flare may be visible within the confines of the lesion.

Diagnosis confirmation

There are conditions of hypomelanosis that may mimic NA and should be considered in the differential. NA can most often be differentiated from these conditions via the mechanical methods described above (such as diascopy and Wood’s lamp examination). Histological examination should be infrequently needed and would reveal no abnormality in the pigmentary system.

Nevus depigmentosus is a congenital nonfamilial leukoderma that presents as a white patch at birth, although in fair-skinned infants it may not be noted until later on. It is due to a functional defect of melanocytes demonstrating abnormal melanization with a normal number of melanocytes. Under EM, stubby dendrites representing decreased melanization, decreased melanosomes within keratinocytes, and aggregation of melanosomes in melanocytes are seen. Mechanical stimulation of nevus depigmentosus induces a triple response of Lewis in the lesion, unlike in a NA where no flare occurs with friction. Also, the hypopigmentation of a nevus depigmentosus will be slightly accentuated with Wood’s lamp examination, unlike NA.

Vitiligo consists of a hypopigmented to depigmented macule or patch that can be distinguished from NA via Wood’s lamp examination, which will accentuate vitiligo but not NA. Also, histological examination of vitiligo demonstrates the absence of melanocytes.

The hypomelanotic macules found in tuberous sclerosis are ovoid or leaf-shaped and seen shortly after birth or in early infancy on the trunk and limbs. Under EM, these macules show decreased melanin synthesis and small melanosomes. The use of a Wood’s lamp will accentuate these lesions.

Bier spots represent a benign physiologic vascular anomaly that manifest as transient, small, hypopigmented macules on the upper and lower extremities of young adults. The intervening skin often appears erythematous and will blanch with pressure, making the hypopigmented macules disappear.

The hypopigmented and hyperpigmented patches with scaling and the presence of Malassezia organisms via potassium hydroxide preparation easily distinguishes tinea versicolor from NA. Tinea versicolor commonly presents during puberty and into adulthood on the chest and back.

Who is at Risk for Developing this Disease?

NA is a rare congenital lesion that may be more common in the female population. It is not hereditary.

What is the Cause of the Disease?

NA is a nonmelanotic disorder caused by localized hypersensitive alpha-adrenergic receptor sites of cutaneous arterioles to catecholamines, inducing active vasoconstriction. This was confirmed in a study describing donor dominance of the hypopigmented skin in a transplanted plug of nevus anemic into normal skin. The group confirmed that the vasoconstriction was due to hypersensitive receptors in the cutaneous blood vessels and not due to the previous belief of increased sympathetic stimulation. Phentolamine, an alpha-adrenergic blocking agent was shown in multiple studies to produce erythema in the nevus anemic to the same degree of the surrounding normal skin, demonstrating the enhanced adrenergic tone of the nevus.

Systemic Implications and Complications

In the majority of cases, NA is an isolated skin finding; however, associations with neurofibromatosis and vascular malformations such as port-wine stains have been described. NA and port-wine stains in the same individual have been explained by the theory of “twin-spotting”, resulting from somatic recombination. NA may coexist with pigmentary nevi as part of phakomatosis pigmentovascularis type II, III, or IV.

Treatment Options

There are no recommended treatment options, as nevus anemic is benign, asymptomatic, and subtle. Cosmetic make-up can make the nevus more aesthetically pleasing when needed.

Optimal Therapeutic Approach for this Disease

NA is a benign congenital nevus; treatment is geared towards aesthetics.

Patient Management

There is no current indication for treatment of nevus anemicus, as it is a benign congenital lesion.

Unusual Clinical Scenarios to Consider in Patient Management

Although usually unassociated with any anomaly, NA may be appreciated in patients with neurofibromatosis and may coexist with pigmentary nevi as part of phakomatosis pigmentovascularis type II, III, or IV.

What is the Evidence?

Daniel, RH, Hubler, WR, Wolf, JE, Holder, WR. “Nevus anemicus. Donor-dominant defect”. Arch Dermatol. vol. 113. 1977. pp. 53-6. (A case report of one patient with NA and a thorough literature review. Various aspects of the nevus were investigated such as histology, pharmacology and exchange transplant study that demonstrated donor dominance. This study also showed that erythema was produced in the NA with alpha-blockers.)

Mountcastle, EA, Diestelmeier, MR, Lupton, GP. “Nevus anemicus”. J Am Acad Dermatol. vol. 14. 1986. pp. 628-32. (A case series of three patients that described the physical properties of NA. Skin biopsies were examined with light and electron microscopy. Other tests included diascopy, Wood’s light examination, sensory evaluation, and pharmacological studies.)

Greaves, MW, Birkett, D, Johnson, C. “Nevus anemicus: a unique catecholamine-dependent nevus”. Arch Dermatol. vol. 102. 1970. pp. 172-6. (A case series consisting of five patients reviewing the physical properties of NA as well as lesional biopsies for histologic and EM evaluation. Physical and pharmacological stimulation of NA was conducted and discussed.

Fleisher, TL, Zeligman, I. “Nevus anemicus”. Arch Dermatol. vol. 100. 1969. pp. 750-5. (Two patients with Neurofibromatosis-1 and NA were studied. Physical and pharmacological stimulation as well as histologic studies were conducted on the areas of NA as well as normal skin and compared.)

Fitzpatrick, TB, Freedberg, IM. Fitzpatrick’s dermatology in general medicine. 2003. (Dermatology textbook with clinical and histopathological description of NA.)

Ahkami, RN, Schwartz, RA. “Nevus anemicus”. Dermatology. vol. 198. 1999. pp. 327-9. (A thorough review of the pathogenesis, clinical manifestations, pathology, differential diagnosis, and treatment of NA.)

Jimbow, K, Fitzpatrick, TB, Szabo, G, Hori, Y. “Congenital circumscribed hypomelanosis: a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebalism”. J Invest Dermatol. vol. 64. 1975. pp. 50-62. (A case series that reviewed and compared several hypomelanotic diseases using light microscopy and discussed the pathophysiology of these various lesions.)

Butterworth, T, Walters, JD. “Observations on the pharmacologic responses of Voerner’s nevus anemic”. AMA Arch Derm Syphilol. vol. 66. 1952. pp. 333-9. (This study investigated the properties of NA that included physical stimulation of the NA and pharmacological stimulation using methacholine, pilocarpine, and epinephrine. The probable pathophysiology of the nevus was discussed.)

Libow, LF. “Phakomatosis pigmentovascularis type IIIb”. J Am Acad Dermatol. vol. 29. 1993. pp. 305-7. (A case report of a patient with Klippel-Trenaunay-Weber syndrome, nevus spilus, nevus flamus, and possibly the second case of phakomatosis pigmentovascularis type IIIb was described.)