Primary care providers are often the first to see and diagnose pigmentary disorders. A misdiagnosis of vitiligo can be made by even the most seasoned primary care provider and lead to delays in care and morbidity to the patient. It is imperative that the provider be familiar with various pigmentary disorders to provide safe and effective care as well as know when to expedite a referral to dermatology or other appropriate specialties. A significant portion of these disorders includes hypopigmentation disorders such as vitiligo, pityriasis alba, nevus depigmentosus, nevus anemicus, idiopathic gutatte hypomelanosis, and piebaldism, in addition to certain significant diagnoses such as tuberous sclerosis complex and localized scleroderma. This guide discusses common assessment characteristics that can help the primary care clinician build their clinical acumen so as to differentiate between the most common conditions of hypopigmentation and depigmentation without missing significant diagnoses.
Vitiligo is an autoimmune disease of the skin mediated by autoreactive CD8+ T cells that destroy melanocytes-the pigment-producing cells-resulting in the appearance of white spots.1 The prevalence of vitiligo ranges from 0.2% to 4% of the population globally with no racial or sexual predilection.2,3 Approximately a third to a half of all cases have onset in childhood.4 This article will briefly review different types of vitiligo to elucidate familiarity with the different lesion patterns of the condition. Furthermore, the differences in assessment characteristics such as onset, texture, coloration, distribution, lesion progression, and comorbidities between vitiligo and other common pigmentation disorders seen in primary care are discussed.
Vitiligo
Vitiligo is considered one of the most common disorders of dyspigmentation seen in primary care. The median age of onset in children is between 5 and 10 years old.4 Onset before age 2 years represents 11% of pediatric-onset cases, but vitiligo presenting at birth or in older adults is exceedingly rare. In adults, the mean age of onset is between 10 and 30, with 70% to 80% occurring before age 30.5 When vitiligo manifests after puberty, it typically presents with more involvement of the face and distal extremities and is more commonly associated with other autoimmune disorders. Vitiligo is often broadly categorized as segmental or nonsegmental vitiligo, with the latter being more prevalent. Included within nonsegmental vitiligo are multiple subtypes, such as focal vitiligo, acrofacial vitiligo, and generalized vitiligo, among others, based on the body sites in which the lesions occur and the manner in which they progress. However, all types share a similar clinical appearance upon examination.
Segmental vitiligo
Segmental vitiligo presents in one focused area of the body, and is usually unilateral and does not cross the midline. This form, which comprises 5% to 30% of all vitiligo cases, is often linear or blocklike in shape and occurs most frequently on the face, trunk, neck, extremities, and scalp.6 Segmental vitiligo most commonly occurs in childhood, progresses rapidly in the affected area over a period of 6 months to 2 years, then typically stabilizes for the rest of the patient's life.7
Nonsegmental vitiligo
Focal vitiligo. Lesions of focal vitiligo also present in one focused area of the body and do not extend to other body parts nor widen or evolve over a time frame of 2 years. This type of vitiligo most closely resembles other conditions that also do not extend, such as segmental vitiligo or nevus depigmentosus.6
Acrofacial vitiligo. Acrofacial vitiligo, like focal vitiligo, has sparse lesions that generally appear bilaterally over the face and on the distal extremities where it can appear as amelanotic macules bilaterally (see Vitiligo of the extremities). Truncal lesions are usually not seen in the initial stages, but may appear over time as the acrofacial variant evolves into generalized vitiligo.6
Generalized vitiligo. In generalized vitiligo, lesions occur in different areas of the body and often present as acrofacial or focal before progressing into generalized presentation in a bilateral, often symmetrical presentation (see Vitiligo of the face).8 The progression of generalized vitiligo leads to nearly complete depigmentation of the skin, body hair, and sometimes oral/genital mucosae.9 At this extent of depigmentation, the condition is known as universal vitiligo.9
Diagnosing vitiligo
Because the disease is localized to the melanocytes, the stratum corneum and underlying epidermis and dermis remain intact and smooth. On palpation, a practitioner does not feel a change in texture between unaffected skin and depigmented patches. Active vitiligo may present in different ways, such as trichrome or confetti lesions, which indicate that melanocytes are in the process of destruction and some pigment is still visible. If untreated, these lesions eventually develop into the characteristic morphology of vitiligo, which present as completely depigmented or amelanotic macules.6 Wood's lamp testing is an essential tool to use when differentiating between hypopigmented or hyperpigmented lesions and other pigmentary disorders. The Wood's lamp emits UV light with wavelengths in the range of 320-450 nm, which are invisible to the naked eye. Although invisible in normal light, in dark settings, it appears to glow purple because it emits wavelengths in the violet section of the electromagnetic spectrum. With vitiligo, a depigmented patch fluoresces a milk-white color because of the absence of melanin and the increased dermal collagen being illuminated. The white fluorescence seen is as white as the fluorescence of a white lab coat. Under a Wood's lamp, skin with little or no pigment is accentuated by fluorescence in contrast to skin with normal quantities of melanin.10 Other factors affect the color and degree of fluorescence as well. A variety of skin conditions can cause variance of fluorescence and the hue and degree with which they present under the Wood's lamp (see Vitiligo differential diagnosis).
Vitiligo lesions are typically first noted on the dorsal aspect of the metacarpophalangeal joints, around the eyes and mouth, feet, and genitalia, which then spread outwardly or in a confetti pattern.5,8 Depigmentation progression can remain extremely active for an invariable amount of time and then stabilize indefinitely. Unless it is the segmental type of vitiligo, the lesions will spread at some or multiple points during a patient's life. In addition, mechanical injury such as lacerations and burns can induce new lesions through the process of koebnerization, whereby local trauma to the skin produces further depigmentation of the skin in the area of trauma. This effect occurs in most patients with vitiligo.10
Twenty percent of patients who develop vitiligo as adults have another autoimmune condition such as Hashimoto's thyroiditis, psoriasis, rheumatoid arthritis, type 1 diabetes, pernicious anemia, systemic lupus erythematosus, or alopecia areata.11 Excluding other autoimmune conditions, patients with vitiligo generally present as healthy individuals with few if any comorbidities.
Common differential diagnoses
Pityriasis alba
A common dyspigmentation condition seen in primary care, which in more long-standing cases can mimic vitiligo, is pityriasis alba (PA). This condition is most associated with atopic dermatitis in infants and younger children and is one of the most frequent hypomelanotic conditions in the younger population.12 It occurs in children of all genders and races, although it is more pronounced in those with darker skin complexions, specifically Fitzpatrick skin types III-IV.13 The condition often begins with subtle erythematous areas, which subsequently scale and form hypopigmented patches with irritated borders. Although the quantity of melanocytes in PA lesions progressively decrease, the melanocytes maintain their presence without complete loss of pigment.14 Therefore, under a Wood's lamp, this condition does not luminesce, but presents an off-white glow.
There are key findings in PA that help differentiate the diagnosis from vitiligo and guide proper management. The patches of PA are considered hypomelanotic, as opposed to the amelanotic patches of vitiligo. Due to the presence of spongiosis, the lesions may have a smooth to somewhat scaly texture and pruritus and irritation may be present, especially on the borders of the lesions.12 The lesions most commonly appear on the patient's face, but may also appear on the limbs, especially after excessive unprotected sun exposure. Because PA does not progress and is self-limited, treatment is not necessary, but patients can be educated about relieving and exacerbating factors. For example, environmental factors such as heat, humidity, and sun exposure can make pigment changes worse in patients with PA. Detrimental hygiene practices such as frequent, lengthy, hot showers may also accentuate pigmentation changes.12 It is imperative to educate the patient and/or the patient's parents/caregivers on the importance of maintaining a healthy skin barrier with emollients, proper hygiene practices such as short showers with lukewarm water, and regular use of sunscreen with a sun protection factor (SPF) of 50 or above. Patients with PA generally appear healthy and the condition is not associated with any other comorbidities.15
Nevus depigmentosus
Nevus depigmentosus (ND), also known as nevus achromicus, is another name for a hypomelanotic nevus. These lesions are common in infants, with up to 1 in 130 newborns having at least one of these lesions.12 The lesions are usually present at birth or appear shortly after, are well circumscribed, smooth, nonprogressive, lighter than surrounding skin, and without associated comorbidities.16 ND occurs sporadically with no known familial pattern of inheritance.17
ND lesions can range in size from 1 cm to over 10 cm and rarely cross the midline. The larger lesions may mimic segmental vitiligo, as this form of vitiligo can be present at an early age. The term depigmentosus is a misnomer, as individual lesions only appear depigmented in contrast to the complete depigmentation of vitiligo. As such, the lesions of ND show an off-white appearance but do not fluoresce under a Wood's lamp.17 ND does not need to be treated unless the appearance affects the quality of life of the individual. Depending on the size of the lesion, one option for removal includes excision. Larger lesions may necessitate multiple excisions or cover up with concealing make-up.
Nevus anemicus
Nevus anemicus (NA) is a congenital, hypopigmented, vascular macule found in 1% to 5% of the general population, and characteristically does not create erythema in response to trauma, heat, or cold. The hypopigmented appearance of NA is attributed to the increased sensitivity to catecholamines such as adrenaline and noradrenaline in the vasculature of the patch, leading to constitutional vasoconstriction. The lack of perfusion is what gives NA its hypopigmented or depigmented appearance, in contrast to the lack of melanocytes characteristic of vitiligo.
NA lesions are flat and smooth to palpation with irregular, nonprogressive borders. Lesions are usually located on the trunk but can also be found on the extremities, head, and neck. One of the characteristic features of NA is the inability of the skin of the lesion to flush when irritated. Therefore, the borders of a lesion can be accentuated by rubbing the area to cause vasodilation. To demonstrate this, the end of a cotton-tipped applicator or edge of a tongue blade may be used to stroke from the outside of the lesion and across to normal skin. The irritated normal skin on the border will become red while the NA will retain its white, vasoconstricted color.16 Another method to differentiate NA from vitiligo or other hypopigmentation disorders is the blanching technique. An edge of a lesion including some normal skin is firmly pressed with a glass slide to blanch the normal skin, which will cause the NA to blend in with the normal skin due to the vasoconstriction. Vitiligo, in contrast, will become red with friction and irritation along with the surrounding skin. No accentuation is noted upon illumination with a Wood's lamp. No treatment is required for NA unless it cosmetically affects the patient, in which case camouflage make-up may be used.16
Idiopathic guttate hypomelanosis
Idiopathic guttate hypomelanosis (IGH) is commonly seen in practice as a white spot or cluster of spots that have no associated itch or pain, unassociated with any other conditions. It is a common hypopigmentation skin disorder, which presents mostly on sun-exposed areas as scattered 2 to 10 mm smooth, hypopigmented macules with distinct margins. Skin aging, sun damage, and mechanical stress are suggested as causative factors, but there also seems to be a genetic tendency for a person's skin to form the lesions.18 IGH predominantly affects middle-aged to older adult populations with a slightly increased prevalence in females.19 Individuals with these lesions are advised to wear sunscreen with SPF 50 to sun-exposed areas to mitigate the appearance of additional lesions.
Of note, although IGH appears clinically depigmented, the skin maintains the presence of melanocytes. Under a Wood's lamp, the lesions do appear to fluoresce bright white in contrast to the surrounding skin, but resemble confetti rather than larger macules like those of vitiligo (see Idiopathic guttate hypomelanosis lesions under Wood's lamp).19 If a patient presents with other signs of sun damage, it is common to find IGH on the sun-exposed areas as well.
Piebaldism
Piebaldism is a rare congenital disorder due to a genetic mutation that affects melanocyte migration and development, clinically showing well-circumscribed depigmented macules and patches, which are present at birth. This is in contrast to vitiligo, which is acquired.20,21 It is commonly characterized by poliosis (white hair) and leukoderma (white skin). Leukoderma is found more prominently around the mid forehead, mid scalp, mid sections of the extremities, and central abdomen. Affecting more than 90% of cases, the most common finding of piebaldism is a triangular poliosis or "white forelock," which is a lock of white hair just above the central forehead.20,21 Medial eyebrows and eyelashes may also be affected. It affects fewer than 1 in 20,000 persons; both males and females are equally affected with no racial predilection.21
A differentiating factor between piebaldism and vitiligo histologically is the absence of inflammatory infiltrates within the dermis of piebaldism.21 While Wood's lamp examination shows lesion fluorescence, the hallmark features including distribution of lesions and poliosis help to distinguish between piebaldism and vitiligo. Piebaldism is rarely associated with extracutaneous manifestations, unlike vitiligo, which is often associated with thyroid and metabolic disease.17 Lastly, piebaldism tends to remain stable whereas vitiligo tends to progress.
Significant differentials
Tuberous sclerosis complex
Tuberous sclerosis complex (TSC) is a genetic disease caused by the mutation of the tumor suppressor genes TSCS1 or TSCS2. This condition is often diagnosed in infancy or within the first few years of life, affecting approximately 1 in 20,000 of the general population.21 TSC is characterized by the growth of numerous benign tumors that can occur in the skin, brain, heart, kidneys, and other organs. Early manifestations may include seizures, hypopigmented macules, and intellectual disability. Children with TSC tend to have significant health problems and behavioral issues.21 TSC can be found in all races and ethnicities and affects both genders equally.
Skin manifestations occur in 96% of TSC cases and usually include three or more off-white macules that are present at birth or develop early in infancy, more commonly found on the trunk, extremities, head, and neck.21 These are commonly referred to as "ash leaf" spots as they have a leaf or thumbprint appearance and can range anywhere from 3 to 12 cm (see "Ash leaf macule" in a patient with tuberous sclerosis). Multiple small discrete "confetti" macules are also considered to be pathognomonic for TSC.17 It is helpful to use a Wood's lamp to identify these characteristic hypomelanotic lesions. In addition to hypomelanotic lesions, 70% of cases will have angiofibromas developing by age 1 to 4 years. These are small, smooth, dome-shaped papules that are red or skin colored and usually found on the central face. In 40% of cases, a plaquelike lesion called a "shagreen" patch may also be present. This represents a connective tissue nevus and is usually a slightly elevated skin colored patch located on the back or buttock areas. Lastly, periungual fibromas or "Koenen" tumors may be found around the nails in up to 22% of cases by late childhood.21
TSC should be diagnosed early to prevent complications from tumors and seizures. Multiple specialties need to be on board when caring for a patient with this disease, including neurology, cardiology, nephrology, dermatology, and ophthalmology. It is vital that the patient's pediatrician or primary care provider act in a timely manner and order appropriate testing and referrals as soon as possible. Genetic counseling is imperative.
Localized scleroderma/morphea
Scleroderma is a collective term referring to a range of autoimmune inflammatory conditions in which skin thickening and tightening, or sclerosing, is a trademark feature. Localized scleroderma, which is also known as morphea, is diagnosed based on clinical assessment of the areas of sclerosis due to the deposition of excessive amounts of collagen in the extracellular matrix.22,23 The lesions of localized scleroderma begin as erythematous, edematous, bruiselike patches. Over time, they evolve into what could potentially mimic vitiligo as the lesions become hypopigmented (see Morphea lesion). The main differentiating factor, however, is the texture of the sclerotic skin.
The skin is unusually smooth, thickened, and has a shiny appearance. Lesions of vitiligo on the contrary maintain the same texture as that of the surrounding skin. Generalized morphea is characterized by the presence of greater than four indurated plaques, each greater than or equal to 3 cm in diameter and/or involving greater than or equal to two body sites. Patients with localized scleroderma generally do not show other systemic changes, but if the diagnosis is systemic scleroderma, other issues present such as Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and microscopic nailfold capillary abnormalities.22 Generalized morphea accounts for 7% to 9% of all cases of morphea and occurs more frequently in women.24
Differentiating morphea versus vitiligo may be challenging at times, but may limit morbidity through early intervention, preventing complications such as limb atrophy, contractures, and disfigurement. The use of a Wood's lamp may help in diagnosis by illuminating new, indurated, subclinical lesions that may not yet appear well demarcated under ambient light.24 The sclerotic lesions appear brighter compared with surrounding skin, but do not fluoresce like the lesions of vitiligo.
Conclusion
Vitiligo affects up to 4% of the population worldwide, and management options hinge on early recognition and initiation of therapy. Several potential management modalities exist for vitiligo. Patients benefit from early referral to dermatology. Other disorders of hypopigmentation are commonly diagnosed in primary care, and may subsequently be managed, treated, and evaluated in this setting. Conditions such as PA, ND, NA, IGH, and piebaldism can be effectively managed by the primary care provider, while other more significant diseases such as TSC and scleroderma may require the involvement of multiple specialties. It is therefore imperative that clinicians possess the knowledge and understanding necessary to differentiate between the different disorders of hypopigmentation.
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