What Are These White Macules?

A 44-year-old female patient with diabetes mellitus and hypothyroidism presented to dermatology with “white spots.” The lesions were not itchy or painful and appeared 2 years ago. Since that time, they have expanded in size. The patient stated that her mother had similar spots growing up. Physical examination showed well-defined white macules scattered across the back (Figure 1). Wood’s lamp examination showed a bright blue-white fluorescence at areas of involvement. There was no discoloration of the hair or mucous membranes or changes of the nail.

Vitiligo

Vitiligo is a chronic, progressive, relapsing-remitting, autoimmune disease of the skin characterized by selective destruction of melanocytes.^1-3 Skin lesions present as well-demarcated white patches and macules characterized as nonsegmental or segmental, according to their bilateral symmetrical or unilateral band-shaped distribution, respectively.¹ Although rates have been reported as high of 8% in India, 0.5% to 2% of the worldwide population is affected.¹ Despite the variation in prevalence, propensity for specific race or ethnic groups has yet to be defined.^1-3 Men and women are affected equally, and the age of onset presents in a bimodal distribution, with two-thirds of patients presenting after 30 years of age.^1-3

         Melanocyte cell death is due to cytotoxic T cell-mediated autoimmunity activated by genetic, environmental, and immune-mediated factors.^1-3 Genes involved in the disease code for antigen presentation (HLA-A, HLA-DQA1/DRB1, and CPVL) and alleles mediating innate and adaptive immunity, cell lysis and apoptosis, and melanocyte cell function.² Despite these genetic associations, vitiligo is inherited in a nonMendelian, polygenic pattern, with incomplete penetrance.³ Environmental factors that may cause disease in susceptible individuals include injury, burn, infection, and stress.³ Activation of immune circuits in vitiligo manifests as destruction of melanocytes and disease relapse by cytotoxic CD8+ T cells and regulatory CD4+ T cells, respectively, as well as propagation of disease by the innate immune response (dendritic cells, natural killer cells, and innate lymphoid cells).²

Patients present with well-demarcated white patches and macules, which may be associated with pruritus.^1-3 Common sites include the mucous membranes, face, extensor surfaces, umbilicus, axillae, and inguinal folds, although any surface can be affected.³ Dermoscopy shows perifollicular pigment or depigment for progressive or stable lesions, respectively.² Wood’s lamp fluoresces a bright blue-white at areas of depigmentation, with clear demarcation of unaffected skin.^1-3

         Comorbid disease is common.^1-3 This includes ocular, auditory, and metabolic disorders, as well as several syndromes of inborn error, such as autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome.³ Additional autoimmune disorders associated with vitiligo are hypothyroidism, hyperthyroidism, diabetes, and psoriasis.³

Histology shows the absence of pigment and melanocytes, suprabasal vacuolization, and epidermal spongiosis.^2,3 An inflammatory cell infiltrate at the dermal-epidermal junction is present at active lesions.³ Additional findings may include perivascular inflammation and degeneration of the hair follicle, sebaceous gland, and dermal nerve.³

The differential diagnosis includes chemical-induced leukoderma, infection (leishmaniasis, leprosy, and tinea versicolor), postinflammatory hypopigmentation (atopic dermatitis, psoriasis, and systemic lupus erythematosus), neoplasm (amelanotic melanoma, melanoma-associated leukoderma, and mycosis fungoides), and idiopathic disease (lichen sclerosus leukoderma, lichen sclerosus et atrophicus, and melasma).³ Nevus depigmentosus, pityriasis alba, and halo nevi should also be considered in children and adolescents.³

Various treatments exist for vitiligo. Topical corticosteroids and calcineurin inhibitors are safe and effective first-line therapies.^2,4 Topical calcipotriene, a vitamin D3 analog, can also be used.⁴ Phototherapeutic modalities, including UV light and laser therapy, are second-line therapies. Narrowband UVB (NBUVB) and psoralen UVA are both effective sources of light therapy, although the elevated risk of melanoma and nonmelanoma skin cancer limits use of the latter.⁴  The monochromatic excimer laser has been best studied for use in vitiligo, but the helium neon laser has provided superior results for patients with segmental vitiligo.⁴ Combination topical and light or laser therapy is more effective than either therapy alone.⁴  

         For stable disease that does not respond to treatment, surgery is an option. Surgical transplantation of melanocyte-rich tissue can be achieved via punch graft, blister graft, or split-thickness skin graft, the latter of which is preferred for larger surface areas.⁴ These same surgical techniques can be used to harvest tissue for autologous melanocyte suspensions, which are then transplanted into the patient’s depigmented skin.⁴

         For patients who do not respond to nonsurgical and surgical interventions, skin depigmentation is an option. Hydroquinone and monobenzone are both US Food and Drug Administration-approved agents used to depigment skin in patients with vitiligo.⁴ Camouflage or pigmentation by cosmetic maneuvers (self-tanner, makeup, and tattoo) can also be considered.⁴

The patient was diagnosed with vitiligo and started on topical fluticasone propionate once daily for 4 weeks.  At the follow-up visit, no new lesions had appeared, but the areas on her back remained the same. She was instructed to continue use of the topical steroid and referred for localized NB-UVB twice weekly. At her 3-month follow up, no new lesions had appeared, and pigment was returning to lesions on the back. She was instructed to stop the topical steroid and continue phototherapy for 1 year or until pigmentation had fully returned, whichever came sooner. 

Vitiligo is a chronic, relapsing-remitting, autoimmune disease of the skin characterized by melanocyte destruction.^1-3 The disease is multifactorial and impacted by genetic, environmental, and immune influence.^1-3 Patients present with well-demarcated white macules, which may be pruritic. Diagnosis is clinical, but lack of melanocytes, suprabasal vacuolization, and epidermal spongiosis on histology can support the diagnosis.³ Topical corticosteroids and calcineurin inhibitors are first-line therapy and can be used to augment the effect of light or laser therapy.⁴  Comorbid autoimmune conditions are common, and the prevalence of psychiatric disease is high.³ Therefore, a multidisciplinary approach tailored to the individual, with an emphasis on quality of life, is essential for comprehensive patient care.

1. Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015;386(9988):74-84. doi:10.1016/S0140-6736(14)60763-7
2. Wang Y, Li S, Li C. Clinical features, immunopathogenesis, and therapeutic strategies in vitiligo. Clin Rev Allergy Immunol, 2021;61(3):299-323. doi:10.1007/s12016-021-08868-z
3. Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview. Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65(3):473-491. doi:10.1016/j.jaad.2010.11.061
4. Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: a comprehensive overview. Part II: treatment options and approach to treatment. J Am Acad Dermatol. 2011;65(3):493-514. doi:10.1016/j.jaad.2010.10.043.

Mallory L. Zaino, MD, is a research fellow at the Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC. Steven Feldman, MD, PhD, is the chief medical editor of The Dermatologist and with the Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, and Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC.