Achromatic patches - Clinical Advisor

Achromatic patches

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  • Case #1

    July 2015 Dermatology Look-Alikes

    Case #1

  • Case #2

    July 2015 Dermatology Look-Alikes

    Case #2

Case #1

A white woman, aged 35 years, presents with an achromatic lesion on her neck. She recalls the spot being present for many years. She states the area occasionally gets darker in the sun. She denies any previous rash or erythema in the area. The lesion is asymptomatic and has not grown in size. She does not recall if she was born with the lesion. The patient reports that she has no history of skin cancer. She is otherwise healthy and taking prenatal vitamins. 


Case #2

A 40-year-old Hispanic woman presents with a one-year history of “loss of color” on her arms. She says the lesions are progressively increasing in size and are occasionally pruritic. She has noticed a few of the areas have gained some of the color back. Her skin easily sunburns when she is outdoors. Her medical history is significant for hypertension for which she has been on metoprolol for two years. The patient’s maternal aunt has a history of hypothyroidism. She has not tried any previous treatments for the lesion.



This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Eroded vesicles on a boy’s face and neck and Blue-violet reticulated patches on an infant. Then take the post-test here.


This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Eroded vesicles on a boy's face and neck and Blue-violet reticulated patches on an infant. Then take the post-test here.Case #1Nevus depigmentosus (ND), also referred to...

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This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Eroded vesicles on a boy’s face and neck and Blue-violet reticulated patches on an infant. Then take the post-test here.


Case #1

Nevus depigmentosus (ND), also referred to as achromic nevus, is a congenital, nonprogressive dyspigmentation that manifests as a well-circumscribed, uniformly hypopigmented lesion with irregular boundaries.1 Often compared to a spot of paint splatter in its most common presentation, ND frequently takes the shape of an isolated ovoid or irregular patch with smaller bordering macules and occasional superimposed lentigines.


However, two other variants exist that present with disparate patterns.2 The segmental variant exhibits midline demarcation and consists of a band or streak with a blocklike formation. The systematized variant involves multiple whorls or streaks of hypopigmentation in Blaschkoid distribution.2,3 Often, ND presents as a single macule on the trunk, but it can also be located on the limbs and exist as more than one lesion.1

The prevalence of ND has been reported to be between 0.4% and 3%.4,5 Occurrence of ND is normally sporadic, as there are no known patterns of inheritance or family tendency.1 ND affects males and females with approximately equal frequency.1,6

Early onset is an important clinical characteristic of ND. Lesions typically present at birth or during early childhood, with approximately 93% of patients with this condition presenting by age 3.7 After presentation, the distribution and location of the lesion remain stable with time, but the lesion may increase slightly in size as the individual grows.6 ND often becomes more visible with age because of the increased contrast between the hypopigmented and tanned skin.1

Four clinical criteria proposed in 1976 by Coupe8 are commonly used in the diagnosis of ND: (1) Leucoderma is present at birth, or its onset is early in life; (2) there is no alteration in the distribution of leucoderma throughout life; (3) the texture of or sensation in the affected area do not change; and (4) the achromic area does not have a hyperpigmented border. 


In 2008, Xu et al.6 noted an exception to the second criterion, reporting that macules may change in size as the patient grows. He also suggested that the fourth criterion be modified to an irregular border with no poliosis. Xu et al.6 further proposed three additional diagnostic criteria: (5) The macule is off-white in color without fluorescence under Wood’s light; (6) when examined histologically, there is no or a slight decrease in melanocytes in the affected area; and (7) under electron microscopy, aggregated melanosomes are found in keratinocytes of depigmented lesional skin. 


Histologic examination reveals a substantial reduction in the density of melanosomes in epidermal lesional skin, but varying effects on the quantity of melanocytes, which is typically assessed with melanocyte markers S-100 and Melan-A.1,7,9 This finding is consistent with the hypothesized pathophysiology that ND is associated with a developmental defect of fetal melanocytes, which impedes the transfer of melanosomes from melanocytes to keratinocytes.3,7,9

Rare systemic and neurologic abnormalities, including seizures and mental retardation, have been associated with the segmental and systematized variants of ND.10 For the majority of patients, however, ND is a benign macular lesion. The main concern for these patients is that the lesions are sensitive to ultraviolet (UV) light and prone to sunburn secondary to their lack of melanosomes. Thus, the standard of care for patients with ND is to apply sunscreen to the affected region in addition to the surrounding skin. That is, reduced tanning of the normal skin will serve to camouflage the affected region by reducing color contrast. Cosmetic makeup also remains a viable option for these patients. 


The differential diagnosis of ND involves other hypopigmented disorders including hypomelanosis of Ito, segmental vitiligo, ash-leaf spots of tuberous sclerosis, and nevus anemicus.11

Hypomelanosis of Ito, which is characterized by hypomelanosis along Blaschko lines, is difficult to distinguish from whorled ND as the two conditions likely represent a phenotypic continuum of genetic mosaicism.11 In general, hypomelanosis of Ito is placed on the severe end of the spectrum, because in approximately 75% of affected individuals, sequelae of the central nervous system, eyes, musculoskeletal system, and teeth are present.12

Discriminating between ND and segmental vitiligo is relatively straightforward. Segmental vitiligo tends to spread quickly after presentation in contrast to the clinically stable lesions of ND.13 Although the term depigmentosus suggests complete depigmentation, the lesions of ND are hypomelanotic and do retain some pigment. On the other hand, vitiligo lesions are amelanotic and therefore, milky white. If there is still diagnostic ambiguity, ND and segmental vitiligo can be differentiated with a Wood’s light: Lesions of ND display off-white accentuation without fluorescence, in contrast to vitiligo lesions, which produce chalky-white accentuation with fluorescence.6

Small lesions of ND may mimic the characteristic ash leaf spots of tuberous sclerosis. In young children, the clinician may have difficulty ruling out tuberous sclerosis, because the other cutaneous and systemic manifestations of tuberous sclerosis do not usually appear until after the age of 5.14 Diagnosis of tuberous sclerosis is more probable when the spots are leaf-shaped (tapered at one end and rounded at the other) and when there are multiple hypomelanotic macules, especially in the context of other multi-organ symptoms.14

ND is best distinguished from nevus anemicus by rubbing the affected area, because lesions of nevus anemicus do not redden upon manipulation, whereas lesions of ND do redden as normal peripheral skin does.11

Newer therapeutic modalities are being developed in an attempt to treat ND lesions; these include melanocyte-keratinocyte transplantation of donor skin, therapy with psoralen and UVA light (PUVA), and excimer laser treatment. Currently, however, these therapies are not common treatments for ND given their questionable efficacy.15

The patient in this case was reassured and educated on the condition, and no treatment was given.


Four criteria commonly used in the clinical diagnosis of nevus depigmentosus8

Leucoderma is present at birth, or its onset is early in life.
There is no alteration in the distribution of leucoderma throughout life.
The texture of or sensation in the affected area do not change.
The achromic area does not have a hyperpigmented border.

Case #2

Vitiligo is the most common depigmentation disorder in the world, affecting between 0.5% and 2% of the population, regardless of age or sex.16 In approximately half of affected individuals, vitiligo presents before age 20 years.13

Vitiligo is characterized by uniformly depigmented, patchy macules. Typically, a normal or hyperpigmented border surrounds the macules, but raised inflammatory borders have also been reported.18 After presentation, the distribution and extent of the vitiligo typically change with time as the lesions grow and spread to new areas.13 Although it may present on any part of the body, vitiligo commonly manifests in orifices, on genitals, and on sun-exposed areas, particularly the hands and face.18 Vitiligo is most easily observed on individuals with dark skin.


There are two main categories of vitiligo: Segmental vitiligo (also called unilateral vitiligo) and nonsegmental vitiligo (also called generalized or bilateral vitiligo). Segmental vitiligo includes generalized, acrofacial, and universal variants. Studies have suggested that segmental vitiligo and nonsegmental vitiligo may not be separate pathologic entities, but instead exist on a continuum with some clinical, genetic, and etiopathologic overlap.19 The idea of a spectrum of vitiligo is supported by the existence of mixed vitiligo, in which the condition begins as segmental vitiligo and develops into nonsegmental vitiligo after months or years.19

The most common type of vitiligo is nonsegmental vitiligo, accounting for approximately 85% to 90% of cases.20 Nonsegmental vitiligo produces depigmented macules that vary in size from a few to several centimeters in diameter and are distributed on the body in a symmetrical pattern.21 Typically, the macules of nonsegmental vitiligo initially contain pigmented hairs, but leukotrichia may develop as the condition progresses. In contrast, leukotrichia regularly occurs in the rapidly developing macules of segmental vitiligo.22 Segmental vitiligo typically presents at an earlier age than nonsegmental vitiligo, spreads more rapidly but reaches a stable course, and is not usually associated with autoimmune disease (approximately 3.4% of patients with segmental vitiligo have an autoimmune disease).20

Vitiligo lesions are characterized by the absence of melanocytes and associated melanin pigment, accompanied by an otherwise normal dermis and epidermis.23 Therefore, pigmentation is completely clinically absent in the macules of vitiligo. 


It is unknown why melanocytes are not present in the lesions of segmental vitiligo and nonsegmental vitiligo. However, it is suspected that nonsegmental vitiligo is autoimmune in origin, largely because of the presence of circulating antimelanocyte antibodies in patients with active nonsegmental vitiligo.24 Moreover, in vitro studies of serum from patients with vitiligo demonstrate melanocyte injury via complement activation and antibody-dependent cellular toxicity.25

The pathogenesis of segmental vitiligo likely involves neuronal mechanisms. Evidence supporting this hypothesis has come from studies demonstrating that local neurological damage can trigger skin whitening and that segmental vitiligo exists in a dermatomal distribution.13,26

Genetic studies that have been conducted have only involved nonsegmental vitiligo. These studies show that, although most cases are sporadic, up to 30% of affected individuals have a positive family history.27 Inheritance is believed to be multifactorial; both genetic and environmental factors are thought to contribute to the pathogenesis.28

Nonsegmental vitiligo often coexists with autoimmune diseases, particularly Hashimoto’s thyroiditis and Graves’ disease.29 Consequently, patients with nonsegmental vitiligo frequently undergo routine examination of their thyroid function and are screened for thyroid autoantibodies.30 Screening for other autoimmune diseases, including thorough analysis of autoantibodies (e.g., antinuclear antibodies), blood counts, and fasting blood glucose, may also be useful, but there are no consistent screening recommendations for patients with nonsegmental vitiligo.30 Vitiligo is also associated with halo nevi and alopecia areata.31,32

Vitiligo is not known to present serious health risks, but patients should be advised to use sun protection, as the affected skin is particularly sensitive to sun exposure. Furthermore, vitiligo can cause significant psychological distress and embarrassment to patients, so a consultation with a psychologist may be indicated.


To combat depigmentation, ultraviolet (UV) therapies and systemic steroids have been shown to halt disease progression, but prolonged use of systemic steroids is not recommended.34,35 Frequently used repigmentation therapies include narrow-band UVB radiation two or three times weekly, photochemotherapy (i.e., psoralen and UVA light [PUVA]) two or three times weekly, and topical agents like corticosteroids and calcineurin inhibitors, particularly for patients with localized macules.33 Combined treatments of topical corticosteroids and phototherapy may accelerate the response in some patients.33 Camouflage techniques like self-tanners and cosmetic cover-ups may also be used. 


Patients should be warned that treatment can be a frustrating process. Because vitiligo is a relapsing disorder, repigmentation is a slow process, and the disease may reappear in treated areas or different areas of the body.33 Surgical methods like minigrafting from an autologous donor site or cellular transplantation using autologous epidermal cell suspensions can be employed for small, persistent areas that are affected or refractory lesions.36,37

Diseases that mimic vitiligo include nevus depigmentosus (ND), postinflammatory hypomelanoses, tuberous sclerosis, pityriasis alba, tinea versicolor, and piebaldism.


Segmental vitiligo can mimic ND, but Wood’s light examination of ND lesions display off-white accentuation without fluorescence, in contrast to vitiligo lesions, which produce chalky-white accentuation with fluorescence.6 Histologically, ND lesions show slight or no decrease in melanocytes, whereas vitiligo lesions contain no melanocytes.3 ND typically presents in the first year of life and lesions maintain a stable size, whereas vitiligo typically presents later and lesions progress over time.6

Postinflammatory hypomelanoses typically develop after inflammatory skin disorders such as dermatitis, acne, or infection, whereas vitiligo does not. Postinflammatory hypomelanoses are also often associated with scaling and show a normal melanocyte count, unlike vitiligo.38

The macules of tuberous sclerosis are typically hypomelanotic and have an ash-leaf shape, as opposed to vitiligo lesions, which are chalk-white and irregularly shaped. In addition, the multisystem involvement with associated hamartomas of tuberous sclerosis is absent in vitiligo.14

Diagnosis of pityriasis alba is favored when lesions are scaly and have indistinct boundaries and when there is a negative family history of vitiligo. Pityriasis alba may have a positive or negative Wood’s light examination.39

The macules in tinea versicolor typically have a fine scale and fluoresce yellow-green under a Wood’s light, distinguishing them from vitiligo lesions. Tinea versicolor can be confirmed with a skin scraping for microscopy.13

Piebaldism is always inherited from a parent and is not progressive, unlike vitiligo.40

The patient in this case was treated with topical triamcinolone ointment twice daily for two months with some repigmentation on the arms.


Differential diagnosis for vitiligo

Nevus depigmentosus
Postinflammatory hypomelanoses
Tuberous sclerosis
Tinea versicolor
Piebaldism

Kate Travis, BA, is a medical student and Rana Mays, MD, is a dermatology resident at Baylor College of Medicine in Houston. 



This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Eroded vesicles on a boy’s face and neck and Blue-violet reticulated patches on an infant. Then take the post-test here.


References


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  2. Molho-Pessach V, Schaffer JV. Blaschko lines and other patterns of cutaneous mosaicism. Clin Dermatol. 2011;29(2):205-225.

  3. Bolognia JL, Pawelek JM. Biology of hypopigmentation. J Am Acad Dermatol. 1988;19(2 Pt 1):217-255. 

  4. Dhar S, Kanwar AJ, Kaur S. Nevus depigmentosus in India: Experience with 50 patients. Pediatr Dermatol. 1993;10(3):299-300. 

  5. Shih IH, Lin JY, Chen CH, Hong HS. A birthmark survey in 500 newborns: Clinical observation in two northern Taiwan medical center nurseries. Chang Gung Med J. 2007;30(3):220-225. Available at memo.cgu.edu.tw/cgmj/3003/300303.pdf 

  6. Xu AE, Huang B, Li YW, Shen H. Clinical, histopathological, and ultrastructural characteristics of naevus depigmentosus. Clin Exp Dermatol. 2008;33(4):400-405. 

  7. Lee HS, Chun YS, Hann SK. Nevus depigmentosus: clinical features and histopathologic characteristics in 67 patients. J Am Acad Dermatol. 1999;40(1):21-26. 

  8. Coupe RL. Unilateral systematized achromic naevus. Dermatologica. 1967;134(1):19-35. 

  9. Jimbow K, Fitzpatrick TB, Szabo G, Hori Y. Congenital circumscribed hypomelanosis: A characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus and piebaldism. J Invest Dermatol. 1975;64(1):50-62. 

  10. Di Lernia V. Segmental nevus depigmentosus: Analysis of 20 patients. Pediatr Dermatol. 1999;16(5):349-353. 

  11. Tey HL. A practical classification of childhood hypopigmentation disorders. Acta Derm Venereol. 2010;90(1):6-11. 

  12. Glover MT, Brett EM, Atherton DJ. Hypomelanosis of Ito: Spectrum of the disease. J Pediatr. 1989;115(1):75-80. 

  13. Taïeb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med. 2009;360(2):160-169. 

  14. Bolognia JL. A clinical approach to leukoderma. Int J Dermatol. 1999;38(8):568-572. 

  15. Mulekar SV, Al Issa A, Al Eisa A. Nevus depigmentosus treated by melanocyte-keratinocyte transplantation. J Cutan Aesthet Surg. 2011;4(1):29-32. Available at jcasonline.com/text.asp?2011/4/1/29/79185 

  16. Krüger C, Schallreuter, K. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012;51(10):1206-1212. 

  17. Buckley WR, Lobitz WC Jr. Vitiligo with a raised inflammatory border. AMA Arch Derm Syphilol. 1953;67(3):316-320. 

  18. Matin R. Vitiligo in adults and children. BMJ Clin Evid. 2011;2011:1717. Available at ncbi.nlm.nih.gov/pmc/articles/PMC3217714 

  19. van Geel N, De Lille S, Vandenhaute S, et al. Different phenotypes of segmental vitiligo based on a clinical observational study. J Eur Acad Dermatol Venereol. 2011;25(6):673-678. 

  20. Hann SK, Lee HJ. Segmental vitiligo: Clinical findings in 208 patients. J Am Acad Dermatol. 1996;35(5 Pt 1):671-674. 

  21. Ezzedine K, Lim HW, Suzuki T, et al. Revised classification/nomenclature of vitiligo and related issues: The Vitiligo Global Issues Consensus Conference. Pigment Cell Melanoma Res. 2012;25(3):E1-E13. Available at ncbi.nlm.nih.gov/pmc/articles/PMC3511780 

  22. Falabella R. Hair involvement in vitiligo. In: Picardo M, Taïeb A, eds. Vitiligo. Berlin Heidelberg: Springer-Verlag; 2010:65-71. 

  23. Castanet J, Ortonne JP. Pathophysiology of vitiligo. Clin Dermatol. 1997;15(6):845-851. 

  24. Hertz KC, Gazze LA, Kirkpatrick CH, Katz SI. Autoimmune vitiligo: Detection of antibodies to melanin-producing cells. N Engl J Med. 1977;297(12):634-637. 

  25. Norris DA, Kissinger RM, Naughton GM, Bystryn JC. Evidence for immunologic mechanisms in human vitiligo: Patients’ sera induce damage to human melanocytes in vitro by complement-mediated damage and antibody-dependent cellular cytotoxicity. J Invest Dermatol. 1988;90(6):783-789. 

  26. Singh A, Kornmehl H, Milgraum S. Segmental vitiligo following encephalitis. Pediatr Dermatol. 2010;27(6):624-625. 

  27. Shankar DS, Shashikala K, Madala R. Clinical patterns of vitiligo and its associated comorbidities: A prospective controlled cross-sectional study in South India. Indian Dermatol Online J. 2012;3(2):114-118. Available at idoj.in/text.asp?2012/3/2/114/96705 

  28. Spritz RA. Recent progress in the genetics of generalized vitiligo. J Genet Genomics. 2011;38(7):271-278. Available at ncbi.nlm.nih.gov/pmc/articles/PMC3513342 

  29. Poojary SA. Vitiligo and associated autoimmune disorders: A retrospective hospital-based study in Mumbai, India. Allergol Immunopathol (Madr). 2011;39(6):356-361. Available at elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-vitiligo-and-associated-autoimmune-disorders-90038001 

  30. Rodríguez-Martín M, Sáez M, Merino de Paz N, et al. When are laboratory tests indicated in patients with vitiligo? Dermatoendocrinol. 2012;4(1):53-57. Available at ncbi.nlm.nih.gov/pmc/articles/PMC3408993 

  31. Harris JE. Vitiligo and alopecia areata: Apples and oranges? Exp Dermatol. 2013;22(12):785-789. Available at ncbi.nlm.nih.gov/pmc/articles/PMC3867815 

  32. Jouary T, Taïeb A. Halo nevi and vitiligo. In: Picardo M, Taïeb A, eds. Vitiligo. Berlin Heidelberg: Springer-Verlag; 2010:61-64. 

  33. Taïeb A., Picardo M. Management overview. In: Picardo M, Taïeb A, eds. Vitiligo. Berlin Heidelberg: Springer-Verlag; 2010:319-323. 

  34. Pasricha JS, Khaitan BK. Oral mini-pulse therapy with betamethasone in vitiligo patients having extensive or fast-spreading disease. Int J Dermatol. 1993;32(10):753-757. 

  35. Radakovic-Fijan S, Fürnsinn-Friedl AM, Hönigsmann H, Tanew A. Oral dexamethasone pulse treatment for vitiligo. J Am Acad Dermatol. 2001;44(5):814-817. 

  36. Paul M. Autologous non-cultured basal-cell-enriched epidermal cell suspension transplantation in vitiligo: Indian experience. J Cutan Aesthet Surg. 2011;4(1):23-28. Available at jcasonline.com/text.asp?2011/4/1/23/79183 

  37. Lee DY, Kim CR, Park JH. Recurrence after epidermal grafting in segmental vitiligo. Dermatol Surg. 2011;37(11):1707-1708. 

  38. Zitelli BJ, McIntire SC, Nowalk AJ, eds. Zitelli and Davis’ Atlas of Pediatric Physical Diagnosis, 6th ed. Philadelphia, Pa.: Elsevier Saunders; 2012. 

  39. Sharquie KE, Noaimi AA, Salmo HM. Pityriasis alba versus vitiligo. Journal of the Saudi Society of Dermatology & Dermatologic Surgery. 2013;17(2):51-54. Available at sciencedirect.com/science/article/pii/S2210836X13000213 

  40. Oiso N, Fukai K, Kawada A, Suzuki T. Piebaldism. J Dermatol. 2013;40(5):330-335. Available at onlinelibrary.wiley.com/doi/10.1111/j.1346-8138.2012.01583.x/full 


All electronic documents accessed on July 7, 2015.



This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Eroded vesicles on a boy’s face and neck and Blue-violet reticulated patches on an infant. Then take the post-test here.


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