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Bluish Gray Hyperpigmentation on the Face and Neck
The Diagnosis: Erythema Dyschromicum Perstans
Erythema dyschromicum perstans (EDP), also referred to as ashy dermatosis, was first described by Ramirez1 in 1957 who labeled the patients los cenicientos (the ashen ones). It preferentially affects women in the second decade of life; however, patients of all ages can be affected, with reported cases occurring in children as young as 2 years of age.2 Most patients have Fitzpatrick skin type IV, mainly Amerindian, Hispanic South Asian, and Southwest Asian; however, there are cases reported worldwide.3 A genetic predisposition is proposed, as major histocompatibility complex genes associated with HLA-DR4⁎0407 are frequent in Mexican patients with ashy dermatosis and in the Amerindian population.4
The etiology of EDP is unknown. Various contributing factors have been reported including alimentary, occupational, and climatic factors,5,6 yet none have been conclusively demonstrated. High expression of CD36 (thrombospondin receptor not found in normal skin) in spinous and granular layers, CD94 (cytotoxic cell marker) in the basal cell layer and in the inflammatory dermal infiltrate,7 and focal keratinocytic expression of intercellular adhesion molecule I (CD54) in the active lesions of EDP, as well as the absence of these findings in normal skin, suggests an immunologic role in the development of the disease.8
Erythema dyschromicum perstans presents clinically with blue-gray hyperpigmented macules varying in size and shape and developing symmetrically in both sun-exposed and sun-protected areas of the face, neck, trunk, arms, and sometimes the dorsal hands (Figures 1 and 2). Notable sparing of the palms, soles, scalp, and mucous membranes occurs.
Occasionally, in the early active stage of the disease, elevated erythematous borders are noted surrounding the hyperpigmented macules. Eventually a hypopigmented halo develops after a prolonged duration of disease.9 The eruption typically is chronic and asymptomatic, though some cases may be pruritic.10
Histopathologically, the early lesions of EDP with an erythematous active border reveal lichenoid dermatitis with basal vacuolar change and occasional Civatte bodies. A mild to moderate perivascular lymphohistiocytic infiltrate admixed with melanophages can be seen in the papillary dermis (Figure 3). In older lesions, the inflammatory infiltrate is sparse, and pigment incontinence consistent with postinflammatory pigmentation is prominent, though melanophages extending deep into the reticular dermis may aid in distinguishing EDP from other causes of postinflammatory pigment alteration.7,11
Erythema dyschromicum perstans and lichen planus pigmentosus (LPP) may be indistinguishable histopathologically and may both be variants of lichen planus actinicus. Lichen planus pigmentosus often differs from EDP in that it presents with brown-black macules and patches often on the face and flexural areas. A subset of cases of LPP also may have mucous membrane involvement. The erythematous border that characterizes the active lesion of EDP is characteristically absent in LPP. In addition, pruritus often is reported with LPP. Direct immunofluorescence is not a beneficial tool in distinguishing the entities.12
Other differential diagnoses of predominantly facial hyperpigmentation include a lichenoid drug eruption; drug-induced hyperpigmentation (deposition disorder); postinflammatory hyperpigmentation following atopic dermatitis; contact dermatitis or photosensitivity reaction; early pinta; and cutaneous findings of systemic diseases manifesting with diffuse hyperpigmentation such as lupus erythematosus, dermatomyositis, hemochromatosis, and Addison disease. A detailed history including medication use, thorough clinical examination, and careful histopathologic evaluation will help distinguish these conditions.
Chrysiasis is a rare bluish to slate gray discoloration of the skin that predominantly occurs in sun-exposed areas. It is caused by chronic use of gold salts, which have been used to treat rheumatoid arthritis. UV light may contribute to induce the uptake of gold and subsequently stimulate tyrosinase activity.13 Histologic features of chrysiasis include dermal and perivascular gold deposition within the macrophages and endothelial cells as well as extracellular granules. It demonstrates an orange-red birefringence on fluorescent microscopy.14,15
Minocycline-induced hyperpigmentation is a well-recognized side effect of this drug. It is dose dependent and appears as a blue-black pigmentation that most frequently affects the shins, ankles, and arms.16 Three distinct types were documented: abnormal discoloration of the skin that has been linked to deposition of pigmented metabolites of minocycline producing blue-black pigmentation at the site of scarring or prior inflammation (type 1); blue-gray pigmentation affecting normal skin, mainly the legs (type 2); and elevated levels of melanin on the sun-exposed areas producing dirty skin syndrome (type 3).17,18
Topical and systemic corticosteroids, UV light therapy, oral dapsone, griseofulvin, retinoids, and clofazimine are reported as treatment options for ashy dermatosis, though results typically are disappointing.7
- Ramirez CO. Los cenicientos: problema clinica. In: Memoria del Primer Congresso Centroamericano de Dermatologica, December 5-8, 1957. San Salvador, El Salvador; 1957:122-130.
- Lee SJ, Chung KY. Erythema dyschromicum perstans in early childhood. J Dermatol. 1999;26:119-121.
- Homez-Chacin, Barroso C. On the etiopathogenic of the erythema dyschromicum perstans: possibility of a melanosis neurocutaneous. Dermatol Venez. 1996;4:149-151.
- Correa MC, Memije EV, Vargas-Alarcon G, et al. HLA-DR association with the genetic susceptibility to develop ashy dermatosis in Mexican Mestizo patients [published online November 20, 2006]. J Am Acad Dermatol. 2007;56:617-620.
- Jablonska S. Ingestion of ammonium nitrate as a possible cause of erythema dyschromicum perstans (ashy dermatosis). Dermatologica. 1975;150:287-291.
- Stevenson JR, Miura M. Erythema dyschromicum perstans (ashy dermatosis). Arch Dermatol. 1966;94:196-199.
- Baranda L, Torres-Alvarez B, Cortes-Franco R, et al. Involvement of cell adhesion and activation molecules in the pathogenesis of erythema dyschromicum perstans (ashy dermatitis). the effect of clofazimine therapy. Arch Dermatol. 1997;133:325-329.
- Vasquez-Ochoa LA, Isaza-Guzman DM, Orozco-Mora B, et al. Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis). Int J Dermatol. 2006;45:937-941.
- Convit J, Kerdel-Vegas F, Roderiguez G. Erythema dyschromicum perstans: a hiltherto undescribed skin disease. J Invest Dermatol. 1961;36:457-462.
- Ono S, Miyachi Y, Kabashima K. Ashy dermatosis with prior pruritic and scaling skin lesions. J Dermatol. 2012;39:1103-1104.
- Sanchez NP, Pathak MA, Sato SS, et al. Circumscribed dermal melaninoses: classification, light, histochemical, and electron microscopic studies on three patients with the erythema dyschromicum perstans type. Int J Dermatol. 1982;21:25-32.
- Vega ME, Waxtein L, Arenas R, et al. Ashy dermatosis and lichen planus pigmentosus: a clinicopathologic study of 31 cases. Int J Dermatol. 1992;31:90-94.
- Ahmed SV, Sajjan R. Chrysiasis: a gold "curse!" [published online May 21, 2009]. BMJ Case Rep. 2009;2009.
- Fiscus V, Hankinson A, Alweis R. Minocycline-induced hyperpigmentation. J Community Hosp Intern Med Perspect. 2014;4. doi:10.3402/jchimp.v4.24063.
- Cox AJ, Marich KW. Gold in the dermis following gold therapy for rheumatoid arthritis. Arch Dermatol. 1973;108:655-657.
- al-Talib RK, Wright DH, Theaker JM. Orange-red birefringence of gold particles in paraffin wax embedded sections: an aid to the diagnosis of chrysiasis. Histopathology. 1994;24:176-178.
- Meyer AJ, Nahass GT. Hyperpigmented patches on the dorsa of the feet. minocycline pigmentation. Arch Dermatol. 1995;131:1447-1450.
- Bayne-Poorman M, Shubrook J. Bluish pigmentation of face and sclera. J Fam Pract. 2010;59:519-522.
The Diagnosis: Erythema Dyschromicum Perstans
Erythema dyschromicum perstans (EDP), also referred to as ashy dermatosis, was first described by Ramirez1 in 1957 who labeled the patients los cenicientos (the ashen ones). It preferentially affects women in the second decade of life; however, patients of all ages can be affected, with reported cases occurring in children as young as 2 years of age.2 Most patients have Fitzpatrick skin type IV, mainly Amerindian, Hispanic South Asian, and Southwest Asian; however, there are cases reported worldwide.3 A genetic predisposition is proposed, as major histocompatibility complex genes associated with HLA-DR4⁎0407 are frequent in Mexican patients with ashy dermatosis and in the Amerindian population.4
The etiology of EDP is unknown. Various contributing factors have been reported including alimentary, occupational, and climatic factors,5,6 yet none have been conclusively demonstrated. High expression of CD36 (thrombospondin receptor not found in normal skin) in spinous and granular layers, CD94 (cytotoxic cell marker) in the basal cell layer and in the inflammatory dermal infiltrate,7 and focal keratinocytic expression of intercellular adhesion molecule I (CD54) in the active lesions of EDP, as well as the absence of these findings in normal skin, suggests an immunologic role in the development of the disease.8
Erythema dyschromicum perstans presents clinically with blue-gray hyperpigmented macules varying in size and shape and developing symmetrically in both sun-exposed and sun-protected areas of the face, neck, trunk, arms, and sometimes the dorsal hands (Figures 1 and 2). Notable sparing of the palms, soles, scalp, and mucous membranes occurs.
Occasionally, in the early active stage of the disease, elevated erythematous borders are noted surrounding the hyperpigmented macules. Eventually a hypopigmented halo develops after a prolonged duration of disease.9 The eruption typically is chronic and asymptomatic, though some cases may be pruritic.10
Histopathologically, the early lesions of EDP with an erythematous active border reveal lichenoid dermatitis with basal vacuolar change and occasional Civatte bodies. A mild to moderate perivascular lymphohistiocytic infiltrate admixed with melanophages can be seen in the papillary dermis (Figure 3). In older lesions, the inflammatory infiltrate is sparse, and pigment incontinence consistent with postinflammatory pigmentation is prominent, though melanophages extending deep into the reticular dermis may aid in distinguishing EDP from other causes of postinflammatory pigment alteration.7,11
Erythema dyschromicum perstans and lichen planus pigmentosus (LPP) may be indistinguishable histopathologically and may both be variants of lichen planus actinicus. Lichen planus pigmentosus often differs from EDP in that it presents with brown-black macules and patches often on the face and flexural areas. A subset of cases of LPP also may have mucous membrane involvement. The erythematous border that characterizes the active lesion of EDP is characteristically absent in LPP. In addition, pruritus often is reported with LPP. Direct immunofluorescence is not a beneficial tool in distinguishing the entities.12
Other differential diagnoses of predominantly facial hyperpigmentation include a lichenoid drug eruption; drug-induced hyperpigmentation (deposition disorder); postinflammatory hyperpigmentation following atopic dermatitis; contact dermatitis or photosensitivity reaction; early pinta; and cutaneous findings of systemic diseases manifesting with diffuse hyperpigmentation such as lupus erythematosus, dermatomyositis, hemochromatosis, and Addison disease. A detailed history including medication use, thorough clinical examination, and careful histopathologic evaluation will help distinguish these conditions.
Chrysiasis is a rare bluish to slate gray discoloration of the skin that predominantly occurs in sun-exposed areas. It is caused by chronic use of gold salts, which have been used to treat rheumatoid arthritis. UV light may contribute to induce the uptake of gold and subsequently stimulate tyrosinase activity.13 Histologic features of chrysiasis include dermal and perivascular gold deposition within the macrophages and endothelial cells as well as extracellular granules. It demonstrates an orange-red birefringence on fluorescent microscopy.14,15
Minocycline-induced hyperpigmentation is a well-recognized side effect of this drug. It is dose dependent and appears as a blue-black pigmentation that most frequently affects the shins, ankles, and arms.16 Three distinct types were documented: abnormal discoloration of the skin that has been linked to deposition of pigmented metabolites of minocycline producing blue-black pigmentation at the site of scarring or prior inflammation (type 1); blue-gray pigmentation affecting normal skin, mainly the legs (type 2); and elevated levels of melanin on the sun-exposed areas producing dirty skin syndrome (type 3).17,18
Topical and systemic corticosteroids, UV light therapy, oral dapsone, griseofulvin, retinoids, and clofazimine are reported as treatment options for ashy dermatosis, though results typically are disappointing.7
The Diagnosis: Erythema Dyschromicum Perstans
Erythema dyschromicum perstans (EDP), also referred to as ashy dermatosis, was first described by Ramirez1 in 1957 who labeled the patients los cenicientos (the ashen ones). It preferentially affects women in the second decade of life; however, patients of all ages can be affected, with reported cases occurring in children as young as 2 years of age.2 Most patients have Fitzpatrick skin type IV, mainly Amerindian, Hispanic South Asian, and Southwest Asian; however, there are cases reported worldwide.3 A genetic predisposition is proposed, as major histocompatibility complex genes associated with HLA-DR4⁎0407 are frequent in Mexican patients with ashy dermatosis and in the Amerindian population.4
The etiology of EDP is unknown. Various contributing factors have been reported including alimentary, occupational, and climatic factors,5,6 yet none have been conclusively demonstrated. High expression of CD36 (thrombospondin receptor not found in normal skin) in spinous and granular layers, CD94 (cytotoxic cell marker) in the basal cell layer and in the inflammatory dermal infiltrate,7 and focal keratinocytic expression of intercellular adhesion molecule I (CD54) in the active lesions of EDP, as well as the absence of these findings in normal skin, suggests an immunologic role in the development of the disease.8
Erythema dyschromicum perstans presents clinically with blue-gray hyperpigmented macules varying in size and shape and developing symmetrically in both sun-exposed and sun-protected areas of the face, neck, trunk, arms, and sometimes the dorsal hands (Figures 1 and 2). Notable sparing of the palms, soles, scalp, and mucous membranes occurs.
Occasionally, in the early active stage of the disease, elevated erythematous borders are noted surrounding the hyperpigmented macules. Eventually a hypopigmented halo develops after a prolonged duration of disease.9 The eruption typically is chronic and asymptomatic, though some cases may be pruritic.10
Histopathologically, the early lesions of EDP with an erythematous active border reveal lichenoid dermatitis with basal vacuolar change and occasional Civatte bodies. A mild to moderate perivascular lymphohistiocytic infiltrate admixed with melanophages can be seen in the papillary dermis (Figure 3). In older lesions, the inflammatory infiltrate is sparse, and pigment incontinence consistent with postinflammatory pigmentation is prominent, though melanophages extending deep into the reticular dermis may aid in distinguishing EDP from other causes of postinflammatory pigment alteration.7,11
Erythema dyschromicum perstans and lichen planus pigmentosus (LPP) may be indistinguishable histopathologically and may both be variants of lichen planus actinicus. Lichen planus pigmentosus often differs from EDP in that it presents with brown-black macules and patches often on the face and flexural areas. A subset of cases of LPP also may have mucous membrane involvement. The erythematous border that characterizes the active lesion of EDP is characteristically absent in LPP. In addition, pruritus often is reported with LPP. Direct immunofluorescence is not a beneficial tool in distinguishing the entities.12
Other differential diagnoses of predominantly facial hyperpigmentation include a lichenoid drug eruption; drug-induced hyperpigmentation (deposition disorder); postinflammatory hyperpigmentation following atopic dermatitis; contact dermatitis or photosensitivity reaction; early pinta; and cutaneous findings of systemic diseases manifesting with diffuse hyperpigmentation such as lupus erythematosus, dermatomyositis, hemochromatosis, and Addison disease. A detailed history including medication use, thorough clinical examination, and careful histopathologic evaluation will help distinguish these conditions.
Chrysiasis is a rare bluish to slate gray discoloration of the skin that predominantly occurs in sun-exposed areas. It is caused by chronic use of gold salts, which have been used to treat rheumatoid arthritis. UV light may contribute to induce the uptake of gold and subsequently stimulate tyrosinase activity.13 Histologic features of chrysiasis include dermal and perivascular gold deposition within the macrophages and endothelial cells as well as extracellular granules. It demonstrates an orange-red birefringence on fluorescent microscopy.14,15
Minocycline-induced hyperpigmentation is a well-recognized side effect of this drug. It is dose dependent and appears as a blue-black pigmentation that most frequently affects the shins, ankles, and arms.16 Three distinct types were documented: abnormal discoloration of the skin that has been linked to deposition of pigmented metabolites of minocycline producing blue-black pigmentation at the site of scarring or prior inflammation (type 1); blue-gray pigmentation affecting normal skin, mainly the legs (type 2); and elevated levels of melanin on the sun-exposed areas producing dirty skin syndrome (type 3).17,18
Topical and systemic corticosteroids, UV light therapy, oral dapsone, griseofulvin, retinoids, and clofazimine are reported as treatment options for ashy dermatosis, though results typically are disappointing.7
- Ramirez CO. Los cenicientos: problema clinica. In: Memoria del Primer Congresso Centroamericano de Dermatologica, December 5-8, 1957. San Salvador, El Salvador; 1957:122-130.
- Lee SJ, Chung KY. Erythema dyschromicum perstans in early childhood. J Dermatol. 1999;26:119-121.
- Homez-Chacin, Barroso C. On the etiopathogenic of the erythema dyschromicum perstans: possibility of a melanosis neurocutaneous. Dermatol Venez. 1996;4:149-151.
- Correa MC, Memije EV, Vargas-Alarcon G, et al. HLA-DR association with the genetic susceptibility to develop ashy dermatosis in Mexican Mestizo patients [published online November 20, 2006]. J Am Acad Dermatol. 2007;56:617-620.
- Jablonska S. Ingestion of ammonium nitrate as a possible cause of erythema dyschromicum perstans (ashy dermatosis). Dermatologica. 1975;150:287-291.
- Stevenson JR, Miura M. Erythema dyschromicum perstans (ashy dermatosis). Arch Dermatol. 1966;94:196-199.
- Baranda L, Torres-Alvarez B, Cortes-Franco R, et al. Involvement of cell adhesion and activation molecules in the pathogenesis of erythema dyschromicum perstans (ashy dermatitis). the effect of clofazimine therapy. Arch Dermatol. 1997;133:325-329.
- Vasquez-Ochoa LA, Isaza-Guzman DM, Orozco-Mora B, et al. Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis). Int J Dermatol. 2006;45:937-941.
- Convit J, Kerdel-Vegas F, Roderiguez G. Erythema dyschromicum perstans: a hiltherto undescribed skin disease. J Invest Dermatol. 1961;36:457-462.
- Ono S, Miyachi Y, Kabashima K. Ashy dermatosis with prior pruritic and scaling skin lesions. J Dermatol. 2012;39:1103-1104.
- Sanchez NP, Pathak MA, Sato SS, et al. Circumscribed dermal melaninoses: classification, light, histochemical, and electron microscopic studies on three patients with the erythema dyschromicum perstans type. Int J Dermatol. 1982;21:25-32.
- Vega ME, Waxtein L, Arenas R, et al. Ashy dermatosis and lichen planus pigmentosus: a clinicopathologic study of 31 cases. Int J Dermatol. 1992;31:90-94.
- Ahmed SV, Sajjan R. Chrysiasis: a gold "curse!" [published online May 21, 2009]. BMJ Case Rep. 2009;2009.
- Fiscus V, Hankinson A, Alweis R. Minocycline-induced hyperpigmentation. J Community Hosp Intern Med Perspect. 2014;4. doi:10.3402/jchimp.v4.24063.
- Cox AJ, Marich KW. Gold in the dermis following gold therapy for rheumatoid arthritis. Arch Dermatol. 1973;108:655-657.
- al-Talib RK, Wright DH, Theaker JM. Orange-red birefringence of gold particles in paraffin wax embedded sections: an aid to the diagnosis of chrysiasis. Histopathology. 1994;24:176-178.
- Meyer AJ, Nahass GT. Hyperpigmented patches on the dorsa of the feet. minocycline pigmentation. Arch Dermatol. 1995;131:1447-1450.
- Bayne-Poorman M, Shubrook J. Bluish pigmentation of face and sclera. J Fam Pract. 2010;59:519-522.
- Ramirez CO. Los cenicientos: problema clinica. In: Memoria del Primer Congresso Centroamericano de Dermatologica, December 5-8, 1957. San Salvador, El Salvador; 1957:122-130.
- Lee SJ, Chung KY. Erythema dyschromicum perstans in early childhood. J Dermatol. 1999;26:119-121.
- Homez-Chacin, Barroso C. On the etiopathogenic of the erythema dyschromicum perstans: possibility of a melanosis neurocutaneous. Dermatol Venez. 1996;4:149-151.
- Correa MC, Memije EV, Vargas-Alarcon G, et al. HLA-DR association with the genetic susceptibility to develop ashy dermatosis in Mexican Mestizo patients [published online November 20, 2006]. J Am Acad Dermatol. 2007;56:617-620.
- Jablonska S. Ingestion of ammonium nitrate as a possible cause of erythema dyschromicum perstans (ashy dermatosis). Dermatologica. 1975;150:287-291.
- Stevenson JR, Miura M. Erythema dyschromicum perstans (ashy dermatosis). Arch Dermatol. 1966;94:196-199.
- Baranda L, Torres-Alvarez B, Cortes-Franco R, et al. Involvement of cell adhesion and activation molecules in the pathogenesis of erythema dyschromicum perstans (ashy dermatitis). the effect of clofazimine therapy. Arch Dermatol. 1997;133:325-329.
- Vasquez-Ochoa LA, Isaza-Guzman DM, Orozco-Mora B, et al. Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis). Int J Dermatol. 2006;45:937-941.
- Convit J, Kerdel-Vegas F, Roderiguez G. Erythema dyschromicum perstans: a hiltherto undescribed skin disease. J Invest Dermatol. 1961;36:457-462.
- Ono S, Miyachi Y, Kabashima K. Ashy dermatosis with prior pruritic and scaling skin lesions. J Dermatol. 2012;39:1103-1104.
- Sanchez NP, Pathak MA, Sato SS, et al. Circumscribed dermal melaninoses: classification, light, histochemical, and electron microscopic studies on three patients with the erythema dyschromicum perstans type. Int J Dermatol. 1982;21:25-32.
- Vega ME, Waxtein L, Arenas R, et al. Ashy dermatosis and lichen planus pigmentosus: a clinicopathologic study of 31 cases. Int J Dermatol. 1992;31:90-94.
- Ahmed SV, Sajjan R. Chrysiasis: a gold "curse!" [published online May 21, 2009]. BMJ Case Rep. 2009;2009.
- Fiscus V, Hankinson A, Alweis R. Minocycline-induced hyperpigmentation. J Community Hosp Intern Med Perspect. 2014;4. doi:10.3402/jchimp.v4.24063.
- Cox AJ, Marich KW. Gold in the dermis following gold therapy for rheumatoid arthritis. Arch Dermatol. 1973;108:655-657.
- al-Talib RK, Wright DH, Theaker JM. Orange-red birefringence of gold particles in paraffin wax embedded sections: an aid to the diagnosis of chrysiasis. Histopathology. 1994;24:176-178.
- Meyer AJ, Nahass GT. Hyperpigmented patches on the dorsa of the feet. minocycline pigmentation. Arch Dermatol. 1995;131:1447-1450.
- Bayne-Poorman M, Shubrook J. Bluish pigmentation of face and sclera. J Fam Pract. 2010;59:519-522.
A middle-aged woman with Fitzpatrick skin type IV was evaluated for progressive hyperpigmentation of several months' duration involving the neck, jawline, both sides of the face, and forehead. The lesions were mildly pruritic. She denied contact with any new substance and there was no history of an eruption preceding the hyperpigmentation. Medical history included chronic anemia that was managed with iron supplementation. On physical examination, blue-gray nonscaly macules and patches were observed distributed symmetrically on the neck, jawline, sides of the face, and forehead. Microscopic examination of 2 shave biopsies revealed subtle vacuolar interface dermatitis with mild perivascular lymphocytic infiltrate and dermal melanophages (inset).
