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Year : 2015  |  Volume : 60  |  Issue : 5  |  Page : 525
Erythema dyschromicum perstans: Response to topical tacrolimus

Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda, Himachal Pradesh, India

Date of Web Publication4-Sep-2015

Correspondence Address:
Vikram K Mahajan
Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda - 176 001, Himachal Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.164452

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Background: Erythema dyschromicum perstans, a rare dermatosis of obscure etiopathogenesis and significant cosmetic morbidity, have no satisfactory treatment. Observations: Two patients with having characteristic asymptomatic and slowly progressive, slate-grey macular lesions with distinct red borders involving the face, neck, upper trunk and limbs were diagnosed clinicopathologically as erythema dyschromicum perstans. Both were treated successfully with topical tacrolimus 0.1% ointment. Conclusions: Overall, response to several therapeutic modalities including clofazimine and dapsone therapy is said to vary from complete failure to variable or inconsistent. Topical tarolimus provides an effective and safe alternative therapeutic option in erythema dyschromicum perstans.

Keywords: Ashy dermatosis, clofazimine, dapsone, lichenoid dermatitis, lichen planus pigmentosus, post-inflammatory hyperpigmentation

How to cite this article:
Mahajan VK, Chauhan PS, Mehta KS, Sharma AL. Erythema dyschromicum perstans: Response to topical tacrolimus. Indian J Dermatol 2015;60:525

How to cite this URL:
Mahajan VK, Chauhan PS, Mehta KS, Sharma AL. Erythema dyschromicum perstans: Response to topical tacrolimus. Indian J Dermatol [serial online] 2015 [cited 2023 Jun 2];60:525. Available from:

What was known?
Erythema dyschromicum perstans is uncommon dermatosis of significant cosmetic morbidity. Therapeutic outcome with clofazimine, dapsone, oral antibiotics, vitamins, isoniazid, choloroquin, gresiofulvin, topical corticosteroids, chemical peels, sun protection, and psychotherapy has been variable and unsatisfactory.

   Introduction Top

Erythema dyschromicum perstans (EDP) is an uncommon dermatosis that occurs worldwide but perhaps more so in Central America. There is no genetic predisposition, it affects both genders equally, and is rare in children. Ingestion of ammonium nitrate, ethambutol, radio-contrast media or chlorthalonil, nematode infestation, and occupational allergy to cobalt have been implicated invariably but its etiology remains obscure. [1],[2] There is also lack of consensus on the exact nature of EDP. It is not unusual to find terms like EDP, ashy dermatosis, idiopathic eruptive macular pigmentation, and lichen planus pigmentosus being used inter-changeably in the literature for various similar looking dermatoses. Zaynoun et al.[3] reviewed the literature and proposed clinical diagnostic criteria to resolve the confusion prevailing in diagnosing these clinically and histologically simulating disorders. Therapeutically only clofazimine and dapsone have been considered of some benefit. [4],[5] A number of other treatment modalities including topical corticosteroids, chemical peels, oral antibiotics, vitamins, isoniazid, choloroquin, gresiofulvin, sun protection, and psychotherapy have been tried with variable results. [5],[6],[7] Topical tacrolimus has not been used previously for treating EDP.

   Case Reports Top


A 29-year-old man presented with numerous asymptomatic slate-grey macules over face, neck, upper trunk and extremities of 6 months duration. The lesions had started over right side of neck and new lesions appeared gradually to involve other body areas. He was an agriculturist and had no history of handling of chemicals or drug intake before or after noticing the skin lesions. His family and medical history was unremarkable. Physical examination showed multiple, round to oval, 0.5-5 cm sized bluish-grey-colored macules over cheeks, chin, neck, upper chest and back, abdomen, and both upper limbs. The lesions around neck showed distinct minimally elevated erythematous borders [Figure 1]a and b. Hair, nails, teeth, palms, soles, mucous surfaces and systemic examination were essentially normal. Laboratory work up including complete hemogram, blood biochemistry, urinalysis, and stool examination for intestinal parasites showed no abnormality. A biopsy specimen showed focal changes of moderate compact hyperkeratosis, epidermal thinning, basal cell degeneration, melanin incontinence, lymphohistiocytic infiltrate in the upper dermis and no colloid bodies [Figure 1]c and d. With the diagnosis of EDP he was prescribed topical tacrolimus ointment (0.1%) to be applied twice daily. No concurrent treatment was prescribed. All the skin lesions disappeared during next 3 months and no recurrence has been observed during follow up of more than a year.
Figure 1: Case-1 (a and b) Multiple, variable sized, round to oval, bluish-grey macules with distinct minimally elevated red borders over neck and upper chest. (c and d) Moderate compact focal hyperkeratosis, epidermal thinning, basal cell degeneration, intense melanin incontinence and lymphohistiocytic infiltrate in the upper dermis (stain, H and E; C ×10, D ×40)

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A 19-year-old girl presented with a 5-month history of asymptomatic slate-grey macules over both sides of neck. She reported that the lesions had started spontaneously over sides of neck and were progressive in number and size. She was a student, and her family and medical history was essentially normal. She had no drug intake before or after her skin lesions. Physical examination showed 0.5-4 cm sized, round to oval, slate-grey-colored macules around the neck [Figure 2]a. The lesions showed distinct minimally elevated erythematous borders. Physical examination for hair, nails, teeth, palms, soles, mucous surfaces and other systems, and laboratory work up as in case-1 revealed no abnormality. A biopsy specimen showed similar features of EDP as in case-1 but were of less intensity [Figure 2]b. Treatment with topical tacrolimus ointment (0.1%) applied twice daily resulted in disappearance of all the skin lesions during follow up of 2 months. She is under follow up.
Figure 2: Case-2 (a) Round to oval, slate-grey-colored macules with distinct minimally elevated erythematous borders around the neck. (b) The histology shows moderate compact hyperkeratosis, focal epidermal thinning, mild focal basal cell degeneration, melanin incontinence and lymphohistiocytic infiltrate in the upper dermis (stain, H and E; ×10)

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   Discussion Top

The diagnosis in our patients was mainly clinicopathologic and based on the criteria proposed by Zaynoun et al. [3] According to them ashy dermatosis comprises patients with idiopathic eruptive hyperpigmented macules, irrespective of the presence or absence of histological interface dermatitis (lichenoid tissue reaction) while distinct raised erythematous borders distinguish EDP lesions which otherwise have similar histology and clinically slate-grey colored lesions. On the other hand, lichen planus (LP) with its variants (lichen planus pigmentosus, actinic LP), and post-inflammatory hyperpigmentation (pityriasis rosea, toxic or drug induced melanoderma, erythema multiforme, mastocytosis, etc.) are described as "simulators" Moreover, concurrent presence of mucosal lesions of LP will delineate LP that may sometimes occur concurrently with EDP. [6] Immunohistologic findings in EDP are similar to those in LP and include keratinocytes having Ia antigen expression, strong OKT4 and OKT6 staining of Langerhans' cells, and dermal infiltrate of helper/inducer and suppressor/cytotoxic phenotypes of T cells. [4],[6] The treatment of EDP is largely unsatisfactory and remains challenging. Treatment with clofazimine is not considered curative despite being used by most workers. [6] Bahadir et al.[5] observed an excellent response without recurrence with oral dapsone 100 mg/d given for 3 months in their patient. Yet the experience with dapsone has mostly been frustratingly poor. [6] We observed highly encouraging results with topical tacrolimus (0.1%) in our patients after 2-3 weeks onwards [Figure 3]. Tacrolimus, a USFDA approved therapeutic modality for atopic dermatitis, is a calcineurin inhibitor and has found several off-label indications for being an effective immunomodulator. Topical tacrolimus 0.1% is considered as effective in atopic dermatitis as potent topical corticosteroids sans their adverse effects. [8] We make no attempt to speculate on the mechanism of its therapeutic efficacy. Topical calicineurin inhibitors (tacrolimus, pimecrolimus) bind with cytoplasmic immunophilin FKBP12 and form a complex that inhibits the activity of the enzyme calcineurin needed for T-cell activation. Inhibition of calcineurin prevents dephosphorylation of cytoplasmic component of the nuclear factor of activated T cells which regulates mRNA transcription of inflammatory cytokines of Th1 and Th2 pathways (IL-2, IFN-g, and IL-4, IL-10). [9] An abnormal cell-mediated immune response has been postulated to play a role in the pathogenesis of EDP possibly as a result of involvement of cell adhesion and activation molecules (ICAM-1, LFA-1α). This is evident from the predominant presence of CD8+ T cells in the dermis, HLA-DR+ and ICAM-1+ expression in epidermal keratinocytes and exocytosis of cutaneous lymphocyte antigen (CLA)+ cells in areas with damaged basal cells. [4] Topical tacrolimus exerts its therapeutic effect in EDP perhaps by virtue of its immunomodulatory effects. We feel that topical tarolimus provides an effective and safe alternative therapeutic option in EDP. Nevertheless, more studies perhaps will be appropriate to make any recommendation.
Figure 3: Case-1 (a) All the skin lesions have improved after topical tacrolimus (0.1%) applied for 2 weeks. (b) Case-2. All skin lesions showed significant improvement following topical application of tacrolimus (0.1%) for 3 weeks

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   References Top

Keisham C, Sarkar R, Garg VK, Chugh S. Ashy dermatosis in an 8-year-old Indian child. Indian Dermatol Online J 2013;4:30-2.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
Srivastava N, Solanki L, Chand S, Garbyal RS, Singh S. Ashy dermatosis-like pigmentation due to ethambutol. Indian J Dermatol Venereol Leprol 2008;74:281-2.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
Zaynoun S, Rubeiz N, Kibbi AG. Ashy dermatoses-a critical review of the literature and a proposed simplified clinical classification. Int J Dermatol 2008;47:542-4.  Back to cited text no. 3
Vásquez-Ochoa LA, Isaza-Guzmán DM, Orozco-Mora B, Restrepo-Molina R, Trujillo-Perez J, Tapia FJ. Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis). Int J Dermatol 2006;45:937-41.  Back to cited text no. 4
Bahadir S, Cobanoglu U, Cimsit G, Yayli S, Alpay K. Erythema dyschormicum perstans: Response to dapsone. Int J Dermatol 2004;43:220-2.  Back to cited text no. 5
Schwartz RA. Erythema dyschormicum perstans: The continuing enigma of Cinderella or ashy dermatosis. Int J Dermatol 2004;43:230-2.  Back to cited text no. 6
Molinero J, Vilata JJ, Nagore E, Obon L, Grau C, Aliaga A. Ashy dermatosis in an HIV antibody-positive patient. Acta Dermatol Venereol 2000;80:78-9.  Back to cited text no. 7
Reitamo S, Rustin M, Ruzicka T, Cambazard F, Kalimo K, Freidmann PS, et al. Efficacy and safety of tacrolimus ointment compared with hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol 2002;109:547-55.  Back to cited text no. 8
Novak N, Kwiek B, Bieber T. The mode of topical immunomodulators in heimmunological network of atopic dermatitis. Clin Exp Dermatol 2005;30:160-4.  Back to cited text no. 9

What is new?
Topical tacrolimus 0.1% ointment provides an effective and safe alternative therapeutic option in erythema dyschromicum perstans.


  [Figure 1], [Figure 2], [Figure 3]

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