Erythema Dyschromicum Perstansin Prepubertal Children

Nanette B. Silverberg, M.D.,* Joshua Herz, M.D.,� Annette Wagner, M.D.,�and Amy S. Paller, M.D.�

*St. Luke’s–Roosevelt Hospital Center, New York, New York, and �Children’s Memorial Hospital, NorthwesternUniversity Medical School, Chicago, Illinois

Abstract: Erythema dyschromicum perstans (EDP) is a rare disorder ofpigmentation that is most common in Hispanic patients. In adults, EDP has aslow onset and is unlikely to resolve spontaneously. The etiology and clin-ical course in children is poorly defined. Physical examinations, chartreviews, and telephone interviews were performed for eight pediatricpatients with EDP who were followed at Children’s Memorial Hospital inChicago between 1990 and 1998. All the patients available for long-termfollow-up (five of the eight) experienced complete clearance without recur-rence in an average of 2.5 years. In all of our patients, the onset was notedfrom July to December. The administration of aminopenicillins was coinci-dent with the development of EDP in two of the patients. Review of theEnglish-language literature reveals that 25 prepubertal children have previ-ously been reported. Including our patients, 69% of prepubertal children withEDP experienced resolution. We concluded that the clinical course ofchildhood (prepubertal) EDP differs from that of adult EDP, and it is morelikely to resolve within 2–3 years.

Erythema dyschromicum perstans (EDP) is an unu-sual disorder of skin pigmentation that primarily occursin young adults. The disorder is characterized by slate-gray oval macules and patches with erythematous bor-ders that range in diameter from 0.5 to 3 cm. Lesionsinitially appear on the trunk and spread centrifugally tothe extremities. Rarely the scalp, palms, and soles areaffected. As the lesions extend, the erythematous borderresolves. Patients often present with no evidence of ery-thema.Erythema dyschromicum perstans was first described

by Ramirez in 1957 (1). This description of 58 patientsincluded those as young as 7 years of age. They wereSouth Americans, whose families referred to them

colloquially as ‘‘los cenescientos,’’ or the ashy people,leading to the commonly used name ‘‘ashy dermatosis.’’Since 1957, 238 additional patients have been described,including those of Caucasian,AfricanAmerican, Indian,Asian and, most commonly, Hispanic descent. EDP hastraditionally been characterized by its poor response tomedication and its tendency to persist indefinitely inadult patients.

METHODS

Charts and photographic records were reviewed ofpatients who were seen between 1990 and 1998 at theDivision of Dermatology, Children’s Memorial

Address correspondence to Nanette B. Silverberg, M.D.,Department of Dermatology, St. Luke’s–Roosevelt Hospital Cen-ter, 1090 Amsterdam Ave., Suite 11D, New York, NY 10025, ore-mail: nsilverberg@slrhc.org.

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Hospital, Chicago, IL. EDP was identified in eight pa-tients based on clinical, histopathologic, and/or photo-graphic documentation. A telephone interview wasconducted with each of the five patients.

RESULTS

Patient information, demographics, and history aresummarized in Tables 1 and 2. Five of our eightpatients were Caucasian. All the patients had onset oftheir lesions between July and December. Lesions wereoval and ranged in size from 0.5 to 2 cm. Most lesions,irrespective of the patient’s ethnicity, were gray in color(Fig. 1) and asymptomatic. The majority of patients

initially developed lesions on the neck or trunk. Lesionsspread peripherally to the extremities and face. None ofthe patients had lesions with erythematous borders atthe time of presentation; erythema and/or scaling priorto the development of lesions was denied. One patient(patient 6) had a recent viral upper respiratory tractinfection. Two patients had been treated with amoxi-cillin and one with anticonvulsants shortly before dis-ease onset. Patients presented for examination onaverage 3 months into the illness. Two patients werebiopsied, with specimens demonstrating dermal mel-anin and melanophages, with mild vacuolar degener-ation, superficial lymphocytic infiltrate, and noeosinophils (patients 7 and 8).

TABLE 1. Patient Profiles

PatientSite of firstlesion

Age of lesions(in months)

Durationof illness

Monthof onset Treatment

1 Trunk 4 3 years July None2 Neck N/A N/A July None3 Face 3 N/A December Midpotency steroid (3 months)4 Trunk 3 1 year August Midpotency steroid (5 months)5 Neck 3 N/A August Selenium sulfide (1 week)6 Trunk 2 1 year December None7 Leg 3 2.5 years December None8 Neck 6 5 years August None

N/A, information not available.

TABLE 2. Summary of Prepubertal Cases

Reference Age at onset (years) Sex Ethnicity/race Clinical course Exposures

1 7 Unknown Hispanic Not noted30 11 M Hispanic Not noted TMP/SMX, PCN15 5 F Caucasian Faded over months6 6 F Caucasian Not noted12 10 F Caucasian Not noted Travel to India2 10 M Caucasian Three clear in 2 years,

one lost to follow-up8 M Caucasian8 F Caucasian11 M Caucasian

18 8 Unknown Unknown Not noted20 5 F Hispanic Mild improvement32 10 ? Hispanic No change at 45 years3 4 F Japanese Worse at 5 months Linear4 6 M Caucasian No change at 6 months Linear, HIV/hemophilia B5 11 Unknown Hispanic Better with clofazimine42 8 Unknown Hispanic No resolution43 7 F Hispanic Worse at 1 yearSilverberg 0.8 (patient 1) F Caucasian Clear at 3 years Amoxicillin

2 (patient 2) M Caucasian Not available3 (patient 3) M Caucasian Not available4 (patient 4) M Caucasian Clear at 1 year Amoxicillin/clavulanate6 (patient 5) F Hispanic Not available Anticonvulsants7 (patient 6) M Caucasian Clear at 1 year Upper Respiratory Infection9 (patient 7) F Hispanic Clear at 2.5 years10 (patient 8) F African-American Clear at 5 years Ferrous sulfate

Silverberg et al: Erythema Dyschromicum Perstans 399

Three patients were treated for their EDP: two withmidpotency steroids on a daily to twice-daily basis for3–5 months (patients 4 and 5) and one with seleniumsulfide lotion in 2-minute exposures for a 1 week (patient6). Patients were given strict sun avoidance instructionsand told to wear protective clothing.Five patients were available for follow-up by tele-

phone or physical examination (patients 1, 4, 6, 7, and 8).All of these patients reported complete remission.Patients 4 and 6noted total clearancewithin 1 year, whilethe lesions of patients 1, 7, and 8 resolved within 3, 2.5,and 5 years, respectively (average clearance time of thefive patients was 2.5 years). No recurrences were noted,with an average follow-up of 3.5 years after clearance(range 1–7 years).Erythema dyschromicum perstans has been des-

cribed in 296 patients from 26 countries in the English-language literature (including adult patients and ourown 8 patients). The average age was 24.7 years, and thesex ratio nearly equal (101 males and 104 females, withno sex information offered for 91 patients). Most wereHispanic (244), with a few Caucasian (30), Asian (10),African American (8), and Indian (2) patients. Sixty-

three patients had associated illnesses, infections, ormedications. Only 26 patients were reported to haveimproved or cleared, 11 of whom were prepubertal.Including the children in our report, 35 patients havebeen described who were younger than 20 years ofage (11.8%). Twenty-five of the patients (8.4% of allpatients with EDP) were prepubertal (younger than12 years of age), with an average age of 7.1 years atpresentation. Of the prepubertal patients, 13 wereCaucasian (52%), 9 Hispanic (36%), 1 African Ameri-can (4%), 1 Asian (4%), and the ethnicity of 1 (4%) wasnot specified. Eleven were female, nine male, and fiveunspecified. Lesions were typical of those described inadult patients.Two previously described children had lesions orien-

ted along Blaschko lines (2,3). Given the usual orienta-tion and failure to resolve of their lesions, these patientsmay have had an alternate diagnosis, such as pigmentmosaicism or a variant of incontinentia pigmenti.Exposures todrugs or infectious agentswere suspected ascausative in five patients. Three children had a recenthistory of penicillin or trimethoprim-sulfamethoxazoleexposure; one had recently traveled to India and Africa,and one had HIV and hemophilia B (no medicationspecified) (4). One patient had been given anticonvul-sants, but there was no temporal association with theeruption. Eleven of these patients eventually had partialor complete resolution.Excluding those forwhomfollow-upor clinical course

was unavailable, the condition resolved or improvedsignificantly in 69% of prepubertal patients and in all ofour patients with a documented course. It should benoted that one of these patients showed clearance afterreceiving clofazimine (5). However, none of the otherpatients had been administered therapy at the time ofresolution or improvement. Three children experiencedno change. The two children whose lesions worsenedover time were observed only during the first year of thedisorder.

DISCUSSION

Most adult patients with EDP have been of Hispanicdescent, although Caucasian patients have been des-cribed from Europe (4,6–11), Scandinavia (2,12,13) andthe United States (14–29). African American (15,19–21,23,26), Asian (3,9,27,28), and Indian (27,29) patientshave also been described. Prepubertal childrenwith EDPare more likely to be Caucasian than Hispanic. Thereappears to be no sexual predilection for EDP, even inprepubertal children.Despite differences in ethnic background and etiol-

ogy, EDP is clinically similar in all patients. The disease

Figure 1. Patient 4 has the typical ashy gray lesions.

400 Pediatric Dermatology Vol. 20 No. 5 September/October 2003

spreads centrifugally and has a characteristic gray colorin all ethnic groups. Often inflammation is subclinical,and lesions begin and progress without erythema.In this study we describe eight prepubertal children

with EDP. In contrast with the preponderance of adultHispanic patients in the literature, five of our patientswere Caucasian, and 52% of reported prepubertalpatients have been Caucasian, suggesting an increasedprevalence in lighter-skinned patients during childhood.Adult patients with EDP have limited to no improve-ment in their dyspigmentation (1,7–10,12,13,16–18,20–26,28–34). The complete resolution of lesions in all of ourpediatric patients (as well as 6 of 11 prepubertal childrenfor whom the clinical course was specified in the litera-ture) (2,5,15,20) suggests that childhood EDP is likely toclear completely; this in contrast with the course of thedisorder in adults.The cause of EDP is unclear, although several triggers

have been proposed, including exposure to environ-mental allergens (35) such as the pesticide chlorothalinol(34), toxins such as ammonium nitrate (7), and the fun-gicide fucilade (11). A single patient with patch test-positive allergic contact dermatitis to cobaltwas found tohave recurrence of gray lesions with cobalt reexposure(10). Oral antibiotics (9,15,17,29) have previously beenlinked to EDP, and two of our patients had taken peni-cillin 1 week before the dyspigmentation began. Use ofbenzodiazepines (22,29) and endocrinopathies, especiallyin thyroid disease (11,20), have also been associated withEDP.The diagnosis of EDP is based on the appearance of

the symmetric, 0.5–2 cm, ashy gray to blue, hyperpig-mented oval plaques and patches. Linear lesions thatresembled EDP, but were oriented along Blaschko lines,have been described in two prepubertal patients (2,3).Although the presence of erythema at lesional borders isinconsistent, dermal lymphohistiocytic infiltrates areregularly seen in biopsy sections of the hyperpigmentedlesions of EDP, with both CD4+ and CD8+ cells dem-onstrated by immunoperoxidase staining (33). Increasedexpression of intercellular adhesion molecule (ICAM)-1and HLA-DR (28) has been demonstrated in the basalcell layer of lesional skin samples. Papillary dermaledema and pigmentary incontinence with numerousdermal melanophages are also characteristic histologicfeatures (27,32,35,36). Immunofluorescent deposits areseen inconsistently, and may be absent (32), but mayappear as colloid or cytoid bodies with IgM (3,4,18–20),IgG (14,19,28), IgA (22),C3 (4,22), fibrinogen (22), orC4(18). Alternatively, granular IgM (21) and fibrinogenmay be deposited at the dermoepidermal junction (13).Ultrastructural analysis of lesional skin has demonstra-ted vacuoles and liquefactive degeneration in the basal

cell layer, intraepidermal lymphocytes, and increasedintercellular spaces without desmosomal alteration(9,25,32).Both EDP and fixed drug eruptions show significant

clinical hyperpigmentation andhistologic features. Fixeddrug eruptions are occasionally extensive in distributionand, although usually characterized by an initialinflammatory phase, may present as hyperpigmentation.Biopsy specimens of fixed drug eruption show moreintense hydropic degeneration of the basal layer withdyskeratotic keratinocytes, and an infiltrate with eosin-ophils. The lack of an underlying drug trigger, theabsence of eosinophilia, and the less extensive hydropicdegeneration, as well as the gray coloration of EDP, helpto distinguish these disorders.Erythema dyschromicum perstans may also be con-

fused with discoid lupus erythematosus because of thevacuolar interface changes. However, the presence of aperiappendageal inflammatory infiltrate and thickeningof the basement membrane in tissue sections favor thediagnosis of discoid lupus erythematosus.While EDP may coexist with lichen planus (21),

lichen planus pigmentosus is a distinct disorder char-acterized by lesions that are more brown in color andoccur on exposed areas and folds of the skin inpatients of skin types IV or V (37,38). EDP may alsocoexist with vitiligo (33). Although the gray-blue colorof the skin lesions of EDP may resemble those ofargyria, the lesions of argyria are accentuated in areasof sun exposure and may involve the mucous mem-branes. The histologic appearance of lesional skinfrom patients with argyria is distinct from that ofEDP, with gray-brown granules in macrophages andthe basal lamina of adnexal structures.Patients with incontinentia pigmenti have vesicular

lesions initially, but biopsy specimens demonstrate pig-mentary incontinence during the stage of hyperpigmen-tation. Although usually brown in color, thehyperpigmentation of incontinentia pigmenti may be agray-brown. In tropical climates, the early stages of pintacan be confused with EDP. Addisonian hyperpigmen-tation occurs primarily in distal and oral locations, andaffected patients tend to have hypovolemia with elec-trolyte alterations.There are no effective therapies for EDP. The

administration of topical agents, including steroids andhydroquinones, has been universally unsuccessful.Recent reports, however, have suggested sulfone medi-cations such as dapsone (11) and clofazimine (5,39) mayprevent subclinical disease extension in adults. Therapiesthat have been reported to be of anecdotal utility includeoral corticosteroids, antibiotics, ultraviolet (UV) lighttherapy, isoniazid, griseofulvin (26), and keratolytics.

Silverberg et al: Erythema Dyschromicum Perstans 401

Although EDP is unlikely to resolve in adults (40,41),our study provides evidence that most prepubertal chil-dren have a course of spontaneous slow resolution.Moreover, recurrences have never been reported afterclearance. In children therefore we recommend educa-tion of parents and patients about the good prognosis ofprepubertal EDP and about the use of sun protection toavoid lesional prominence while awaiting spontaneousresolution.

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