Ashy dermatosis

Erythema dyschromicum perstans

(Ashy dermatosis)

By/Azza Samy Amer

C. Oswaldo Ramirez of San Salvador, El Salvador, first described erythema dyschromicum perstans (EDP) in 1957.

He called the patients with this eruption Los cenicientos, meaning the ashen ones.

Background

The Spanish term cenicienta also means Cinderella because of this folklore character's close association with ashes from sitting at home alone by the fireplace.

Later, erythema dyschromicum perstans was called dermatosis ceniciento, meaning ashy dermatosis, because of its ashy bluish gray color.

Background(cont.)

The term erythema dyschromicum perstans is credited to Marion B. Sulzberger, who suggested it when examining Convit‘s patients in Caracas.

Sulzberger's comment, in discussion of another paper, is as follows:

The narrow red border (which is often hard to find), represents the active lesions. This is why I suggested a name which contains the term "erythema" and which also suggests the variety and persistence of the final dyschromias.

Background(cont.)

In South America, another name, erythema chronicum figuratum melanodermicum, is also used.

Erythema dyschromicum perstans (ashy dermatosis) is a distinct and somewhat controversial cutaneous eruption that may be best regarded as a form of lichen planus or lichen planus actinicus.

Background(cont.)

The etiology of erythema dyschromicum perstans is unknown, but many consider erythema dyschromicum perstans to be a variant of lichen planus actinicus.

A variety of predisposing factors have been cited. These include:

Pathophysiology

Ingestion of ammonium nitrite. An intestinal parasitosis caused by nematodes

(whipworm infection, control of which produced erythema dyschromicum perstans remission).

Orally administered radiographic contrast media. Possibly, an occupationally associated cobalt

allergy in a plumber. Chlorothalonil exposure among banana farm

workers is another possible cause of erythema dyschromicum perstans.

Drug induced.

Pathophysiology(environmental)

An abnormality in cell-mediated immunity might play a role. However, substantial immune dysfunction is limited at present to 1 report of an HIV-seropositive 41-year-old homosexual of Chinese lineage with erythema dyschromicum perstans.

Pathophysiology(immunological)

There is HLA-DR association with the genetic susceptibility to develop ashy dermatosis.

The most frequent allele is HLA-DR4.

Pathophysiology(genetic)

International: Erythema dyschromicum perstans is most

common in Latin America and Asia; most of the cases occur in El Salvador where the first case was identified. Cases in Europe have also been described, including in Italy.

Mortality/Morbidity: Erythema dyschromicum perstans has a

benign outcome, with most complaints relating to cosmetic issues.

Epidemiology

Race: Darker-skinned individuals seem to be

affected more often than lighter-skinned individuals.

Unlike adult patients, who are most commonly of Hispanic origin, children with erythema dyschromicum perstans are usually white.

Epidemiology(cont.)

Sex: Both sexes are affected, but women are

affected more often than men. Age: The age range affected is wide, both in

Latin America and around the world. Erythema dyschromicum perstans has been observed in children aged 1 year and adults aged 80 years.

Epidemiology(cont.)

Erythema dyschromicum perstans has asymptomatic, gray-blue hyperpigmented patches of variable shape and size and an elevated erythematous border in the early stages .

The eruption is symmetrically distributed on the face, the trunk, and the upper extremities.

The oral cavity and the genitals are spared.

Clinical Presentation

Clinical Presentation(cont.)

Ash-colored, partially confluent, macular lesions over the patient's back


Close-up photograph shows ash-colored macular lesions and lack of an inflammatory border.


we report 2 cases of unilateral ashy dermatosis

a, b Asymptomatic slate-gray pigmented plaques on the left thigh (a) and left abdomen (b; case 1). c Ashy-gray pigmented area on the left femur (case 2).

Several other skin conditions may appear similar to erythema dyschromicum perstans because they also result in discoloured skin patches:

Lichen planus pigmentosus (erythema dyschromicum perstans may be a variant of this disorder).

Multiple lesions of fixed drug eruption.Post inflammatory hyperpigmentation.Urticaria pigmentosa.

Differential Diagnosis:

Incontinentia pigmenti.Pinta(Pinta is an endemic treponematosis caused

by Treponema carateum:the initial lesion is a papule that slowly enlarges to become a pruritic plaque. Lesions become pigmented with age and may change colors from copper to grey to slate blue).

Allergic Contact Dermatitis. Dermatologic Aspects of Addison Disease. Dermatologic Manifestations of

Hemochromatosis.

Differential Diagnosis(cont.):

Late pigmented pinta (blue variety)

Idiopathic eruptive macular pigmentation (IEMP): is a rare disease that can be distinguished by different clinical appearance of the macules: gray with an erythematous border and possibly confluent in erythema dyschromicum perstans, versus brownish and nonconfluent in IEMP.

Differential Diagnoses(cont.):

Idiopathic eruptive macular pigmentation :brown pigmented macules on theback.

Idiopathic eruptive macularpigmentation: normal epidermis and greatnumber of melanophages in the papillary dermis

Drug reactions should be considered: Ashy dermatosis–like pigmentation has

been described attributed to ethambutol. Poikiloderma vasculare atrophicans: may

initially show features of erythema dyschromicum perstans.(

PVA with an epidermotropism of CD4-CD8+ atypical T cells)

Differential Diagnoses(cont.):

Laboratory Studies: All cases of erythema dyschromicum perstans

(EDP), to date, have resulted in negative laboratory study results, which include the following:

Bacterial, viral, and mycologic cultures.Erythrocyte sedimentation rate.Glucose studies.Liver function test.Urinalysis.

Workup:

Imaging Studies: Radiographic studies in erythema dyschromicum

perstans patients have not shown abnormalities. Histologic Findings: The biopsy specimen is obtained as much to rule

out other diagnoses as to confirm that of erythema dyschromicum perstans because the erythema dyschromicum perstans histologic pattern is relatively non specific.

Workup(cont.):

One should attempt to obtain a biopsy sample of the border of an active macule, which usually demonstrates:

Mild basal cell layer vacuolar degeneration. The upper dermis shows mild perivascular

mononuclear cell infiltrate and increased melanophages.

In the inactive stage of ashy dermatosis, there is no vacuolization of the basal cell layer, and a diminished dermal infiltrate.

Workup(cont.):

Histopathology

Normal basket weaven stratum corneum, focal interface with exocytosis of lymphocytes within the epidermis, no band like lymphocytic infiltrate but dense perivascular melanophges (the deep deposition of melanin gives this blue-gray hue according to Tendal’s phenomenon).No eosinophils were seen(drug eruption was ruled out) .These pathological findings are typical for erythema dyschromicum perstans

Distinguishing ashy dermatosis from lichen planus pigmentosus (LPP) is not always easy:

A Mexican study of 20 patients with erythema dyschromicum perstans and 11 with LPP provided clear clinical delineation between the 2 often histologically indistinguishable disorders:

LPP has pruritic brownish black macules or patches, with no active border, on the face and the flexor folds.

Erythema dyschromicum perstans does not involve mucosal surfaces, where LPP does.

Histopathology (cont.)

lichen planus pigmentosus

In favor of erythema dyschromicum perstans being either a subset of idiopathic lichen planus or a lichenoid drug eruption are:

Reports of lichen planus and erythema dyschromicum perstans occurring in the same patient.

The clinical resemblance of erythema dyschromicum perstans to atrophic lichen planus.

Similar histologic patterns with immunofluorescence in both erythema dyschromicum perstans and LPP.

Immunopathologic study of erythema dyschromicum perstans shows:

Immune-associated (Ia) antigen expression in keratinocytes .

Strong OKT 4 and OKT 6 staining of Langerhans cells.

It also shows dermal infiltration by T lymphocytes of both helper-inducer and suppressor-cytotoxic phenotypes, a pattern commonly seen with lichen planus.

Workup(cont.):

CD36 expression (a thrombospondin receptor that is not expressed in normal skin) in the

strata spinosum and granulosum of the active lesions

of AD. Apparently, CD36 correlates its presence with the active lymphocytes of the skin’s inflammatory infiltrate and may imply a delayed hypersensitivity reaction.

Beneath, in the dermis, the cellular infiltrate has been found to express CD69 and the cytotoxic cell marker CD94.

Workup(cont.):

In addition, as with lichen planus, the colloid bodies stained immunoglobulin G positive.

Such findings endorse the immunologic origin that AD may have and suggest a probable genetic predisposition of the disease.

Ultrastructural findings demonstrate: Immature, small, irregular-shaped melanosomes in melanocytes and peripheral localization of melanosomes in keratinocytes.

Workup(cont.):

Many therapeutic options are available for erythema dyschromicum perstans (EDP), but few have been effective, except for clofazimine.

In one series of 8 patients, 7 had a good or excellent response to clofazimine administered either 100 mg every other day to patients weighing less than 40 kg or 100 mg every day to patients weighing more than 40 kg. This medication was continued for 3 months, then reduced to 200 mg/wk and 400 mg/wk, respectively.

Treatment & Management

Clofazimine is a lipophilic rhimophenazine dye with antimicrobial and anti-inflammatory properties originally developed to treat tuberculosis. It inhibits mycobacterial growth and binds preferentially to mycobacterial DNA.

Although the mechanism of action is unclear, clofazimine produces a uniform skin coloration masking the dyschromias, and exerts immunomodulatory and anti-inflammatory effects.

Treatment & Management(cont.)

Dapsone (Avlosulfon) : Dapsone is bactericidal and bacteriostatic

against mycobacteria; its mechanism of action is similar to that of sulfonamides, in which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.

Besides its antimicrobial potency, it is effective in poly morphonuclear as well as lymphocytes rich dermatoses.

Dapsone possibly plays a role in the regulation of immune responses involved in the pathogenesis of Ashy dermatosis.


Many other therapeutic modalities have been attempted, none with satisfactory results. These include:

Ultraviolet exposure.Ultraviolet avoidance.Antibiotics. Antihistamines. Griseofulvin. Chemical peels.


Antibiotics. Corticosteroids. Vitamins. Isoniazid. Chloroquine.Psychotherapy.


The use of narrow-band UVB phototherapy has shown success in a few patients.

A low-potency topical steroid applied twice a day to the affected areas may be used, with or without a 4% hydroquinone cream for the hyperpigmentation.


No significant complications have been described in erythema dyschromicum perstans (EDP).

Complications are associated with clofazimine therapy:

Its most common adverse effects are in the skin, the gut, and the eye.

It gives a temporary orange discoloration of the skin and the eye (ie, cornea, conjunctivae).

It also may produce ichthyosis. Its most serious adverse effect is crystal deposition

in the gut that produces a potentially fatal enteropathy.

Complications

(erythema dyschromicum perstans)

induced by omeprazole:a report of three cases

A review of adult patients diagnosed with omeprazole associated ashy dermatosis between 2012 and 2014 in the Singapore General Hospital was conducted.

History and presentation: The patients had no previous medical or

dermatological history. Omeprazole was prescribed for gastritis in

all three patients at a daily dose of 20 mg.

omeprazole-induced ashy dermatosis

The latency between drug initiation and the onset of cutaneous lesions was between 9 and 12 months.

No other medications were initiated during this period.

Asymptomatic ashy gray macules occurred initially on the trunk before extending to the neck and extremities.

There was no involvement of the palms, soles, or mucosa.


Histopathological examination showed: pigmentary incontinence and moderate numbers of melanophages.

Omeprazole was stopped with no further progression of the dermatoses.


The postulated mechanisms of drug-induced hyperpigmentation include:

(i) Accumulation of melanin due to hyperproduction from the epidermal melanocytes.

( ii ) lack of clearing of drug from the dermal

– melanocytes due to melanin drug binding.

( iii ) , synthesis of special pigments such as lipofuscin and deposition of iron created by the

damage of blood vessels caused by the drug.


In a previous report of omeprazole-induced ashy dermatosis, high-performance liquid chromatography and mass spectrometry detected the presence of sulfur in granules within upper dermal macrophages,suggesting that pigmentation resulted from accumulation of the drug metabolite as sulfur, which is part of the omeprazole chemical structure and is rarely found naturally in the human skin.

Recognition of this association is important due to the widespread use of omeprazole.


Erythema Dyschromicum Perstans :

A New Manifestation Of Sjogren’s Syndrome.Case

ReportThe Internet Journal of Rheumatology. 2009 Volume 6 Number 2.

A 38-year-old woman first presented with a sudden eruption of scattered non-pruritic skin lesions on the face and arms in 2008.

The lesions continued to evolve into extensive patchy hyperpigmented areas on the face, neck and chest and showed no signs of resolution.

There is no history of photosensitivity or alopecia.

She was seen by multiple dermatologists and tried multiple ointments and creams with no improvement.

Erythema Dyschromicum Perstans: A New Manifestation Of Sjogren’s Syndrome

Her past medical history includes migraines and anemia and is on iron supplementation.

She subsequently developed keratoconjunctivitis sicca and was referred for a rheumatology evaluation.

On examination, she had extensive hyperpigmented lesions with a bluish discoloration on her face and forehead without papules, vesicles, or discoid lesions.

General examination was unremarkable.


Laboratory tests including complete blood count, erythrocyte sedimentation rate, comprehensive metabolic panel, ferritin, iron, thyroid stimulating hormone, serum protein electrophoresis and complement levels were normal.

Further investigations revealed a positive SS-A, however the ANA, SS-B and lupus anti-coagulant were all negative.


She underwent a shave biopsy of the left forehead to determine the etiology of the vague rash. It revealed sections of skin showing

lichenoid infiltrate of lymphocytes Vacuolar changes and dyskeratotic

keratinocytes Many scattered melanophages in the papillary

and reticular dermis. These are consistent with erythema

dyschromicum perstans.


She was subsequently diagnosed with primary Sjogren’s syndrome (pSS) based on her symptoms and serology.



It is reported that the skin is affected in nearly half of Sjogren’s syndrome patients.

Cutaneous features include xerosis, pruritus, angular cheilitis, eyelid dermatitis, annular erythema, and vasculitis mainly presenting as palpable purpura. Most of them are nonspecific and less severe than the oral, ocular or musculoskeletal symptoms.

The peculiar cutaneous finding in this patient : erythema dyschromicum perstans.

This patient improved with the use of clofazamine


From our department

38 years old female presented to our department by asymptomatic, hyperpigmented patches of variable shape and size in both upper limbs of gradual onset,progressive course and 4 months duration.

From history: The condition started 5 years ago by dry

eyes and mouth then the pt asked medical advice and diagnosed as sjogren’s syndrom and started methotrexate amp and arth free tab then shifted to hostacortin 5 -10 mg tab /day and hydroquine 200 mg tab/day.

On examination:The pt has asymptomatic, gray-blue hyperpigmented patches of variable shape and size symmetrically distributed on upper extremities. The oral cavity is spared.

Our differential diagnosis was:

Ptyriasis rosea

Drug eruption

Ashy dermatosis

Punch biopsy was taken and showed non specific changes :

Hyperkeratosis

Spongiosis Edema and ch. inflammatory cells of upper dermis

From history–examination and histopathology our provisional diagnosis was :

Ashy dermatosis (Erythema dyschromicum

perstans)

Thank you

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Ashy dermatosis