ppt

1. By/Azza Samy Amer

2.  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

3.  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.

4.  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.

5.  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.

6.  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

7.  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.

8.  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.

9.  There is HLA-DR association with the genetic
susceptibility to develop ashy dermatosis.
 The most frequent allele is HLA-DR4.

10.  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

11.  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.

12.  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.

13.  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

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

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

17. we report 2 cases of unilateral ashy dermatosis

18. 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).

19.  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:

20.  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.

21. Late pigmented pinta (blue variety)

22.  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.

23. Idiopathic eruptive macular pigmentation:
brown pigmented macules on the
back.
Idiopathic eruptive macular
pigmentation: normal epidermis and great
number of melanophages in the papillary dermis

24.  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)

25.  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:

26.  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.

27.  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.

28. 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

29.  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.

30. lichen planus pigmentosus

31.  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.

32.  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.

33.  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.

34.  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.

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

36.  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

37.  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.

38. 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.

39.  Many other therapeutic modalities have been
attempted, none with satisfactory results.
These include:
 Ultraviolet exposure.
 Ultraviolet avoidance.
 Antibiotics.
 Antihistamines.
 Griseofulvin.
 Chemical peels.

40.  Antibiotics.
 Corticosteroids.
 Vitamins.
 Isoniazid.
 Chloroquine.
 Psychotherapy.

41.  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.

42.  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.

43. (erythema dyschromicum perstans)
induced by omeprazole:a report
of three cases

44.  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.

45.  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.

46.  Histopathological examination showed:
pigmentary incontinence and moderate
numbers of melanophages.
 Omeprazole was stopped with no further
progression of the dermatoses.

48.  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.

49.  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.

50. Erythema Dyschromicum Perstans:
A New Manifestation Of Sjogren’s
Syndrome.Case Report
The Internet Journal of Rheumatology. 2009 Volume 6 Number 2.

51.  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.

52.  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.

53.  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.

54.  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.

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

57.  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

58. From our department

59.  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.

60. 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.

61.  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.

63. Our differential diagnosis was:
 Ptyriasis rosea
 Drug eruption
 Ashy dermatosis

64. Punch biopsy was taken and showed non
specific changes :
 Hyperkeratosis
 Spongiosis
 Edema and ch. inflammatory cells of
upper dermis

65.  From history–examination and histopathology
our provisional diagnosis was :
Ashy dermatosis
(Erythema dyschromicum perstans)