Transcript Dowling-Degos Disease - Abdel Hamid Derm Atlas

Dowling-Degos Disease
Classification of
Reticulate Dermatoses
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Vascular
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Cutis marmorata
Cutis marmorata telangiectatica congenita (CMTC)
Livedo reticularis (LR)
Livedo racemosa
Livedoid vasculopathy
Reticulate purpura
Pigmentary
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Dowling-Degos disease (DDD)
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Galli-Galli disease
Dermatopathia pigmentosa reticularis
Dyschromatosis universalis hereditaria (DUH)
Reticulate acropigmentation
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Syndromes associated with reticulate pigmentation
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Reticulate acropigmentation of Dohi
Reticulate acropigmentation of Kitamura
Naegeli-Franceschetti-Jadassohn syndrome
Mendes da Costa-van der Valk syndrome
Hoyeraal-Hreidarrson syndrome
Partington syndrome
Atopic dirty neck
Epidermolysis bullosa with mottled pigmentation
Systemic sclerosis
Classification of
Reticulate Dermatoses :Continue
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Poikilodermatous
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Inherited
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Rothmund-Thomson syndrome More Details
Dyskeratosis congenita
Xeroderma pigmentosum
Cockayne syndrome
Fanconi anemia
Mendes da Costa syndrome
Kindler syndrome
Degos-Touraine syndrome
Hereditary sclerosing poikiloderma of Weary
Hereditary acrokeratotic poikiloderma of Weary
Werner's syndrome (adult progeria)
Chanarin-Dorfman syndrome
Diffuse and macular atrophic dermatosis
Acquired
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Poikiloderma of Civatte
Injury by cold, heat, or ionizing radiation
Chronic graft-versus-host disease (cGVHD)
Others
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Dermatomyositis
Lupus erythematosus
Parapsoriasis
Mycosis fungoides
Poikiloderma-like cutaneous amyloidosis
Classification of
Reticulate Dermatoses: Continue
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Infectious
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Metabolic
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Macular amyloidosis
Amyloidosis cutis dyschromica
Reticular erythematous mucinosis
Hunter's syndrome
Others
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Confluent and reticulate papillomatosis (CRP)
Erythema infectiosum
Erythema marginatum (EM)
Congenital rubella syndrome
Erythema ab igne
Prurigo pigmentosa
Mucosal lichen planus
Leukoplakia
Neonatal lupus erythematosus (LE)
Hereditary angioedema
Extensive congenital erosions and vesicles healing with reticulate scarring
Atrophodermia vermiculata
Nekam's disease
Dowling-Degos Disease
• DDD is a late-onset genodermatosis, occurring usually in adulthood,
with the appearance of hyperpigmented macules. The onset of the
disease - a rare genodermatosis of autosomal dominant
transmission with variable penetrance - usually occurs in the third or
fourth decade of life. It is also referred to as 'Dark Dot Disease'. It
affects predominantly women in a ratio of 2:1 and has no race
predilection.
• The pigmentation gradually increases over time. The disease initially
affects the armpits and groin and later the intergluteal,
inframammary regions and the neck and trunk. Pruritus in the folds
may be reported. Over time comedo-like lesions also appear on the
back and neck, and perioral cribriform scars and follicular cysts. The
disease has been associated with Hidradenitis Suppurativa (HS),
also known as 'Acne Inversa', and multiple keratoacanthomas,
perhaps because DDD causes a defect in the pilo sebaceous
epithelial proliferation. .
Dowling-Degos Disease
• The disease is characterized by acquired reticulated skin
hyperpigmentation, which begins in the armpits, groin
and later spreads to other skin folds. It can affect
(although more uncommonly), the wrist, the antecubital
and popliteal space, the face, scalp, scrotum and vulva
. Some patients complain of itching in the macula.
These lesions do not change with sun exposure.
Comedo-type black lesions on the face, back and in the
same areas described above can also be observed , as
well as cribriform scars and perioral acne in patients with
no history of acne. Other features may be present such
as mental retardation and pilar cyst. While at the benign
stage the disease shows no inflammatory phenomena, it
is nevertheless very unsightly
Dowling-Degos Disease with Asymmetrical Axillary Distribution and No
KRT 5 Exon 1 Mutation Acta Dermato0venereologica, 2OO7
• a) Multiple, small brown
macules and papules in
reticular distribution
localized on the axilla.
The lesion on the left
side was more
pronounced than that on
the right.
• (b) Close-up of the left
axilla.
• . Histopathological
picture showing
irregular elongation of
rete ridges and basal
pigmentation
Dowling-Degos Disease
involving the vulva and back
Dermatology Online Journal 17 (7): 1
Dowling-Degos Disease involving the vulva and back
Vulvar biopsy: The epidermis shows thin elongated, branching rete ridges that
contain dense pigmentation in the lower one third. Scattered melanophages are
present in the upper dermis. There is mild hyperkeratosis overlying the epidermis.
Dermatology Online Journal 17 (7): 1
Dowling-Degos Disease involving the vulva and back
The histology is distinctive with marked, heavily pigmented, slender, and often branched,
elongation of the rete ridges Perianal biopsy: A small keratin cyst is present within one of
the rete ridges Dermatology Online Journal 17 (7): 1
Dowling-Degos Disease
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It is also known as ‘pigmented reticulate anomaly of the flexures’. It is important to distinguish this from acanthosis nigricans, which can
be a skin sign of internal diseases.
There are a number of probable variants of Dowling-Degos disease:
Localised Dowling-Degos
Generalised Dowling-Degos
Galli-Galli disease
Reticulate acropigmentation of Kitamura
Haber disease
Symmetrical acropigmentation of Dohi
In a few cases, pigmentation is absent.
What are the clinical features of Dowling-Degos disease?
Dowling-Degos disease affects only the skin and there are no internal effects. Skin affected by Dowling-Degos disease can be itchy,
especially in summer when the effects of heat, perspiration and friction aggravate the pigmentation and itch. Blistering is not a feature of
this disease.
Five patterns of classic Dowling-Degos and Galli-Galli disease are described.
1. Increased pigmentation
Freckle-like pigmentation usually first appears in early adult life in the great folds of the skin such as armpits, groin, between and under
the breasts. Common sites also include the upper arms, upper inner thighs, behind the knees and neck. It may be localized to one area
such as the genitalia (scrotum or vulva) (localized Dowling-Degos disease) or gradually extend to affect most of the skin surface
(generalized Dowling-Degos disease). The pigmentation may worsen in pregnancy and with sun exposure.
A number of patterns have been described:
Dappled or reticulate patterns
‘Dark spots’ – small black dots centered on hair follicles
Flat spots (macules) or slightly raised small spots (papules)
Varying shades of brown or black.
2. Follicular papules
These are small raised scaly pigmented or non-pigmented spots based on hair follicles
Dowling-Degos Disease
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3. Reduced pigmentation
These are small flat spots (macular) or raised (papular) spots that are paler than the normal skin.
4. Comedones
These are blackhead-like spots most often found on the neck.
5. Scars
These are pitted acne-like scars most often occurring on the chin.
Associated disorders with Dowling-Degos disease
@ Hidradenitis suppurativa has been reported in association with Dowling-Degos disease more often than would
be expected by chance. Thus patients with Dowling-Degos disease are more likely to also have hidradenitis
suppurativa.
Other conditions of uncertain relevance have been rarely reported in association with classic Dowling-Degos
disease:
@ Squamous cell carcinomas and keratoacanthomas
Abnormalities of skin appendages such as nail dystrophy and absence of vellus hair.
@ Seborrhoeic keratoses
@ Epidermoid or trichilemmal cysts
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Diagnosis of Dowling-Degos disease
The diagnosis is made on the clinical features and confirmed on skin biopsy.
There are two histological (pathological) variants:
Classic Dowling-Degos disease – the epidermis shows elongated branched (antler-like) rete ridges with increased
melanin pigmentation at the tips. There is no increase in melanocyte number.
Galli-Galli disease – in addition to the above features, there is also acantholysis (separated skin cells) with
overlying parakeratosis (horny layer cells retaining their nuclei
Dowling-Degos Disease
I.J.Derm. : 2014 : 59 : 1 : 3
Dowling-Degos Disease
Dowling-Degos Disease
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perioral pitting scars
hyperpigmentation
genitalia
Pathology Dowling Degos
dermatoscopie
Dowling-Degos Disease
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A) The epidermal down
growths showed a
misinform or antler-like
pattern with irregular
elongation of the rete
ridges in the lesion (H&E,
×100).
(B) There is increased
melanin pigment at the tips
of the epidermis (H&E,
×200).
(C) There is increased
pigmentation of the rete
ridges on Fontana-Masson
staining (Fontana-Masson,
×200).
(D) Compared with
perilesional normal skin,
the S100 protein staining
reveals no increase in the
number of melanocytes
(S100 protein, ×200).
Dowling-Degos Disease
• Histopathological findings of DDD include moderate
orthokeratosis or hyperkeratosis, thinning of the
suprapapillary epithelium and elongation of the papillae
with basal layer hyperpigmentation. These threadlike
growths of the epidermis have the appearance of
"antlers" and generally involve the follicle with a follicular
plug. A perivascular lymphohistiocytic infiltrate in the
papillary dermis and pseudo-horny cysts can also be
observed. Staining for S100 does not generally show
increased numbers of melanocytes, suggesting that the
pigment does not arise from increased density of
melanocytes.
Dowling-Degos Disease
The characteristic reticulate appearance of Dowling Degos disease
Dowling-Degos Disease
Dowling-Degos Disease
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acantholytic form of
Dowling-Degos disease
(DDD) in skin biopsy
specimens from axilla.
A , Typical histologic
features of DDD
characterized by
downward elongations
of rete ridges with
reticulated or
fenestrated pattern and
occasional horn cysts.
Suprabasal
acantholysis is present
at margin.
B , Higher power view
of suprabasal
acantholysis.
C , Lacunae or clefts in
suprabasal areas.
D , Intracellular edema
(spongiosis) of upper
epidermis.
Dowling-Degos Disease
Dowling-Degos disease and hidradenitis suppurativa: Co occurrence or
association?
I Derm. Online J.2013 : 4 : 3: 191
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@ Multiple nodules and plaques with sinuses discharging pus involving the buttocks
@ Nodules, plaques and scars involving the inner aspect of the upper thigh and anogenital region
Dowling-Degos disease and hidradenitis suppurativa: Co
occurrence or association?
I Derm. Online J.2013 : 4 : 3: 191
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@ Crusted plaque over the right leg
@ Multiple dark brown pigmented macules and comedo like lesions (dark dot follicle) involving the
right axilla
Dowling-Degos disease and hidradenitis
suppurativa: Co occurrence or association?
I Derm. Online J.2013 : 4 : 3: 191
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@ Multiple dark brown pigmented
macules and comedo (dark dot follicle)
involving the left axilla
@ Scattered comedo-like lesions (dark
dot follicles) involving the right thigh
@ Multiple discrete pitted scars over the
face
Dowling-Degos disease and hidradenitis suppurativa: Co
occurrence or association?
I Derm. Online J.2013 : 4 : 3: 191
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@ Neutrophilic and histiocytic
infiltration around the pilosebaceous
apocrine units
@ Irregular epidermis, acanthosis and
elongation of rete ridges with increased
basal melanin pigmentation
Dowling-Degos disease
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@ Areas of hyperplasia and
microcystic transformation of
the sweat glands
@ Areas of cystic
transformation of the sweat
glands
Dowling-Degos disease and malignant melanoma: Association
I J D V L ,2015 : 81 : 6 : 627
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A] Multiple
grouped shiny
skin-colored
to
erythematous
nodules and
plaques on
the left side of
the scrotum
with adjacent
papules and
nodules.
b) Face
showing
discrete,
hyperpigment
ed macules on
the forehead.
Pitted scars
prominent on
the nose,
perinasal and
perioral
regions.
(c) Brown
hyperpigment
ed macules in
the right axilla
Dowling-Degos disease and malignant melanoma: Association
IJDVL
,2015 : 81 : 6 : 627
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Elongation and branching of rete pegs with basal
hyperpigmentation, consistent with Dowling-Degos
disease
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(a) Nests of
tumor cells
having
pleomorphic
vesicular
nuclei,
prominent
eosinophilic
nucleoli and
moderate
amount of
cytoplasm
(H and E
stain, ×400),
(b) HMB-45
monoclonal
antibody
staining the
cytoplasm
of the tumor
cells (×100)
Dowling-Degos disease
Hyperkeratosis, acanthosis and
papillomatosis with scant perivascular
lymphocytic infiltration was observed in
the lesional skin (
Dowling-Degos Disease
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Some authors refer to Acropigmentation of Kitamura, and Galli-Galli disease as differential
diagnoses of DDD.
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@Reticulate Acropigmentation of Kitamura (RAPK) is a sporadic autosomal dominant disease of
unknown origin. It prevails in Japan, but has been observed worldwide. Its clinical features consist
of hyperpigmented atrophic macules on the backs of the hands and feet. Its onset is in childhood.
The lesions darken with time and worsen with sun exposure. Pitting on the palms and soles and
dorsa of the fingers can also be found. .
@Galli-Galli disease is an acantholytic variant of Dowling-Degos disease which presents in
people aged between 15 and 5o While the mechanism of acantholysis is unknown authors have
suggested that it results from of loss of epidermal cell stability due to a keratin 5 defect. Clinical
symptoms include the presence of hyperpigmentation of the flexures together with itching, and
sometimes with erythematous, scaly papules on these sites as well as on the trunk and proximal
extremities. The histopathology resembles that of DDD, but with foci of acantholysis. Another
differential diagnosis with Galli-Galli disease would be epidermolysis bullosa with mottled
pigmentation, although this disease has other additional features such as blisters and
palmoplantar hyperkeratosis. Treatment usually consists of topical steroids and retinoids, with little
success.
@DDD must also be differentiated from acanthosis nigricans which also shows a predilection for
skin folds, but with the emergence of velvety plaques. Histopathologically the papillae are less
elongated and without follicular involvement. Patients with neurofibromatosis may also have
freckle-like (ephelides) lesions in the armpits, but this disease is easily distinguished from DDD.
No other complementary examination exists to aid diagnosis of DDD apart from a typical
histopathologic examination associated with compatible clinical features, as we did in this case
Dowling-Degos Disease
• A variety of treatments can be tried but
with unsatisfactory outcomes: topical
hydroquinone, tretinoin, adapalene and
corticosteroids, as well as Er:YAG lasers.
Isotretinoin would be an option since it
produces an alteration in the pattern of
keratinization, 20mg/day of oral and
topical isotretinoin.
Reticulate acropigmentation of Kitamura
Dermatology Online Journal 14 (8): 7
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RAPK was first described in Japan: about 100 cases have been reported, mostly in Asian ethnic
groups. The characteristic presentation of RAPK is as pigmented, angulated, irregular freckle-like
lesions with atrophy on the surface, arranged in a reticular pattern on the dorsa of the hands and
feet. The lesions usually start in the first and second decades of life and gradually extend onto the
extremities and rarely on the face and eyelids. The lesions usually slowly darken over time .
Sunlight may aggrevate the condition. Pits and breaks in the dermatoglyphics are found on the
palms, soles and dorsal phalangeal surfaces .
Histopathological examination classically shows epidermal atrophy associated with club-like
elongation of the rete ridges and an excess of melanin in the basal layer .
The differential diagnosis of RAPK include diseases presenting with reticulated or punctate
hyperpigmentation like dyskeratosis congenita, dyschromatosis universalis herediteria,
Franceschetti-Jadassohn's syndrome, dermatopathia pigmentosa reticularis, acropigmentation of
Dohi (RAD) and Dowling-Degos Disease (DDD) . RAD is also an acral type of dyschromatosis
(dyschromatosis symmetrica herediteria) that usually starts in infancy or early childhood as
hypopigmented and hyperpigmented macules over the dorsa of the hands and feet. The
differentiation between RAD and RAPK is based on clinical and histological findings. In RAPK
there are usually no hypopigmented macules and histologically there is epidermal atrophy and
increase in the number of basal melanocytes. DDD is also an autosomal dominant pigmented skin
disorder characterized by reticular hyperpigmentation on flexor areas such as the neck, axilla,
antecubital fossa, submammary area and groin. Dark comedo-like lesions and pitted perioral
acneiform scars may be present. Rarely hypopigmented macules or papules are observed.
Histologically there are pigmented filiform epidermal projections involving the follicular
infundibulum as well as the epidermis
Variants of Dowling-Degos disease
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There have been a number of case reports describing patients with overlapping features between
classic Dowling-Degos disease and the following conditions, but these are now thought to be
variants of Dowling-Degos disease.
@ Kitamura reticulate acropigmentation
Kitamura reticulate acropigmentation tends to first appear in childhood or adolescence as:
Dark freckled pigmentation on the backs of the hands and tops of feet
Palmar pits
Discontinuity of the fingerprint lines
Epidermoid cysts
Flat (macular) or raised (papular) spots with reduced or absent pigment
@ Gali & Gali disease
Acantholytic variant of Dowling Degos disease .Galli-Galli disease is a benign but very pruritic
and unaesthetic genodermatosis. Its mode of inheritance is believed to be autosomal dominant
with variable penetrance, but it can occur sporadically , as in our patient. As with DDD it is
believed to be linked to mutations in the KRT5 gene . Clinically it is characterized by reticulated
hyperpigmentation predominantly affecting the flexures along with pruritic, erythematous, scaly
papules, similar to the DDD. Histopathologic examination reveals digitiform elongation of the rete
ridges seen in DDD, together with suprabasal focal acantholysis .
@ Symmetrical acropigmentation of Dohi
Symmetrical acropigmentation of Dohi starts to appear in infancy or early childhood as pinpoint to
pea sized flat (macular) spots of increased and decreased pigmentation on the backs of the
hands.
Galli-Galli Disease: A Rare Acantholytic Variant of Dowling-Degos Disease
Case Reports in Medicine
Volume 2011 (2011)
• Galli-Galli
disease
(GGD) is a
very rare
variant of the
DowlingDegos disease
(DDD) with the
histologic
finding of focal
acantholysis.
• Photo: A, B
Galli-Galli Disease: A Rare Acantholytic Variant of Dowling-Degos Disease
Case Reports in Medicine
Volume 2011 (2011)
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Hematoxylin and eosin. (a)
Discrete hyperkeratosis,
elongated rete ridges with
digitiform projections, and
focal acantholysis with
formation of linear clefts.
Presence of mixed dermal
inflammatory infiltrate.
(b) Dyskeratotic cells in the
interior of a acantholytic cleft.
(c) and (d) Digitiform
elongation of the rete ridges,
with hyperpigmentation of
the basal layer confined to
the tips of the rete ridges.
Suprabasal
Photo: C, D
Reticulate acropigmentation
of Kitamura
Dermatology Online Journal 14 (8): 7
Reticulate acropigmentation
of Kitamura
Dermatology Online Journal 14 (8): 7
Presentation of Reticulate Acropigmentation of Kitamura and
Dowling-Degos Disease Overlap J Clin Aesthet Dermatol. 2012 ; 5(5): 41.
Presentation of Reticulate Acropigmentation of Kitamura and
Dowling-Degos Disease Overlap J Clin Aesthet Dermatol. 2012 ; 5(5): 41.
A case of reticulate acropigmentation of Kitamura: Dowling Degos disease
overlap with unusual clinical manifestations I L Derm2014
: 59 : 3 : 290-
Reticulate hyperpigmentation on: (a) Dorsa of both hands (b) Dorsa of both feet (c) Neck
(d) Axilla
A case of reticulate acropigmentation of Kitamura: Dowling Degos disease
overlap with unusual clinical manifestations I L Derm2014
: 59 : 3 : 290-
Unusual features: (a) Reticulate hyperpigmentation in periorbital area (b)
Reticulate hyperpigmentation on scrotum (c) Hypopigmented macules on trunk (d)
Acneiform scars on nose
A case of reticulate acropigmentation of Kitamura: Dowling Degos
disease overlap with unusual clinical manifestations I L Derm2014 : 59 : 3
:
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Histopathology of skin
lesions: (a) Biopsy
from axillary lesion
demonstrating filiform
elongation of the rete
ridges,
hyperpigmentation of
basilar keratinocytes,
and clusters of
melanocytes at the tip
of the rete ridges
along with follicular
plugging (H and E,
×10) (b) High-power
view of the same (H
and E, ×40) (c) Melan-A
staining
demonstrating the
increased melanocytes
(×40) (d) Biopsy from
hypopigmented
macules showing
reduced number of
melanocytes (H and E,
×40)
Differential diagnosis of DDD, RAK, HS and RAD
DDD: Dowling-Degos disease, RAK: reticulate acropigmentation of Kitamura, HS:
Haber's syndrome, RAD: reticulate acropigmentation of Dohi, AD: autosomal dominant,
AR: autosomal recessive
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Dermatopathia pigmentosa reticularis
I. Drm. Online J. : 2013 : 4 : 1 : 40
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Reticulate pigmentation on the
trunk
Diffuse nonscarring alopecia
Dermatopathia
pigmentosa reticularis
I. Drm. Online J. : 2013 : 4 : 1 : 40
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Onychodystrophy of finger nails
Plantar hyperkeratosis
Dermatopathia pigmentosa reticularis
I. Drm. Online J. : 2013 : 4 : 1 : 40
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Histopathology; showing
melanophages and
absence of skin adenexa
Reticulate Acropigmentation of Dohi
Indian J Dermatol. 2012 ; 57(1): 42
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Reticulate acropigmentation
of Dohi also called
dyschromatosis symmetrica
hereditaria or symmetrical
dyschromatosis of the
extremities is an autosomal
dominant inherited disorder.
It is characterized by
mottled pigmentation with
patchy depigmentation
commonly over the back of
the hands and feet and
sometimes on the arms and
legs
Hyperpigmented and
hypopigmented macules
over dorsum of hands
Hyperpigmented macules
over both palms
Reticulate Acropigmentation of Dohi
Indian J Dermatol. 2012 ; 57(1): 42
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Freckle like macules over face
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Mottled pigmentation over buttocks
Reticulate Acropigmentation of Dohi
Indian J Dermatol. 2012 ; 57(1): 42
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Biopsy from hyperpigmented macule showing abundance of melanocytes in basal layer and the presence of
melanocytes in other epidermal layers
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Biopsy from hypopigmented macule showing relatively less melancyte
Reticulate Acropigmentation of Dohi