DARIER’S DISEASE, Keratosis folliculiris, rare genetic disorder that is manifested predominantly by skin changes, due to ATP2A2 mutation, The histology is characteristic, known as focal acantholytic dyskeratosis associated with varying degrees of papillomatosis
10. This gene codes for the
SERCA2 enzyme or pump
(Sarco-Endoplasmic
Reticulum Calcium-ATPase)
that is required to transport
calcium within the cell.
11.
12.
13. mutation in ATP2A2 gene
that affects the activity of
SERCA2, pumps which
causes a complete loss of
Ca++ transport activity
into ER cytosolic Ca++
14. normal extra cellular calcium
level is important in
maintaining structure and
function of desmosomal
proteins as well as cell cycle
check points otherwise;
42. The symptoms and signs of Darier’s disease
vary markedly between individuals.
Some have very subtle signs that are
asymptomatic and found only on careful
inspection. Others have extensive lesions
which can cause considerable distress to the
affected individual.
Moderate itch
Malodor
In an affected person the severity of the
disease can fluctuate over time.
44. persistent, greasy, scaly papules which
tend to occur over the "seborrhoeic"
areas of the face (scalp margins,
forehead, ears, around the nostrils and
sides of nose, eyebrows, and beard
area), neck, and central chest and back.
The flexures and skin under breasts
and between buttocks are also
commonly affected.
45. The papules have a firm, harsh feel like
coarse sandpaper and may be skin-colored,
yellow-brown or brown in color.
If several of the small papules grow together
they may form larger warty lesions which
can become quite smelly within skin folds.
The scalp is often affected with a heavily
crusted rash which can be similar to
seborrhoeic dermatitis but is usually harsher
to the touch.
47. Small pits (tiny indentations) on the
palms and soles may occur and are
very characteristic of Darier disease.
Small warty lesions or areas of
bleeding under the skin can also be
seen on the palms and soles as well
as the dorsum of the hands and feet.
These are known as acrokeratosis
verruciformis.
48. Most patients with Darier’s
disease will have longitudinal
broad stripes of white and
reddish color on the nails
(erytheronychia).
V-shaped notch at the free
edge of the nail
“pathognomonic”
51. Patients with Darier‘s disease
may uncommonly have a
white cobblestone pattern or
small papules affecting the
mucous membranes.
Overgrowth of the gums is
also seen.
52. Other presentations
Some patients develop a
linear pattern of lesions,
often following the lines of
embryonal development of
the skin segmental Darier
57. histology of Darier's
disease skin. The
suprabasal cleft of the
epidermis contains
acantholitic cells
(indicated by
arrowheads), associated
with hyperkeratosis
(indicated by white
arrows) and rounded
dyskeratotic cells
(indicated by yellow
arrows).
63. Irregular acanthosis, papillomatosis, hyperkeratosis.
Suprabasal acantholysis clefts and lacunae
containing dyskeratotic cells.
Irregular upward proliferation of one layer of basal
keratinocytes (villi) into the lacunae.
CORPS RONDS rounded cells with dark pyknotic
nuclei and perinuclear halo encircled by
eosinophilic cytoplasm in the granular layer.
GRAINS elongated cells with shrunken
parakeratotic nuclei in corneal layer.
Dermal chronic inflammation