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

1. DARIER’SDISEASE
facebook.com/groups/dermatologycourseonline

2. DARIER’S DISEASE
previously also known as
Keratosis folliculiris

3. DARIER’S DISEASE
rare genetic disorder that is
manifested predominantly
by skin changes

4. Like benign chronic familial
pemphigus (Hailey-Hailey
disease), Darier’s disease is
classified as a hereditary
acantholytic dermatosis.

5. AD with complete
penetrance & variable
expressivity

6. Onset 6-20y.

8. Pathogenesis

9. ATP2A2 on12q

10. This gene codes for the
SERCA2 enzyme or pump
(Sarco-Endoplasmic
Reticulum Calcium-ATPase)
that is required to transport
calcium within the cell.

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;

15.  acantholysis

16.  apoptosis

17. X- ray crystallography of the pump

19. Clinical Picture

23. Darier disease on
the mid-back

31. Darier’s Disease: Warty papules on
dorsum of hands & feet

32. Palmar
pits

36. acrokeratosis
verruciformis

37. Segmental Darier

38. Segmental
Darier

40. Facial
cysts

41. Exacerbations
Oftenbysunlight
Heat
Sweat
Occlusion
Occasionallybycorticosteroiduse(althoughthismaybe
usefulforotherpatients).
Infections:BacterialorviralWidespreadinfectionwith
theherpessimplexvirusisawellrecognized
complicationcalledeczemaherpeticum.

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.

43. The skin
lesions

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.

46. Lesionsonthe
hands &
nails

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”

49. Lesions
affecting
the mucous
membranes

50. Raised
papular
lesions on
the
palate.

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

53. Other presentations
Comedones & N.C. acne

54. Other presentations
Vesiculo-bullous type

56. Histopathology

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).

62. Histopathology
The histology is
characteristic, known as focal
acantholytic dyskeratosis
associated with varying
degrees of papillomatosis

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

65. Treatment

66. Treatment
Localized disease
Mild cases
Sever cases
2ry infection

67. Localized
disease

68. Dermabrasion, laser,
surgical excision & PDT
may be effective; may also
be treated successfully
with topical retinoids.

69. Mild
disease

70. simple moisturizers, sun
protection and selection of
the right clothing to avoid
heat and sweating are
usually sufficient.

71. Sever
disease

72. a trial of an oral retinoid
medication such as
acitretin or isotretinoin
may be effective

73. Result of one month's acitretin

74. Ciclosporin has been
reported to be effective in
a few patients.

75. Rx of 2ry
infections

76. 2ry bacterial infection (usually
due to S. aureus) should be
treated with antibiotics, and
herpes simplex with antiviral
agents.

78. References
google images
Bolognia 3rd ed.
Dermntnz.org

79. YOU
Thank