Dermatologic

1. Tewfik Kassa
Dermatologist
Mekelle University

2. CUTANEOUS LE (CLE)
• LE is a multisystem heterogeneous
autoimmune connective-tissue disorder.

3. • Skin disease is the second most frequent clinical
manifestation of LE
1 malar rash
2 discoid rash
3 photosensitivity
4 oral ulcers
5 arthritis
6 serositis
7 renal disorder
8 neurological disorder
9 anaemia, leucopenia, lymphopenia, thrombocytopenia
10 ENA ds DNA, ENA Sm, antiphospholipid antibodies
11 ANA

4. Prevalence of cutaneous manifestations in SLE
over the Entire Course of Disease
Cutaneous 80%
• Photosensitivity 70%
• Malar rash 50%
• Oral ulcers 40%
• Alopecia 40%
• Discoid rash 20%
• Vasculitis rash 20%
• Other (e.g., urticaria, SCLE) 15%

5. • Interplay of
genetic,
Environmental (UV Viruses Drugs Chemicals)
hormonal factors.
-Loss of self-
tolerance
-Induction of
Autoimmunity

6. CLE
• limited cutaneous involvement to devastating
systemic disease.
-Nephritis
-CNS dis.
-Vasculitis

7. Cutaneous Lupus Erythematosus
• 3 categories of LE–specific skin diseases
1. acute cutaneous LE (ACLE),
2. subacute cutaneous LE (SCLE), and
3. chronic cutaneous LE (CCLE).
Clinical characteristics of each group are
unique

9. CLE
EPIDEMIOLOGY
• ACLE
All races are affected
much more common in women than men
(8:1).
the malar rash in 20-60% of patients in LE
Age
– the malar rash is associated with a younger age of
disease onset

10. Epidemiology
• SCLE
• constitute 7 to 27% of LE patient populations.
• SCLE is more common in whites (85%).
• is primarily a disease of white females
• Male-to-female ratio of 1:4.
• SCLE typically occurs in patients aged 15-70
years.

11. Epid….
• DLE
is present in 15 to 30% of SLE
most common → 20 and 40 years of age.
can occur in infants and the elderly
F:M ratio of 3:2 to 3:1
All races are affected
might be more prevalent in blacks.

12. Etiology
ETIOLOGY AND PATHOGENESIS
• The cause(s) and pathogenetic mechanisms
are not fully understood.
• Intertwined with SLE pathogenesis.

13. Lupus Erythematosus
• Auto-immune disease
• Diverse clinical presentations
• Production of autoantibody to components of
cell nucleus
• Primary pathological processes
– Complement activation
– Inflammation
– Vasculopathy

14. Immunological defects
• T cell dysregulation
• Polyclonal B cell activation
• Defective immunoregulatory
mechanisms
– Autoantibody production
– Clearance of immune complexes
– Clearance apoptotic cells

15. Host factors
 Role of Genetics
• Genetic - concordance in twin studies
– 25-50% monozygotic vs. 5% dizygotic

16. Role of Genetics…
• Linkage to >24 genes in human
– Far more than other polygenic diseases
– May explain diversity
• Estimated that at least 4 susceptibility genes
needed to develop disease
– MHC II (HLA DR2 & 3)
– Complement C1q/C2/C4
– TNFα,
– T Cell receptor

17. Role of Genetics…
ACLE associated with HLA-DR2 and -DR3.
SCLE →HLA-DR3, DQA1*0501, DQB1*0502
haplotype
DLE → significant increases of HLA-B7, -B8, -DR2, -
DR3, and -DQA0102
→ a significant decrease in HLA-A2

18. Host factors
Sex Hormones
• SLE → F:M ratio of 9:1
• Effect of sex hormones on the immune system
• High levels of estrogen and progesterone
promote humoral autoreactivity
• Androgens shift the cytokine profile to that of
a Th1 CMI response

19. Environmental factors
• Ultraviolet radiation
• Drugs
• Viruses
• Chemicals
• Tobacco

20.  Role of UV Light
• The most important
Environmental
factor in the
induction phase.

21. Role of UV Light…
• UV light → induce keratinocyte apoptosis
• →displace autoantigens such as Ro/SS-A and
La/SS-B from inside epidermal keratinocytes to the
cell surface.
• → cell surface autoantigen expression.

24.  Role of Tobacco Exposure
smokers are at a greater risk of developing SLE
than are nonsmokers (Lipogenic aromatic amines)
an increased frequency of DLE in smokers

25.  Role of Drugs
• inducing altered repair of DNA (T cell DNA hypomethylation)
• increased biological autoreactivity of
lymphocytes.
• drugs reported to precipitate SCLE include
– procainamide
– Hydralazine

26. • Chemicals have been known to induce SLE–
like illness.
L-canavanine (alfalfa sprouts)
Heavy metals

27.  Role of Viruses
• Infections of all types exacerbate SLE.
• Rubella and CMV able to induce cell surface
expression of Ro/SS-A
• EBV can trigger SLE in susceptible individuals
• HIV

29. • In one study the onset of DLE lesions started with
1. Trauma → 11%,
2. Mental stress → 12%,
3. Sunburn → 5%,
4. Infection → 3%,
5. Exposure to cold → 2%
6. Pregnancy → 1%
7. Spontaneously → In the
remainder (2/3).

30. Key Constituents in the Pathogenesis of Lupus
• DCs (present self-Ags to T-cells)
• IFN-α
Plays a central role in the pathogenesis of SLE
• TLRs
circulating DNA/anti-DNA complexes trigger TLR signaling

31. • Apoptosis
Increased apoptosis of
• peripheral blood mononuclear cells (SLE)
• Keratinocytes (CLE)

32. • Complement
Genetic deficiency of C1q, C4, and C2 is very
strongly ass. with the development of SLE

33. Pathogenesis…
• TNF-α
Induces apoptosis (Fas/Fas-L)
• T cells
Autoreactive T cells
Provide help to
autoreactive B cells

34. • B cells
The production of autoantibodies by B cells
against nuclear antigens is the hallmark of SLE

35. Pathogenesis…
• Four theoretical sequential phases:
1. Inheritance of susceptibility genes,
2. Induction of autoimmunity,
3. Expansion of autoimmune processes, and
4. Immunologic injury.

37. Pathogenesis…
 The first phase
Susceptibility phase
• Inheritance of genes that confer
predisposition to SLE.

38.  The second phase
the induction phase
• Initiation of autoimmunity
– appearance of autoreactive T cells that exhibit
the loss of self-tolerance.

39. Pathogenesis…
 The third phase
Expansion phase
• Perpetuation and expantion of aberrant clone.
• Autoantibodies produced by clonally
expanded B cells.
• Directed against nuclear antigens.

40. Pathogenesis…
• Three major targets are the
1) Nucleosome (anti-DNA and antihistone antibodies),
2) Spliceosome (anti-Sm and anti-RNP antibodies) and
3) Ro and La molecules (anti-Ro and anti-LA)

41.  The fourth stage
 immunologic injury
 heralds the onset of clinical disease
 action of autoantibodies and the immune
complexes they form

42.  cause tissue damage by means of
– direct cell death,
– cellular activation,
– opsonization, and
– the blocking of target molecule function.

43. Presentation
 CLINICAL MANIFESTATIONS
• It is important to distinguish
among the subtypes of CLE
–because the type of skin
involvement can reflect the
underlying pattern of SLE activity.

44. Presentation…
• ACLE almost always occurs in the setting
of acutely flaring SLE
• CCLE often occurs in the absence of SLE
• SCLE occupies an intermediate position

45. Presentation…

47. Presentation…
• not uncommon to
see more than one
subtype of CLE in
the same patient

48. ACLE
Butterfly malar rash
Symmetric
Erythematous
Edematous
Mildly scaly

51. • Oral ulcerations

52. lesions on hands → Knuckles typically spared

53. • TEN-like lesions
Full-thickness
epidermal
necrosis
Denudation
Bullae

54. SCLE
Typically photosensitive
Lesions confined to sun exposed skin

55. SCLE…
Lesions may have
– Annular variant
– papulosquamous variant
• Eczematous or psoriasiform

56. SCLE…
• 10-15% develop SLE
• Regular ass. with Anti-Ro autoantibody.
strongly supports a diagnosis of SCLE

58. • EM-like lesions (Rowel syndrome)

59. CCLE
DLE is the most common form of CCLE
Hyper- and
hypopigmentation,
Atrophic scarring,
Follicular plugging
Adherent scales

60. • sharply demarcated, coin-shaped (i.e., discoid)
erythematous plaques covered by a
prominent, adherent scale.

61. • Mucosal DLE lesions
Erythematous
chronic plaques

62. • Generalized DLE lesions occur both above and
below the neck.
Painful
Erosive
Disabling

63. • DLE characteristically affects the external ear
Hyperpigmented
Dilated
Plugged follicles

64. DLE…
Tendency for scarring

65.  Prominent involvement of the adnexa
o Follicular plugging
o Scarring alopecia (Irreversible)

66. Dyspigmentation
– Central hypopigmentation
– Peripheral hyperpigmentation
– Sts. Vitiligo-like depigmentation

67. ~5% DLE → SLE
Risk factors for the development of SLE:
• diffuse nonscarring
alopecia;
• generalized
lymphadenopathy;
• periungual nail fold
telangiectasia;
• Raynaud's phenomenon;
• SCLE/ACLE skin lesions;
• vasculitis;
• unexplained anemia;
• Marked leukopenia;
• false-positive tests for
syphilis;
• persistently positive
high-titer ANA assay;
• anti–single-stranded
DNA antibody;
• hypergammaglobulinemia;
• an elevated ESR
(especially >50 mm/h);
• Positive lupus band test;

69. LESS COMMON SUBTYPES
Lupus Panniculitis/Profundus
Indurated plaques
Can evolve into disfiguring, depressed areas

70. Less common…
Lupus Tumidus
Indurated erythematous lesions
No scale or follicular plugging

71. Chilblain Lupus
Red or dusky
purple plaques
on the fingers,
toes.
After cold
exposure

72. Rare variants of CLE
Bullous LE
– Distinct variant with autoantibodies
to type VII collagen

73. Rare…
Neonatal LE (NLE)
o In children whose mothers have anti-Ro
autoantibodies
o SCLE-like lesions

74. Non-specific cutaneous lesions
o Vascular lesions are common
– Periangual telngiectasia
– Urticarial papules
– Ulcerations
– Atrophie blanche

75. – Purpura
– Palmar erythema

76. –Raynaud’s phenomenon
-The most common vascular reaction in lupus pts
-Herald a worse prognosis
–Livedo reticularis

77. Rare…
o Non-scarring, reversible alopecia
– ‘Lupus hairs’
Coarse
Dry
Brittle

78. DDX
DDX.
• ACLE
Sun burn
Rosacea
Photodermatitis
dermatomyositis

79. • Sun burn

80. Rosacea

81. DDX
• SCLE
o Photosensitive eczema
o Psoriasis
o Dermatophytosis
o Annular erythemas

82. DDX
• DLE
PMLE
Lymphoma cutis
Sarcoidosis
Leishmaniasis
Cut. tbc
Granuloma faciale
LP

83. Diagnosis

85. Diagnosis…
Histopathology
To establish the Dx
Less important for subtyping
Considerable overlap

87. Diagnosis…
• ACLE
 Non-specific
 Damaged keratinocytes
 Edema in the upper dermis
 Lymphohistiocytic infiltrates in the upper dermis
 Vasodilatation with extrvasation of erythrocytes

88. Diagnosis…
• SCLE
Epidermal atrophy
Dyskeratotic keratinocytes
 Lymphohistiocytic infiltrates in the upper dermis
Interface and perivascular pattern

89. Diagnosis…
• DLE
 Keratinocyte damage
 Colloid bodies
 Hyperkeratosis
 Melanin deposits within macrophages
 Thickened DEJ (PAS staining)
 Lymphohistiocytic infiltrates in the upper and lower dermis
– Interface, perivascular, and periadnexal locations
 Folicullar plugging

93. Diagnosis…
Lupus panniculitis
Predominantly lobular Lymphohistiocytic
panniculitis

94. Lupus tumidus
Pronounced Lymphohistiocytic dermal
infiltrates (prominent in the lower dermis)
Marked deposition of mucin

95. Immunofluorescence
• Deposition of Ig and/or complement at the
DEJ is a characteristic feature of LE.
• All 3 immunoglobulin classes IgG, IgM, IgA and a
variety of complement components
• Examination of tissue may be performed on
lesional or nonlesional skin.
• Nonlesional biopsies may be performed on
sun-exposed or nonexposed surfaces.

96. Diagnosis…
• Testing of nonlesional nonexposed skin is
termed the lupus band test (LBT).
• Nonlesional positive LBT correlate strongly
with an aggressive course of systemic disease
(LE-Nephritis)

98. Treatment
Topical therapy
Topical or IL corticosteroids→ mainstay of therapy
High potency steroids (for DLE lesions even on the face)
Systemic therapy
Antimalarials (the gold standard systemic therapy)
Hydroxychloroquine (the most commonly chosen)
– 200mg qd/bid
The response is slow → 2 to 3 months

99. • patients with LE skin disease who smoke are
less responsive to antimalarial treatment.

100. Treatment…
• For antimalarial-resistant patients
– Oral retinoids
– Thalidomide
– Gold
– Clofazimine
– Sulphasalazine
– Immunosuppressive agents
– Systemic corticosteroids
– Dapsone

101. Adjunctive therapy
• Sun avoidance
• Sun protection
Broad-spectrum, high SPF sunscreens
Protective clothing
• Cosmetic cover-up
• Discontinue smoking

103. THANK YOU