Lupus Erythematosus Flashcards
What are the cutaneous variants of Lupus?
Acute cutaneous lupus
- Localised
- Generalised
- TENS like
Subacute cutaneous lupus Erythematosus
Chronic Cutaneous Lupus Erythematosus
- Discoid Lupus
- Lupus Profundus
- Chilblain Lupus
Lupus Tumidus
Lupus Panniculitis
What is Lupus?
A chronic autoimmune condition (body attacks its own cells)
- can be limited to the skin (connective tissue disease)
- can be systemic / multisystem
Who does Lupus effect?
Female > Male
Adults > Children
African Americans > Caucasians
What causes cutaneous lupus?
Multifactorial
Genetic susceptibility
- High incidence among family members
Hormones (women during childbearing years)
Environmental factors
- Cigarette smoking
- Sun exposure
- Medications
- Viral infections
Innate and adaptive immune responses
- autoantibodies.
Triggers an inflammatory cascade of cytokine, chemokine and inflammatory cell responses
If a patient has SCLE, what is the risk of developing SLE?
10% will develop SLE - clinically significant
(50% meet criteria)
What are the genes involved in SLE?
Genes that affect overall immunoreactivity
- B and T cell function
–> HLA DR
–> PTPN22
–> STAT4 - innate immunity
–> IRF5
–> TREX1
–>STAT4 - immune complex clearance,
–> C1Q - apoptosis
–> STAT4 - Ubiquitination
- DNA methylation
- Cellular adhesion
What are the cutaneous manifestations of acute cutaneous LE?
Malar erythema
- transient (few hours to several weeks)
- following sun exposure
- resolves without scarring
- typically nasolabial sparing
Can have a widespread eruption
Sparing of the knuckles
Periungal erythema and ragged cuticles
Oral ulceration
Malar rash is associated with lupus nephritis and anti-dsDNA antibodies? (T/F).
True - however not always ass with this.
What are the clinical features of malar erythema?
Bilateral cheeks affects
Nasolabial sparing
Can have:
- telangiectasias
- erosions
- dyspigmentation and
- epidermal atrophy
What are the extra-cutaneous organ systems invovled in SLE?
Kidneys - Lupus Nephritis
Pulmonary -
Joints
CNS
Cardiovascular
Haematological
What are the clinical manifestations of Discoid Lupus?
Well defined, red, scaly plaques
Heal with atrophy, scarring and pigmentary changes
Scaly is thick and adherent
- sometimes the tic-tack sign
Normally limited to the head and neck
Can be more widespread
Alopecia when it occurs on the scalp
Who does discoid lupus affect?
Females: Males = 2:1
Peak decade = 30s
Asian, Afro-Caribeans, Hispanic Americans
What dieseases are associated with Discoid Lupus?
Porphyria (PCT, varigate porphyria and acute and EPP)
Pemphigus
Myasthenia Gravis
Thymoma
What are the histological features of cutaneous Lupus? (8)
Lymphocytic interface dermatitis
Basal Layer Degeneration
Basement membrane thickening
Peri-vascular and peri-adnexal lymphohistiocytic infiltrate
Follicular plugging
Dermal mucinosis
Epidermal atrophy
What are the dermoscopic features of DLE?
Follicular keratotic plugs
White perifollicular halo,
White scale,
Speckled brown pigmentation,
White structureless areas
Arborising vessels
What is the pathophysiology of DLE?
Is it TH1 or TH2 based?
What cells are invovled?
What is the result on t
Interferons (type 1 and 3) induce Th1 based inflammation
predominantly lymphocytic infiltration
causes epidermal damage, basement membrane thickening and a scarring tissue response associated with a loss of follicular stem cells
Cells involved
- CD4, CD8, T cells, natural IFN-producing plasmacytic dendritic cells
Triggering factors to DLE (7)
Trauma (inc X-rays and thermal burns)
Stress
UV exposure
Infection -
Drug
Seasonal Exacerbation (winter and summer)
Cold Exposure
What are the Trichoscopic features of DLE?
follicular red dots
large yellow dots
absent follicular openings
thick arborising vessels
speckled brown or blue-grey dots
discoloration
What is chillblain lupus?
Describe the clinical features
Subtype of chronic CLE
Painful or pruritic
Red to violaceous papules and plaques
Involving the hands and feet, involvement of the nose and ears can occur too
Ulceration, fissuring and hyperkeratosis can occur
Occurs in ~6% of patients with lupus
What are common triggers for chilblain lupus?
Cold exposure
Damp exposure
Pregnancy
Antibodies ass with chillblain Lupus?
a positive ANA, anti-Ro/SSA or anti-La/SSB
Some patients may have cryo-fibrinogenaemia or cold agglutinins.
What are the risk factors for chillblain lupus
Female
Smoking
Markedly abnormal peripheral circulation with low resting blood flow
Management of chillblain Lupus?
General:
- maintaining a warm core and peripheral temperature
- avoiding damp conditions.
Topical treatments
- high-potency corticosteroids
- tacrolimus
- pimecrolimus
Systemics:
- oral nifedipine
- hydroxychloroquine
- quinacrine
- mycophenolate mofetil
- JAK inhibitors
How does lupus panniculitis present and who does it affect?
Middle aged women
chronic and recurring tender, red, indurated subcutaneous nodules or plaques
located on fatty areas of the body.
- proximal extremities, face, back and scalp
Long-term sequalae include
- ulceration, atrophy, calcinosis and disfigurement.
What is lupus profundus
Lupus paniculitis with overlying DLE (occurs in 1/3 of patients with Lupus Paniculitis)
What is the histology findings of lupus profundus?
lymphoplasmacytic
lobular or mixed panniculitis
hyalinising fat necrosis and lymphoid follicles
In chronic lesions - dermal or subcutaneous calcium deposits
What is the treatment for lupus Profundus?
First Line:
- antimalarials
Adjunct:
- systemic corticosteroids (short term)
Intralesional steroids, dapsone, mycophenolate mofetil, ciclosporin, rituximab and intravenous immunoglobulins
What are the key antibodies you in CLE? And rates of positivity / Associations
ANA - Positive in 60-80% of CLE
- DLE 5 - 17%
- SCLE - ~60 - 80%
- ACLE - 94 - 100%
Anti - dsDNA
- positive in ACLE
- 56 - 70% sensitivity
- ass with renal disease and poor prognosis
Anti Ro/SSA
- Positive in 70 - 90 % of SCLE
- Ass. with Neonatal Lupus
- Ass with Sjogrens
- can also be seen in DLE
Anti La / SSB
- positive in 30 - 50% of SCLE
- Ass. with Sjogrens
- Can also be seen in DLE
Anti Sm
- Specific to LE
- present in 19 - 25%
Anti U1 RNP
- 23 - 49% of SLE
- 8 - 10% of ACLE
- rare in CLE
How would you work up someone you suspect has lupus?
Ix to confirm diagnosis and exclude Ddx
- Histology –> interface dermatitis
- DIF –> DEJ staining for C3 / IgG (occ IgM)
- ANA, ds-DNA, ENA
- Complement (c3 / c4)(
- CRP, ESR
- RF
- Antiphospholipid Abx (anti - cardiolipin, Beta 2 micro globulin and lupus anticoagulant)
- CK
- Myositis panel
- serum IgE
- FBC, UEC, LFTs
Ix for associations:
- Urine ACR
- Urine MCS for protein casts
- Consider joint imaging
- MRI brain
- Renal biopsy
- CTPA / PFTs
- TFTs, thyroid Abs
Pre-Rx
- vitamin D
- baseline eye assessment
- G6PD
- pre- immunosuppression screen
What is the risk of progression to SLE for the different subtypes of CLE?
- ACLE: 90 - 100%
- SCLE: 50% meet criteria, only 10% will develop clinically significant systemic disease
- DLE: 5% in limited disease, 15% in generalised disease
Negligible risk fo lupus tumidus
What percentage of SCLE cases are drug induced?
And what epidemiological factors would make you think of drug?
(33%) - 1/3 of cases
Older age
Widespread disease
Bullous or targeted lesions
Common Drugs for Drug induced SCLE
- Anti-fungals
- Terbinafine - Anti-hypertensives
- Thiazide diuretics
- Calcium channel blocker
- ACEi - NSAIDs
- Anti-coagulants
- Apixaban / rixaroxiban - Chemotherapy
- Immunotherapy
- ICIs - PPIs
- Statins
Drugs that can cause DLE?
Very rare
Pembrolizumab
TNF alpha
5 FU
Approach to treatment for Cutaneous Lupus?
GENERAL MEASURES
Strict photo-protection (UVA and UVB)
- avoid peak UV times (11 - 3pm)
- Long sleeve pants and shirts with adequate clothing weave
- Broad brimmed hat
- Tint car windows (UVA)
- suncream: 50+, UVA, UVB protection - 2mg / cm2 applied 20 - 30 mins prior to sun exposure
Avoid photo-sensitising agents (tetracyclines, frusemide, NSAIDS, HCT)
Vit D and calcium supplements
Cosmetic camouflage with green tints
Stop smoking
TOPICALS
- steroids in an ointment base; twice daily for up to 4 weeks, then Rx break
- Intralesional steroids (2.5-5mg /ml on the face; 10mg/ml on the body)
- Topical calcinurin inhibitors
PHYSICAL Therapies
- C02 laser for DLE
- Pulse Dye Laser - DLE, SCLE - limited evidence
SYSTEMICS
HCQ response rates 50 - 95%
- <5mg / kg to reduce risk of ocular SEs
Other antimalarials Mepacrine quinacrine - lowest retinopathy risk
Chloroquine - can use as combination Rx
2nd line
- oral corticosteroids (up to 1mg/ day)
- MTx
- Acitretin and isotretinoin
- Dapsone
- MMF
3rd line
- thalidomide
- lenalidomide
- ivig
- clofazimine
What is Rowell Syndrome?
Rare entity
Erythema multiforme-like lesions coexisting with lupus erythematosus (LE)
characteristic immunological findings
- Speckled ANA
- Postive RF
-Anti Sj - T
Treatment of CLE in Pregnancy
HCQ - cat D, however first line
Dapsone + Folic acid second line
What are the non-specific cutaneous features of lupus?
Raynaud’s
Livedo reticularis
Palmar erythema
Nail for telangiectasia’s, splinter haemorrhages
Vasculitis - pupura, urticarial papules or ulcers
Atrophie blanche
- livedo reticularis, thromboses, ulcerations, and lesions resembling Degos disease have each been associated with antiphospholipid antibodies
Alopecia
Sclerodactyl, calcinosis, rheumatoid nodules
Erythromelegia
Papulonodular mucinosis
Periorbital oedema
Sweet syndrome like presentation
Ddx of SLE
Contact dermatitis,
Seborrhoeic dermatitis,
Dermatomyositis,
Erysipelas,
Rheumatoid arthritis,
Sjogren’s (almost all SLE cases have some features of Sjogren’s),
Sweet’s
What are the nail changes that might be seen in SLE? (6)
What % of patients have nail changes?
Nail changes (25%):
- splinter haemorrhages,
- pitting,
- ridging,
- onycholysis,
- striate leukonychia
- red lunulae
Associations with SLE?
Rheumatoid arthritis,
Systemic sclerosis,
Lichen sclerosus,
Morphoea,
Sjogren’s,
Primary biliary cirrhosis,
Myasthenia gravis/thymoma,
Angioedema from C1-esterase deficiency,
Hashimoto’s thyroiditis,
Pernicious anaemia,
Lymphoma, haemolytic anaemia, internal malignancy (debatable)
Prognosis of DLE
Tends to be chronic, eventually remits in 50%
5% risk of developing SLE (20% in disseminated DLE)
risk factors: generalised DLE, lymphadenopathy, C1q on IF, HLA-B8
Prognosis of SCLE
Mainly cutaneous disease
50% fulfil the criteria for SLE
Only 10% have clinically significant features
Risk factors for development of SLE: papulosquamous, leukopaenia, ANA >640, dsDNA positive
What nail findings might you find in Lupus
Peri-ungal erythema
Splinter Haemmorrhage
Pitting
Ridges
Erythronychia
Onycholysis
What types of Alopecia might you see in Lupus?
AA - AI association
Telogen Effluvium (stress)
Lupus Hairs (short, fragile hairs, frontal hairline)
What are markers of disease activity is SLE?
CRP, ESR
dsDNA
C3 / C4
What haematological findings might you see in SLE?
Anaemia
- due to haemolysis
- due to chronic disease
Thrombocytopaenia
Leukocytosis (or paenia)
Neuropaenia
What antibodies may be positive on ENA?
Anti SSA / Ro
Anti SSB / La
Anti Smith
Anti U1RNP (MCTD)
