Teaching Clinic - Various Facets of the Clinical Manifestations of SLE Flashcards
PWM M/26 factory worker
- In 1992, he presented with sudden onset of malar rash and non-itchy, non painful erythematous plaque-like lesions over both upper limbs
- photosensitivity was also noted
- he was diagnosed to have discoid lupus
by the dermatologist
- initially treated with topical steroid only
What should dermatologist do?
- Check ANA (anti-nuclear) antibody [high sensitivity test, but non-specific (SCREENING), test for other antibodies if +ve]
Recorded in titres (1/120, 1/360, 1/1080 = still +ve after dilution, if 1/1080, it means that it is strongly +ve, underlying connective tissue disease)
- Anti-Ro, Anti-Smith (high specificity but low sensitive, may be a/w with neurological involvement), anti-La, anti-RNP (high levels in MCTD)
- anti-dsDNA (very specific, diagnostic)
CRITERIA FOR THE CLASSIFICATION OF SLE 1982
Need 4 out of 11 to be diagnosed with SLE
2012 SLICC* SLE Criteria
How is this different to SLE 1982 criteria?
Includes more immunologic criteria
Specific cutaneous manifestations in lupus erythematosus
- Discoid
- Subacute cutaneous (Papulosquamous & Annular/polycyclic)
- Malar rash
What is the burden of cutaneous manifestation of lupus?
Skin is second most commonly affected organ, prevalence is about 80%, cutnaeous lesions second most common presenting clinical features
Caries consideralbe morbidiities, psychosocial well-being and medical costs
Discoid lupus
- Characteristics
- Special indications
- Well-demarcated, palpable, indurated, hyper or hypopigmentation, heals with scarring, rash can be diffused
- Association with systemic involvement will be relatively less! = 5%
What are the two types of subacute cutaneous lupus erythematosus (SCLE)?
Two types of cutaneous lesions
- papulosquamous (psoraiform)
- annular/polycyclic
In contrast to discoid lesions, they are nonindurated and have little or no telangiectasia or follicular plugging [NO SCARRING]
[Photosensitivity is a hallmark for SCLE = AVOID SUN]
Psoriasis is more common in lupus patients
What are the associations of Subacute Cutaneous Lupus Erythematosus (SCLE)?
- 75% are female
- 30% to 50% of these patients may demonstrate systemic features
- systemic disease tends to be mild and nephritis rarely occurs
What is this a mimic of?
Erythema maginatum like lesions (acute rheumatic fever)
What is malar rash?
- typically occurs acutely in patients with SLE
- does not necessarily indicate the presence of active systemic disease
- Photosensitive dermatitis and discoid lesions may occur in a malar distribution in patients with both SCLE and DLE
Major DDx is dermatomyositis (doesn’t spare nasolabial folds)
Non-specific cutaneous manifestations in Lupus Erythematosus
Nonspecific Lesions
* Photosensitivity
* Alopecia
* Raynaud’s phenomenon (pallor [ischaemia], cyanosis [hypoxia], rubor [reactive vasodilation]) = think of systemic sclerosis
* Livedo reticularis (exposed to cold environment, excitement) = must screen for anti-phospholipid antibodies
* Bullous (pemphigoid / pemphigus / zoster)
* Lupus panniculitis (Erythema nodosum)
* Vasculitis (vasculitic lesions over hypothenar and thenar eminence, periungual telangiectasia, splinter haemorrhages = secondary vasculitic lesions)
* Urticaria-like vasculitis (hives usually last less than 24 hours, if it is more than 24 hours, there may be underlying vasculitis)
* Oral ulcerations
* Nail dystrophy
- Types:
◦ Diffuse
◦ Patchy
‣ Also describe the scalp:
‣ Inflammed: Scaring;
‣ Clean: NO Scarring
Livedo reticularis
Usually forearm and front of knee
- Panniculitis (Loss of subcutaneous fat: Depression)
- Lupus profundus
Vasculitis lesions
Periungual erythema
Periungual telangiectasia
Conventional Therapy for Cutaneous LE
- Education, lifestyle modification (i.e. photoprotection)
- Topical steroids
- Intralesional steroids
- Antimalarial drugs
How to counsel lupus patient for photoprotection?
- To avoid sun exposure especially between 10am to 3pm
- To wear photoresistant clothing and broad rimmed hats
- To apply sunscreen with a sun protective factor of 15 or higher at least 20 to 30 minutes before sun exposure
- Both ultraviolet A and ultraviolet B may induce lesions in photosensitive individuals
- Broad spectrum sunscreens may offer better protection
- Patients should take protective measures during prolonged car travel
Major S/E of topical steroids
- Commonly prescribed to treat cutaneous LE
- To minimise the risks of atrophy, the protency of the corticosteroid preparation is tailored to the location of the lesions being treated i.e.
– low potency for facial lesions
– medium potency for the trunk and extremities
– high potency for palms and soles
– adrenal crisis
Skin atrophy = underlying vessels will be more visible = reddish
- They are probably of limited value in the treatment of widespread DLE and in most patients with SCLE
- Application over large body surface may lead to significant specific absorption with its associated toxicity
Intralesional Steroids
- When is it used?
- When is it not recommended?
What is the role of antimalarials in cutaneous LE?
- Their effectiveness in the treatment of cutaneous LE has been well established
- Response rates generally exceed 80% for both DLE and SCLE
- The most commonly used agents are hydroxychloroquine sulphate, (chloroquine phosphate) and quinacrine hydrochloride
Side Effects of Antimalarial Drugs
- Bull’s eye maculopathy (refer to ophthalmologist)
- Blue black skin discoloration in sun exposed areas may occur
- Light coloured hair may also turn white
- Yellow discolouration of the skin, sclerae and bodily secretion occurs with the use of quinacrine
- Bone marrow toxcity, haemolytic anaemia and neuropathy may rarely occur
How are antimalarials used for SLE?
Dapsone
Originally used to treat leprosy
Medication was discovered to help with cutaneous manifesations
Articular manifestations in SLE
Arthralgia and arthritis are the most common presenting manifestations in SLE
Typically, the small joints of the hands, wrists and knees are symmetrically involved
May be migratory or persistent and chronic
Soft tissue swelling is common but effusions tend to be minimal
Deforming but non-errosive arthritis may occur with ulnar deviation of fingers, subluxations, and contractures (Jaccoud’s arthritis) = will not lead to errosions!
Renal manifesations in SLE
Blood is rich in protein, ask woman to skip urinalysis when she is on her period!!!
WHO classification of lupus nephritis 1982
No Man Faces Diffuse Menstrual Situation
When giving big doses of steroids, what should we think of?
- Steroid sparing agent should be started in 4-6 weeks
- 1 mg/kg/day will be the full immunosuppresion dose of steroid (high dose)
What do we need to test before azathioprine therapy?
- TPMT (thiopurine methyltrasnferase)
- NUDT15 (more specific for Asia-Pacific patients) = increased risk of marrow suppression
SLE pts with acute visual loss
-
Retinal or choroidal ischaemia
immune complex mediated vasculitis
occlusion associated with antiphospholipid antibodies -
Retinal tears
choroidal disease can lead to multifocal serous elevations of retinal pigment epithelium and adjacent retinal sensory tissue with resulting macular pathology and retinal detachment -
Glaucoma
known complication of steroid
occasionally observed in nonsteroid treated lupus - Optic/retrobulbar neuritis
- Cortical infarcts of the brain
- Side effect of drugs
What can be seen here?
- cytoid bodies were seen at his left macula region
- Dot blot haemorrages
- Exudates
DDx:
- Non-proliferative Diabetic retinopathy
- HTN-retinopathy (Type III)
- Cytoid bodies (SLE):
◦ ~Roth spot in infective endocarditis
◦ Cytoid in SLE: White spots
◦ Occuring in wide range of patients
What are cytoid bodies?
- Small white spots in SLE patients’ fundi, which Roth first described in 1872
- Occur in 5 to 24 % of SLE patients
- Represent infarction from vasculitis or thromboemboli
- Characterized histologically by hypertrophy or ganglioform degeneration of the nerve fibres
ACR nomenclature of 19 neuropsychiatric syndromes in SLE: Central nervous system
Central nervous system
* Aseptic meningitis
* Cerebrovascular disease
* DemyeliInating syndrome
* Headache
* Movement disorder
* Myelopathy (not transverse myelitis, but LONGITUDINAL myelitis since it involves more levels)
* Seizure disorder
* Acute confusional state
* Anxiety disorder
* Cognitive dysfunction
* Mood disorders
* Psychosis
ACR nomenclature of 19 neuropsychiatric syndromes in SLE: Peripheral nervous system
- Peripheral nervous system
- Gullain-Barre syndrome
- Autonomic neuropathy
- Mononeuropathy (single/multiplex)
- Myasthenia gravis
- Cranial neuropathy
- Plexopathy
- Polyneuropathy
ACR nomenclature of 19 neuropsychiatric syndromes in SLE: Neuropsychiatric syndromes in SLE
Psychiatric:
◦ Depression
◦ Psychosis
◦ Anxiety
◦ Confusion
◦ Mood disorders
In a patient with SLE and CNS involvement, what factors other than SLE can cause CNS involvement?
Could have psychological reaction: depressed due to Cushingnoid features, alopecia, self-steem issues
Haematological Manifestations of SLE
Anaemia
* Chronic inflammation
* Deficiency states : iron, vitamin B12
* Autoimmune haemolysis
* Medications related
* Thrombotic microangiopathies
* Pancytopenia
* Anaemia
* Chronic inflammation
* Deficiency states : iron, vitamin B12
* Autoimmune haemolysis
* Medication-related
* Thrombotic microangiopathies
* Fe deficiency: Due to steroids: Leading to gastritis/ PUD
Leucopenia in SLE
Leucopenia
Common and often correlates with disease
activity
Neutropenia : viral infection
immunosuppressive medication
hypersplenism
Lymphopenia
Thrombocytopenia in SLE
Could be the presenting problem Causes : autoimmune
medications related splenomegaly
thrombotic microangiopathy
Antiphospholipid syndrome * Splenomegaly
Pancytopenia in SLE
THROMBOTIC MICROANGIOPATHY (TMA)
* A pathology that results in thrombosis in capillaries and arterioles due to an endothelial injury
* May be seen in association with thrombocytopenia, anaemia, purpura and kidney failure
410
* Classic TMAs are
Hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
* Other conditions:
Atypical hemolytic uremic syndrome
Disseminated intravascular coagulation
Scleroderma renal crisis
Malignant hypertension
Antiphyosolipid antibody syndrome
MACROPHAGE ACTIVATION SYNDROME/SECONDARY
HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Diagnostic criteria:
1. A molecular diagnosis consistent with HLH
2. Fulfilment of 5 out of the following 8 criteria:
* fever
* splenomegaly
* decreased blood cell counts affecting
* at least 2 of 3 lineages hypertriglyceridemia
* hyperferrtinemia
* haemophagocytosis in bone marrow, spleen or lymph nodes low or absent natural killer cell activity high soluble CD25 (soluble IL-2 receptor)
Cardiac manifestations of SLE
- Pericardial disease
- Myocarditis
- Valvular disease (Libman-Sacks endocarditis)
- Conduction abnormalities
- Coronary artery disease (Myocardial infarction / ECG may be normal due to vasculitis effecting vessels)
PULMONARY MANIFESTATIONS OF SLE
- Pleural involvement
- Interstitial lung disease
- Lupus pneumonitis (culture negative)
- Pulmonary hypertension
- Shrinking lung syndrome (involvement of diaphragm)
ILD more associated with systemic sclerosis, dermatomyositis
Patient w/ SLE on systemic steroids, presented with diffuse skin lesions. What could this be?
◦ Fungal infections
◦ Papular eczema
◦ Refractory lupus:
‣ DO NOT respond to conventional treatment
◦ Secondary syphilis: Generalized rash (especially: prefominantly palm region) = should have Hx of primary chancre + has more palmar involvement
‣ Trepenomal movilization syndrome
Treatment of Refratory Cutaneous Lupus
Rheumatological conditions which might respond to Thalidomide
- Cutaneous lupus
- Rheumatoid arthritis
- Ankylosing spondylitis
- Behcet’s syndrome
Weak anti-TNF blocker
Other topical treatment for cutaneous lupus
- Calcineurin inhibitor eg. Tacrolimus especially for facial lesions
Systemic treatment for cutaneous lupus
Retinoids not too good
Methotrexate is useful for joint!
Mycophenolate (steroid staring)
Voclosporin (just approved 2 years ago)
Intravenous immunoglobulins
Belimumab (monoclonal antibody against B cell activating factors [BAFF])
Aniforlumab: anti-interferon alpha (just approved 3 years ago)
Which valve is most commonly effected in SLE? What antibodies is cardiac involvement associated with? What therapy may valvular heart disease in SLE respond to? What medications may we consider giving long-term?
CONDUCTION ABNORMALITIES IN SLE
CAD in SLE. What population may it affect the most?
