Lupus - Abu-Shakra

Question 1

What is the pathogenesis of SLE?

Answer 1

Susceptible genes with triggering factor (usually EBV or UV)
• Activation of APCs and Dentritic cells, B Cells
• Activation of T cells which activate B cell
• Production of pathogenic AAs
• 3 years later- IgG complement fixing AAs, and
pathogenic I.C
• Tissue inflammation and damage.

• Impaired apoptosis, cell proliferation
• Persistent pathogenic autoantibodies.
• Persistent pathogenic Immune Complexes
• Persistent autoactive T cells
Increased Ig secreting B cells.
• Increased CD4/CD8 ratio.
• Impaired I.C clearance.

• Inflammation and cellular proliferation
• Blood vessels abnormalities (vasculopathy
and vasculitis)
• Immune-complexes deposition
• Thrombosis
• Tissue ischemia and necrosis

Question 2

What are the skin manifestations of SLE?

How many lupus patients have skin manifestations?

Answer 2

80%

I. Lupus specific Rashes
• Acute rash (good response to treatment, doesn’t relapse)
• Subacute rash (difficult to treat but if cured no scarring)
• Chronic rashes (highly resistant to treatment and leave scars)

1. Butterfly rash (30-60%)
   Elevated over cheeks and nose
   nasolabial sparing.
   Photosensitive.
   Last from days to weeks.
2. Maculopapular rash
3. Bullous lesions

Subacute cutaneous rash (10-25%)
• Psoriasis like
• Annular forms.
Highly photosensitive and non scarring
Occur in sun-exposed areas
Associated with anti-Ro, DR3, Sjogren’s syndrome
ANA may be negative.

III. Chronic rash
• Discoid lesions. (15-30%)
• Erythematous papules, Scarring, central atrophy.
• Sun-exposed areas.
In the scalp- permanent alopecia.
Pathologically: hyperkeratosis, follicular
plugging, edema, MN infiltrate.

Non-Specific Lupus rashes
• Panniculitis- deep, firm nodule + skin
changes
• Lupus profundus.
• Utricaria (5-10%) . May be chronic
• Vasculitis
• Raynauds (red and blue)

• Alopecia- common, diffuse or patchy (reversible unless discoid related)
• Ulcers- oral, vagina, nasal septum (20-
50%, painless).
• Nasal Septum Perforation
• Nodules (10%).

Question 3

What are the renal manifestations in lupus and how are they classified?

How many lupus patients have renal manifestations?

Answer 3

Most patients will have histological changes.
50% clinical features.
Classification:
• Class I- normal
• Class II- mesangial GN
Class III- focal segmental (<50% glomeruli affected).
Most patients present before here
• Class IV- Diffuse proliferative GN (>50% glomeruli afected).
• Class V- membranous GN (thickening of basement membrane).
• Class VI- end stage.

See casts, WBC and RBC in urine, proteinuria, nephrotic/nephritic syndromes, renal failure if not treated

Question 4

What are neuropsychiatric SLE manifestations (NPSLE)?

Answer 4

More than one manifestation.
May have neurological (peripheral or central) and psychiatric
features.
2/3 of SLE patients develop NPSLE
19 clinical entities.

Usually more than one type of presentation depending on the antibody

Seizures and psychosis necessary for diagnosis

Headache most common, doesn’t respond to steroids

Not infectious, aseptic meningitis, inflammatory mediated

• Retinopathy : vasculitis of retinal arteries.
Specific exudates (cytoid bodies seen on oscilloscope)- cotton-wool like
• Papilledema
• Sinus thrombosis
• Aseptic meningitis
• Delirium
• com

Question 5

What are manifestations of SLE involving the pleura and other lung and cardiac tissue?

At what rates do these happen in SLE patients?

Answer 5

SLE can deposit on any serosal membrane: the pericardium, peritoneum and pleura

• Pleural involvement 30-60%.
• Pleuritic pain (unilateral, difficulty breathing deep)
• Pleural effusion- usually small.
• Exudate-
– normal glucose level
– LE-cells and high protein
– low complements
– ANA positive and it is highly sensitive

• Pericarditis: 20-30%.
– May be silent
– Tamponade is rare.
– Effusion- low glucose, low complement,
elevated ANA, LE cells.

• Peritonitis: 10%
– In small numbers it may become chronic.

• Pneumonitis
Acute or chronic form.
– Acute Pneumonitis: simulates pneumonia.
– Chronic Pneumonitis:
• diffuse infiltrates
• dyspnea, cough, Short of breath.

• Pulmonary Hemorrhage: d/t vasculitis., high DLCO
• Pulmonary hypertension:
Short of breath
normal X-ray
hypoxemia
Low DLCO (diffusion lung capacity with CO).
Poor prognosis

Cardiac Involvement
• Myocarditis:
Cardiomegaly, arrhythmia,
unexplained tachycardia , CHF.
• Endocarditis:
Valvular abnormalities in 40-60%.
Nonbacterial verrucous vegetations.
(Libman and Sacks endocarditis)
• Coronary A. Disease
Mostly d/t accelerated AS
Occasionally coronary vasculitis.

Question 6

What are lab findings in SLE?

Answer 6

• Elevated ESR and CRP
• Anemia- chronic diseases
-Hemolytic Anemia
• Leukopenia/Lymphopenia
• Thrombocytopenia
• Low complements (with active disease)
• Autoantibodies

Anti-dsDNA in 60-90%, very specific to SLE, relevant to nephritis

anti-ssDNA in 90% but not specific to SLE

anti-histones in 50-70%

anti-H2A and H2B in drug-induced lupus

Anti-Ro(SS-A) in 20-60% and anti-La(SS-B) in 15-40% for subacute cutaneous lupus and congenital heart block

Anti-Sm in 10-30%, very specific to SLE

Anti-RNP is high in MCTD

Anti-ribosomal P in lupus pschosis

Question 7

What are the classifications of lupus?

How many indicate diagnosis?

(Hint: MD BRAIN SOAP)

Answer 7

• M: malar rash, the butterfly rash
• D: discoid rash
• B: blood with hemolytic anemia, thrombocytopenia or leucopenia
• R: renal with casts or protein above 0.5 grams a day
• A: arthritis
• I: immunological with anti-DNA or Anti-SM
• N: neurological - psychosis or seizures
• S: serositis - peritoneum, pleura, pericaditis
• O: oral ulcers
• A: ANA+
• P: photosensitivity

• If there are four of these criteria, this is diagnostic for lupus

Question 8

What are treatments for lupus?

Answer 8

• There is no treatment for the disease but you treat the clinical presentations
• NSAID is not chronic treatment, only for a short time
• Corticosteroids: used topically for skin or systemic
○ Has a role of preventing a flare up of the disease
-MTX and azothiaprine are steroid sparine
• All patients with lupus should be on antimalarial drugs
○ Azathioprine: used for mild renal disease
○ Cyclophosphamide: highly toxic with high rate of infection with 50% of young women becoming infertile and even go into menopause
○ Mycophenolate mofetil: used more common now since it’s as good as cyclophosphamide with no infertility, now first line for 2-3 years of tx
-Retuximab given for severe thrombocytopenia
-Recently approved B-cell cytokine stimulator used for mild cases (arthritis and skin, not severe).
• Immunosuppressive
• BLyS: used for only mild version of the diseas

Question 9

How is drug induced lupus different from SLE?

Answer 9

• Constitutional symptoms, fever, fatigue, weight loss
• arthritis
• serositis.
• No CNS and renal involvement.
• LAB: cytopenia, positive ANA and RF.
• 90% anti-histones positive.
• Anti-dsDNA negative

Question 10

How does SLE manifest in pregnancy and neonatally?

Answer 10

• Neonatal lupus
Associated with anti-Ro antibodies
• Only 1-2% of mothers with anti-Ro develop NLE
-IgG crosses placenta and affects neonatal organs especially the heart
• Dermatitis
• hepatitis
• Complete Heart Block- if they survivie they will need a permanent pacemaker, 20% mortality
• hemolytic anemia
• low platelets.
• All of the non-cardiac disappear after 6 months, if no cardiac manifestations not considered lupus