SLE Therapeutics

Type of hypersensitivity reaction in SLE

Type III — antibody/immune-complex mediated (same as RA)

Population SLE occurs in most frequently

Women of reproductive age (15–45 years)

SLE in men and children

Rarer, but MORE SEVERE when it occurs

3 components of SLE etiology

Genetics (susceptible individual) + Environmental triggers + Hormones (estrogen/progesterone; X chromosome may contribute)

⭐ Drug-induced lupus (DILE)

Similar clinical + lab features to SLE, but NOT immune-driven; usually resolves within weeks after stopping the drug → don't treat as SLE, just discontinue the drug

⭐ 3 highest-yield DILE drugs (NAPLEX)

Methyldopa, Hydralazine, Anti-TNF agents

Full list of DILE drugs from slide

Methimazole, propylthiouracil, methyldopa, minocycline, procainamide, anti-TNF agents, terbinafine, isoniazid, quinidine, hydralazine

Methyldopa and hydralazine are used for

Hypertension

Where do SLE immune complexes deposit?

On any nucleated cell → can affect ANY organ system

Result of chronic/inadequately treated SLE

End-organ damage (e.g., kidney damage → dialysis or kidney transplant); also atherosclerosis, pulmonary fibrosis, stroke, damage from treatment

Why is SLE difficult to diagnose?

Can involve almost any organ, symptoms are often nonspecific (fatigue, fever), and it's sometimes found incidentally on labs

ANA

Antinuclear antibodies — antibodies against the nucleus of the patient's own cells

Anti-dsDNA

Antibodies against double-stranded DNA

Anti-Smith (anti-Sm)

Highly specific for SLE diagnosis; named after the first patient found positive (Stephanie Smith)

Cutaneous manifestations

Malar (butterfly) rash, discoid rash, other rashes (maculopapular, urticarial, bullous), photosensitivity, oral ulcers, alopecia

Musculoskeletal manifestations

Arthralgias/myalgias, nonerosive polyarthritis, hand deformities, myopathy, ischemic necrosis of bone

Systemic manifestations

Fatigue, malaise, fever, nausea, anorexia, weight loss

Renal manifestations

Proteinuria (>500 mg/24 hr), cellular casts, nephrotic syndrome, renal failure

Cardiovascular manifestations

Pericarditis, myocarditis, endocarditis

Neurologic manifestations

Cognitive dysfunction, headaches, psychosis, seizures, depression/anxiety from chronic illness (neuropsychiatric lupus)

Hematologic manifestations

Anemia of chronic disease, hemolytic anemia, leukopenia, thrombocytopenia, lupus anticoagulant, splenomegaly

Malar rash

"Butterfly" rash across the bridge of the nose and cheeks; hallmark but often subtle and not always present

Discoid rash

Looks like a bite mark; smooth (NOT raised/bumpy), does not itch or hurt

Non-pharm: aerobic exercise benefits

↓ CV events, helps osteoporosis, improves fatigue, depression, anxiety, sleep disturbance, weight loss

Non-pharm: photosensitivity counseling

Protective clothing, broad-brim hats, UVA + UVB sunscreen, avoid tanning beds (UV light triggers symptoms)

Non-pharm: why smoking cessation?

↓ CV risk; smoking exacerbates SLE, ↓ effectiveness of antimalarials and belimumab, damages skin (↑ cutaneous lupus activity); smoking can also ↑ clearance of some drugs

⭐ First-line drug for ALL SLE patients

Hydroxychloroquine — regardless of severity (mild, moderate, severe) unless contraindicated (rare)

⭐ General first-line framework for SLE

Hydroxychloroquine for everyone + bridge therapy (NSAIDs and/or corticosteroids) for symptoms and flares

⭐ Why is bridge therapy needed in SLE?

Hydroxychloroquine takes 3–6 months to work; NSAIDs/steroids control symptoms immediately

When are immunosuppressive/immunomodulatory drugs added?

If first-line therapy is ineffective or major organs are involved

Off-label agents used in SLE

NSAIDs, cyclophosphamide, mycophenolate mofetil (MMF), azathioprine, methotrexate, rituximab

Key counseling point for all SLE therapy

Adherence — chronic disease; meds prevent flares and organ damage

⭐ NSAID role in SLE

First-line for arthritis, musculoskeletal complaints, fever, serositis; best for MILD disease; symptom relief only — NOT disease modifying

NSAID mechanism

Inhibit COX-1/COX-2 → ↓ prostaglandins (and bradykinin, serotonin, substance P, histamine) → ↓ inflammation, pain, fever

⭐ NSAID dosing in SLE

Must be anti-inflammatory doses — OTC doses may not be enough (e.g., ~600–800 mg q6–8h)

⭐ NSAID GI risk

Nonselective COX inhibition → gastric irritation, ulcers, bleeding; co-prescribe a PPI for gastroprotection

⭐ NSAID renal risk

↓ renal blood flow and GFR → monitor closely in lupus nephritis/existing kidney damage

⭐ NSAID CV risk

↑ blood pressure; serious CV/thrombotic events (MI, stroke)

NSAID monitoring

CBC, platelets, SCr, AST/ALT, blood pressure

Hydroxychloroquine drug class

Antimalarial

⭐ Hydroxychloroquine 3 main effects

Anti-inflammatory, immunomodulatory, antithrombotic

⭐ Is hydroxychloroquine disease modifying?

YES — patients must keep taking it even if they don't feel different

⭐ Hydroxychloroquine onset

3–6 months

⭐ Hydroxychloroquine dose

200–400 mg PO daily (single or divided). On a case, pick ONE number, not a range. Often start 400 mg/day, then 200 mg/day

Why is hydroxychloroquine first line? (high-quality evidence)

↓ disease activity and improves survival

⭐ Hydroxychloroquine major toxicity

Ocular: cycloplegia, corneal deposits, rare but serious retinal toxicity (retinopathy damage can be permanent)

⭐ Hydroxychloroquine eye exam schedule

Baseline, then every 6–12 months — catch changes early and hold the drug

Hydroxychloroquine other ADRs

CNS (headache, nervousness, insomnia), rash/dermatitis, pigment changes of skin and hair, GI upset/nausea

⭐ Hydroxychloroquine monitoring

Fundoscopic & visual field exams, CBC, AST/ALT, albumin

⭐ Corticosteroid role in SLE

Control flares AND maintain low disease activity; topical or systemic; foundation for most forms of SLE

Topical + oral steroids together?

No — if on systemic steroids, topical steroids aren't needed

Steroid dose categories (prednisone/prednisolone)

Low: <10 mg/day; Medium: 10–20 mg/day; High: >20 mg/day

Steroid dose for severe SLE (organ damage)

HIGH dose: 1–2 mg/kg/day (not common at presentation)

Steroid dose you'll usually see in practice

Low–medium, e.g., 10–20 mg/day prednisone

⭐ Steroid maintenance goal

Lowest dose that suppresses symptoms (prefer <10 mg/day); ideally taper to zero once on steroid-sparing therapy

Pulse methylprednisolone

Used intermittently for disease flares

⭐ Tapering steroids in lupus

May taper even if patient doesn't meet adrenal suppression criteria — to keep disease activity low (chronic inflammatory disease)

⭐ Steroid immunosuppression threshold (NAPLEX)

≥2 mg/kg/day or ≥20 mg/day prednisone equivalent for >2 weeks → no live vaccines, high infection risk, must taper (HPA axis suppression)

Steroid dose equivalents

Cortisone 25, hydrocortisone 20, prednisone 5, prednisolone 5, methylprednisolone 4, triamcinolone 4, dexamethasone 0.75, betamethasone 0.6 mg

Steroid potency mnemonic

Cute Hot Pretty Pharmacist Makes Triple Digits Boom (cortisone → betamethasone, least → most potent)

Short-term steroid ADRs

↑ appetite/weight gain, mood swings, insomnia, fluid retention, GI upset, ↑ IOP, hypertension/hyperglycemia

Long-term steroid ADRs

Adrenal suppression, infection/impaired wound healing, GI bleed/ulcers, osteoporosis, glaucoma/cataracts, fat deposits (face, abdomen, upper back), menstrual irregularities

Topical steroid ADRs

Skin atrophy, hypo/hyperpigmentation, striae, steroid acne, hirsutism (depends on potency & duration)

Steroid monitoring

BP, serum glucose, lipids, bone density, ophthalmic exams

What you need to know about non-first-line SLE drugs (per professor)

That they exist as options + their unique features; NOT their line of therapy. Only dose to memorize = hydroxychloroquine

Cyclophosphamide role

Alkylating chemo agent; only for severe organ-threatening disease (ILD, lupus nephritis, neuropsychiatric lupus) with steroids; IV induction limited to 3–6 months; ↓ risk of end-stage renal failure

Cyclophosphamide ADRs

Carcinogenic, mutagenic (avoid in pregnancy), N/V, anorexia, alopecia, pigment changes, rash, myelosuppression, infection, pneumonitis, hemorrhagic cystitis, bladder malignancy

Azathioprine role

Recurrent flares; steroid-sparing maintenance; not first-line; less effective AND less toxic than cyclophosphamide; ORAL

Azathioprine ADRs

Myelosuppression, hepatotoxicity, infection, N/V, rash, alopecia

Belimumab (Benlysta) MOA

B-cell activating factor (BAFF/BLyS) inhibitor — monoclonal antibody

Belimumab indication

Adults with active, autoantibody-positive SLE on standard therapy; OR active lupus nephritis (first drug approved for LN)

Belimumab warnings

Serious infections, hypersensitivity/anaphylaxis, infusion reactions, depression/suicidal thoughts, malignancy, mortality

What to think of for ANY monoclonal antibody

Immunosuppression/infection risk + hypersensitivity/infusion reactions

Rituximab MOA

Chimeric (-xi-) anti-CD20 mAb → nearly complete depletion of peripheral B cells; recovery over several months

Rituximab role

Last line — severe refractory disease not responding to other immunosuppressants; may help lupus nephritis

Rituximab premedications

Methylprednisolone 30 min before + antihistamine + acetaminophen (older chimeric mAb → more infusion reactions)

Rituximab ADRs

Infusion reactions, infections, neutropenia, mucocutaneous reactions, PML

Methotrexate in SLE

An option but NOT first line (unlike RA); dosed WEEKLY

Mycophenolate mofetil (MMF) in SLE

Immunosuppressant option (details covered in transplant); used especially for lupus nephritis

SLE algorithm: no specific organ involvement

NSAIDs, antimalarials, glucocorticoids → if no sustained response: belimumab, methotrexate, azathioprine, MMF, or cyclophosphamide (no set order) → last line: rituximab