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Hydroxychloroquine (HCQ)
- Class: 4-aminoquinolines
- Derived from Cinchona tree (all antimalarials)
- <5mg/kg (real weight)
- In PCT: 100mg 3x/week
Anti-inflammatory
- ↓IL1,6 (B cell diff to plasma), TNF, IFNγ), ↑IL10
- ↓WBC chemotaxis
- ↓ AA pathway → ↓ prostaglandins, leukotrienes
Immunosuppressive
- ↓ Ag presentation (↑lysosomal pH –↓Ag breakdown→ no TLR7, TLR9 activation) → inhibition of cell mediated immunity
Light filtration
- Bind melanin → absorbs light→ ↓ UVR mediated injury
Antiproliferative
- Intercalates DNA → inhibits synthesis
- Modest antiviral (HIV)
- Anti-thrombocyte aggregation (Antiphospholipid syndrome)
- ↓ Lipids (HMG-CoA reductase)
- ↓ Glycemia
- May ↓ Vitamin D levels
FDA
- Malaria
- Rheumatoid arthritis
- Discoid lupus
- Systemic lupus erythematosus (arthralgias, myalgias, serositis, B-symptoms, aphthae & skin response)
Off label
- Photosensitive disorders (PCT, PMLE, solar urticarial, DM)
- Granulomatous (sarcoidosis, GA)
- Lymphocytic infiltrates (Lymphocytoma cutis, Jessner, REM syndrome)
- Panniculitis (EN, lupus)
- Other (oral LP, chronic ulcerative stomatitis, PF, AD, urticarial vasculitis, localized scleroderma, follicular mucinosis, psoriatic arthritis)
Absolute
- Hypersensitivity
- Retinopathy
Relative
- Pregnancy
- Lactation
- Retinal/visual field changes
- Severe blood dyscrasias
- Significant Hepatic disorder
- Significant Neurologic impairment e.g. myasthenia gravis
- Psoriasis (may lead to erythrodermic psoriasis)
Most common
- Gastrointestinal SE
- Blurry vision (transient & self-limited from muscle)
- Skin pigmentations (10-30% with long-term use→ blue-black cutaneous discoloration shins, face, hard palate, & nail beds. More pronounced with HCQ)
- Rashes (10-20%)
Most important
Ocular toxicity:
- Reversible
-
- Corneal deposits
- Premaculopathy (reversible retinopathy)
- Loss of accommodation
- Irreversible
-
- True retinopathy (bull’s eye, central scotoma, changes in visual acuity)
Cutaneous side effects
- Minor hypersensitivity reactions: lichenoid> eczematous, & morbilliform eruption
- Major hypersensitivity reactions: erythroderma, urticaria, AGEP
- Induction or worsening of psoriasis/ erythrodermic psoriasis
- Bleaching of hair root: in 10% (interference with melanosome function)
- Skin pigmentation (as above) + transverse nail pigmentation
- Dose-related yellowish staining with QE (skin, sclera, body fluid)
Reported
- Leukopenia (reversible)
- Agranulocytosis (CQ)
- G6PD hemolysis (rare)
- Neurologic & cardiac SE
- Transaminitis
Intoxication
- Blurry vision
- Cardiovascular toxicity
- Cardiovascular/respiratory arrest
- Neurologic toxicity
↓ Efficacy
- Smoking (dose-dependant)
- Antacids (↓ absorption)
↑ Toxicity
- HCQ + CQ = retinal toxicity
- Local anesthetics (benzocaine, prilocaine): ↑Methemoglobenemia
- Cimetidine (↓ metabolism)
Antimalarial ↑ toxicity of
- Cyclosporine
- Digoxin
- Antiarrhythmics
Baseline
- Baseline eye exam (within 1st year): slit lamp, Funduscopy, visual fields & acuity
- CBC, chemistry profile, creatinine, LFT
- G6PD (with 8- aminoquinolines mainly/ Unnecessary to screen for G6PD due to low risk of hemolysis at doses of antimalarials utilized in dermatology) +/- urine porphyrins
FU
- CBC, LFT, creatinine qmonthly x3months, then q3-6months
- Eye exam annually after 5 years of use
Retinopathy risk factors
- Cumulative dose & daily dose
- Elderly (> 60 years)
- Impaired liver &/or renal function
- Pre-existing macular/retinal disease
- Tamoxifen with HCQ
- HCQ + CQ combined
Notes
- Half-life 40-50 days (except QE 1-2 weeks)
- Likes melanin rich tissue (skin & retina)
- Response seen within 2-3 months
- Should be continued in pregnant systemic lupus patients as benefits out-weight risks (↓ risk of clots & neonatal lupus heart block)
- Skin pigmentation on histopathology → hemosiderin around capillaries & dermal melanin
- Highest risk for drug eruption (HCQ) is with anti-SAE DM & no risk with anti- MDA-5 DM (1)