Hydroxychloroquine, commonly known as HCQ, is a well-established medication with a long and evolving clinical journey. Originally developed as an anti-malarial drug, HCQ has since become a cornerstone in the treatment of autoimmune and inflammatory diseases. Its versatility has made it indispensable in rheumatology and beyond.
To simplify the vast therapeutic uses of hydroxychloroquine, educators and clinicians often use the high-yield mnemonic:
“LIAARR – Mona”, which stands for:
- L – Lupus arthritis
- I – Inflammatory myopathy
- A – Autoimmune disease
- A – Arthritis
- R – Rheumatoid arthritis
- R – Renal arthritis (autoimmune)
- M – Malaria
This guide will explore each indication in depth—explaining the mechanisms, medical relevance, and real-world use of hydroxychloroquine.
What is Hydroxychloroquine?
Hydroxychloroquine sulfate (brand name Plaquenil) is a disease-modifying antirheumatic drug (DMARD). It’s a derivative of chloroquine with fewer side effects, making it safer for long-term use in chronic conditions. It is available in oral tablet form, commonly as 200 mg HCQ tablets.
Originally used for malaria, hydroxychloroquine gained major recognition for its immunomodulatory properties, making it valuable in diseases like lupus, rheumatoid arthritis, and dermatomyositis.
Mechanism of Action: How HCQ Works
Hydroxychloroquine works by:
- Increasing the pH inside lysosomes and endosomes, interfering with antigen processing
- Inhibiting Toll-like receptor signaling, reducing inflammatory cytokine production
- Decreasing the activation of autoimmune T and B cells
- Exerting anti-thrombotic effects, especially in systemic lupus erythematosus (SLE)
These properties make HCQ uniquely effective in dampening autoimmune responses without overt immunosuppression.
Breaking Down the “LIAARR – Mona” Mnemonic
Let’s decode the mnemonic and discuss each condition in which HCQ is used.
L – Lupus Arthritis (Systemic Lupus Erythematosus)
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease where the immune system attacks its own tissues, affecting the skin, joints, kidneys, brain, and other organs.
Why HCQ?
- Reduces flare frequency and severity
- Controls arthritic symptoms like joint pain and swelling
- Prevents damage to organs (especially renal involvement)
- Improves long-term survival in SLE patients
Clinical Benefits:
- Reduces need for steroids
- Decreases thrombosis risk
- Improves lipid profile
Hydroxychloroquine is considered a first-line, long-term treatment for all patients with lupus, unless contraindicated.
I – Inflammatory Myopathy
Inflammatory myopathies include conditions like:
- Polymyositis
- Dermatomyositis
- Overlap syndromes with SLE or RA
These are autoimmune disorders that lead to progressive muscle weakness, inflammation, and fatigue.
HCQ’s Role:
- Reduces inflammation in muscle fibers
- Improves skin manifestations in dermatomyositis
- Acts as a steroid-sparing agent
While HCQ is not curative, it is part of the multidrug regimen used in mild to moderate disease.
A – Autoimmune Diseases (General Use)
Hydroxychloroquine is commonly prescribed in several non-lupus autoimmune diseases, including:
- Sjögren’s syndrome
- Mixed connective tissue disease
- Antiphospholipid syndrome (APS)
- Undifferentiated connective tissue disorders
Why It’s Used:
- Broad immunomodulatory effects
- Mild side effect profile
- Delays disease progression
Its low cost and relatively safe profile make it a valuable first-line or adjunctive therapy in many autoimmune cases.
A – Arthritis (Non-rheumatoid)
Hydroxychloroquine is also used in non-specific inflammatory arthritis, including:
- Seronegative arthritis
- Juvenile idiopathic arthritis (selected cases)
- Palindromic rheumatism
Key Effects:
- Reduces joint inflammation and stiffness
- Slows erosive joint damage
- Improves patient mobility
Although not as potent as methotrexate, HCQ is often used in early or mild arthritis when NSAIDs are insufficient.
R – Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune joint disorder that causes symmetrical joint pain, morning stiffness, and potential disability.
Role of HCQ:
- Classified as a conventional synthetic DMARD
- Used in early RA, either alone or in combination (e.g., with methotrexate and sulfasalazine as part of “triple therapy”)
- Offers symptom control and disease modification
Benefits:
- Delays radiological joint damage
- Less hepatotoxic than other DMARDs
- Especially useful in seronegative RA
It is usually not sufficient alone in aggressive RA but excellent for milder disease forms or as adjunct therapy.
R – Renal Arthritis (Lupus Nephritis/Autoimmune Kidney Disease)
In systemic lupus, kidney involvement (lupus nephritis) is a serious concern. HCQ’s role here is preventive and supportive, especially when used alongside immunosuppressants like mycophenolate mofetil or cyclophosphamide.
Clinical Evidence:
- HCQ improves renal outcomes
- Reduces progression to end-stage renal disease
- Controls systemic inflammation without nephrotoxicity
Because it doesn’t burden the kidneys, HCQ is ideal for patients with renal sensitivity.
M – Malaria
HCQ’s original use was in treating and preventing malaria, especially:
- Plasmodium vivax
- Plasmodium ovale
- Chloroquine-sensitive P. falciparum
Although resistance has limited its use in many parts of the world, it remains a WHO-approved drug for travelers in malaria-endemic regions with chloroquine-sensitive strains.
Dosage and Administration of Hydroxychloroquine
| Condition | Typical HCQ Dose | Duration |
|---|---|---|
| Lupus | 200–400 mg/day | Lifelong maintenance |
| RA | 200–400 mg/day | Ongoing |
| Dermatomyositis | 200 mg/day | As needed |
| Malaria prophylaxis | 400 mg/week | 1–2 weeks before, during, and 4 weeks after travel |
| Malaria treatment | 800 mg initially, then 400 mg at 6, 24, 48 hrs | 3-day course |
Always tailor dosing to ideal body weight and monitor for toxicity.
Hydroxychloroquine Side Effects
While generally well-tolerated, HCQ can cause:
Common Side Effects:
- Gastrointestinal upset (nausea, vomiting)
- Headaches
- Skin rash
- Hair thinning
Rare but Serious Side Effects:
- Retinopathy: Irreversible damage to the retina; routine eye exams are essential
- QT prolongation (cardiac arrhythmia risk)
- Hypoglycemia
- Blood dyscrasias (rare)
Monitoring Guidelines:
- Baseline and annual retinal screening
- ECG monitoring in high-risk patients
- Routine CBC, LFTs if used long-term
Myths and Misconceptions: HCQ in the COVID Era
Hydroxychloroquine received global attention during the COVID-19 pandemic as a potential antiviral agent. However:
- Clinical trials failed to show benefit in preventing or treating COVID-19
- It is not recommended by WHO, CDC, or major medical bodies for COVID management
- Inappropriate use led to shortages and toxicity cases
The pandemic misuse should not overshadow HCQ’s proven value in autoimmune and rheumatic diseases.
Hydroxychloroquine in Pregnancy and Lactation
HCQ is generally considered safe in pregnancy, especially in women with:
- SLE
- RA
- APS
It reduces the risk of flare-ups and helps maintain fetal outcomes. It is also safe during breastfeeding as it has minimal secretion into breast milk.
Alternatives to Hydroxychloroquine
| Alternative | Indications | Comparison |
|---|---|---|
| Methotrexate | RA, Psoriasis | Stronger but more toxic |
| Sulfasalazine | RA, UC | Often combined with HCQ |
| Leflunomide | RA | Longer half-life, teratogenic |
| Biologics (e.g., Etanercept) | Moderate-to-severe RA | Expensive, more potent |
| Chloroquine | Malaria, SLE | Similar action, more side effects |
Frequently Asked Questions (FAQs)
How long does HCQ take to work?
It may take 4–8 weeks for effects to appear and up to 6 months for full benefit in autoimmune diseases.
Is HCQ safe for long-term use?
Yes, with regular eye exams and monitoring, HCQ is safe for years of continuous use.
Can HCQ be stopped suddenly?
In autoimmune diseases, sudden withdrawal may trigger flares. Always taper under medical supervision.
Is hydroxychloroquine an immunosuppressant?
Not directly—it’s an immunomodulator, meaning it adjusts immune activity rather than suppressing it entirely.
Does HCQ affect fertility?
No, it does not impair male or female fertility. In fact, it's safe in preconception and during pregnancy in autoimmune cases.
Summary Table: Hydroxychloroquine Uses by Mnemonic “LIAARR-Mona”
| Mnemonic | Indication | Clinical Role |
|---|---|---|
| L | Lupus arthritis | First-line maintenance |
| I | Inflammatory myopathy | Adjunct for dermatomyositis |
| A | Autoimmune disease | Broad use across CTDs |
| A | Arthritis | Mild/moderate cases |
| R | Rheumatoid arthritis | DMARD, monotherapy or combo |
| R | Renal arthritis | Kidney-safe lupus therapy |
| M | Malaria | Prophylaxis and treatment (chloroquine-sensitive) |
Final Thoughts
Hydroxychloroquine is a veteran drug with modern value. From taming flares in systemic lupus to managing joint stiffness in rheumatoid arthritis, HCQ continues to be a pillar of autoimmune disease management. The “LIAARR-Mona” mnemonic helps you remember its diverse indications—from lupus to malaria.
