Weils disease
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leptospirosis "Weil disease"
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leptospirosis Weil disease jaundice clinical findings
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Weil's Disease (Icteric Leptospirosis)
Weil's disease is the severe, icteric form of leptospirosis - a zoonotic infection caused by Leptospira interrogans, the most common pathogenic spirochete. It represents about 10% of all leptospirosis cases and is defined by the classic triad of jaundice, acute renal insufficiency, and bleeding.
Causative Organism
- Leptospira interrogans, serovar Icterohaemorrhagiae is the most common cause
- Thin spirochetes (0.1 µm × 6-20 µm) with characteristic hooked ends
- Over 250 serovars exist; genome has extensive horizontal gene transfer
- The name comes from Greek: leptos (thin) + speira (coil)
Epidemiology
- The world's most common zoonosis, causing ~1 million cases and 60,000 deaths annually (likely an underestimate)
- Transmitted via contact with urine-contaminated water or soil through broken skin or mucous membranes
- Reservoir: Urban brown rat (Rattus norvegicus) is the primary source; also dogs, pigs, cattle, horses
- Endemic in tropical countries with high rainfall: India, Malaysia, Brazil
- High-risk groups: sewer workers, farmers, slaughterhouse workers, veterinarians, rat catchers, flood victims, adventure travelers
- Outbreaks spike after flooding - Goldman-Cecil Medicine notes incidence will likely rise with climate change-driven extreme rainfall
Biphasic Disease Course
| Phase | Timing | Features |
|---|---|---|
| Leptospiremic phase | Days 1-7 | Bacteraemia; organism in blood and urine. Fever, myalgia, headache, conjunctival suffusion |
| Immune/Leptospiruric phase | Day 7 onward | Antibody formation, organism cleared from blood. Either resolves (mild) or progresses to Weil's |
Weil's Disease: Classic Triad
1. Jaundice
- Results from hepatocellular disruption in hepatic sinusoids by spirochetes causing bile leakage
- Serum bilirubin markedly elevated; liver enzymes are only moderately raised (unlike viral hepatitis)
- Hepatic failure per se is unusual - jaundice is mainly cholestatic
2. Acute Kidney Injury (AKI)
- Kidney involvement is almost universal; AKI incidence ranges from <10% to >80% in different series
- Typically non-oliguric and associated with hypokalemia (paradoxical, due to tubular wasting)
- Proximal tubular infection → reduced Na⁺/K⁺-ATPase activity → impaired sodium/water reabsorption → K⁺ wasting
- High urinary fractional excretion of Na⁺ and K⁺ precedes GFR reduction
- Histology: tubulointerstitial nephritis with cellular infiltration and interstitial oedema
- Long-term: CKD can develop after severe AKI
3. Bleeding
- Thrombocytopenia + coagulation disorders disrupt haemostasis
- Usually mild: petechiae, ecchymoses
- Severe: GI haemorrhage or pulmonary haemorrhage (diffuse alveolar haemorrhage/ARDS) - carries high mortality
Clinical Features of Weil's Disease
Incubation period: 6-29 days (median ~15 days)
| System | Manifestations |
|---|---|
| General | Abrupt-onset high fever, rigors, severe prostration |
| Musculoskeletal | Severe myalgia (especially calves and lower back), calf tenderness |
| Eyes | Conjunctival suffusion (pathognomonic - injection without exudate), subconjunctival haemorrhage, scleral icterus |
| Skin | Jaundice, petechiae, purpura, pretibial maculopapular rash |
| Renal | Proteinuria, haematuria, oliguria/anuria, non-oliguric AKI with hypokalemia |
| Hepatic | Deep jaundice, moderate transaminase elevation |
| Pulmonary | Cough (up to 50%), haemoptysis, ARDS |
| Neurological | Severe bitemporal/frontal headache, photophobia, meningism |
| Cardiac | Arrhythmias |
| GI | Nausea, vomiting, diarrhoea, abdominal pain, pancreatitis |
The photograph below shows the characteristic appearance in Weil's disease - conjunctival suffusion (red injection) combined with deep scleral icterus in a patient with confirmed Weil's disease:
Diagnosis
Case Definitions (WHO framework)
- Suspect: Acute fever (≥38.5°C) + headache + myalgia/prostration/conjunctival suffusion + history of exposure
- Probable (clinical): Suspect case + any 2 of: calf tenderness, cough ± haemoptysis, dyspnoea, skin rash, jaundice, haemorrhage, meningism, oliguria/proteinuria, arrhythmia
- Confirmed: Suspect/probable + any one of: organism isolation, positive PCR, seroconversion, MAT titer ≥400
Diagnostic Tests by Phase
| Timing | Best Test |
|---|---|
| Week 1 (leptospiremic) | Blood PCR (high sensitivity), blood cultures, dark-field microscopy |
| Week 2+ (immune) | Urine PCR, urine cultures, serology (MAT, IgM ELISA) |
- MAT (Microscopic Agglutination Test) is the gold standard serological test
- IgM ELISA and rapid tests are useful bedside adjuncts
- Labs: leukocytosis (15,000-30,000 cells/mm³), thrombocytopenia, elevated bilirubin (predominantly direct), mildly raised transaminases, raised creatinine, hypokalemia
Treatment
| Severity | Antibiotic | Regimen |
|---|---|---|
| Mild | Doxycycline | 100 mg BD × 7 days |
| Mild alternative | Azithromycin | Effective alternative |
| Severe (Weil's) | IV Penicillin G | 1.5 MU 6-hourly |
| Severe alternatives | IV Ampicillin or IV Ceftriaxone | Either effective |
Supportive care is equally important:
- Non-oliguric AKI with hypokalemia: aggressive fluid repletion + potassium supplementation
- Oliguric renal failure: early haemodialysis or peritoneal dialysis
- Pulmonary haemorrhage/ARDS: mechanical ventilation
- Thrombocytopenia: platelet support if bleeding
Prevention
- Limit contact with rodents and contaminated water/soil
- Protective footwear and clothing for occupational exposure
- Prophylaxis: Doxycycline 200 mg once weekly during high-risk exposure (e.g., flood relief work, travel to hyperendemic areas) - supported by a 2024 Cochrane meta-analysis on antibiotic prophylaxis for leptospirosis
- Vaccines are available for animals; human vaccines exist in some countries (Cuba, China, Japan)
Mortality
- Uncomplicated leptospirosis: very low
- Weil's disease: 5-10% mortality (from renal failure, vascular collapse, or haemorrhage)
- With pulmonary haemorrhage/ARDS: mortality can exceed 50%
- A 2023 meta-analysis of clinical predictors identified oliguria, jaundice, arrhythmias, thrombocytopenia, and elevated creatinine as predictors of severe AKI and death
Sources: Goldman-Cecil Medicine (26th Ed.) | Comprehensive Clinical Nephrology, 7th Ed. | Andrews' Diseases of the Skin
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I now have comprehensive data from both the 2026 ACC/AHA and 2025 ESC/EAS guidelines. Let me compile the full answer.
LDL Cholesterol Guidelines (2025-2026 Updates)
Two major guideline updates have just been released:
- 2026 ACC/AHA Dyslipidemia Guideline (March 13, 2026) - replaces the 2018 guideline, reintroduces specific LDL targets
- 2025 ESC/EAS Focused Update (August 29, 2025) - updates the 2019 ESC/EAS guideline
1. Risk Stratification
2026 ACC/AHA (Primary Prevention)
Uses the new PREVENT (Predicting Risk of CVD EVENTs) equations - replacing the old 2013 Pooled Cohort Equations, which overestimated 10-year ASCVD risk by ~40-50%. PREVENT is validated for adults aged 30-79 without existing ASCVD, with LDL 70-189 mg/dL, and provides both 10-year and 30-year risk estimates.
| 10-Year ASCVD Risk | Category |
|---|---|
| < 3% | Low |
| 3% to <5% | Borderline |
| 5% to <10% | Intermediate |
| ≥ 10% | High |
2025 ESC/EAS
Uses SCORE2 and SCORE2-OP (Older Persons) for risk assessment, with additional risk modifiers including family history, ethnicity, comorbidities, elevated hs-CRP, and Lp(a).
2. LDL-C Treatment Targets
2026 ACC/AHA Guideline (NEW - the return of specific LDL targets)
| Risk Category | LDL-C Goal |
|---|---|
| Borderline or Intermediate risk (primary prevention) | < 100 mg/dL |
| High risk (primary prevention) | < 70 mg/dL |
| Very High Risk ASCVD (secondary prevention) | < 55 mg/dL |
Very High Risk ASCVD = prior MI/stroke + additional high-risk features (multiple ASCVD events, ASCVD + diabetes/CKD/FH, or very high LDL despite therapy)
Note: A key shift - the 2026 guidelines move AWAY from the 2018 guideline's percent-reduction approach BACK to specific numeric LDL targets.
2025 ESC/EAS Guideline (maintained from 2019)
| Risk Category | LDL-C Goal |
|---|---|
| Moderate risk | < 100 mg/dL (<2.6 mmol/L) |
| High risk (incl. FH without other major risk factors) | < 70 mg/dL (<1.8 mmol/L) |
| Very High risk (incl. FH + ASCVD or another major risk factor) | < 55 mg/dL (<1.4 mmol/L) |
| Extreme risk (recurrent ASCVD events within 2 years on max therapy) | < 40 mg/dL (<1.0 mmol/L) |
3. Treatment: Step-Up Approach
First-line: Lifestyle Modification
- Heart-healthy diet (reduce saturated fat, increase fibre, plant sterols)
- Regular aerobic exercise
- Weight management, smoking cessation
Second-line: Statin Therapy (First Drug)
| Intensity | LDL-C Reduction | Examples |
|---|---|---|
| High-intensity | ≥ 50% | Atorvastatin 40-80 mg, Rosuvastatin 20-40 mg |
| Moderate-intensity | 30-50% | Atorvastatin 10-20 mg, Rosuvastatin 5-10 mg, Simvastatin 20-40 mg |
| Low-intensity | < 30% | Simvastatin 10 mg, Pravastatin 10-20 mg |
- High-intensity statin is recommended in high/very high risk patients
- For ACS: immediate high-intensity statin ± ezetimibe (per 2025 ESC/EAS)
Third-line: Add-on Nonstatin Therapies (if not at goal)
| Drug | Mechanism | Additional LDL Reduction | Notes |
|---|---|---|---|
| Ezetimibe | Inhibits NPC1L1 (intestinal cholesterol absorption) | ~20% | First add-on; oral, well tolerated |
| Bempedoic acid | Inhibits ATP-citrate lyase (upstream of HMG-CoA reductase) | ~18-25% | Newly endorsed in both ESC/EAS 2025 and ACC/AHA 2026; good for statin-intolerant patients |
| PCSK9 monoclonal antibodies (evolocumab, alirocumab) | Block PCSK9 - increase LDL-receptor expression | ~60% on top of statin | For high/very high risk not at goal; injectable (2-weekly or monthly) |
| Inclisiran | siRNA - silences PCSK9 production | ~50% | Still under study for outcomes (2026 ACC/AHA: not yet recommended pending outcome trials) |
| Evinacumab | Anti-ANGPTL3 antibody | Significant | For homozygous FH ≥5 years old failing max therapy (ESC/EAS 2025) |
Combination therapy can achieve up to 86% LDL reduction according to the 2025 ESC/EAS guidelines.
Important 2026 ACC/AHA note on supplements: The guidelines explicitly advise against supplements and vitamins (e.g. red yeast rice, fish oil, plant sterols alone) as substitutes for evidence-based lipid-lowering therapy.
4. Special Populations
| Population | Recommendation |
|---|---|
| Familial Hypercholesterolaemia (FH), heterozygous | LDL < 70 mg/dL; if FH + clinical ASCVD, aim < 55 mg/dL |
| Homozygous FH | Evinacumab considered if not at goal on max therapy |
| Diabetes (high-risk features) | LDL < 70 mg/dL; future guidelines may push toward < 55 |
| HIV patients | ESC/EAS 2025: statin from age 40 regardless of LDL |
| On anthracycline chemotherapy (high risk) | Statin recommended per ESC/EAS 2025 |
| CKD | Treat as high/very high risk depending on GFR and proteinuria |
| Older adults (SCORE2-OP) | Risk-adapted targets; 10-20% SCORE2-OP = high risk → LDL < 100 |
| Statin intolerant | Bempedoic acid or ezetimibe monotherapy; PCSK9i as alternative |
5. Lp(a) - New Emphasis in 2025 ESC/EAS
- Lp(a) should be measured at least once in every adult's lifetime
- Lp(a) > 50 mg/dL (105 nmol/L) is a CV risk-enhancing factor
- Higher Lp(a) = greater CV risk (independent of LDL)
- New Lp(a)-lowering agents (e.g. pelacarsen, olpasiran) are in late-stage trials; not yet in routine recommendations
6. Side-by-Side Comparison: ACC/AHA vs ESC/EAS
| Feature | 2026 ACC/AHA | 2025 ESC/EAS |
|---|---|---|
| Risk tool | PREVENT equations | SCORE2 / SCORE2-OP |
| Lowest LDL target | < 55 mg/dL (very high risk) | < 40 mg/dL (extreme risk) |
| Returns to LDL targets? | Yes (key change from 2018) | Yes (maintained from 2019) |
| Bempedoic acid | Recommended as add-on | Recommended for statin-intolerant |
| Inclisiran | Awaiting outcomes data | Mentioned |
| Evinacumab | Not specified | For HoFH ≥5 years |
| Supplements | Explicitly discouraged | Explicitly discouraged |
| Lp(a) | Risk enhancer | Full dedicated section |
Key takeaway: Both 2025-2026 guidelines align on the principle of "lower is better, longer is better." The 2026 ACC/AHA marks a significant return to specific numeric LDL goals after years of a percent-reduction framework, and introduces the more accurate PREVENT risk calculator. The ESC/EAS adds an extreme risk (<40 mg/dL) category not present in the ACC/AHA, and has gone further with novel agents like evinacumab for refractory FH.
Sources: 2026 ACC/AHA Dyslipidemia Guideline | 2025 ESC/EAS Focused Update | ESC guidelines on dyslipidemia update 2025 review [PMID: 41366604]
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