1. Essential Hypertension

1.1 Overview and Definition

• Hypertension is a state of chronically and abnormally high arterial blood pressure.
• Systemic arterial hypertension is defined as persistent systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg, or both.
• Ideal blood pressure is considered to be <120/80 mmHg.
• High normal blood pressure (pre-hypertension) ranges:
  • Systolic: 120–139 mmHg
  • Diastolic: 80–89 mmHg
• Essential hypertension (also known as primary or idiopathic hypertension) accounts for approximately 95%of all hypertension cases, with no identifiable pathological cause.

1.2 Epidemiology

• Global Prevalence: Hypertension affects nearly 1 billion people worldwide, projected to rise to 1.5 billion by 2025.
• Cardiovascular Impact: Hypertension is the major risk factor for cardiovascular disease, the commonest cause of death globally.
• Regional Variations:
  • High Prevalence: Africa, South America, Eastern Europe, South East Asia (>45% of adults affected)
  • Lower Prevalence: USA, Western Europe, Australia (<40% of adults affected)
• Ethnic Disparities:
  • African–Caribbean populations have a higher prevalence of hypertension compared to white and Asianpopulations (ratio ~3:2).
  • In North America, African Americans have a prevalence >10% higher than white individuals.
  • Cardiovascular Complications: Black individuals with hypertension have a greater tendency to develop stroke.
• Age and Gender Distribution:
  • Under 50 years: More prevalent in men.
  • Above menopause: Prevalence equalises between men and women.

1.3 Aetiology and Risk Factors

1.3.1 Primary (Essential) Hypertension

• Unknown Etiology: No identifiable pathological cause; multifactorial in nature.
• Risk Factors:
  • Modifiable:
    • Excessive alcohol intake
    • Smoking
    • Stress
    • Salt intake
    • Obesity
    • Sedentery lifestyle
  • Non-modifiable:
    • Family history of hypertension
    • Advanced age
    • African–Caribbean heritage
    • Male gender (<50 years)

1.3.2 Secondary Hypertension

• Prevalence: Approximately 5% of hypertension cases.
• Suspected When:
  • Hypertension is resistant to therapy.
  • Occurs at a young age.
  • Accompanied by features suggesting a secondary cause.

1.4 Clinical Features

• Asymptomatic: Hypertension is largely silent, presenting no symptoms until significant target organ damageoccurs.
• Severe Cases: May present with symptoms such as headaches, dizziness, or blurred vision, but these are not specific.
• Target Organ Damage:
  • Organ System Complications
    • Cardiac:
      • Left ventricular hypertrophy
      • Diastolic heart failure
      • Arrhythmia (especially atrial fibrillation)
      • Coronary artery disease (myocardial infarction and angina)
    • Renal:
      • Hypertensive nephropathy
      • Renal insufficiency
      • End-stage renal disease
    • Cerebral:
      • Stroke
      • White matter ischaemia with impaired cognition or dementia
      • Hypertensive encephalopathy (at very high blood pressure)
    • Ophthalmic
      • Hypertensive retinopathy
      • Reduced vision

1.5 Diagnostic Approach

1.5.1 Blood Pressure Measurement

• Accurate Measurement: Essential for diagnosis; requires proper technique and repeated measurements.
• Procedure:
  • If a reading of >140/90 mmHg is obtained, repeat the measurement during the same consultation.
  • If the second reading significantly differs, measure again.
  • Document the lower of the latter two readings as the blood pressure.

1.5.2 Ambulatory and Home Blood Pressure Monitoring

• Ambulatory Blood Pressure Monitoring (ABPM):
  • Records blood pressure every 2 hours over 24 hours during normal daily activities.
  • Diagnostic Threshold: Average waking blood pressure >130/85 mmHg.
• Home Blood Pressure Monitoring:
  • Measurements taken by the patient or another person with the patient at rest and seated.
  • Taken several times daily over 5–7 days and recorded in a diary.

1.5.3 Investigations

1.5.3.1 Laboratory Investigations

• Evaluate Cardiovascular Risk:
  • Fasting Blood Glucose: Elevated levels indicate increased risk; normal levels exclude diabetes.
  • Lipid Profile: Measures total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.
• Evidence of Target Organ Damage:
  • Organ System Investigation(s):
    • Heart: 12-lead ECG –> Left ventricular hypertrophy; signs of coronary heart disease
    • Kidneys: Laboratory tests (urea, electrolytes, creatinine clearance, estimated glomerular filtration rate, dipstick urinalysis) –> Impaired renal function; Urine dipstick for proteinuria, haematuria
    • Eyes: Fundoscopy –> Hypertensive retinopathy

1.5.3.2 Identification of Secondary Causes

• Indications for Further Investigation:
  • Young age of onset.
  • Extremely high blood pressure.
  • Resistant hypertension despite therapy.
  • Presence of clinical features suggestive of secondary causes.

1.5.4 Differential Diagnosis

• Distinguish from Secondary Hypertension: Ensure no underlying pathological causes are present, especially in cases suspected of secondary hypertension.

1.6 Management

1.6.1 Risk Assessment

• Cardiovascular Risk Estimation: Influences management strategies.
  • High-Risk Groups: Patients with established cardiovascular disease (e.g., coronary artery disease, stroke, peripheral vascular disease).
  • Other Patients: Based on a 10-year cardiovascular risk >20%.
• Goals:
  • Reduce Morbidity and Mortality: By managing blood pressure and modifying risk factors.
  • Individualised Treatment: Based on blood pressure levels, cardiovascular risk, and presence of target organ damage.

1.6.2 Lifestyle Modifications

• Salt Intake: Reduce to <6 g/day; avoid adding salt and processed foods.
• Weight Management and Exercise:
  • Weight Loss: Achieves blood pressure reduction.
  • Physical Activity: At least 30 minutes of aerobic exercise most days of the week.
• Alcohol Intake:
  • Men: No more than 3–4 units (24–32 g) per day.
  • Women: No more than 2–3 units (16–24 g) per day.
• Smoking Cessation: Essential for reducing cardiovascular risk; consider nicotine replacement therapy.
• Referral: For dietary advice, physical training, or specialist smoking cessation services as needed.

1.6.3 Pharmacological Therapy

• First-Line Agents:
  • Angiotensin-Converting Enzyme (ACE) Inhibitors or Angiotensin II Receptor Blockers (ARBs)
  • Beta-Blockers
  • Calcium Channel Blockers
  • Diuretics (chiefly thiazide and thiazide-like diuretics)
  • Alpha-Blockers
• Stepwise Approach:
  • Step 1: Start with a single drug.
  • Step 2: Add a second agent if response is suboptimal.
  • Step 3: Add a third agent if necessary.
• Resistant Hypertension:
  • Referral to a hypertension specialist.
  • Address poor adherence through patient education and simplifying prescriptions.
• Ethnic Considerations:
  • African–Caribbean Patients:
    • Often have low-renin, salt-sensitive hypertension.
    • Calcium Channel Blockers or Diuretics are preferred first-line agents.
    • Renin–Angiotensin System Antagonists are reserved for second-line therapy.

1.6.4 Emerging Therapies

• Vagal Nerve Stimulation: Electrical stimulation to balance sympathetic and parasympathetic activity.
• Renal Denervation: Ablation of renal sympathetic nerves to reduce blood pressure.

1.7 Monitoring Blood Pressure Targets

• General Aim: Normalise blood pressure to <140/90 mmHg.
• Elderly Patients (>80 years): Target <150/85 mmHg due to natural BP increases with age.
• Patients with Diabetes, High Cardiovascular Risk, or Renal Dysfunction:
  • Tighter Control: Aim for <130/80 mmHg.
  • Challenges: Achieving targets may be limited by adverse effects, especially in the elderly.
• Regular Monitoring: Use clinic blood pressure measurements for most patients.

1.8 Prognosis

• Essential Hypertension:
  • Prognosis depends on the degree of target organ damage and cardiovascular risk.
  • Cardiovascular Mortality: Every 20/10 mmHg increase in blood pressure is associated with a doubling of cardiovascular mortality.
• Long-Term Management:
  • Appropriate Medication: Prolongs life and reduces complications.
  • Lifestyle Modifications: Improve overall health and reduce disease progression.

1.9 Complications of Hypertension

2. Secondary Hypertension

2.1 Overview and Definition

• Secondary hypertension is defined as elevated arterial blood pressure with an identifiable underlying pathological cause.
• It accounts for approximately 5% of all hypertension cases.
• The commonest cause of secondary hypertension is renal artery stenosis (renovascular hypertension).

2.2 Epidemiology and Aetiology

• Prevalence: Secondary hypertension is identified in about 5% of hypertensive patients.
• Renovascular Hypertension: The most common secondary cause, often resulting from renal artery stenosisdue to atherosclerosis (common in elderly males) or fibromuscular dysplasia (common in young females).

2.2.1 Secondary Causes of Hypertension

• Secondary hypertension can arise from various categories, each with distinct underlying mechanisms and diagnostic approaches.

2.3 Clinical Features

Secondary hypertension often presents with features that differentiate it from essential hypertension. These distinguishing features are typically related to the underlying cause.

2.3.1 Clues Suggesting Secondary Hypertension

• Early-Onset Hypertension: Onset before 40 years of age.
• Unexpectedly Severe Hypertension: Significantly elevated blood pressure readings.
• Resistant Hypertension: Hypertension that remains uncontrolled despite the use of three antihypertensive agents of different classes.
• Clinical Signs Suggestive of a Secondary Cause: Specific physical findings related to the underlying condition.

2.3.2 General Features

• Symptoms arising directly from hypertension are similar to those of essential hypertension but may be more pronounced or accompanied by specific signs related to the secondary cause.
• For example:
  • Aortic coarctation may present with upper body hypertension and radiofemoral delay.
  • Phaeochromocytoma presents with paroxysms of hypertension, flushing, tachycardia, anxiety, and headaches.

2.4 Diagnostic Approach

2.4.1 Initial Assessment

• Clinical History:
  • Duration and severity of hypertension.
  • Presence of modifiable and non-modifiable risk factors.
  • Family history of hypertension or related conditions.
  • History of medication use, substance abuse, or other relevant exposures.
• Physical Examination:
  • Peripheral Pulses: Assess for asymmetry indicating coarctation.
  • Auscultation: Listen for carotid bruits (renovascular causes) or abdominal bruits.
  • Fundoscopy: Check for hypertensive retinopathy.
  • Body Mass Index (BMI): Assess for obesity.
  • Dipstick Urinalysis: Look for proteinuria or haematuria indicating renal involvement.

2.4.2 Investigations

• Laboratory Tests:
  • Estimated Glomerular Filtration Rate (eGFR): Assess renal function.
  • Serum Potassium: Identify hypokalaemia in primary hyperaldosteronism.
  • Aldosterone–Renin Ratio: Elevated in primary hyperaldosteronism.
  • 24-Hour Urinary Catecholamines or Metanephrines: Diagnose phaeochromocytoma.
  • 24-Hour Urine Cortisol and Dexamethasone Suppression Test: Diagnose Cushing’s syndrome.
• Imaging Studies:
  • Renal Ultrasound: Detect polycystic kidney disease.
  • Renal Doppler Ultrasound, CT, or MRI Angiography: Identify renal artery stenosis.
  • Echocardiogram or CT Scan: Diagnose aortic coarctation.
  • Sleep Studies (Oximetry and Polysomnography): Diagnose obstructive sleep apnoea.
• Ambulatory Blood Pressure Monitoring (ABPM) or Home Blood Pressure Monitoring:
  • ABPM: Records blood pressure every 2 hours over 24 hours during normal daily activities.
    • Diagnostic Threshold: Average waking blood pressure >130/85 mmHg.
  • Home Blood Pressure Monitoring:
    • Measurements taken by the patient or another person with the patient at rest and seated.
    • Taken several times daily over 5–7 days and recorded in a diary.

2.5 Management

2.5.1 General Principles

• Aim: Correct the underlying cause of hypertension.
• Approaches: May include pharmacological therapy, surgical intervention, or renal dialysis, depending on the underlying condition.
• Antihypertensive Medication: Required during and after correction of the underlying cause if blood pressure remains elevated.

2.5.2 Specific Management Based on Cause

2.5.3 Resistant Hypertension

• Definition: Blood pressure that remains above target despite the use of three antihypertensive agents of different classes, typically including a diuretic.
• Management:
  • Confirm adherence to therapy and ensure accurate blood pressure measurement.
  • Simplify medication regimens to improve adherence.
  • Add a fourth agent if necessary (e.g., mineralocorticoid receptor antagonist).
  • Consider referral to a hypertension specialist if control remains elusive.

2.6 Prognosis

• Secondary Hypertension:
  • Good Prognosis if the underlying cause is promptly diagnosed and effectively treated.
  • Prognosis Dependent on the severity and treatability of the underlying condition.
  • Control of Blood Pressure: Essential to reduce the risk of target organ damage and cardiovascular events.
• Essential Hypertension:
  • Prognosis determined by the degree of target-organ damage and overall cardiovascular risk.
  • Every 20/10 mmHg Increase: Associated with a doubling of cardiovascular mortality.

2.7 Complications of Hypertension

3. Hypertension in Other Groups

3.1 Overview

• Hypertension management principles are broadly applicable across various patient groups. However, certain populations require specific considerations due to unique physiological, clinical, or lifestyle factors.

3.2 Specific Patient Groups

3.2.1 Patients with White Coat Hypertension

• Definition: Blood pressure is elevated in clinical settings but remains normal outside of medical environments.
• Clinical Significance:
  • Often diagnosed inadvertently during clinic visits.
  • Does not necessarily warrant pharmacological therapy.
• Diagnostic Approach:
  • Ambulatory Blood Pressure Monitoring (ABPM) or Home Blood Pressure Monitoring should be utilised to confirm the diagnosis.
  • Stage 1 and 2 Hypertension: Use ABPM or home monitoring to distinguish white coat hypertension from true hypertension.
• Management:
  • Focus on cardiovascular risk assessment.
  • Emphasise patient education and lifestyle modifications.
  • Pharmacological treatment is not typically indicated unless other risk factors or organ damage are present.
• Prognosis:
  • Generally favourable with appropriate risk management and lifestyle changes.

3.2.2 Elderly Patients

• Physiological Changes:
  • Arterial Stiffness: Leads to increased systolic blood pressure.
• Management Considerations:
  • Benefit of Treatment: Proven to be beneficial even in patients over 80 years.
  • Adverse Effects:
    • Higher risk of drug side effects, contraindications, and polypharmacy-related interactions.
    • Postural Hypotension: Can lead to falls and decreased mobility.
• Pharmacological Management:
  • Careful Selection of Antihypertensive Agents to minimise adverse effects.
  • Regular monitoring to adjust therapy as needed.
• Prognosis:
  • Improved with appropriate management, though vigilance for side effects is essential.

3.2.3 Patients with Diabetes Mellitus

• Increased Risks:
  • Cardiovascular Disease, Retinopathy, Renal Damage, Peripheral Neuropathy.
• Management Goals:
  • Stringent Blood Pressure Control: Target <130/80 mmHg, especially with target organ damage or high cardiovascular risk.
• Pharmacological Therapy:
  • Renin–Angiotensin System Antagonists (ACE inhibitors or ARBs) are first-line agents due to their nephroprotective effects.
  • Effective even in elderly and African-Caribbean patients, often combined with diuretics or calcium channel blockers for optimal control.
• Lifestyle Modifications:
  • Essential alongside pharmacotherapy to reduce overall cardiovascular risk.
• Prognosis:
  • Significant reduction in morbidity and mortality with effective blood pressure and diabetes management.

3.2.4 Patients with Coexisting Diseases

• Prevalence: Increasing due to ageing populations with multiple comorbidities.
• Management Principles:
  • Choice of Antihypertensive Drugs influenced by coexisting conditions.
  • Certain drug classes offer combined benefits for multiple conditions.
• Examples:

3.2.5 Metabolic Syndrome

• Definition: Combination of central obesity, insulin resistance (and type 2 diabetes mellitus), hypertension, and dyslipidaemia.
• Diagnostic Criteria: Presence of at least three of the aforementioned conditions.
• Prevalence: Affects between 25% and 33% of adults in American and Western European populations.
• Risk Implications:
  • High Risk for cardiovascular disease and mortality.
  • Driven by increasing levels of obesity.
• Management:
  • Comprehensive approach addressing all components: weight loss, glycaemic control, lipid management, and blood pressure reduction.
  • Lifestyle modifications are paramount.

3.2.6 Pregnant Patients

• Prevalence: Hypertension affects about 10% of pregnancies.
• Clinical Significance:
  • Separate disease entity with unique pathophysiology.
  • Increases risks for both mother and baby.
  • May indicate obstetric complications such as pre-eclampsia and eclampsia.
• Management:
  • Requires specialist management.
  • Pharmacological Options:
    • Beta-Blockers (e.g., labetalol)
    • Methyldopa
    • Hydralazine
  • Surgical Intervention: Limited due to fetal risks; severe cases may necessitate early delivery.
• Prognosis:
  • Usually benign with appropriate management.
  • Prevention and timely treatment of obstetric complications are critical.

3.2.7 Patients with Hypertensive Emergencies

• Definition: Severe elevation in blood pressure with evidence of acute target organ damage.
• Clinical Scenarios:
  • Encephalopathy (typically >200/110 mmHg)
  • Left Ventricular Failure
  • Myocardial Ischaemia or Infarction
  • Aortic Dissection
  • Cerebral Haemorrhage
  • Phaeochromocytoma Hypertensive Crisis
• Management:
  • Immediate and Controlled Blood Pressure Reduction in a secondary care setting.
  • Intravenous Medications:
    • Glyceryl Trinitrate
    • Labetalol
  • Targets:
    • Reduce systolic BP below 220 mmHg or diastolic BP below 120 mmHg within 1–2 hours.
    • Further reduce to <160/100 mmHg over the next 12–24 hours.
• Prognosis:
  • Dependent on the underlying cause and timeliness of intervention.
  • Prompt management can prevent irreversible organ damage and reduce mortality.

3.3 Summary of Hypertension in Other Groups

3.4 Clinical Importance

• Tailored Management: Essential to consider the unique needs and risks of different patient groups to optimise outcomes.
• Risk Assessment: Integral to identifying high-risk individuals and implementing appropriate interventions.
• Lifestyle Modifications: Fundamental across all groups, though specific strategies may vary based on the patient’s circumstances.
• Pharmacological Therapy: Must be carefully selected to address both hypertension and any coexisting conditions, minimising adverse effects and interactions.

3.5 Prognosis

• Hypertensive Emergencies: Prognosis depends on the underlying cause and promptness of intervention.
• Varies by Group:
• White Coat Hypertension: Generally good with appropriate monitoring and risk management.
• Elderly Patients: Improved with careful management, though higher risk of adverse effects.
• Diabetic Patients: Significantly reduced morbidity and mortality with effective BP and diabetes control.
• Patients with Coexisting Diseases: Dependent on the management of both hypertension and the underlying conditions.
• Metabolic Syndrome: High cardiovascular risk necessitates aggressive risk factor modification.
• Pregnant Patients: Good prognosis with specialist management, though risks of obstetric complications persist.

4. Hypertensive Emergencies and Classification of Hypertension

4.1 Overview

• Understanding the distinctions between the different severities of hypertension is important for timely treatment to prevent severe complications.

4.2 Hypertensive Emergencies

4.2.1 Definition

• Hypertensive emergencies are severe elevations in blood pressure that are associated with acute and potentially life-threatening target organ damage.
• They necessitate immediate medical intervention to rapidly reduce blood pressure and prevent irreversible damage.

4.2.2 Clinical Scenarios

• Hypertensive emergencies include accelerated hypertension and hypertension associated with the following conditions:
  • Encephalopathy: Typically occurs with blood pressure >200/110 mmHg.
  • Left Ventricular Failure: Acute decompensation leading to heart failure symptoms.
  • Myocardial Ischaemia or Infarction: Acute coronary syndromes triggered by severe hypertension.
  • Aortic Dissection: A tear in the aorta’s inner layer, requiring urgent surgical intervention.
  • Cerebral Haemorrhage: Bleeding within the brain tissue, a life-threatening condition.
  • Phaeochromocytoma Hypertensive Crisis: A catecholamine-secreting tumour causing sudden, severe hypertension.

4.2.3 Clinical Features

• Patients presenting with hypertensive emergencies may exhibit:
  • Neurological Symptoms: Severe headache, confusion, seizures, or loss of consciousness (in encephalopathy).
  • Cardiac Symptoms: Acute chest pain, shortness of breath, or signs of heart failure.
  • Vascular Symptoms: Sudden, severe pain in the chest or back (aortic dissection), or neurological deficits (cerebral haemorrhage).

4.2.4 Diagnostic Approach

• Immediate Assessment:
  • Blood Pressure Measurement: Confirm significantly elevated BP (>220/120 mmHg).
  • Clinical Examination: Identify signs of target organ damage (e.g., papilloedema on fundoscopy, heart murmurs, neurological deficits).
• Imaging and Tests:
  • CT or MRI Scan: For suspected cerebral haemorrhage or aortic dissection.
  • Electrocardiogram (ECG): To assess for myocardial ischaemia or infarction.
  • Echocardiogram: To evaluate left ventricular function in heart failure.
  • Urine and Blood Tests: To identify phaeochromocytoma (e.g., catecholamines, metanephrines).

4.2.5 Management

• Setting: Requires management in a secondary care setting (e.g., emergency department, intensive care unit).
• Pharmacological Intervention:
  • Intravenous Glyceryl Trinitrate: For rapid vasodilation and BP reduction.
  • Intravenous Labetalol: A beta-blocker with alpha-blocking properties, effective in reducing BP.
• Blood Pressure Targets:
  • Initial Reduction: Systolic BP below 220 mmHg or diastolic BP below 120 mmHg within 1–2 hours.
  • Subsequent Reduction: Further reduce to <160/100 mmHg over the next 12–24 hours.
• Monitoring: Continuous blood pressure monitoring and assessment of organ function.
• Specific Interventions:
  • Aortic Dissection: Surgical intervention is often required.
  • Cerebral Haemorrhage: May require neurosurgical procedures.
  • Phaeochromocytoma: Surgical removal of the tumour after stabilising BP.

4.2.6 Prognosis

• Dependent on Underlying Cause and Timeliness of Intervention:
  • Prompt Management: Can prevent irreversible organ damage and reduce mortality.
  • Delayed Treatment: Increases the risk of permanent neurological deficits, renal failure, and death.

4.3 Classification of Hypertension

• Hypertension can be categorised into Benign and Malignant forms based on severity and associated clinical features.

4.3.1 Benign Hypertension

• Definition: Mild to moderate elevation in blood pressure.
• Prevalence: Constitutes the majority of hypertension cases.
• Clinical Features:
  • Clinically Silent: Typically asymptomatic.
  • Progressive Organ Damage: Vessels and organs are damaged slowly over time without acute symptoms.
• Management:
  • Regular Monitoring: To detect gradual organ damage.
  • Lifestyle Modifications: Emphasised to prevent progression.
  • Pharmacological Therapy: Initiated based on blood pressure levels and presence of risk factors or target organ damage.

4.3.2 Malignant Hypertension

• Definition: Severe elevation in blood pressure, typically >180/120 mmHg.
• Prevalence: Accounts for <5% of hypertension cases.
• Clinical Features:
  • Acute End-Organ Damage: Presents with signs of acute damage such as:
    • Acute Renal Failure
    • Severe Headache
    • Papilledema: Swelling of the optic disc observed on fundoscopy.
  • Medical Emergency: Requires immediate intervention to prevent life-threatening complications.
• Management:
  • Urgent Blood Pressure Reduction: Similar to hypertensive emergencies, often requiring intravenous medications.
  • Monitoring and Support: Intensive care monitoring to manage and mitigate organ damage.
• Prognosis:
  • Potentially Life-Threatening: Requires rapid and effective treatment to improve outcomes.

4.4 Summary of Hypertension Classification and Emergencies

4.5 Clinical Importance

• Early Recognition and Classification:
  • Differentiating between benign and malignant hypertension is crucial for appropriate management.
  • Identifying hypertensive emergencies ensures timely intervention to prevent irreversible damage and reduce mortality.
• Comprehensive Management:
  • Requires a combination of pharmacological therapy, lifestyle modifications, and monitoring based on the severity and underlying causes.
• Preventive Strategies:
  • Emphasis on regular blood pressure monitoring and risk factor modification to prevent progression to more severe forms of hypertension.

4.6 Prognosis

• Benign Hypertension:
  • Depends on Control and Risk Factor Management: Effective management can prevent organ damage and reduce cardiovascular risk.
• Malignant Hypertension and Hypertensive Emergencies:
  • Dependent on Rapid Intervention and Underlying Cause: Prompt and effective treatment can improve outcomes, whereas delayed management may result in significant morbidity and mortality.