🩺 MedAtlax

IM2-CS-main

53 min read

Collection from previous batches, made by Abdulmalik Abdulghani, Dania AbuObaid, Faisal Alkharji, Haneen H. Alsultan, Husna Merza, Lina Serhan, Maha Alasmari, Mujahid N Al-muhaydib, Yousef Edress

اللهم يا معلّم موسى علّمني، ويا مفهم سليمان فهّمني، ويا مؤتي لقمان الحكمة وفصل الخطاب آتني الحكمة وفصل الخطاب اللهم اجعل ألستنا عامرة بذكرك، وقلوبنا بخشيتك، وأسرارنا بطاعتك، إنك على كل شيء قدير، حسبنا الله ونعم الوكيل

Any updates of this file would be within https://medatlax.com/Clinical/Level-12/IM-2/Internal-Medicine-2 OSCE & OSPE-CS link.

Contents

  • Cardiovascular Disease — arrhythmias · AF · cardiac arrest · pericardium
    • Arrhythmia Diagnosis and Management — SVT · VT · torsades · bradyarrhythmia
    • Atrial Fibrillation
    • Cardiac Arrest — shockable · non-shockable
    • Pericarditis & Myocarditis — pericarditis · tamponade · constrictive · myocarditis
  • Respiratory Disease (Pulmonology) — bronchiectasis · PE
    • Bronchiectasis
    • Pulmonary embolism — low · intermediate · high risk
  • Gastroenterology and Hepatology — cirrhosis · coeliac
    • Cirrhosis Part 1 — compensated · decompensated
    • Cirrhosis Part 2 — PBC · haemochromatosis · autoimmune hepatitis
    • Coeliac disease
  • Endocrinology and Metabolism — acromegaly · hypopituitarism
    • Acromegaly
    • Panhypopituitarism
  • Hematology and Oncology — leukaemias · myeloma · anaemia
    • Acute lymphoblastic leukaemia · acute myeloid leukaemia
    • Chronic lymphocytic leukaemia · chronic myeloid leukaemia
    • Polycythaemia — primary · secondary
    • Multiple myeloma
    • Anaemia — iron deficiency · megaloblastic · haemolytic · sickle · thalassaemia · marrow failure · chronic disease
  • Rheumatology and Connective Tissue Diseases — gout · MCTD · scleroderma
    • Gout — acute · tophaceous · pseudogout
    • Mixed connective tissue disease
    • Systemic sclerosis — limited/CREST · diffuse
  • Neurology — GBS · MND · MS · myasthenia · Alzheimer
    • Guillain–Barré syndrome — typical · Miller Fisher
    • Motor neuron disease
    • Demyelinating disease — relapsing–remitting · progressive MS
    • Myasthenia gravis — ocular · generalised · crisis
    • Alzheimer’s disease

Cardiovascular Disease

Arrhythmia Diagnosis and Management

A. Supraventricular tachycardia (SVT)

Scenario. Young adult with sudden-onset regular palpitations, neck fullness, dizziness and polyuria — a regular narrow-complex tachycardia above 160/min from re-entry at the AV node.

History — what will you ask?

  • Sudden onset and offset of palpitations; regular
  • Neck fullness, light-headedness, dyspnoea, polyuria (ANP)
  • Previous episodes; caffeine, alcohol, thyrotoxicosis

Signs — what will you find?

  • Regular tachycardia >160/min, narrow QRS
  • BP — hypotension if unstable
  • No cannon waves; signs of the precipitant

Investigations — what will you order?

  • ECG — regular narrow-complex tachycardia, P waves hidden
  • Holter, echo; thyroid function and electrolytes
  • Electrophysiology for ablation planning

DDx — what else could it be?

  • Sinus tachycardia
  • Atrial flutter
  • Atrial fibrillation
  • VT with a narrow-looking QRS
  • Anxiety

Management — what will you do?

  • Vagal manoeuvres first (carotid massage, Valsalva)
  • Adenosine or verapamil second line
  • Chronic — class 1A/1C, amiodarone or sotalol; ablation is curative in young patients
B. Ventricular tachycardia

Scenario. Adult with structural heart disease and a broad-complex tachycardia — palpitations, dizziness, hypotension or collapse; VT can degenerate into VF.

History — what will you ask?

  • Palpitations, dizziness, syncope; chest pain
  • Known ischaemic heart disease or cardiomyopathy
  • Family history of sudden death; long QT, Brugada

Signs — what will you find?

  • Wide and bizarre QRS, rate 100–220 (up to 250)
  • Hypotension, cool peripheries, impaired consciousness
  • Cannon ‘a’ waves may be present

Investigations — what will you order?

  • ECG — wide-complex tachycardia, 3 or more ventricular beats, regular or irregular
  • Electrolytes, magnesium, troponin; echo for structural disease
  • EPS; assess QT and family screening

DDx — what else could it be?

  • SVT with aberrancy
  • Torsade de pointes
  • VF
  • Pre-excited AF (WPW)
  • Artifact

Management — what will you do?

  • Unstable — immediate DC cardioversion
  • Stable — amiodarone; lidocaine (1b) or procainamide (1a)
  • Treat the cause — ischaemia, electrolyte, drug; ICD for secondary prevention
C. Torsade de pointes

Scenario. Adult on a QT-prolonging drug, or with hypokalaemia or ischaemia, who collapses with a polymorphic wide-complex tachycardia that twists around the baseline.

History — what will you ask?

  • Palpitations, syncope, seizure at onset
  • Drugs — quinidine (class 1A), other QT prolongers; diuretics
  • Vomiting/diarrhoea, hypokalaemia; family history of long QT

Signs — what will you find?

  • Wide bizarre QRS twisting up and down around the baseline, rate 150–220, irregular
  • Hypotension, impaired consciousness
  • Signs of hypokalaemia or ischaemia

Investigations — what will you order?

  • ECG — QT prolongation, polymorphic VT
  • Potassium, magnesium, calcium
  • Drug history and toxicology; ECG on family members

DDx — what else could it be?

  • Monomorphic VT
  • VF
  • SVT with aberrancy
  • Artifact

Management — what will you do?

  • Unstable — synchronised cardioversion
  • IV magnesium; IV potassium to correct the electrolyte
  • Overdrive pacing; stop the offending drug; correct ischaemia
D. Bradyarrhythmia and complete heart block

Scenario. Older adult with syncope, dizziness, fatigue and confusion, a slow pulse and a collapsing pulse — sinus node disease or complete AV block; may present with heart failure.

History — what will you ask?

  • Syncope or near-syncope, dizziness, fatigue, confusion
  • Exercise intolerance, dyspnoea (sick sinus, brady–tachy)
  • Drugs — beta-blockers, verapamil, digoxin; hypothyroidism; raised ICP

Signs — what will you find?

  • Slow, regular or irregular pulse; hypotension
  • Complete block — atrial rate faster than ventricular, P waves not married to QRS, ventricular <70
  • Signs of the cause — hypothyroidism, raised ICP, jaundice

Investigations — what will you order?

  • ECG — 1st degree (PR >0.20), Mobitz I (progressive PR, dropped P), 2:1, or 3rd degree complete block
  • Electrolytes, digoxin level, thyroid function
  • Holter; echo; assess for infarction or conduction-tissue degeneration

DDx — what else could it be?

  • Sinus bradycardia (drugs, hypothyroidism, vasovagal, raised ICP, hypothermia)
  • Sick sinus syndrome
  • 2nd-degree block
  • Drug toxicity

Management — what will you do?

  • Atropine + external pacing for acute symptomatic episodes
  • Permanent pacemaker for chronic complete heart block or symptomatic sick sinus
  • Stop the offending drug; treat the cause

Atrial Fibrillation-2

Scenario. Usually elderly (>90% above 60) with rapid irregular atrial contraction and irregular ventricular response; 15% idiopathic. Cardiac causes: ischaemic heart disease, valvular (rheumatic) disease, cardiomyopathy, heart failure. Non-cardiac: hyperthyroidism, excess caffeine/energy drinks, cocaine and stimulants. Acute-onset AF is usually symptomatic; chronic AF often found incidentally. Valvular AF = valve disease or artificial valve.

History — what will you ask?

  • Palpitations, chest pain, dizziness/light-headedness, dyspnoea, syncope
  • exercise tolerance
  • precipitant screen — thyroid symptoms, caffeine/energy drinks, stimulant drugs
  • known valve disease, rheumatic fever, heart failure, cardiomyopathy
  • May be completely asymptomatic for a long time

Signs — what will you find?

  • Tachycardia with irregularly irregular pulse
  • sometimes normal or slow but still irregular rate
  • hypotension or chest pain = unstable
  • signs of pulmonary oedema (basal crackles)
  • signs of underlying cause — valve murmurs, thyromegaly, HF

Investigations — what will you order?

  • ECG: fast irregular rate, absent P waves, irregular baseline fibrillatory waves
  • Then search aetiology: serum electrolytes, thyroid function tests, 2-D echo for valve disease, drug toxicology (cocaine, amphetamines), plus CXR/coronary angiogram as indicated

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Thyrotoxicosis
  • electrolyte disturbance
  • stimulant/drug-induced
  • valvular vs non-valvular AF
  • other irregular tachycardias (atrial flutter, multifocal atrial tachycardia)
  • sinus arrhythmia

Management — what will you do?

  • Correct the underlying cause
  • Unstable → immediate DC shock (cardioversion)
  • Stable → two steps: rate control (1st beta-blocker or diltiazem/verapamil, not amlodipine; 2nd digoxin; last amiodarone) then rhythm control (chemical: ibutilide/amiodarone, or electrical)
  • Asymptomatic → rate control + warfarin for intracardiac clot prevention
  • persistent symptoms → antiarrhythmics

Cardiac Arrest-2

A. Shockable arrest — VF or pulseless VT

Scenario. Collapsed, unresponsive, pulseless and apnoeic patient whose monitor shows ventricular fibrillation or pulseless ventricular tachycardia — the rhythm to defibrillate immediately.

History — what will you ask?

  • Collapse, unresponsiveness; witnessed or unwitnessed
  • Preceding chest pain, palpitations or syncope
  • Bystander CPR and AED availability; time of collapse

Signs — what will you find?

  • Absence of pulse is the most reliable sign (carotid = gold standard)
  • No breathing, no BP; pupils dilating within 45 s
  • Cyanosed lips and nail beds; seizures may occur

Investigations — what will you order?

  • Continuous ECG — VF or pulseless VT
  • Hs and Ts screen — hypoxia, hypovolaemia, hydrogen ion, hypo/hyperkalaemia, hypothermia; thrombosis, tamponade, tension pneumothorax, toxins, trauma

DDx — what else could it be?

  • Asystole
  • PEA/EMD
  • Artifact or loose lead
  • Misdiagnosed pulse

Management — what will you do?

  • Recognise arrest → call help → CPR (DRSCABD) → early defibrillation/AED
  • Chest compressions, airway (head tilt–chin lift, jaw thrust if trauma), rescue breaths, advanced airway
  • ACLS drugs (amiodarone), therapeutic hypothermia, ECMO; treat reversible Hs and Ts
B. Non-shockable arrest — asystole or PEA

Scenario. Collapsed, pulseless patient with a flat line or organised electrical activity without a pulse — CPR and a hunt for the reversible cause, not a shock.

History — what will you ask?

  • Collapse; possible drowning, trauma, overdose, hypothermia
  • Recent MI or cardiac disease; dialysis patient; bleeding
  • Time of collapse; bystander CPR

Signs — what will you find?

  • No pulse, no breathing, no BP; pupils dilate within 45 s
  • Death-like appearance, cyanosis

Investigations — what will you order?

  • ECG — asystole or electrical activity without output
  • Hs and Ts work-up — the reversible causes
  • Glucose, potassium, ABG, echo (tamponade), CXR (pneumothorax)

DDx — what else could it be?

  • VF (fine VF may look flat)
  • PEA from any cause
  • Artifact

Management — what will you do?

  • CPR (DRSCABD) with minimal interruption
  • Treat the Hs and Ts — oxygen, fluids/blood, bicarbonate, calcium/insulin, warm, thrombectomy/thrombolysis, pericardiocentesis, needle decompression, antidotes
  • Atropine and artificial pacing for asystole; adrenaline per protocol

Pericarditis & Myocarditis

A. Acute pericarditis

Scenario. Young adult with sharp stabbing central chest pain radiating to the left shoulder, worse on deep breathing, coughing, swallowing and lying flat, relieved by sitting forward; a friction rub and diffuse ST elevation.

History — what will you ask?

  • Sharp pleuritic pain, radiation to the left shoulder, neck and back
  • Worse leaning down, breathing, coughing, swallowing; relieved sitting forward
  • Fever, dyspnoea
  • Recent viral illness, MI, chest injury, cardiac surgery, uraemia, autoimmune disease, drugs (INH, phenytoin, procainamide, hydralazine)

Signs — what will you find?

  • Pericardial friction rub
  • Weak, small-volume pulse; distended neck veins
  • Muffled heart sounds; fever

Investigations — what will you order?

  • ECG — universal ST elevation with concave-upward PR depression
  • Echo — effusion; CXR; cardiac CT/MRI; blood tests; biopsy if needed
  • Diagnostic criteria — chest pain, rub, ECG change, effusion on echo

DDx — what else could it be?

  • Myocardial infarction
  • Pulmonary embolism
  • Pneumothorax
  • Aortic dissection
  • Pneumonia

Management — what will you do?

  • NSAIDs + colchicine
  • Steroids for recurrent or autoimmune disease
  • Treat the cause; pericardiocentesis if a large effusion develops
B. Cardiac tamponade

Scenario. Adult who collapses with dyspnoea, hypotension and grossly raised JVP — acute heart failure from compression by a large pericardial effusion, complicating any pericarditis, malignancy, trauma or free-wall rupture after MI.

History — what will you ask?

  • Sudden collapse, dyspnoea
  • Chest pain or the features of the underlying cause
  • Recent MI, malignancy, trauma, uraemia

Signs — what will you find?

  • Tachycardia, hypotension, grossly elevated JVP
  • Soft heart sounds; pulsus paradoxus; Kussmaul’s sign
  • Cold peripheries, low output

Investigations — what will you order?

  • ECG; CXR; echo — RV collapse
  • Consider CT if echo is equivocal

DDx — what else could it be?

  • Tension pneumothorax
  • Massive PE
  • Cardiogenic shock of other cause
  • Constrictive pericarditis

Management — what will you do?

  • Emergency percutaneous pericardiocentesis — dramatic improvement
  • Fluid resuscitation while preparing drainage
C. Constrictive pericarditis

Scenario. Adult with fatigue, oedema and ascites whose heart is encased in a thick, fibrotic, calcified pericardium — after tuberculosis, haemopericardium, viral or purulent pericarditis, or rheumatoid arthritis.

History — what will you ask?

  • Fatigue and progressive exercise intolerance
  • Abdominal swelling and peripheral oedema
  • History of TB, pericarditis, cardiac surgery or rheumatoid arthritis

Signs — what will you find?

  • Rapid, low-volume pulse; elevated JVP with Kussmaul’s sign
  • Hepatomegaly, ascites, peripheral oedema
  • Pulsus paradoxus

Investigations — what will you order?

  • CXR (calcification); echocardiography; CT scan
  • Look for the cause — TB work-up, rheumatoid factor

DDx — what else could it be?

  • Cardiac tamponade
  • Restrictive cardiomyopathy
  • Cirrhosis with ascites
  • Nephrotic syndrome

Management — what will you do?

  • Diuretics — loop diuretic + spironolactone
  • Surgical resection of the diseased pericardium
D. Myocarditis

Scenario. Previously well adult with a viral prodrome who develops heart failure or cardiogenic shock — inflammation of the myocardium reducing pump function; higher risk in diabetes, HIV, ESRD, cancer chemotherapy, skin infection and chest injury.

History — what will you ask?

  • Viral prodrome then dyspnoea, fatigue, palpitations
  • Chest pain, oedema, syncope
  • Risk factors — DM, HIV/AIDS, ESRD, cancer therapy, skin infection, chest injury

Signs — what will you find?

  • Tachycardia, S3, signs of HF or cardiogenic shock
  • Arrhythmia; pericardial rub if pericarditis coexists

Investigations — what will you order?

  • ECG — non-specific changes
  • CXR — normal or cardiomegaly; echo — LV dysfunction
  • Troponin for severity; cardiac MRI is the best investigation; endomyocardial biopsy to confirm

DDx — what else could it be?

  • Myocardial infarction
  • Pericarditis
  • Cardiomyopathy
  • Sepsis with myocardial depression

Management — what will you do?

  • Supportive — treat failure and arrhythmias, avoid intense exertion
  • Specific antimicrobial therapy when a cause is found
  • No proven benefit from glucocorticoids or immunosuppression

Respiratory Disease (Pulmonology)

Bronchiectasis-2

Scenario. Adult with chronic daily cough and copious purulent, often foul-smelling sputum, haemoptysis, recurrent chest infections and dyspnoea/wheeze, from permanent abnormal bronchial dilatation after chronic infection and inflammation (vicious cycle of impaired clearance, bacterial colonisation, neutrophilic inflammation and protease/elastase destruction of the bronchial wall). Causes: post-infectious (TB, pneumonia, measles, pertussis), cystic fibrosis, primary ciliary dyskinesia/Kartagener, immune deficiency (hypogammaglobulinaemia, HIV), ABPA.

History — what will you ask?

  • Chronic cough with copious purulent sputum, haemoptysis, recurrent chest infections, dyspnoea and wheeze
  • childhood infections (measles, pertussis, TB, pneumonia)
  • CF features — young age, pancreatic insufficiency, malabsorption
  • Kartagener — sinusitis and situs inversus
  • ABPA — asthma and eosinophilia
  • recurrent bacterial infections suggesting immunodeficiency

Signs — what will you find?

  • Coarse inspiratory crepitations/crackles especially at the bases
  • wheeze and rhonchi
  • digital clubbing in advanced disease
  • signs of chronic hypoxia
  • nasal polyps and sinusitis in CF/Kartagener

Investigations — what will you order?

  • Sputum culture (Pseudomonas, H. influenzae, Staph aureus)
  • blood — immunoglobulin levels, CBC, eosinophils
  • CXR (tram-track opacities, ring shadows)
  • HRCT gold standard (signet ring sign)
  • CF testing — sweat chloride and genetic testing
  • ciliary function tests (nasal brush biopsy, electron microscopy)
  • Aspergillus-specific IgE/IgG for ABPA

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Post-infectious bronchiectasis
  • cystic fibrosis
  • primary ciliary dyskinesia/Kartagener
  • immunodeficiency
  • ABPA
  • COPD
  • tuberculosis
  • bronchial carcinoma

Management — what will you do?

  • Treat the cause (CF, ABPA, immunodeficiency)
  • vaccinate
  • smoking cessation
  • Airway clearance — chest physiotherapy (postural drainage, percussion, oscillatory devices), mucolytics (hypertonic saline, nebulised DNase in CF). Antibiotics for exacerbations (oral/IV by severity)
  • chronic Pseudomonas — long-term azithromycin or inhaled tobramycin
  • Macrolides for immunomodulation
  • corticosteroids only in ABPA
  • Surgery for localised uncontrolled disease
  • bronchial artery embolisation for massive haemoptysis
  • transplantation for advanced diffuse disease

Pulmonary embolism-2

A. Low-risk pulmonary embolism

Scenario. Haemodynamically stable adult with sudden dyspnoea and pleuritic pain, a positive CTPA, no RV strain and a low PESI — suitable for outpatient or early-discharge anticoagulation.

History — what will you ask?

  • Sudden dyspnoea, pleuritic pain, cough/haemoptysis
  • Risk factors — surgery, immobilisation, cancer, oestrogen, previous VTE
  • No syncope or hypotension

Signs — what will you find?

  • HR >100, RR >20, normal BP
  • Clear chest or pleural rub; unilateral calf swelling
  • No raised JVP or RV heave

Investigations — what will you order?

  • ECG — sinus tachycardia, S1Q3T3; CXR often normal
  • CTPA confirms; troponin and BNP normal
  • Wells/Geneva, PERC/YEARS; PESI/sPESI low

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Pneumonia
  • Pleurisy
  • Musculoskeletal pain
  • Anxiety

Management — what will you do?

  • DOAC — apixaban 10 mg BD ×7 d then 5 mg BD, or rivaroxaban 15 mg BD ×21 d then 20 mg daily
  • Warfarin with ≥5 d heparin overlap if DOAC unsuitable; LMWH for cancer/pregnancy
  • Outpatient or early discharge with follow-up; 3 months if provoked
B. Intermediate-risk pulmonary embolism

Scenario. Stable BP but RV strain on echo/CT or raised troponin/BNP — needs admission, monitoring and rescue reperfusion if deteriorating.

History — what will you ask?

  • Dyspnoea, pleuritic pain, syncope
  • Risk factors for VTE
  • No sustained hypotension

Signs — what will you find?

  • Tachycardia, tachypnoea, low SpO₂
  • Raised JVP, loud P2, RV heave
  • Signs of RV failure without shock

Investigations — what will you order?

  • CTPA; echo — RV dilation/strain; troponin and BNP raised
  • ECG — T inversion V1–V4, RBBB, S1Q3T3
  • PESI/sPESI intermediate-high

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Pneumonia
  • ACS
  • Aortic dissection
  • Pericarditis

Management — what will you do?

  • Anticoagulate; LMWH preferred to UFH; DOAC when stable
  • Close monitoring; rescue reperfusion if deterioration
  • PERT review; consider catheter-directed therapy
C. High-risk (massive) pulmonary embolism

Scenario. Adult in shock or arrest from PE — SBP <90 or a drop ≥40 mmHg for >15 minutes, with RV failure and obstructed pulmonary arteries.

History — what will you ask?

  • Sudden collapse, syncope, severe dyspnoea
  • Recent surgery, immobility, cancer, pregnancy
  • Chest pain, haemoptysis

Signs — what will you find?

  • Hypotension, cool peripheries, raised JVP
  • Tachycardia, hypoxia, loud P2, RV heave
  • Signs of arrest

Investigations — what will you order?

  • ECG — tachycardia, right-axis deviation, RBBB, S1Q3T3
  • Echo — RV strain/dilation; CTPA if stable enough
  • Troponin/BNP high; ABG hypoxaemia

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Cardiac tamponade
  • Tension pneumothorax
  • Acute MI
  • Aortic dissection

Management — what will you do?

  • Systemic alteplase 100 mg IV over 2 h
  • Catheter-directed lysis, aspiration thrombectomy, surgical embolectomy, VA-ECMO via PERT
  • IVC filter if anticoagulation contraindicated; treat shock

Gastroenterology and Hepatology

Cirrhosis Part 1

A. Compensated cirrhosis

Scenario. Adult with chronic liver disease found on routine review — spider naevi, palmar erythema and splenomegaly, but no ascites, bleeding or encephalopathy. Causes: alcohol, hepatitis B/C, NAFLD, PBC, autoimmune hepatitis, haemochromatosis, drugs, Wilson, α1-antitrypsin deficiency.

History — what will you ask?

  • Alcohol intake and duration; hepatitis risk — transfusion, tattoos, IV drugs
  • Metabolic risk — obesity, diabetes, high-fat diet; drugs (methotrexate)
  • Family history; fatigue, weight loss, pruritus

Signs — what will you find?

  • Spider naevi, gynaecomastia, loss of axillary hair
  • Clubbing, leuconychia, palmar erythema, Dupuytren’s contracture
  • Splenomegaly; liver enlarged or small; no ascites

Investigations — what will you order?

  • CBC, LFTs, albumin (low), PT/INR (high)
  • Ultrasound; AFP; viral serology
  • Aetiology — AST >2× ALT (alcohol), HBsAg/HCV Ab, AMA, ANA/ASMA, iron studies, ceruloplasmin, α1-antitrypsin
  • Child-Turcotte-Pugh for prognosis

DDx — what else could it be?

  • Chronic alcoholism
  • Chronic hepatitis B/C
  • NAFLD
  • PBC
  • Autoimmune hepatitis
  • Haemochromatosis
  • Drug-induced
  • Wilson

Management — what will you do?

  • Nutrition and multivitamins; treat the cause; stop alcohol; avoid NSAIDs and sleeping pills
  • Screen for HCC 6-monthly with ultrasound + AFP
  • Portal hypertension — propranolol/beta-blocker; variceal ligation; transplant in selected cases
B. Decompensated cirrhosis

Scenario. Known cirrhotic presenting with ascites, jaundice, haematemesis, confusion or oliguria — the complications of portal hypertension and liver failure.

History — what will you ask?

  • Abdominal swelling, leg oedema, easy bruising
  • Haematemesis or melena; confusion and disturbed sleep pattern
  • Fever, abdominal pain (spontaneous bacterial peritonitis); reduced urine output

Signs — what will you find?

  • Distended abdomen, caput medusae, shifting dullness, fluid thrill
  • Hepatomegaly or a small liver; splenomegaly; pedal oedema
  • Asterixis (grades 1–4); jaundice; scratch marks

Investigations — what will you order?

  • Diagnostic paracentesis (cell count, culture, albumin); ascitic fluid neutrophil count for SBP
  • LFTs, albumin, INR, renal function, electrolytes
  • Endoscopy for varices; ultrasound/Doppler of portal vein
  • AFP and imaging for HCC

DDx — what else could it be?

  • Variceal bleed
  • Portal vein thrombosis
  • Budd-Chiari
  • Nephrotic syndrome
  • Heart failure
  • Peritoneal TB

Management — what will you do?

  • Variceal bleed — resuscitate, IV octreotide, banding/sclerotherapy, prophylactic ceftriaxone; beta-blocker for prevention
  • Encephalopathy — lactulose, rifaximin/neomycin/Flagyl, treat precipitants (bleed, hypokalaemia, constipation, sedatives, protein load, SBP), hold protein briefly
  • Hepatorenal syndrome — dialysis and transplant; ascites — salt restriction, diuretics, paracentesis

Cirrhosis Part 2

A. Primary biliary cholangitis (PBC)

Scenario. Middle-aged woman with years of itching and fatigue followed by jaundice; a cholestatic picture with a diagnostic antimitochondrial antibody and xanthelasma.

History — what will you ask?

  • Pruritus (often first), jaundice, fatigue
  • Dry eyes and mouth; weight loss, steatorrhoea
  • Associated autoimmune disease

Signs — what will you find?

  • Xanthelasma, jaundice, scratch marks
  • Hepatosplenomegaly; signs of cirrhosis

Investigations — what will you order?

  • AMA positive (diagnostic)
  • Alkaline phosphatase and bilirubin very high — obstructive pattern; AST/ALT minimally raised
  • High serum cholesterol; biopsy — destruction of intrahepatic ducts

DDx — what else could it be?

  • Primary sclerosing cholangitis
  • Cholangiocarcinoma
  • Drug-induced cholestasis
  • Gallstones

Management — what will you do?

  • No cure except transplant — ursodeoxycholic acid
  • Pruritus — cholestyramine, antihistamines, rifampicin
  • Vitamins A, D, E; monitor progression
B. Haemochromatosis

Scenario. Adult with cirrhosis, diabetes, bronzed skin, joint pain and fatigue — genetic (C282Y) iron overload deposited in liver, pancreas, skin, heart, joints, brain and testes.

History — what will you ask?

  • Fatigue, arthralgia, loss of libido
  • Symptoms of diabetes; skin darkening
  • Family history; palpitations (cardiomyopathy)

Signs — what will you find?

  • Grey/bronze discoloration of cheeks, chin and nose
  • Hepatomegaly, arthropathy, testicular atrophy
  • Signs of diabetes, cardiomyopathy, cirrhosis

Investigations — what will you order?

  • Serum ferritin and iron high, transferrin saturation high
  • Liver biopsy and genetic analysis (C282Y) — gold standards
  • Screen family members

DDx — what else could it be?

  • Alcoholic liver disease
  • NAFLD
  • PBC
  • AIH
  • Diabetes of other cause

Management — what will you do?

  • Repeated phlebotomy — first choice, lifelong
  • Deferoxamine if phlebotomy not possible
  • Screen relatives; treat diabetes and cardiac disease
C. Autoimmune hepatitis

Scenario. Woman with fatigue, jaundice and myalgia, or an incidental transaminitis — autoantibody-mediated hepatitis that can present acutely or as established cirrhosis; more common in females with other autoimmune disease.

History — what will you ask?

  • Fatigue, jaundice, anorexia, myalgia
  • Other autoimmune disease — Graves, thyroid, coeliac, rheumatoid arthritis
  • Family history

Signs — what will you find?

  • Jaundice, hepatomegaly
  • Stigmata of chronic liver disease if cirrhotic
  • Signs of other autoimmune disease

Investigations — what will you order?

  • ALT/AST much higher than ALP (hepatocellular pattern)
  • High serum globulins; anti-SLA, ANA, ASMA (type 1), anti-LKM1 (type 2)
  • Biopsy — piecemeal necrosis with lymphocytic infiltration

DDx — what else could it be?

  • Viral hepatitis
  • Drug-induced hepatitis
  • Wilson’s disease
  • PBC
  • Haemochromatosis

Management — what will you do?

  • Prednisone alone, or prednisone + azathioprine; treat a year then taper
  • Lifelong in most; relapse after stopping is frequent
  • Transplant for end-stage cirrhosis — cirrhosis is not reversible

CELIAC DISEASE-2

Scenario. Genetically susceptible patient (HLA-DQ2/DQ8 — risk markers, not confirmatory) with malabsorption of nutrients from immune reaction against gluten (wheat, rye, barley — including khubus), causing intestinal mucosal inflammation with villous atrophy and excess lymphocytes. Onset in childhood when solids start, or in adult life; many are asymptomatic (silent disease, ~40% antibody-positive). Presentation is usually abdominal pain, gas and chronic diarrhoea after eating wheat, with features of protein, fat, carbohydrate, vitamin and mineral deficiency.

History — what will you ask?

  • Chronic diarrhoea after wheat, abdominal pain, gas, bloating
  • weight loss and muscle wasting
  • steatorrhoea
  • bone pain and fractures
  • bleeding tendency (epistaxis, bruising)
  • paraesthesias and cramps
  • lactose intolerance (bloating, cramps, diarrhoea after milk)
  • reduced fertility
  • itchy blistering rash
  • family history
  • other autoimmune disease

Signs — what will you find?

  • Wasted, growth-retarded child or adult
  • low BMI, muscle wasting
  • pallor
  • Chvostek’s sign (tap below and in front of ear → facial twitching) and Trousseau’s sign (BP cuff inflated 1–4 min → carpal spasm in palmar flexion) for hypocalcaemia
  • bruising
  • dermatitis herpetiformis — very itchy vesicles on extensor surfaces of limbs, elbows, front of knees, gluteal area, hairline and scalp, symmetrical

Investigations — what will you order?

  • Serology first: tTG IgA (first test, high sensitivity/specificity) plus total serum IgA
  • if IgA deficient — tTG IgG or endomysial antibody
  • then duodenal bulb or jejunal biopsy — villous atrophy with inflammation (confirmatory)
  • Other: CBC (anaemia), Ca and Mg low, DEXA for osteoporosis, PT/INR high, serum albumin low, iron studies low
  • Patient must be eating gluten before serology

DDx — what else could it be?

  • Any malabsorption syndrome — lactose intolerance, intestinal bacterial overgrowth, IBD, chronic pancreatitis, giardiasis, IgA deficiency, tropical sprue

Management — what will you do?

  • Gluten-free diet (no wheat, barley, rye) is the only curative treatment — symptoms improve within weeks, antibodies disappear, mucosa normalises
  • If osteoporosis has developed, lifetime calcium and vitamin D. Prognosis excellent on diet
  • restarting gluten returns all problems, raises antibody levels and damages the mucosa again
  • Complications: small bowel carcinoma and lymphoma (rare)

Endocrinology and Metabolism

Acromegaly

Scenario. Adult with excess GH secretion, usually from a pituitary macroadenoma (>10 mm), either solitary or part of MEN type 1; rarely ectopic hormone from small-cell bronchial cancer or carcinoid, or hypothalamic GHRH. GH stimulates hepatic IGF-1, producing progressive acral and soft-tissue overgrowth, metabolic and cardiovascular disease, and mass effect on the optic chiasm.

History — what will you ask?

  • Headache, visual field loss (bitemporal), excessive sweating, increase in ring and shoe size, skin tags, deepening voice, arthralgia, snoring/obstructive sleep apnoea, carpal tunnel symptoms, proximal weakness, symptoms of diabetes and hypertension, loss of libido, fatigue
  • family history of MEN 1 or pituitary disease

Signs — what will you find?

  • Frontal bossing and deepened supraorbital ridges, enlarged nose, enlarged lower lip, prognathism with lower-jaw overbite, widened teeth spacing, goitre (usually euthyroid), acanthosis nigricans, cardiomegaly, gynaecomastia, hepatosplenomegaly, lower-limb oedema from heart failure, bitemporal visual loss, hypertension

Investigations — what will you order?

  • Prove excess GH — GH not suppressed to <1 after 75 g glucose, high IGF-1
  • cause — serum calcium (MEN 1), MRI pituitary, CT chest/abdomen for ectopic source
  • complications — HbA1c and BP, perimetry and fundoscopy, echo, NCS for carpal tunnel, knee X-ray (joint narrowing, chondrocalcinosis), MRI spine, colonoscopy every 5 years, sleep studies, other pituitary hormones
  • Death from cardiovascular complications and colorectal cancer

DDx — what else could it be?

  • Pituitary macroadenoma (solitary or part of MEN 1)
  • Ectopic GH secretion (small-cell bronchial cancer, carcinoid)
  • Hypothalamic GHRH secretion (very rare)

Management — what will you do?

  • Transsphenoidal tumour resection first-line (transfrontal if very large)
  • complications include panhypopituitarism and encephalitis
  • Medical suppression of GH — somatostatin analogues (octreotide; gallstones), dopamine agonists (bromocriptine; valvulopathy, retroperitoneal fibrosis), GH receptor blocker pegvisomant (GH level remains high)
  • Radiation therapy only after failure of other methods (cognitive decline, cranial nerve palsies, panhypopituitarism)

Panhypopituitarism

Scenario. Adult with deficiency of all anterior pituitary hormones from a non-functioning pituitary adenoma, post-surgery, infiltration (TB, sarcoidosis, haemochromatosis, histiocytosis X), pituitary infarction (Sheehan syndrome), pituitary apoplexy (haemorrhage) or empty sella. Deficiency of GH, gonadotrophins, TSH and ACTH produces a predictable sequence of features depending on whether onset precedes or follows puberty.

History — what will you ask?

  • Fatigue, short stature (if before puberty), menstrual disturbance/amenorrhoea, loss of libido, infertility, breast atrophy, testicular atrophy, gynaecomastia, cold intolerance and hypothyroid symptoms, postural dizziness and hypoglycaemia, weight loss, visual field loss and headache, obstetric haemorrhage (Sheehan), history of pituitary surgery or apoplexy

Signs — what will you find?

  • Short stature
  • delayed or absent puberty
  • amenorrhoea, breast atrophy
  • testicular atrophy and gynaecomastia
  • alabaster (pale) skin with reduced pigmentation
  • hypotension and postural drop
  • hyponatraemia and hypoglycaemia
  • weight loss

Investigations — what will you order?

  • Blood — pituitary hormones, baseline hypoglycaemic (insulin tolerance) test (no rise in GH/ACTH in response to hypoglycaemia is diagnostic), target hormones (oestrogen, T4/T3, cortisol)
  • potassium usually normal because RAAS functions
  • iron profile
  • MRI pituitary
  • CT chest and abdomen for TB/sarcoidosis

DDx — what else could it be?

  • Polyglandular failure (Schmidt and Carpenter syndrome) — hypoadrenalism, hypothyroidism and type 1 diabetes; hypopituitarism instead shows weight loss, low glucose and reduced pigmentation

Management — what will you do?

  • Replacement of target hormones — 1) cortisone + compression stockings, 2) thyroxine, 3) sex hormones or gonadotrophins if fertility is required, 4) desmopressin if craniogenic diabetes insipidus develops, 5) GH only if intractable fatigue persists despite adequate cortisol and thyroxine

Hematology and Oncology

Acute Lymphoblastic Leukemia

Scenario. Child (peak 2–5 years; second peak above 50) with malignancy of lymphoblasts that do not mature into B and T lymphocytes; increased risk in Down’s syndrome. Leukemic cells infiltrate the marrow and replace RBCs, WBCs and platelets, then spread to blood and other organs. Acute leukaemias arise from precursors, progress rapidly and kill within weeks to months if untreated.

History — what will you ask?

  • Fatigue and weakness, fever (most common presentation), recurrent infections, bleeding and easy bruising, bone pain, headache and cranial nerve palsies (CNS involvement), neck lumps and abdominal fullness
  • Down’s syndrome
  • family history

Signs — what will you find?

  • Pallor, petechiae/purpura and bruising, fever, tachycardia and systolic murmur
  • lymphadenopathy, hepatomegaly, splenomegaly
  • gum hypertrophy
  • cranial nerve palsies and papilloedema
  • signs of anaemia or infection

Investigations — what will you order?

  • CBC — anaemia, low platelets, very high WBC with lymphoblasts
  • peripheral smear — excess lymphoblasts (large abnormal cells, large nucleus and scanty cytoplasm)
  • bone marrow biopsy — >30% lymphoblasts
  • flow cytometry — TdT positive
  • CT scan after diagnosis for metastases
  • Intrathecal chemotherapy for CNS prophylaxis

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • AML (Auer rods, >20% myeloblasts, older adults)
  • CLL (mature lymphocytes, smudge cells, elderly)
  • lymphoblastic lymphoma
  • aplastic anaemia
  • infectious mononucleosis
  • ITP

Management — what will you do?

  • Chemotherapy — vincristine, dexamethasone, asparaginase, daunorubicin, cytarabine (“Very Dark And Dirty Clothes”) via port-a-cath in three phases: induction (remission), consolidation (reduce residual), maintenance 2–3 years (oral methotrexate, mercaptopurine, vincristine, prednisone). Intrathecal cytarabine + methotrexate (sometimes radiotherapy) for CNS prophylaxis
  • stem cell transplant if relapse
  • gene therapy
  • local radiotherapy for bone pain
  • Cure ~90% in children, ~30% in adults

Acute Myeloid Leukemia

Scenario. Adult with malignancy of myeloblasts from the myeloid stem cell; genetic damage causes excess abnormal myeloblasts that accumulate in marrow, blood and organs. Risk factors: myelodysplastic syndrome, prior chemotherapy, radiation exposure, Down’s syndrome (10–18 times higher risk for both AML and ALL). Acute course, fatal within months if untreated; may be asymptomatic and found on routine blood tests.

History — what will you ask?

  • Fatigue and weakness (anaemia), fever and infections (low WBC), bruising and bleeding (low platelets), bone pain, gum swelling, weight loss
  • prior MDS, chemotherapy or radiotherapy
  • Down’s syndrome
  • older age

Signs — what will you find?

  • Pallor, petechiae/purpura, fever
  • hepatomegaly, splenomegaly, lymphadenopathy
  • gum hypertrophy
  • CNS involvement
  • signs of anaemia, infection or bleeding

Investigations — what will you order?

  • CBC — very high WBC (mostly myeloblasts), anaemia, low platelets (rarely normal or low WBC)
  • peripheral smear — myeloblasts with Auer rods (“Professor AMaL beats with RODS”)
  • bone marrow — >20% immature myeloblasts with reduced other lines
  • flow cytometry for abnormal surface antigens
  • cytogenetics for prognosis and treatment choice

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • ALL (lymphoblasts, TdT positive, children)
  • CML (Philadelphia chromosome, mature myeloid cells, massive spleen)
  • MDS
  • aplastic anaemia
  • acute promyelocytic leukaemia

Management — what will you do?

  • Pathology curable depending on chromosome pattern. Treat anaemia, thrombocytopenia and infection before chemotherapy. Chemotherapy — cytarabine + daunorubicin, induction by the “7+3” pattern (7 days IV cytarabine, first 3 days IV daunorubicin) to achieve remission
  • consolidation with high-dose cytarabine
  • Stem cell transplant if chemotherapy fails or relapse
  • Prognosis poor if secondary to MDS, radiation or chemotherapy, with adverse cytogenetics, or age >60

Chronic Lymphocytic Leukemia

Scenario. Elderly patient (usually above 50) with malignancy of B lymphocytes that look normal but cannot produce antibodies; slow-growing and may be asymptomatic for years. Leukemic cells infiltrate marrow, replace RBCs, platelets and other WBCs, then spread to blood and organs. Split into acute (precursors, rapid, blasts) versus chronic (mature cells, slow) leukaemias by cell line.

History — what will you ask?

  • Asymptomatic with incidental high WBC on routine CBC
  • lymph node enlargement
  • abdominal fullness (hepatosplenomegaly)
  • fatigue and weakness (anaemia)
  • recurrent infections (non-functional B lymphocytes)
  • bleeding (low platelets)

Signs — what will you find?

  • Lymphadenopathy, hepatomegaly, splenomegaly
  • pallor
  • petechiae/ecchymoses
  • fever
  • signs of infection
  • features of autoimmune haemolysis

Investigations — what will you order?

  • CBC — very high lymphocyte count with low RBCs and platelets
  • peripheral smear — excess B lymphocytes and smudge cells (damaged B lymphocytes from slide preparation)
  • bone marrow — excess B lymphocytes
  • flow cytometry — abnormal B lymphocytes
  • RAI staging (0 lymphocytosis only; 1 + nodes; 2 + hepatosplenomegaly; 3 + anaemia; 4 + thrombocytopenia)
  • Features of autoimmune haemolysis (antibodies destroying red cells and platelets)

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • AML/ALL
  • CML
  • follicular lymphoma
  • mantle cell lymphoma
  • infectious lymphocytosis
  • reactive lymphadenopathy
  • Waldenström macroglobulinaemia

Management — what will you do?

  • No treatment in early stage 0–1 — it does not improve survival and many lead normal active lives
  • Chemotherapy for advanced disease — chlorambucil, cyclophosphamide, fludarabine (“Chocolate Cake From Riyadh”)
  • rituximab monoclonal antibody
  • tyrosine kinase inhibitors
  • stem cell transplant if poor response
  • Anaemia and thrombocytopenia from marrow infiltration or autoimmune haemolysis

Chronic Myeloid Leukemia

Scenario. Middle-to-old-aged patient (around 55, rare in children, slightly more in males) with excess mature but functionally abnormal myeloid cells (neutrophils, basophils, eosinophils); slow insidious onset with the Philadelphia chromosome / bcr-abl gene. Three phases: chronic (initial, lasts 3–4 years untreated), accelerated (fast-rising WBC), blast crisis (behaves like acute leukaemia, rapid death). Accounts for 8% of leukaemias in the UK.

History — what will you ask?

  • Asymptomatic with high WBC on routine CBC
  • fatigue, weakness, weight loss, fever, night sweats, recurrent infections
  • abdominal heaviness from huge spleen
  • early satiety
  • bleeding
  • symptoms of anaemia

Signs — what will you find?

  • Massive splenomegaly, hepatomegaly, lymphadenopathy
  • pallor
  • fever
  • bruising/bleeding
  • signs of infection

Investigations — what will you order?

  • Blood — very high WBC (often ~150,000) with high neutrophils, basophils and eosinophils, low Hb and platelets (may be normal)
  • bone marrow — hypercellular with excess myeloid series
  • cytogenetics — Philadelphia chromosome / bcr-abl gene
  • FBC monitoring of response

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • AML (acute, blasts, Auer rods)
  • CLL (lymphocytes, smudge cells)
  • leukaemoid reaction
  • myeloproliferative neoplasms (polycythaemia vera, myelofibrosis, essential thrombocythaemia)
  • MDS

Management — what will you do?

  • Chronic phase — imatinib (tyrosine kinase inhibitor), introduced 1999/2000, response in >95%, given for 2 years and repeatable on relapse. Accelerated and blast phase — treat like acute leukaemia with aggressive chemotherapy plus imatinib
  • Bone marrow/stem cell transplant
  • Prognosis greatly improved with TKIs

Polycythemia-2

A. Polycythaemia vera

Scenario. Adult over 50 with headache, dizziness, visual blurring, facial plethora, itching after a hot shower and splenomegaly — a myeloproliferative marrow tumour with JAK2 mutation raising RBCs, WBCs and platelets; EPO is suppressed.

History — what will you ask?

  • Headache, vertigo, blurred vision
  • Intense itching after a hot shower
  • Burning hands and feet (erythromelalgia); peptic ulcer symptoms
  • Thrombotic events — stroke, MI, DVT

Signs — what will you find?

  • Plethoric facial redness and hyperaemic conjunctiva
  • Splenomegaly
  • Signs of thrombosis or peptic ulcer; erythromelalgia
  • Gout

Investigations — what will you order?

  • CBC — high Hb/Hct and RBCs, WBC and platelets also raised
  • EPO low; JAK2 mutation
  • Hypercellular marrow; diagnostic criteria — Hb >16.5 g/dL male, >16 g/dL female; Hct >49% male, >48% female

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Secondary polycythaemia
  • Relative polycythaemia
  • CML
  • Essential thrombocythaemia
  • Myelofibrosis

Management — what will you do?

  • No cure — target Hct <45% male, <42% female
  • Phlebotomy lifelong; hydroxyurea, interferon, anagrelide, JAK2 inhibitors
  • Aspirin for itching and erythromelalgia; allopurinol to prevent gout
B. Secondary polycythaemia

Scenario. Adult with raised RBCs and high erythropoietin — an appropriate response to chronic hypoxia (altitude, COPD, cyanotic congenital heart disease, smoking) or an EPO-secreting tumour (renal cell carcinoma).

History — what will you ask?

  • Headache, dizziness, blurred vision; facial redness
  • Chronic lung disease, smoking, high altitude
  • Flank pain or haematuria (renal tumour)

Signs — what will you find?

  • Plethora, conjunctival injection
  • Splenomegaly absent (unlike vera)
  • Signs of the underlying cause — cyanosis, clubbing, COPD

Investigations — what will you order?

  • CBC — high Hb/Hct and RBCs, normal WBC and platelets
  • EPO high; no JAK2 mutation
  • CXR, ABG, echo (cyanotic heart disease); renal imaging; carboxyhaemoglobin

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Polycythaemia vera
  • Relative polycythaemia
  • EPO-secreting tumour
  • Smoking-induced

Management — what will you do?

  • Treat the cause — oxygen, stop smoking, correct the cardiac lesion
  • Resect an EPO-secreting tumour
  • Phlebotomy only if symptomatic or Hct very high; aspirin if thrombotic risk

Multiple Myeloma

Scenario. Older patient (60 and above) with malignancy of plasma cells producing abnormal IgG/IgA paraprotein and excess light chains (Bence-Jones proteins). Marrow is replaced (anaemia, low platelets, low WBC), osteoclasts activated (bone pain, fractures, hypercalcaemia), blood thickened (hyperviscosity) and light chains deposited in the glomerulus as amyloid causing nephrotic syndrome. MGUS is the related premalignant state (<10% plasma cells, paraprotein <3 g/L, no organ damage).

History — what will you ask?

  • Low back pain is the most common symptom
  • bone pain and fractures
  • fever, weight loss, weakness
  • recurrent infections
  • symptoms of anaemia and bleeding
  • symptoms of hypercalcaemia (mental status change, constipation, polyuria)
  • renal failure
  • hyperviscosity — headache, dizziness, vertigo, blurred vision
  • symptoms of spinal cord compression

Signs — what will you find?

  • Pallor, petechiae
  • bone tenderness especially spine, skull and long bones
  • deformity or cord compression signs
  • hepatosplenomegaly
  • signs of hypercalcaemia
  • signs of renal failure
  • fever

Investigations — what will you order?

  • CBC (anaemia, low platelets/WBC)
  • high ESR
  • high serum calcium
  • SPEP — very high IgG/IgA paraprotein with high gamma globulins
  • UPEP — Bence-Jones proteins
  • beta-2 microglobulin high
  • X-rays — multiple lytic “rain drop” lesions in spine, skull and long bones plus fractures
  • bone CT/MRI better than X-ray, bone scan not helpful
  • bone marrow biopsy — >10% plasma cells

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • MGUS
  • smouldering myeloma
  • Waldenström macroglobulinaemia
  • bone metastases
  • osteoporosis
  • primary hyperparathyroidism
  • renal failure of other cause
  • amyloidosis

Management — what will you do?

  • Chemotherapy combinations — lenalidomide (immunomodulator), proteasome inhibitors, dexamethasone, monoclonal antibodies, melphalan
  • stem cell transplant after aggressive combination chemotherapy
  • Supportive: local radiotherapy for bone pain, transfusion for anaemia, prompt treatment of infection, bisphosphonates routinely to prevent fractures, treat hypercalcaemia, surgery for vertebral fracture
  • Prognosis improving
  • most survive 7–10 years
  • usually not curable

Anemia

A. Iron deficiency anaemia

Scenario. Woman with fatigue, pallor and pica, or an older man with anaemia — microcytic red cells, low ferritin, koilonychia and angular cheilitis; blood loss is the usual cause (menorrhagia, GI bleeding).

History — what will you ask?

  • Fatigue, lethargy, headache, dizziness, tinnitus
  • Heavy menses; GI bleeding; NSAIDs; diet, pregnancy
  • Pica, restless legs; family history of anaemia

Signs — what will you find?

  • Pale conjunctiva and oral mucosa, nail pallor
  • Koilonychia, brittle nails; angular cheilitis
  • Glossitis; tachycardia and systolic murmur

Investigations — what will you order?

  • CBC — microcytic, hypochromic; low ferritin, low iron, high TIBC
  • Reticulocytes low
  • Find the source — endoscopy/colonoscopy, coeliac serology; stool occult blood

DDx — what else could it be?

  • Thalassaemia (normal/high ferritin, family history)
  • Anaemia of chronic disease
  • Sideroblastic anaemia
  • Lead poisoning

Management — what will you do?

  • Oral or IV iron replacement
  • Treat the source of blood loss
  • Transfuse only if severe or symptomatic
B. Megaloblastic anaemia (B12 / folate)

Scenario. Adult with fatigue, macrocytosis, glossitis and, with B12 deficiency, peripheral neuropathy or subacute combined degeneration — from dietary lack, pernicious anaemia, malabsorption or drugs.

History — what will you ask?

  • Fatigue, breathlessness, sore tongue
  • Paraesthesiae, unsteadiness, memory change (B12)
  • Diet (vegan), alcohol, pregnancy, metformin, PPIs, gastrectomy, coeliac, ileal disease

Signs — what will you find?

  • Glossitis; pallor; mild jaundice (ineffective erythropoiesis)
  • Peripheral neuropathy and subacute combined degeneration (B12)
  • Posterior column signs — vibration and proprioception loss

Investigations — what will you order?

  • CBC — macrocytic (MCV high), hypersegmented neutrophils
  • B12 and folate levels; methylmalonic acid if borderline
  • Antibody to intrinsic factor/parietal cells; endoscopy for pernicious anaemia
  • Bone marrow — megaloblastic change

DDx — what else could it be?

  • Alcohol
  • Hypothyroidism
  • Liver disease
  • Myelodysplasia
  • Drugs (methotrexate, phenytoin)
  • Reticulocytosis

Management — what will you do?

  • IM hydroxocobalamin or oral B12, oral folic acid
  • Treat the cause
  • Never give folate alone in B12 deficiency — it can precipitate neurological damage
C. Haemolytic anaemia

Scenario. Patient with anaemia, jaundice and splenomegaly, dark urine and a high reticulocyte count — red-cell destruction from autoimmune antibodies, G6PD deficiency, membrane defects or microangiopathy.

History — what will you ask?

  • Jaundice, dark urine, fatigue
  • Drug or fava-bean trigger (G6PD); family history (spherocytosis)
  • Recent transfusion, infection, lymphoma; prosthetic valve

Signs — what will you find?

  • Jaundice, splenomegaly, pallor
  • Leg ulcers (sickle); gallstones
  • Signs of the trigger

Investigations — what will you order?

  • Reticulocytes high; bilirubin (unconjugated) high; LDH high; haptoglobin low
  • Coombs test (autoimmune); blood film — spherocytes, schistocytes (MAHA)
  • G6PD assay; Hb electrophoresis; osmotic fragility

DDx — what else could it be?

  • Autoimmune haemolysis (warm/cold)
  • G6PD deficiency
  • Hereditary spherocytosis/elliptocytosis
  • MAHA (DIC, malignant hypertension, pre-eclampsia, vasculitis, mechanical valve)
  • Thalassaemia

Management — what will you do?

  • Treat the cause; stop the drug
  • Autoimmune — steroids, immunosuppressants; splenectomy if indicated
  • Transfuse for severe anaemia; folate supplementation
D. Sickle cell disease

Scenario. Young patient of African or Mediterranean origin with chronic haemolytic anaemia, recurrent painful crises, jaundice and splenomegaly — autosomal recessive HbS; vaso-occlusion drives the crises.

History — what will you ask?

  • Recurrent severe bone or abdominal pain (vaso-occlusive crisis)
  • Dactylitis in infancy; acute chest syndrome; priapism
  • Chronic anaemia, jaundice, gallstones, leg ulcers
  • Family history; consanguinity

Signs — what will you find?

  • Pallor, jaundice, splenomegaly (autosplenectomy in older patients)
  • Leg ulcers; signs of acute chest syndrome
  • Signs of stroke or aplastic crisis

Investigations — what will you order?

  • Blood film — sickle cells, target cells; sickling test
  • Hb electrophoresis — diagnostic
  • CBC, reticulocytes, bilirubin, LDH, haptoglobin
  • Screen family members; transcranial Doppler in children

DDx — what else could it be?

  • Iron deficiency
  • Thalassaemia
  • G6PD deficiency
  • Autoimmune haemolysis
  • Hereditary spherocytosis

Management — what will you do?

  • Hydroxyurea, folic acid
  • Blood transfusion/exchange transfusion for severe or acute chest syndrome; hydration and analgesia for crises
  • Penicillin prophylaxis and pneumococcal vaccination; transplant in selected cases
E. Thalassaemia

Scenario. Child or adult of Mediterranean, Middle Eastern or Asian origin with microcytic anaemia out of proportion to iron deficiency, jaundice, splenomegaly and frontal bossing — a quantitative globin-chain defect (autosomal recessive).

History — what will you ask?

  • Chronic anaemia, fatigue, poor growth
  • Jaundice, gallstones; abdominal fullness
  • Family history; transfusion history; iron chelation

Signs — what will you find?

  • Pallor, jaundice, splenomegaly, hepatomegaly
  • Frontal bossing, maxillary hypertrophy (thalassaemic facies)
  • Signs of iron overload — bronzed skin, diabetes, cardiomyopathy

Investigations — what will you order?

  • CBC — microcytic, target cells; reticulocytes raised
  • Hb electrophoresis — diagnostic (↑HbF, ↑HbA2 in β-thalassaemia)
  • Iron studies — ferritin high with transfusions
  • Family screening and genetic counselling

DDx — what else could it be?

  • Iron deficiency (low ferritin)
  • Sickle cell disease
  • Anaemia of chronic disease
  • Sideroblastic anaemia
  • Lead poisoning

Management — what will you do?

  • Regular blood transfusion to suppress ineffective erythropoiesis
  • Iron chelation — deferoxamine, deferasirox
  • Splenectomy if hypersplenism; transplant curative in selected patients
F. Marrow failure and pancytopenia

Scenario. Adult with fatigue, infections and bruising — pancytopenia with low reticulocytes, from aplastic anaemia, marrow infiltration (leukaemia, myeloma, metastases), myelodysplasia or drugs.

History — what will you ask?

  • Fatigue (anaemia), fever/infections (neutropenia), bruising (thrombocytopenia)
  • Drugs, radiation, toxins; viral hepatitis
  • Weight loss, bone pain

Signs — what will you find?

  • Pallor, petechiae/purpura, oral ulcers, fever
  • Lymphadenopathy, hepatosplenomegaly (infiltration)
  • Gum hypertrophy (leukaemia); sternal tenderness

Investigations — what will you order?

  • CBC with differential and reticulocyte count (low)
  • Bone marrow biopsy — indicated in unexplained pancytopenia
  • Cytogenetics/flow cytometry; B12, folate, viral screen; LFTs and ultrasound

DDx — what else could it be?

  • Aplastic anaemia
  • Acute leukaemia
  • Myelodysplasia
  • Marrow infiltration by tumour
  • Hypersplenism
  • B12/folate deficiency

Management — what will you do?

  • Treat the cause — stop the drug, treat infection
  • Transfuse red cells and platelets as needed; growth factors
  • Allogeneic stem cell transplant for aplastic anaemia in the young; immunosuppression if not eligible
G. Anaemia of chronic disease and acute blood loss

Scenario. Two common anaemias: the normocytic anaemia of chronic disease (CKD, inflammation, malignancy) and acute blood loss, where haemoglobin is initially normal and falls after a day or two as water is retained.

History — what will you ask?

  • Chronic disease — CKD, rheumatoid arthritis, cancer, infection
  • Acute bleeding — trauma, GI bleed, menorrhagia, surgery
  • Fatigue, dizziness; bleeding history

Signs — what will you find?

  • Pallor; signs of the chronic disease (uraemia, synovitis, cachexia)
  • Tachycardia, postural drop in acute loss
  • Signs of the bleeding source

Investigations — what will you order?

  • CBC — normocytic; reticulocytes low in chronic disease, high after acute loss
  • Iron studies (low iron, low TIBC, normal/high ferritin); creatinine
  • Cross-match; look for the bleeding source

DDx — what else could it be?

  • Iron deficiency
  • Thalassaemia
  • Haemolysis
  • Marrow disease

Management — what will you do?

  • Acute loss — resuscitate, cross-match and transfuse, stop the bleeding
  • Chronic disease — treat the underlying disease; erythropoietin for anaemia of CKD; iron if deficient
  • Avoid unnecessary transfusion

Rheumatology and Connective Tissue Diseases

Gout

A. Acute gout

Scenario. Adult man, often obese, woken by an exquisitely painful, red, hot, swollen first metatarsophalangeal joint; uric acid may be normal, so joint fluid is the diagnostic test.

History — what will you ask?

  • Sudden severe monoarthritis, most often the big toe; also ankle, knee, wrist
  • Precipitants — infection, fasting, alcohol, red meat/liver/kidneys, surgery, drugs
  • Previous attacks; renal stones; diuretics, aspirin

Signs — what will you find?

  • Hot, red, swollen, exquisitely tender joint
  • Low-grade fever possible
  • No tophi in a first attack

Investigations — what will you order?

  • Serum uric acid — normal in 20%
  • Joint aspiration — needle-shaped, negatively birefringent urate crystals (diagnostic)
  • Leucocytosis, high ESR; X-ray may be normal

DDx — what else could it be?

  • Septic arthritis
  • Pseudogout (CPPD)
  • Cellulitis
  • Reactive arthritis

Management — what will you do?

  • NSAIDs first — indometacin 50 mg TID or diclofenac 50 mg BD; resolve in 24–48 h
  • Corticosteroids oral/intra-articular if NSAIDs contraindicated (asthma) or failing; colchicine alternative
  • Never start urate-lowering during an attack
B. Chronic tophaceous gout

Scenario. Adult with years of recurrent attacks, now with chronic joint pain, deformity and tophi — uric acid deposits in the pinna, fingers, olecranon and Achilles tendon, with erosions on X-ray and urate nephropathy.

History — what will you ask?

  • Chronic joint pain and deformity; recurrent acute attacks
  • Tophi — painless nodules on ear, fingers, elbow, heel
  • Stones, renal colic, reduced renal function

Signs — what will you find?

  • Tophi on the helix of the ear, fingers, olecranon, Achilles
  • Joint deformity; restricted movement
  • Signs of renal impairment

Investigations — what will you order?

  • Serum uric acid raised; urea and creatinine
  • X-ray — erosions with overhanging edges, joint destruction, tophi
  • Uric acid stones on imaging; joint fluid if needed

DDx — what else could it be?

  • Rheumatoid arthritis
  • Osteoarthritis with nodes
  • Septic arthritis
  • CPPD with tophi
  • Psoriatic arthritis

Management — what will you do?

  • Urate-lowering lifelong if ≥3 attacks/year, tophi, stones or urate nephropathy — allopurinol, febuxostat, uricase (reduce production) or probenecid (increase excretion)
  • Start 2–3 weeks after an attack, with NSAID cover for weeks
  • Weight loss, low-purine diet, stop alcohol, stop thiazides/aspirin
C. Pseudogout (CPPD)

Scenario. Older woman with acute monoarthritis of the knee, wrist or symphysis pubis — calcium pyrophosphate crystals; often associated with haemochromatosis or hyperparathyroidism.

History — what will you ask?

  • Acute mono-/oligoarthritis, or chronic polyarthritis resembling RA/OA
  • Knee, wrist, symphysis pubis
  • Haemochromatosis, hyperparathyroidism, age

Signs — what will you find?

  • Swollen, tender joint without tophi
  • Signs of the associated disease

Investigations — what will you order?

  • Joint fluid — rhomboid, positively birefringent CPPD crystals (urate is needle-shaped and negative)
  • X-ray — linear opacity in the cartilage (chondrocalcinosis)
  • Calcium, PTH, ferritin to find the cause

DDx — what else could it be?

  • Gout
  • Septic arthritis
  • Rheumatoid arthritis
  • Osteoarthritis

Management — what will you do?

  • NSAIDs, steroids or colchicine — no role for allopurinol or probenecid
  • Colchicine for chronic cases
  • Treat the underlying cause

Mixed Connective Tissue Disease

Scenario. Young woman (20–40 years) with an overlap syndrome of SLE, systemic sclerosis and polymyositis (± RA), first described by Sharp; hallmark is high-titre anti-U1 RNP antibody forming immune complexes with inflammation of joints, muscles and vessels, and endothelial dysfunction causing Raynaud’s and pulmonary hypertension. HLA-DR4 and DR2 associations.

History — what will you ask?

  • Fatigue, low-grade fever, weight loss
  • arthritis/arthralgia and malar rash
  • Raynaud’s phenomenon, puffy hands, tight finger skin and reflux/dysphagia
  • proximal muscle weakness and myositis
  • breathlessness and palpitations (pulmonary hypertension, ILD, pericarditis, myocarditis)
  • facial numbness (trigeminal neuropathy)
  • cold/stress triggers

Signs — what will you find?

  • Raynaud’s phenomenon, puffy hands and sclerodactyly, malar rash, arthritis/synovitis, proximal muscle weakness and tenderness, signs of pulmonary hypertension (loud P2, RV heave, raised JVP, oedema) and ILD (velcro crackles), pericardial rub

Investigations — what will you order?

  • ANA positive with speckled pattern and very high anti-U1 RNP (diagnostic hallmark)
  • normocytic anaemia, leucopenia, thrombocytopenia, raised ESR
  • ↑CK, abnormal EMG, muscle biopsy
  • HRCT chest for ILD, echocardiography/right heart catheterisation for pulmonary hypertension. Alarcón-Segovia criteria: high-titre anti-U1 RNP plus ≥3 of — hand oedema, synovitis, myositis, Raynaud’s, acrosclerosis.

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • SLE (anti-dsDNA, anti-Sm; renal involvement)
  • systemic sclerosis (anti-centromere, anti-Scl-70; renal crisis)
  • polymyositis/dermatomyositis
  • rheumatoid arthritis
  • undifferentiated CTD
  • Sjögren syndrome
  • primary pulmonary hypertension

Management — what will you do?

  • Avoid Raynaud’s triggers (cold, stress)
  • low-to-moderate corticosteroids for arthritis, serositis and myositis
  • DMARDs — methotrexate, azathioprine, mycophenolate
  • NSAIDs for mild arthritis and serositis
  • calcium channel blockers (nifedipine, amlodipine) for Raynaud’s
  • pulmonary hypertension — bosentan, sildenafil, prostacyclin analogues
  • ILD — cyclophosphamide or mycophenolate
  • Better prognosis than diffuse systemic sclerosis, worse than mild SLE
  • 5-year survival ~80–90%
  • death from pulmonary arterial hypertension and ILD
  • renal crisis rare

Systemic Sclerosis (Scleroderma)

A. Limited cutaneous systemic sclerosis (CREST)

Scenario. Middle-aged woman with years of Raynaud’s, tight skin of the fingers and face, heartburn, and calcinosis or telangiectasia — limited, slow disease with anti-centromere antibody and pulmonary arterial hypertension.

History — what will you ask?

  • Raynaud’s phenomenon, often the first symptom
  • Heartburn, dysphagia, reflux
  • Skin tightening of fingers and face; calcinosis

Signs — what will you find?

  • CREST — Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasia
  • Sclerodactyly; digital ulcers; telangiectasia
  • Signs of pulmonary hypertension — loud P2, RV heave, oedema

Investigations — what will you order?

  • Anti-centromere antibody; ANA >90%
  • Nailfold capillaroscopy — capillary dropout and dilatation
  • Echocardiography/right heart catheterisation for PAH; HRCT for ILD; barium swallow/manometry

DDx — what else could it be?

  • Diffuse systemic sclerosis
  • MCTD
  • Primary Raynaud’s
  • Dermatomyositis
  • Nephrogenic systemic fibrosis

Management — what will you do?

  • Avoid cold, stop smoking, vaccinate
  • Raynaud’s — calcium channel blockers, PDE-5 inhibitors, prostacyclin analogues, bosentan
  • PAH — sildenafil, bosentan, epoprostenol; PPIs for reflux, prokinetics
B. Diffuse cutaneous systemic sclerosis

Scenario. Adult with rapidly progressive skin thickening of the trunk and proximal limbs, early interstitial lung disease or scleroderma renal crisis — anti-Scl-70 or anti-RNA polymerase III; more severe in patients of African ancestry.

History — what will you ask?

  • Rapid skin tightening over weeks to months, involving upper arms, thighs and trunk
  • Breathlessness (ILD); hypertension and oliguria (renal crisis)
  • Raynaud’s, reflux, arthralgia

Signs — what will you find?

  • Skin thickening proximal to elbows and knees, tight shiny skin, digital ulcers
  • Hypertension with AKI (renal crisis)
  • Crackles (ILD), raised JVP and oedema (cardiac/PAH), pericardial rub

Investigations — what will you order?

  • Anti-Scl-70 (topoisomerase I) — ILD; anti-RNA polymerase III — renal crisis and cancer
  • HRCT — interstitial fibrosis; PFTs restrictive with ↓DLCO
  • Creatinine, BP, urinalysis and blood film (MAHA) for renal crisis
  • Echo — pericardial effusion, PAH, restrictive cardiomyopathy

DDx — what else could it be?

  • SLE
  • MCTD
  • Dermatomyositis
  • Eosinophilic fasciitis
  • Scleroderma-like drug reaction

Management — what will you do?

  • Renal crisis — ACE inhibitors (captopril), avoid high-dose steroids
  • ILD — mycophenolate, cyclophosphamide, nintedanib
  • Skin — methotrexate, mycophenolate; stem cell transplant in severe diffuse disease; screen for cancer with anti-RNA polymerase III

Neurology

Guillain-Barre Syndrome

A. Typical Guillain–Barré syndrome

Scenario. Adult with rapidly progressive, symmetrical ascending weakness days to weeks after diarrhoea, respiratory infection or vaccination — areflexia, mild sensory symptoms and the risk of respiratory failure.

History — what will you ask?

  • Preceding Campylobacter jejuni (30%), CMV, EBV, Mycoplasma, Zika, influenza, COVID-19
  • Weakness starts in legs → arms → cranial nerves, maximum within 4 weeks
  • Tingling, numbness, moderate-to-severe pain (50%); dysphagia, facial weakness
  • Autonomic symptoms — palpitations, BP fluctuation, sweating

Signs — what will you find?

  • Areflexia (absent deep tendon reflexes); flaccid symmetrical weakness
  • Sensory loss; facial weakness, ophthalmoplegia
  • Respiratory compromise in 20–30% — falling vital capacity
  • Autonomic instability — arrhythmia, BP swings

Investigations — what will you order?

  • CSF — albuminocytologic dissociation (↑protein, normal cells)
  • Nerve conduction studies — demyelination/axonal loss
  • Vital capacity/PFTs; ECG monitoring
  • Brighton criteria for diagnostic certainty; blood tests to exclude mimics

DDx — what else could it be?

  • Poliomyelitis (asymmetric)
  • Myasthenia gravis (fluctuating)
  • Botulism (descending)
  • Spinal cord disease
  • Hypokalaemic periodic paralysis
  • Critical illness neuropathy

Management — what will you do?

  • Monitor respiration and autonomic function; ICU and ventilation in ~20%
  • Plasma exchange or IV immunoglobulin
  • Steroids are NOT effective; physiotherapy and rehabilitation
B. Miller Fisher syndrome

Scenario. Adult with the triad of ophthalmoplegia, ataxia and areflexia after an infection — the cranial variant of Guillain–Barré syndrome.

History — what will you ask?

  • Recent infection; diplopia, unsteadiness
  • Blurred vision, gait difficulty

Signs — what will you find?

  • Ophthalmoplegia; ataxia; areflexia
  • Normal power; may have mild limb signs

Investigations — what will you order?

  • CSF — albuminocytologic dissociation
  • Anti-GQ1b antibody; nerve conduction studies
  • Monitor vital capacity

DDx — what else could it be?

  • Brainstem stroke
  • Myasthenia gravis
  • Wernicke encephalopathy
  • Botulism

Management — what will you do?

  • IVIG or plasma exchange; supportive care
  • Monitor respiration and swallow
  • Rehabilitation — recovery is usually good

Motor Neuron Disease

Scenario. Adult (peak 50–70, male 1.5:1; ~2 per 100,000/year) with progressive selective degeneration of motor neurons — corticospinal tract (UMN) and anterior horn cell plus cranial motor nuclei (LMN). 90% sporadic; 10% familial, of which 25% have SOD1 mutations. Excitotoxicity (glutamate) and oxidative stress implicated. ALS is the commonest form with mixed UMN and LMN signs; also progressive muscular atrophy, primary lateral sclerosis, progressive bulbar palsy. Median survival ~3 years.

History — what will you ask?

  • Progressive asymmetrical distal weakness, wasting, cramps and fasciculations
  • stiffness and clumsiness
  • slurred speech and difficulty swallowing
  • emotional lability
  • no sensory, cognitive, ocular or sphincter symptoms
  • family history

Signs — what will you find?

  • UMN — spasticity, hyperreflexia, extensor plantar (Babinski), stiffness and clumsy movements
  • LMN — asymmetrical weakness (distal > proximal), muscle wasting, fasciculations, cramps
  • bulbar — dysarthria, dysphagia, tongue wasting and fasciculations, spastic tongue
  • split hand sign (wasting of thenar with sparing of hypothenar — 1st dorsal interossei and abductor pollicis brevis)
  • pseudobulbar affect

Investigations — what will you order?

  • Clinical diagnosis — no specific diagnostic test
  • El Escorial criteria (definitive, probable, possible)
  • EMG — denervation and fasciculations
  • NCS — normal sensory, reduced motor amplitude
  • MRI brain and spinal cord to exclude other causes
  • genetic testing in familial cases

DDx — what else could it be?

  • Multifocal motor neuropathy
  • Cervical myelopathy (C8 radiculopathy — distinguished by sensory involvement and hypothenar wasting)
  • Multiple sclerosis
  • Myasthenia gravis
  • Inclusion body myositis

Management — what will you do?

  • No cure — supportive and symptomatic. Riluzole prolongs survival by a few months (ALS)
  • edaravone slows progression in some cases
  • non-invasive ventilation for respiratory failure
  • multidisciplinary care — physiotherapy, speech therapy, nutrition support (gastrostomy), palliative care
  • Progressive and ultimately fatal
  • median survival 3–5 years
  • respiratory failure is the commonest cause of death
  • better with younger onset and slowly progressive variants

Demyelinating Disease

A. Relapsing–remitting multiple sclerosis

Scenario. Young woman with a subacute relapse — painful monocular visual loss (optic neuritis), limb numbness or unilateral weakness — resolving over weeks, with a previous separate episode or typical MRI lesions.

History — what will you ask?

  • Relapsing episodes over time and space: sensory, motor, visual, cerebellar
  • Uhthoff — heat worsens symptoms; Lhermitte — electric shock on neck flexion
  • Bladder, bowel and erectile dysfunction; fatigue, depression
  • Family history, vitamin D, EBV

Signs — what will you find?

  • Optic neuritis — reduced acuity/colour, relative afferent pupillary defect
  • Internuclear ophthalmoplegia — adduction failure + contralateral nystagmus
  • Spastic weakness, hyperreflexia, upgoing plantar; ataxia, intention tremor
  • Sensory loss, hyperaesthesia

Investigations — what will you order?

  • MRI — most sensitive and usually diagnostic: DIS (≥1 T2 lesion in ≥2 of periventricular, cortical/juxtacortical, infratentorial, spinal) and DIT (simultaneous enhancing/non-enhancing, or new lesion)
  • CSF oligoclonal bands (~90%); evoked potentials
  • Exclude mimics — B12, NMO, lupus, sarcoid, infection

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Optic neuritis of other cause (including neurosyphilis)
  • ADEM
  • Neuromyelitis optica
  • Transverse myelitis
  • B12 deficiency
  • CNS lupus
  • Compressive myelopathy

Management — what will you do?

  • Acute relapse — high-dose IV steroids; steroid-refractory → plasma exchange
  • DMT started early — interferon-β, glatiramer, teriflunomide, dimethyl fumarate, fingolimod, natalizumab (JC virus screening)
  • Symptoms — baclofen/tizanidine, carbamazepine for trigeminal neuralgia, gabapentin, SSRIs, oxybutynin
B. Progressive multiple sclerosis

Scenario. Adult with steadily worsening spastic paraparesis, ataxia and bladder dysfunction without distinct relapses (primary progressive, ~10%), or after an initial relapsing course (secondary progressive).

History — what will you ask?

  • Gradual decline in walking, balance, bladder and cognition
  • No or few discrete relapses; insidious onset
  • Age, male sex and smoking predict worse outcome

Signs — what will you find?

  • Spastic paraparesis, hyperreflexia, upgoing plantars
  • Ataxia, dysmetria; pseudobulbar signs late
  • Bladder urgency; cognitive slowing

Investigations — what will you order?

  • MRI — spinal and brain lesions, atrophy
  • CSF oligoclonal bands; evoked potentials
  • PFTs and 6MWT for function; exclude compressive myelopathy

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Compressive myelopathy
  • Motor neuron disease
  • B12 deficiency (subacute combined degeneration)
  • Hereditary spastic paraplegia
  • NMO

Management — what will you do?

  • No cure — DMT to slow progression where indicated
  • Spasticity — baclofen, tizanidine; bladder — antimuscarinics or self-catheterisation
  • Rehabilitation, fatigue and mood management

Myasthenia Gravis-2

A. Ocular myasthenia

Scenario. Adult with drooping eyelids and double vision that worsen through the day and after reading or looking up — antibodies blocking acetylcholine receptors at the ocular muscles; pupils are spared.

History — what will you ask?

  • Ptosis and diplopia worsening with sustained activity — worse in the evening
  • No limb weakness, chewing or swallowing difficulty
  • Fatigue; thyroid disease

Signs — what will you find?

  • Ptosis (unilateral or bilateral), diplopia, ophthalmoplegia with normal pupils
  • Ice test — ptosis improves; sustained upgaze provokes ptosis
  • No sensory or reflex abnormality

Investigations — what will you order?

  • ACh receptor antibodies; anti-MuSK in some
  • Single-fibre EMG — most sensitive (decrementing response)
  • CT chest for thymoma; thyroid function

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Brainstem lesion
  • Thyroid eye disease
  • Ocular myopathy/mitochondrial disease
  • Lambert–Eaton
  • Botulism

Management — what will you do?

  • Cholinesterase inhibitors — pyridostigmine
  • Steroids if inadequate; immunosuppressants
  • Thymectomy if thymoma; monitor for generalisation
B. Generalised myasthenia

Scenario. Adult with fluctuating weakness of limbs, chewing, swallowing and facial muscles, worse in the afternoon and with repeated use — the same autoimmune neuromuscular junction defect, but generalised.

History — what will you ask?

  • Difficulty chewing (worse through the meal), dysphagia, slurred speech
  • Difficulty raising arms, writing, climbing stairs, rising from a chair
  • Symptoms worst in the afternoon/evening; no sensory symptoms

Signs — what will you find?

  • Fatiguable limb weakness; masked facies
  • Bulbar weakness; normal reflexes and sensation
  • No pupillary abnormality

Investigations — what will you order?

  • ACh receptor antibodies ± anti-MuSK; single-fibre EMG
  • CT chest for thymoma/thymus
  • PFTs at intervals for respiratory muscle weakness

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Lambert–Eaton (improves with exercise, calcium channel antibodies)
  • Botulism
  • GBS
  • Motor neuron disease
  • Congenital myasthenic syndrome

Management — what will you do?

  • Pyridostigmine first; steroids if inadequate; azathioprine
  • Thymectomy — in every patient with thymoma; without thymoma only if >60 years (as the note states)
  • Regular follow-up to detect respiratory involvement
C. Myasthenic crisis

Scenario. Known myasthenic with rapidly worsening weakness and breathlessness, weak cough and nasal speech — respiratory muscle failure needing ventilatory support.

History — what will you ask?

  • Precipitant — infection, aminoglycosides, beta-blockers, surgery, trauma, non-compliance
  • Rapidly worsening bulbar and limb weakness
  • Breathlessness, weak cough, inability to swallow secretions

Signs — what will you find?

  • Respiratory distress, weak cough, paradoxical breathing
  • Bulbar weakness; inability to swallow
  • Anxiety, sweating, tachycardia

Investigations — what will you order?

  • Vital capacity and negative inspiratory force — falling values
  • ABG — hypoxia/hypercapnia
  • CXR for infection; electrolytes

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Pulmonary embolism
  • Pneumonia with respiratory failure
  • GBS
  • Organophosphate poisoning

Management — what will you do?

  • Ventilatory support
  • Plasmapheresis to remove antibodies
  • IV immunoglobulin to neutralise them; treat the precipitant; avoid contraindicated drugs

Alzheimer’s Disease

Scenario. Older adult with progressive neurodegeneration and the commonest cause of dementia (60–70%); begins with anterograde amnesia, later aphasia, disorientation, behavioural change and loss of daily function. Amyloid cascade (APP cut by β- and γ-secretase → Aβ42 plaques) then hyperphosphorylated tau tangles and neuron loss with reduced acetylcholine and excess glutamate; hippocampus affected first. Sporadic late-onset (>95%, after 65) vs familial early-onset (<1%, APP chr21, PSEN1 chr14, PSEN2 chr1); APOE ε4 is a risk gene (one copy ~3×, two copies ~8–12×); Down syndrome gives AD from about 40.

History — what will you ask?

  • Memory complaints (patient and family), orientation, language, behaviour and function
  • onset and progression
  • reversible causes to exclude — B12, thyroid, depression, subdural haematoma, normal pressure hydrocephalus, medications
  • family history, Down syndrome, hypertension, diabetes, inactivity, hearing loss
  • swallowing and continence in advanced disease

Signs — what will you find?

  • MMSE cognitive testing
  • disorientation and aphasia
  • primitive reflexes
  • signs of the reversible mimics
  • in advanced disease cachexia, incontinence, bedbound state and aspiration

Investigations — what will you order?

  • Clinical history plus MMSE
  • MRI brain — medial temporal/hippocampal atrophy and exclusion of other causes
  • CSF — low Aβ42/40 ratio and high p-tau
  • amyloid PET
  • plasma p-tau217
  • B12, thyroid function, depression screening
  • APOE ε4 testing required before anti-amyloid therapy
  • Stages: MCI → mild → moderate → severe dementia

DDx — what else could it be? (standard differential; the note gives no list of its own)

  • Mild cognitive impairment
  • depression (pseudodementia)
  • vascular dementia
  • dementia with Lewy bodies
  • frontotemporal dementia
  • normal pressure hydrocephalus (gait, incontinence, dementia)
  • subdural haematoma
  • B12 and thyroid deficiency
  • medication effects
  • neurosyphilis

Management — what will you do?

  • Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine (moderate–severe)
  • NICE NG97: AChEI mild
  • add memantine moderate
  • continue AChEI + memantine severe
  • memantine alone if intolerant
  • not in MCI. **Lecanemab/donanemab for early AD with confirmed amyloid — modest slowing, not a cure
  • ARIA needs MRI monitoring**
  • SFDA lecanemab for 0–1 APOE ε4. Behaviour: exclude pain/infection, non-drug first, SSRIs, short-term antipsychotics
  • Lifestyle: exercise, cognitive stimulation, vascular risk, hearing aids, carer support

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