Rheumatology & Haematology

Rheumatology & Haematology UK Medical PG Question 1: A 38-year-old woman presents with recurrent episodes of severe abdominal pain and psychiatric symptoms. Her urine turns dark during attacks. Family history reveals similar episodes. What is the inheritance pattern?

• A. Autosomal recessive
• B. Autosomal dominant (Correct Answer)
• C. X-linked recessive
• D. X-linked dominant
• E. Mitochondrial

Rheumatology & Haematology Explanation: ***Autosomal dominant*** - The clinical picture of recurrent severe abdominal pain, psychiatric symptoms, and dark urine during attacks is highly suggestive of **Acute Intermittent Porphyria (AIP)**. - AIP is caused by a deficiency in **hydroxymethylbilane synthase (PBG deaminase)** and is inherited in an **autosomal dominant** fashion, which explains the positive family history. *Autosomal recessive* - **Autosomal recessive** disorders typically manifest if two copies of the defective gene are inherited, often presenting in siblings but not consistently across multiple generations (vertical transmission) as implied by the family history. - Conditions like **Congenital erythropoietic porphyria** are autosomal recessive but primarily cause photosensitivity and hemolytic anemia, not neurovisceral crises. *X-linked recessive* - **X-linked recessive** disorders predominantly affect males and are transmitted from carrier mothers to sons, a pattern inconsistent with a female patient with similar episodes in the family. - Common examples like **Hemophilia** or **Duchenne Muscular Dystrophy** have sex-linked inheritance patterns that do not match the presented symptoms or inheritance. *X-linked dominant* - **X-linked dominant** inheritance would show affected fathers passing the trait to all daughters but none of their sons, and affected mothers passing it to half of their children, which is not the typical pattern for AIP. - **X-linked protoporphyria**, a rare porphyria, follows this pattern but presents primarily with severe photosensitivity and hepatobiliary complications, not the neurovisceral attacks seen here. *Mitochondrial* - **Mitochondrial inheritance** is characterized by exclusive **maternal transmission**, meaning all children of an affected mother are affected, but no children of an affected father. This pattern differs from the general family history for AIP. - Mitochondrial disorders primarily affect high-energy-demand organs, and while they can have neurological components, most porphyrias are nuclear-encoded genetic disorders, making mitochondrial inheritance highly unlikely.

Rheumatology & Haematology UK Medical PG Question 2: A 28-year-old woman presents with sudden onset severe headache during exercise. She vomits and has neck stiffness. CT head shows subarachnoid hemorrhage. What is the most likely cause?

• A. Arteriovenous malformation
• B. Berry aneurysm (Correct Answer)
• C. Carotid dissection
• D. Hypertensive hemorrhage
• E. Trauma

Rheumatology & Haematology Explanation: ***Berry aneurysm*** - The sudden onset of a severe, explosive **thunderclap headache** coupled with signs of meningeal irritation (vomiting, neck stiffness) and the finding of **subarachnoid hemorrhage (SAH)** on CT head is the classic presentation of a ruptured saccular (**berry**) aneurysm. - Exertion (exercise) acts as a common trigger for aneurysm rupture due to the sudden increase in **intracranial pressure** and transmural wall stress. *Arteriovenous malformation* - AVMs more commonly present with **intraparenchymal hemorrhage** (ICH) or seizures, rather than isolated SAH, especially when triggered by exertion. - While AVMs can cause SAH, they are a less frequent cause of widespread spontaneous SAH compared to ruptured **berry aneurysms**. *Carotid dissection* - Carotid artery dissection typically manifests as severe neck/facial pain, headache, and signs of **cerebral ischemia** (stroke symptoms) due to vessel stenosis or occlusion. - Dissections rarely cause primary, widespread SAH; they are more often associated with **subintimal hemorrhage** leading to stroke or pseudoaneurysm formation. *Hypertensive hemorrhage* - Hemorrhage due to chronic or severe hypertension (hypertensive hemorrhage) almost exclusively causes deep **intraparenchymal hemorrhage** (ICH), usually in the basal ganglia, thalamus, or brainstem. - The primary finding of SAH, rather than ICH and the patient's young age, makes uncontrolled hypertension highly unlikely as the underlying cause. *Trauma* - Although trauma is the single most frequent overall cause of SAH, the clinical history describes a **spontaneous event** triggered by exertion (exercise) without any external injury. - Traumatic SAH is clinically differentiated by the history of a specific injury and usually involves bleeding adjacent to the site of impact.

Rheumatology & Haematology UK Medical PG Question 3: A 42-year-old woman presents with fatigue, muscle aches, and widespread pain. She has multiple tender points but normal inflammatory markers. Sleep is poor. What is the most appropriate initial treatment?

• A. NSAIDs
• B. Prednisolone
• C. Pregabalin (Correct Answer)
• D. Methotrexate
• E. Physiotherapy alone

Rheumatology & Haematology Explanation: ***Pregabalin*** - **Pregabalin** is a **gabapentinoid** drug that modulates voltage-gated calcium channels, decreasing the release of excitatory neurotransmitters involved in central pain sensitization characteristic of **fibromyalgia**. - It is one of the FDA-approved medications (along with duloxetine and milnacipran) specifically recommended for managing the **widespread pain** and associated symptoms like **poor sleep** in fibromyalgia. *NSAIDs* - Non-steroidal anti-inflammatory drugs (NSAIDs) target inflammatory pain, which is generally absent in **fibromyalgia** as evidenced by **normal inflammatory markers**. - NSAIDs are usually **ineffective** in treating the centralized pain and hyperalgesia seen in this condition, making them a poor choice for monotherapy. *Prednisolone* - **Prednisolone** is a powerful corticosteroid used for conditions driven by **inflammation** (e.g., active arthritis or vasculitis). - The patient has normal inflammatory markers and a clinical presentation consistent with a non-inflammatory central pain syndrome, making steroids **inappropriate** and potentially harmful. *Methotrexate* - **Methotrexate** is a **Disease-Modifying Anti-Rheumatic Drug (DMARD)** indicated for managing autoimmune inflammatory diseases like **Rheumatoid Arthritis** or **Psoriatic Arthritis**. - Since the patient does not show evidence of an inflammatory or autoimmune joint disease, this immunosuppressant drug treatment is **not warranted**. *Physiotherapy alone* - While non-pharmacological therapies like **aerobic exercise** and **Cognitive Behavioral Therapy (CBT)** are essential long-term components, they are often insufficient alone to manage severe initial symptoms, particularly **poor sleep** and disabling pain. - Initial treatment typically requires a combination of pharmacological agents (like **Pregabalin**) combined with supportive non-pharmacological management for optimal symptom control.

Rheumatology & Haematology UK Medical PG Question 4: A 52-year-old man presents with progressive dysphagia and weight loss. He has tight skin on his hands and Raynaud's phenomenon. What is the most likely esophageal abnormality?

• A. Esophageal carcinoma
• B. Achalasia
• C. Esophageal dysmotility (Correct Answer)
• D. Peptic stricture
• E. Eosinophilic esophagitis

Rheumatology & Haematology Explanation: ***Esophageal dysmotility***- The combination of **tight skin (scleroderma)** and **Raynaud's phenomenon** is characteristic of **Systemic Sclerosis**, which causes atrophy and fibrosis of smooth muscle in the distal two-thirds of the esophagus.- This loss of smooth muscle function leads to decreased peristalsis (dysmotility) and, crucially, incompetence of the **lower esophageal sphincter (LES)**, causing severe GERD and the resulting dysphagia.*Esophageal carcinoma*- While progressive **dysphagia** and **weight loss** are concerns for malignancy, the patient's systemic features (**tight skin**, **Raynaud's**) strongly suggest a connective tissue disorder as the etiology.- Carcinoma often occurs in the context of significant risk factors (e.g., smoking, alcohol, HPV) and typically does not present with the classic dermatologic or peripheral vascular signs of Scleroderma.*Achalasia*- Achalasia involves impaired relaxation of the **LES** and aperistalsis, but it is a primary esophageal motility disorder and lacks the systemic features (Raynaud's, sclerodactyly) seen in this patient.- Dysphagia in achalasia tends to be prominent for both **liquids and solids** from the start, often without significant GERD symptoms.*Peptic stricture*- A **peptic stricture** is a *consequence* of chronic acid exposure resulting from the incompetent LES caused by Scleroderma-related esophageal dysmotility.- While a stricture may eventually explain the severe dysphagia, the primary diagnostic link between the systemic symptoms and the esophageal pathology is the **underlying smooth muscle failure** (dysmotility).*Eosinophilic esophagitis*- This condition is typically associated with **atopic disorders** (allergies, asthma) and presents histologically with excessive **eosinophil infiltration**.- It typically causes dysphagia, often for solids, and sometimes **food impaction**, but it is not linked to generalized fibrosis or vascular changes like those causing tight skin and Raynaud's phenomenon.

Rheumatology & Haematology UK Medical PG Question 5: A 48-year-old man presents with progressive muscle weakness affecting proximal muscles. CK is elevated at 3200 U/L. Muscle biopsy shows inflammatory infiltrates. What is the cancer screening recommendation?

• A. No screening needed (Correct Answer)
• B. Chest X-ray only
• C. CT chest/abdomen/pelvis
• D. Colonoscopy only
• E. PSA testing only

Rheumatology & Haematology Explanation: ***No screening needed***- The clinical presentation of **progressive proximal muscle weakness**, elevated **CK**, and **inflammatory infiltrates** on muscle biopsy is consistent with **polymyositis**.- Unlike **dermatomyositis**, which has a strong association with occult malignancies, **polymyositis** is generally not associated with an increased risk of cancer, therefore **routine cancer screening** is not indicated. *Chest X-ray only*- A **chest X-ray** is a limited screening tool and would be insufficient to detect a wide range of potential malignancies associated with paraneoplastic syndromes.- It would miss cancers in other vital organs, making it an inadequate approach if malignancy were suspected. *CT chest/abdomen/pelvis*- This extensive imaging is typically recommended for patients with **dermatomyositis** due to its strong association with various occult malignancies.- In the absence of dermatomyositis-specific features (e.g., characteristic skin rashes) or other malignancy risk factors, such broad screening is not indicated for **polymyositis**. *Colonoscopy only*- While gastrointestinal malignancies can be associated with paraneoplastic syndromes, performing **colonoscopy** alone is insufficient for comprehensive cancer screening.- This approach would overlook other common cancer sites linked to inflammatory myopathies, such as lung, breast, or ovarian cancers. *PSA testing only*- **PSA testing** is specific for prostate cancer screening and would be part of a more comprehensive workup, not the sole screening measure for malignancy.- Focusing solely on prostate cancer would miss other potential malignancies that might be associated with paraneoplastic syndromes in other forms of inflammatory myopathies.

Rheumatology & Haematology UK Medical PG Question 6: A 35-year-old woman presents with recurrent miscarriages and thrombosis. She has positive lupus anticoagulant and anticardiolipin antibodies. What is the mechanism of thrombosis?

• A. Platelet activation
• B. Endothelial dysfunction (Correct Answer)
• C. Protein C deficiency
• D. Factor V Leiden mutation
• E. Hyperhomocysteinemia

Rheumatology & Haematology Explanation: ***Endothelial dysfunction***- This is the primary mechanism in **Antiphospholipid Syndrome (APS)**, where **antiphospholipid antibodies (aPL)** bind to complexes involving plasma proteins, particularly **$eta_2$-glycoprotein I**, on the endothelial surface.- This binding activates and injures the endothelium, leading to the expression of pro-coagulant factors and adhesive molecules, resulting in a systemic shift toward **thrombosis**.*Platelet activation*- While aPL antibodies do cause platelet activation and aggregation, this effect is often considered downstream or secondary to the primary interaction the antibodies have with **endothelial cells** and plasma proteins.- aPL antibodies binding to platelets via **$eta_2$-glycoprotein I** enhances the production of thromboxane A2 and promotes thrombus stabilization.*Protein C deficiency*- This is typically an inherited disorder causing decreased levels or function of the key anticoagulant Protein C, a mechanism distinct from **autoimmunity**.- Although aPL antibodies can sometimes interfere with Protein C and S function indirectly, the underlying mechanism generating the thrombotic state remains **endothelial activation**.*Factor V Leiden mutation*- This is the most common inherited thrombophilia, leading to resistance to activated **Protein C** degradation of Factor Va and VIIIa.- This inherited defect is separate from the acquired, autoimmune mechanism responsible for thrombosis in **Antiphospholipid Syndrome**.*Hyperhomocysteinemia*- Elevated **homocysteine** levels create a prothrombotic state primarily via direct cytotoxicity and oxidative stress to the **vascular endothelium**.- This condition is an independent risk factor for thrombosis and is not the pathognomonic mechanism of acquired thrombophilia defined by **lupus anticoagulant** and **anticardiolipin antibodies**.

Rheumatology & Haematology UK Medical PG Question 7: A 61-year-old man presents with progressive weakness in his hands and difficulty swallowing. EMG shows myopathic changes. Muscle biopsy shows rimmed vacuoles and eosinophilic inclusions. What is the most likely diagnosis?

• A. Polymyositis
• B. Dermatomyositis
• C. Inclusion body myositis (Correct Answer)
• D. Myasthenia gravis
• E. Muscular dystrophy

Rheumatology & Haematology Explanation: ***Inclusion body myositis*** - The combination of **progressive distal weakness** (hands) and **dysphagia**, particularly in an older man, is highly characteristic. - Definitive diagnosis relies on muscle biopsy findings of **rimmed vacuoles** and **eosinophilic inclusions**, as well as **myopathic changes** on EMG. *Polymyositis* - Typically presents with **proximal muscle weakness**, affecting hips and shoulders, rather than predominant distal hand weakness or prominent dysphagia. - Muscle biopsy shows **endomysial inflammatory infiltrates** but lacks the characteristic rimmed vacuoles or inclusions seen in IBM. *Dermatomyositis* - Shares **proximal muscle weakness** with polymyositis but is uniquely identified by specific **cutaneous manifestations** like heliotrope rash and Gottron's papules, which are not mentioned. - Muscle biopsy shows **perifascicular atrophy** and perimysial inflammation, differing from IBM's distinctive pathology. *Myasthenia gravis* - A **neuromuscular junction disorder** causing fluctuating weakness that worsens with activity, often affecting ocular, bulbar, and limb muscles. - EMG would show a **decremental response** on repetitive nerve stimulation, not primary myopathic changes, and muscle biopsy would be normal. *Muscular dystrophy* - A broad category of **genetic muscle diseases** that cause progressive weakness and myopathic changes, but the specific biopsy findings of rimmed vacuoles and eosinophilic inclusions are not typical. - Different types of muscular dystrophy have distinct genetic causes and biopsy findings (e.g., dystrophin absence in Duchenne) that do not match the features presented.

Rheumatology & Haematology UK Medical PG Question 8: A 52-year-old woman presents with progressive dysphagia and weight loss. She has tight skin on her face and hands. ANA shows nucleolar pattern. What is the most concerning complication to screen for?

• A. Renal crisis
• B. Pulmonary hypertension (Correct Answer)
• C. Cardiac involvement
• D. Esophageal stricture
• E. Digital ulceration

Rheumatology & Haematology Explanation: ***Pulmonary hypertension*** - This patient's presentation (tight skin on face/hands, dysphagia, nucleolar ANA pattern) strongly suggests **Systemic Sclerosis (SSc)**, likely the limited cutaneous form. - **Pulmonary arterial hypertension (PAH)** is a leading cause of mortality in SSc, particularly associated with the nucleolar ANA pattern (often linked to anti-U3 RNP/fibrillarin antibodies), requiring regular screening with **echocardiograms**. *Renal crisis* - **Scleroderma Renal Crisis (SRC)** involves acute onset of **malignant hypertension** and rapid kidney failure. - SRC is more commonly associated with **diffuse cutaneous SSc** and **Anti-RNA Polymerase III antibodies**, rather than the nucleolar ANA pattern. *Cardiac involvement* - Direct **cardiac involvement** (e.g., myocarditis, pericarditis, conduction defects) can occur in SSc. - While serious, **pulmonary hypertension** is statistically the most common and acutely life-threatening cardiopulmonary complication in SSc patients, making it the priority for routine screening. *Esophageal stricture* - **Dysphagia** and weight loss are highly suggestive of **esophageal dysmotility**, a nearly universal finding in SSc. - While **esophageal strictures** can occur from chronic reflux in SSc, they are a local complication, not the most concerning *systemic* or *life-threatening* complication requiring primary screening compared to PAH. *Digital ulceration* - **Digital ulcerations** are caused by severe **Raynaud's phenomenon** and microvascular ischemia, leading to pain and potential tissue loss. - Though causing significant morbidity, digital ulcerations are a peripheral manifestation and not the most acutely life-threatening *systemic* complication requiring broad mortality screening compared to **pulmonary hypertension**.

Rheumatology & Haematology UK Medical PG Question 9: A 41-year-old woman presents with recurrent episodes of severe abdominal pain and confusion. During attacks, her urine turns dark red. She has a family history of similar symptoms. What is the most appropriate acute treatment?

• A. High-carbohydrate diet
• B. Hemin therapy
• C. Avoid precipitating drugs
• D. IV fluids and analgesia
• E. All of the above (Correct Answer)

Rheumatology & Haematology Explanation: ***All of the above*** - The clinical presentation (severe abdominal pain, confusion, dark urine, and family history) is highly suggestive of an acute **porphyria attack**, such as **Acute Intermittent Porphyria (AIP)**. - Acute management requires a multifaceted approach, encompassing **hemin therapy**, **high-carbohydrate diet**, **avoidance of precipitating drugs**, and **supportive care** with IV fluids and analgesia. *High-carbohydrate diet* - Administering a high-dose **glucose (dextrose)** intravenously is crucial as a high carbohydrate load represses the activity of **$\delta$-aminolevulinic acid (ALA) synthase**, thereby reducing the production of neurotoxic porphyrin precursors. - This therapy is often initiated promptly for all acute attacks, especially mild ones, and while awaiting the preparation or administration of **hemin therapy**. *Hemin therapy* - **Hemin (or hematin)** is considered the most specific and definitive treatment for a severe acute attack, as it directly suppresses hepatic **$\delta$-aminolevulinic acid (ALA) synthase** through negative feedback. - Early initiation of intravenous hemin significantly shortens the duration of the attack and helps prevent or mitigate **neurological damage**. *Avoid precipitating drugs* - Many medications (e.g., barbiturates, sulfa drugs, some antiepileptics) are potent **inducers of cytochrome P450 enzymes**, which in turn accelerate the production of porphyrin precursors, worsening the attack. - Rapidly identifying and discontinuing all porphyrinogenic agents is mandatory to halt the exacerbation and reduce the accumulation of neurotoxic intermediaries like **ALA** and **porphobilinogen**. *IV fluids and analgesia* - Severe abdominal pain, often disproportionate to physical findings, is a hallmark of acute porphyria and necessitates potent **opioid analgesics** (e.g., morphine) for effective pain management. - Patients are frequently volume-depleted, requiring **IV fluid resuscitation**, and may also need correction of **electrolyte derangements**, such as **hyponatremia** and **hypomagnesemia**, often associated with SIADH.

Rheumatology & Haematology UK Medical PG Question 10: A 32-year-old woman presents with recurrent miscarriages and livedo reticularis. Blood tests show thrombocytopenia and prolonged APTT. What is the most likely diagnosis?

• A. Systemic lupus erythematosus
• B. Antiphospholipid syndrome (Correct Answer)
• C. Thrombotic thrombocytopenic purpura
• D. Factor V Leiden
• E. Protein S deficiency

Rheumatology & Haematology Explanation: ***Antiphospholipid syndrome***

Rheumatology & Haematology Flashcard 1 of 10

Question: Haemochromatosis can cause arthropathy, especially in _____ joints with "hook-like" osteophytes

Answer: metocarpophalangeal (MCP)

Rheumatology & Haematology Flashcard 2 of 10

Question: The variables involved in assesing the ORBIT score is: _____ Age >74 Bleeding History (GI bleeding, Intracranial bleeding or haemorrhagic stroke Renal Impairment (GFR <60) Treatment with antiplatelet agents

Answer: Haemoglobin <130g/L in makes <120g/L in females Anaemia

Rheumatology & Haematology Flashcard 3 of 10

Question: Rheumatoid arthritis often has _____cytic anaemia

Answer: normo

Rheumatology & Haematology Flashcard 4 of 10

Question: What investigations should be ordered for suspected psoriatic arthritis? _____, inflammatory markers, Rheumatoid factor, Anti-CCP

Answer: X-ray of hands and feet

Rheumatology & Haematology Flashcard 5 of 10

Question: D-Dimer is a marker of _____

Answer: fibrin degredation

Rheumatology & Haematology Flashcard 6 of 10

Question: Management of No Bleeding on warfarin when INR 5.0-8.0 involves: _____ Reduce subsequent maintenance dose

Answer: Withhold 1 or 2 doses of warfarin

Rheumatology & Haematology Flashcard 7 of 10

Question: Sodium valproate can cause _____ and Hyponatremia

Answer: thrombocytopenia

Rheumatology & Haematology Flashcard 8 of 10

Question: Metastatic Bone Pain may responsd to _____, bisphosphonates or radiotherapy

Answer: strong opioids

Rheumatology & Haematology Flashcard 9 of 10

Question: APL can be distinguised from other types of AML based on: _____ Repsonsivness to all-trans retinoic acid (ATRA: tretinoin)

Answer: Prescence of promyelocytes containing multiple Auer Rods

Rheumatology & Haematology Flashcard 10 of 10

Question: Management of No Bleeding on warfarin when INR >8.0 involves: _____ Repeat dose of vit K if INR still too high after 24 hours Restart when INR <5.0

Answer: Give vitamin K 1-5mg by mouth, using the IV preparation orally