A 44-year-old man presents with a 9-week history of fatigue and 7kg unintentional weight loss. He reports daily alcohol consumption of 8-10 units for 20 years but denies recent increase. Examination shows mild jaundice, spider naevi on the chest, palmar erythema, and hepatomegaly 3cm below the costal margin. Blood tests reveal: Hb 108 g/L, MCV 103 fL, platelets 95 × 10⁹/L, bilirubin 48 μmol/L, ALT 124 U/L, AST 268 U/L, ALP 156 U/L, albumin 32 g/L. What is the most important initial investigation to exclude an alternative diagnosis?
Q12
A 31-year-old woman presents with a 10-week history of fatigue and 5kg weight loss. She reports episodes of sweating and tremor that resolve after eating. Her mother has type 1 diabetes. Examination reveals a BMI of 19, pulse 92 bpm regular, BP 118/74 mmHg, and a smooth, non-tender thyroid enlargement. Blood tests show: fasting glucose 3.1 mmol/L, HbA1c 34 mmol/mol, TSH 0.1 mU/L, free T4 28 pmol/L. What is the most appropriate next investigation?
Q13
According to current evidence-based guidelines for the assessment of undifferentiated symptoms in primary care, which statement best reflects the concept of 'safety netting' in patients presenting with non-specific symptoms such as fatigue or weight loss?
Q14
A 59-year-old woman with chronic widespread pain managed with amitriptyline 50mg nocte presents for pain review. She describes the pain as 'burning and tingling' in her feet and legs, worse at night, partially relieved by walking around. She has had type 2 diabetes for 12 years. Examination reveals diminished sensation to light touch and pinprick in both feet in stocking distribution, absent ankle reflexes, but normal proprioception and vibration sense. Her HbA1c is 76 mmol/mol (9.1%). What is the most appropriate next step in pain management?
Q15
A 43-year-old man with well-controlled HIV (CD4 count 520 cells/mm³, undetectable viral load on antiretroviral therapy) presents with a 9-week history of fever up to 38.7°C, night sweats, and 6kg weight loss. He reports no respiratory symptoms. Examination reveals temperature 38.4°C, cervical and axillary lymphadenopathy (multiple nodes 1-2cm, rubbery, non-tender), and mild hepatosplenomegaly. Chest X-ray is normal. Blood tests show: Hb 110 g/L, WCC 4.1×10⁹/L (lymphocytes 0.9×10⁹/L), platelets 165×10⁹/L, LDH 580 U/L (elevated). What is the most important next investigation?
Q16
Which of the following patient presentations would meet the NICE definition for requiring a 2-week wait referral under the suspected cancer pathway for unexplained weight loss in adults?
Q17
A 74-year-old man presents with a 14-week history of progressive fatigue, loss of appetite, and 11kg unintentional weight loss. He has noticed increasing abdominal distension and ankle swelling. He has a 40 pack-year smoking history. Examination reveals cachexia, mild jaundice, ascites (positive fluid thrill), hepatomegaly (liver edge 6cm below costal margin, irregular and hard), and bilateral pitting ankle oedema. What is the most appropriate initial investigation?
Q18
A 38-year-old woman presents with a 6-month history of severe fatigue, unrefreshing sleep, and post-exertional malaise lasting >24 hours after minimal activity. She reports cognitive difficulties ('brain fog'), orthostatic intolerance with dizziness on standing, and flu-like symptoms. She was previously very active but now struggles with daily activities. Symptoms began after a viral illness. Examination and extensive investigations including FBC, TFTs, glucose, vitamin B12, folate, ferritin, CRP, and cortisol are all normal. What is the most appropriate diagnosis?
Q19
A 69-year-old man with no significant past medical history presents with a 12-week history of fever (documented temperatures 38.2-38.9°C), 8kg weight loss, and progressive fatigue. He has diffuse myalgia but no specific pain. Examination reveals temperature 38.6°C, no lymphadenopathy, heart sounds normal, chest clear, and no organomegaly. Blood tests show: Hb 102 g/L (normochromic, normocytic), WCC 11.2×10⁹/L, platelets 445×10⁹/L, ESR 95 mm/hr, CRP 88 mg/L, ALP 156 U/L (other LFTs normal). Blood cultures (3 sets) are negative. Chest X-ray and urine culture are normal. What is the single most important investigation to perform next?
Q20
A 51-year-old woman presents with a 9-month history of widespread pain affecting her neck, back, shoulders, and hips bilaterally. She reports severe fatigue, non-restorative sleep despite 9 hours in bed, and difficulty concentrating. Pain scores 7/10 daily. She has tried paracetamol and ibuprofen with minimal benefit. Examination reveals multiple tender points but no synovitis or muscle weakness. Blood tests including FBC, CRP, ESR, TFTs, calcium, and vitamin D are normal. What is the most appropriate next management step?
Undifferentiated Symptoms UK Medical PG Practice Questions and MCQs
Question 11: A 44-year-old man presents with a 9-week history of fatigue and 7kg unintentional weight loss. He reports daily alcohol consumption of 8-10 units for 20 years but denies recent increase. Examination shows mild jaundice, spider naevi on the chest, palmar erythema, and hepatomegaly 3cm below the costal margin. Blood tests reveal: Hb 108 g/L, MCV 103 fL, platelets 95 × 10⁹/L, bilirubin 48 μmol/L, ALT 124 U/L, AST 268 U/L, ALP 156 U/L, albumin 32 g/L. What is the most important initial investigation to exclude an alternative diagnosis?
A. Hepatitis B and C serology
B. Abdominal ultrasound with Doppler
C. Serum ferritin and transferrin saturation
D. Alpha-fetoprotein (Correct Answer)
E. Liver biopsy with histological assessment
Explanation: ***Alpha-fetoprotein***- In a patient with **chronic liver disease** (suggested by spider naevi and palmar erythema) and **unintentional weight loss**, excluding **hepatocellular carcinoma (HCC)** is the clinical priority.- **Alpha-fetoprotein (AFP)** is a key tumor marker used alongside imaging to screen for and support the diagnosis of HCC in cirrhotic patients.*Hepatitis B and C serology*- While essential to identify the **underlying etiology** of liver disease, it does not explain the acute clinical concern of **rapid weight loss**.- Viral hepatitis can coexist with alcohol-related damage, but it is not the most urgent test to exclude the immediate threat of **malignancy**.*Abdominal ultrasound with Doppler*- This is a critical imaging tool to visualize **liver masses** and assess **portal vein flow**, but it is typically performed in conjunction with blood markers.- Although indicated, biochemical screening for **HCC** via AFP is often prioritized or performed simultaneously to assess the risk of malignancy in a primary care setting.*Serum ferritin and transferrin saturation*- These tests screen for **hereditary haemochromatosis**, which can lead to cirrhosis and increased HCC risk.- While relevant for a complete **liver screen**, they do not address the high suspicion of **HCC** suggested by the patient's weight loss and jaundice.*Liver biopsy with histological assessment*- Biopsy is generally **not the initial investigation** for suspected HCC due to the risk of **tumor seeding** and bleeding complications in cirrhotic patients.- Diagnosis of HCC in a cirrhotic liver is often made using **non-invasive criteria** (triphasic CT/MRI and AFP) rather than histology.
Question 12: A 31-year-old woman presents with a 10-week history of fatigue and 5kg weight loss. She reports episodes of sweating and tremor that resolve after eating. Her mother has type 1 diabetes. Examination reveals a BMI of 19, pulse 92 bpm regular, BP 118/74 mmHg, and a smooth, non-tender thyroid enlargement. Blood tests show: fasting glucose 3.1 mmol/L, HbA1c 34 mmol/mol, TSH 0.1 mU/L, free T4 28 pmol/L. What is the most appropriate next investigation?
A. 72-hour fast with glucose and insulin monitoring
B. Thyroid antibodies (anti-TPO and anti-TSH receptor) (Correct Answer)
C. CT pancreas with contrast
D. Serum insulin, C-peptide and sulphonylurea screen
E. Thyroid ultrasound scan
Explanation: ***Thyroid antibodies (anti-TPO and anti-TSH receptor)***
- The patient presents with clear biochemical **thyrotoxicosis** (low TSH, high free T4) and clinical features like **tachycardia**, weight loss, and a **smooth, non-tender thyroid enlargement**, all highly suggestive of **Graves' disease**.
- Testing for **TSH receptor antibodies (TRAb)** is crucial for confirming Graves' disease, while **anti-TPO antibodies** help establish the autoimmune nature of the thyroid disorder.
*72-hour fast with glucose and insulin monitoring*
- This investigation is the gold standard for diagnosing causes of endogenous hyperinsulinemic hypoglycemia, such as an **insulinoma**.
- However, the patient's prominent **thyrotoxicosis** must be investigated first, as it could be contributing to the observed hypoglycemia through increased glucose utilization.
*CT pancreas with contrast*
- This imaging modality is typically used to localize a pancreatic lesion like an **insulinoma** once biochemical evidence strongly points towards endogenous hyperinsulinism.
- It is not the appropriate initial step given the overt signs and biochemical confirmation of a **thyroid disorder** as the primary issue.
*Serum insulin, C-peptide and sulphonylurea screen*
- These tests are essential for characterizing hypoglycemia by evaluating endogenous insulin production and ruling out exogenous insulin or **sulfonylurea** use.
- While the patient has hypoglycemia, the most pressing diagnostic priority is to confirm the cause of **thyrotoxicosis**, which could explain the other symptoms.
*Thyroid ultrasound scan*
- A thyroid ultrasound provides detailed anatomical information about the thyroid gland, assessing for **nodules**, size, and vascularity.
- However, for a diffuse, smooth goiter with overt hyperthyroidism, **antibody testing** is more specific for determining the etiology (e.g., Graves' disease versus other causes of thyrotoxicosis) than structural imaging.
Question 13: According to current evidence-based guidelines for the assessment of undifferentiated symptoms in primary care, which statement best reflects the concept of 'safety netting' in patients presenting with non-specific symptoms such as fatigue or weight loss?
A. Arranging routine follow-up in 4-6 weeks to review symptom progression regardless of initial investigation results
B. Providing clear verbal and written information about symptoms/signs that should prompt re-consultation, with specific timeframe for review or re-contact (Correct Answer)
C. Performing comprehensive screening investigations to exclude serious pathology before discharging the patient
D. Referring all patients with persistent symptoms lasting >6 weeks to secondary care for specialist assessment
E. Documenting that the patient has been advised to return if symptoms worsen or new symptoms develop
Explanation: ***Providing clear verbal and written information about symptoms/signs that should prompt re-consultation, with specific timeframe for review or re-contact***- **Safety netting** is a diagnostic strategy that empowers patients by providing specific **red flags**, expected timeframes for symptom resolution, and clear instructions for re-accessing care.- It manages **diagnostic uncertainty** effectively by ensuring that serious pathology is caught early if symptoms evolve beyond the initial presentation.*Arranging routine follow-up in 4-6 weeks to review symptom progression regardless of initial investigation results*- This approach is a **fixed review** strategy rather than true safety netting, which focuses on identifying **concerning changes** as they occur.- Routine follow-up for every patient is often **inefficient** and may delay care if critical symptoms develop before the scheduled appointment.*Performing comprehensive screening investigations to exclude serious pathology before discharging the patient*- This describes a **rule-out strategy** using investigations, which can lead to **over-diagnosis** and incidental findings in primary care.- Safety netting is intended to supplement, not replace, clinical judgment when **initial low-risk** symptoms do not yet justify invasive testing.*Referring all patients with persistent symptoms lasting >6 weeks to secondary care for specialist assessment*- This is a **referral pathway** protocol rather than a primary care consultation technique used to manage individual patient risk.- Safety netting aims to maintain the **continuity of care** in the community unless specific clinical triggers for specialist intervention are met.*Documenting that the patient has been advised to return if symptoms worsen or new symptoms develop*- Documentation is a **medicolegal requirement**, but vague advice to "return if worse" is considered **ineffective safety netting** due to lack of specificity.- High-quality safety netting requires **specific symptoms** (e.g., "if you develop a new lump") and a defined **time-limited** action plan.
Question 14: A 59-year-old woman with chronic widespread pain managed with amitriptyline 50mg nocte presents for pain review. She describes the pain as 'burning and tingling' in her feet and legs, worse at night, partially relieved by walking around. She has had type 2 diabetes for 12 years. Examination reveals diminished sensation to light touch and pinprick in both feet in stocking distribution, absent ankle reflexes, but normal proprioception and vibration sense. Her HbA1c is 76 mmol/mol (9.1%). What is the most appropriate next step in pain management?
A. Switch to duloxetine 60mg once daily (Correct Answer)
B. Add tramadol 50mg when required for breakthrough pain
C. Increase amitriptyline to 75mg nocte
D. Add gabapentin starting at 300mg nocte with gradual titration
E. Refer to pain clinic for specialist management
Explanation: ***Switch to duloxetine 60mg once daily***
- The patient presents with **diabetic peripheral neuropathy** (burning pain, stocking distribution, absent reflexes); **duloxetine** is a first-line agent specifically licensed and highly effective for this condition.
- Switching is preferred over adding medications to limit **polypharmacy** and side effects, and duloxetine may provide better relief for this specific neuropathic profile than continuing TCAs.
*Add tramadol 50mg when required for breakthrough pain*
- **Tramadol** is generally not recommended for the long-term management of **neuropathic pain** due to the risk of dependence and limited efficacy compared to first-line agents.
- NICE guidelines prioritize **modifying maintenance therapy** (like duloxetine or gabapentinoids) rather than using "as required" opioids for chronic nerve pain.
*Increase amitriptyline to 75mg nocte*
- While **amitriptyline** is a first-line option, the maximum dose for neuropathic pain is usually reached at 75mg, but higher doses carry a significant burden of **anticholinergic side effects**.
- Given the suboptimal response and the clear development of diabetic-specific symptoms, switching to a different **first-line class** like an SNRI is often more effective than pushing TCA limits.
*Add gabapentin starting at 300mg nocte with gradual titration*
- While **gabapentin** is a valid first-line choice for neuropathic pain, adding it to amitriptyline increases the risk of **sedation and dizziness** compared to switching to a single agent.
- Monotherapy with **duloxetine** is typically prioritized for diabetic neuropathy before attempting combination therapy with **gabapentinoids**.
*Refer to pain clinic for specialist management*
- **Specialist referral** is indicated for refractory cases where multiple first- and second-line pharmacological treatments have failed.
- This patient has only tried one medication (amitriptyline), so further **primary care management** with agents like duloxetine or pregabalin should be attempted first.
Question 15: A 43-year-old man with well-controlled HIV (CD4 count 520 cells/mm³, undetectable viral load on antiretroviral therapy) presents with a 9-week history of fever up to 38.7°C, night sweats, and 6kg weight loss. He reports no respiratory symptoms. Examination reveals temperature 38.4°C, cervical and axillary lymphadenopathy (multiple nodes 1-2cm, rubbery, non-tender), and mild hepatosplenomegaly. Chest X-ray is normal. Blood tests show: Hb 110 g/L, WCC 4.1×10⁹/L (lymphocytes 0.9×10⁹/L), platelets 165×10⁹/L, LDH 580 U/L (elevated). What is the most important next investigation?
A. CT chest, abdomen and pelvis
B. Excision biopsy of lymph node (Correct Answer)
C. Blood cultures and mycobacterial blood cultures
D. Bone marrow aspiration and trephine
E. Serum cytomegalovirus (CMV) PCR and Epstein-Barr virus (EBV) serology
Explanation: ***Excision biopsy of lymph node***
- This patient presents with classic **B symptoms** (fever, weight loss, night sweats), **generalized lymphadenopathy**, and **elevated LDH**, which are highly suggestive of **HIV-associated lymphoma** even with a high CD4 count.
- An **excision biopsy** is the gold standard as it preserves **lymph node architecture**, allowing for precise histological classification, immunohistochemistry, and flow cytometry for definitive diagnosis.
*CT chest, abdomen and pelvis*
- While **CT imaging** is essential for **staging** a suspected malignancy, it cannot provide the definitive **histopathological diagnosis** required to begin treatment.
- Imaging may identify further deep lymphadenopathy but will not distinguish between **lymphoma**, **tuberculosis**, or **sarcoidosis** without tissue sampling.
*Blood cultures and mycobacterial blood cultures*
- These are useful in evaluating **Fever of Unknown Origin (FUO)**, but the presence of persistent, rubbery lymphadenopathy and high LDH strongly shifts the priority toward **malignancy**.
- **Mycobacterial infections** usually present with more significant immunosuppression (CD4 <200) or specific pulmonary findings, which are not present here.
*Bone marrow aspiration and trephine*
- **Bone marrow examination** is typically part of the **staging process** for lymphoma rather than the initial diagnostic step for accessible peripheral lymphadenopathy.
- It is less likely to yield a definitive subtype diagnosis compared to direct **tissue biopsy** of an enlarged node.
*Serum cytomegalovirus (CMV) PCR and Epstein-Barr virus (EBV) serology*
- While **EBV** is associated with HIV-related lymphomas, serology or PCR is not diagnostic of the tumor itself and cannot replace **tissue histology**.
- **CMV** usually presents with specific organ involvement (e.g., retinitis, colitis) and is rare in a patient with a stable **CD4 count of 520 cells/mm³**.
Question 16: Which of the following patient presentations would meet the NICE definition for requiring a 2-week wait referral under the suspected cancer pathway for unexplained weight loss in adults?
A. A 62-year-old man with 4kg weight loss over 6 months and lethargy with normal examination
B. A 58-year-old woman with 6kg weight loss over 8 weeks and upper abdominal pain with normal blood tests
C. A 71-year-old man with 5kg weight loss over 12 weeks and change in bowel habit with iron deficiency anaemia (Correct Answer)
D. A 48-year-old woman with 8kg weight loss over 4 months and loss of appetite with normal examination and investigations
E. A 55-year-old man with 4% body weight loss over 10 weeks with night sweats and normal chest X-ray
Explanation: ***A 71-year-old man with 5kg weight loss over 12 weeks and change in bowel habit with iron deficiency anaemia***
- Under **NICE NG12 guidelines**, patients aged **60 and over** with unexplained **iron deficiency anaemia** or **changes in bowel habit** meet criteria for a 2-week wait (2WW) referral for suspected **colorectal cancer**.
- The presence of significant **unexplained weight loss** in combination with these site-specific red flags reinforces the urgent need for a suspected cancer pathway referral.
*A 62-year-old man with 4kg weight loss over 6 months and lethargy with normal examination*
- **Lethargy** and weight loss are non-specific symptoms; without localized findings or abnormal investigations, they do not automatically trigger a **2WW referral** under NG12.
- The appropriate clinical step is to perform **primary care investigations** (e.g., FBC, ESR/CRP, U&Es) before referring to a specific pathway.
*A 58-year-old woman with 6kg weight loss over 8 weeks and upper abdominal pain with normal blood tests*
- While **upper abdominal pain** and weight loss in those over 55 can warrant **urgent direct access endoscopy**, the description of "normal blood tests" would generally precede or be part of the initial workup for a lower-risk profile.
- For a 2WW for **pancreatic cancer**, NICE specifically looks for weight loss plus specific features like **jaundice** or age over 60 with new-onset diabetes.
*A 48-year-old woman with 8kg weight loss over 4 months and loss of appetite with normal examination and investigations*
- Significant **unexplained weight loss** alone in a patient under 60 without site-specific symptoms or abnormal **blood tests** does not meet the 2WW threshold.
- This patient requires careful monitoring and potentially a **non-site-specific** (vague symptoms) pathway referral if available, but not a standard 2WW organ-specific pathway.
*A 55-year-old man with 4% body weight loss over 10 weeks with night sweats and normal chest X-ray*
- **Night sweats** and weight loss may suggest **lymphoma**, but NICE criteria prioritize physical signs like **lymphadenopathy** or splenomegaly for urgent referral.
- A **4% weight loss** is just below the typical clinical threshold of **5%** used to define significant weight loss, and a normal CXR reduces the urgency for a lung cancer pathway.
Question 17: A 74-year-old man presents with a 14-week history of progressive fatigue, loss of appetite, and 11kg unintentional weight loss. He has noticed increasing abdominal distension and ankle swelling. He has a 40 pack-year smoking history. Examination reveals cachexia, mild jaundice, ascites (positive fluid thrill), hepatomegaly (liver edge 6cm below costal margin, irregular and hard), and bilateral pitting ankle oedema. What is the most appropriate initial investigation?
A. Upper gastrointestinal endoscopy
B. Ultrasound abdomen with Doppler (Correct Answer)
C. Liver function tests, alpha-fetoprotein, and hepatitis B/C serology
D. CT chest, abdomen and pelvis with contrast
E. Ascitic tap for cell count, culture, and cytology
Explanation: ***Ultrasound abdomen with Doppler***- **Ultrasound** is the recommended **initial investigation** for suspected hepatic malignancy as it is non-invasive, quick, and highly effective at identifying **liver lesions** and confirming **ascites**.- The addition of **Doppler** allows for the assessment of **vascular patency**, which is crucial to rule out complications like **portal vein thrombosis** in a patient with new-onset ascites.*Upper gastrointestinal endoscopy*- This is primarily used to investigate suspected **upper GI cancers** or to screen for **oesophageal varices** in known cirrhotics but is not the first-line tool for an irregular, hard **hepatomegaly**.- While the patient has weight loss, the physical examination findings of an enlarged, irregular liver point specifically toward **primary or metastatic liver disease**.*Liver function tests, alpha-fetoprotein, and hepatitis B/C serology*- Although these blood tests provide essential diagnostic information regarding **liver dysfunction** and potential **Hepatocellular Carcinoma (HCC)**, they do not provide the anatomical detail needed for initial evaluation.- **Imaging** must take precedence over tumor markers like **AFP** to characterize the structural abnormalities detected on palpation.*CT chest, abdomen and pelvis with contrast*- **CT scanning** is a vital tool for **staging** and detailed characterization of malignancy, but it is typically performed after an initial screening ultrasound identifies a mass.- Ultrasound is more readily available and safer as a first step to confirm the presence of **ascites** and guide the focus of further cross-sectional imaging.*Ascitic tap for cell count, culture, and cytology*- An **ascitic tap** is necessary to calculate the **SAAG** and look for **malignant cells**, but it should be performed following or alongside imaging to ensure the procedure is safe.- Imaging like ultrasound is required first to determine if the fluid is **loculated** and to define the underlying cause of the ascites, such as a **liver mass**.
Question 18: A 38-year-old woman presents with a 6-month history of severe fatigue, unrefreshing sleep, and post-exertional malaise lasting >24 hours after minimal activity. She reports cognitive difficulties ('brain fog'), orthostatic intolerance with dizziness on standing, and flu-like symptoms. She was previously very active but now struggles with daily activities. Symptoms began after a viral illness. Examination and extensive investigations including FBC, TFTs, glucose, vitamin B12, folate, ferritin, CRP, and cortisol are all normal. What is the most appropriate diagnosis?
A. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) (Correct Answer)
B. Fibromyalgia
C. Depression with somatic symptoms
D. Post-viral fatigue syndrome
E. Functional neurological disorder
Explanation: ***Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)***
- The diagnosis is confirmed by the presence of debilitating **fatigue**, **unrefreshing sleep**, **cognitive dysfunction**, and the hallmark sign of **post-exertional malaise (PEM)** lasting over 24 hours.
- These symptoms, persisting for at least **6 months** and with **normal extensive investigations**, meet the criteria for CFS/ME, often triggered by a preceding **viral illness**.
*Fibromyalgia*
- While it shares symptoms like fatigue and sleep issues, the primary feature of fibromyalgia is **widespread chronic pain** and tenderness at specific points.
- This patient's presentation is dominated by **post-exertional malaise** and fatigue rather than the characteristic diffuse musculoskeletal pain required for fibromyalgia.
*Depression with somatic symptoms*
- Depression frequently causes fatigue and sleep disturbance, but it typically lacks the characteristic **post-exertional malaise** and **orthostatic intolerance** seen in CFS/ME.
- Patients with depression often experience an **improvement in energy** with activity, whereas patients with CFS/ME experience a clinical worsening (PEM).
*Post-viral fatigue syndrome*
- This term describes fatigue following an infection that lasts **less than 3 to 6 months**; once symptoms persist beyond this duration with specific criteria, it is classified as **CFS/ME**.
- Since this patient has been symptomatic for **6 months**, the more definitive diagnosis of CFS/ME is appropriate.
*Functional neurological disorder*
- FND typically involves specific **motor or sensory symptoms** (e.g., limb weakness, non-epileptic seizures) that are often inconsistent on examination.
- While fatigue can co-occur, FND does not explain the full cluster of **orthostatic intolerance**, **PEM**, and **flu-like symptoms** provided in this history.
Question 19: A 69-year-old man with no significant past medical history presents with a 12-week history of fever (documented temperatures 38.2-38.9°C), 8kg weight loss, and progressive fatigue. He has diffuse myalgia but no specific pain. Examination reveals temperature 38.6°C, no lymphadenopathy, heart sounds normal, chest clear, and no organomegaly. Blood tests show: Hb 102 g/L (normochromic, normocytic), WCC 11.2×10⁹/L, platelets 445×10⁹/L, ESR 95 mm/hr, CRP 88 mg/L, ALP 156 U/L (other LFTs normal). Blood cultures (3 sets) are negative. Chest X-ray and urine culture are normal. What is the single most important investigation to perform next?
A. Temporal artery ultrasound or biopsy (Correct Answer)
B. CT chest, abdomen and pelvis with contrast
C. Echocardiography (transthoracic)
D. Bone marrow aspiration and trephine
E. Autoimmune screen including ANA, ANCA, and rheumatoid factor
Explanation: ***Temporal artery ultrasound or biopsy***- This patient presents with **fever of unknown origin (FUO)**, **weight loss**, and **anemia of chronic disease**, which in an elderly patient with high **ESR/CRP**, **diffuse myalgias**, and elevated **ALP**, strongly suggests **Giant Cell Arteritis (GCA)**.- Prompt diagnosis via **temporal artery ultrasound** (looking for the **halo sign**) or **biopsy** is crucial for GCA due to the risk of **irreversible vision loss**, making it the most urgent next investigation.*CT chest, abdomen and pelvis with contrast*- While a comprehensive **CT scan** is often part of a **FUO workup** to identify occult malignancy or deep-seated infection, the specific clinical picture points more strongly towards **vasculitis**.- Although GCA can cause **aortitis** which may be seen on CT, it is not the initial diagnostic test for GCA itself, which requires direct assessment of the temporal arteries.*Echocardiography (transthoracic)*- This investigation is primarily used to diagnose **infective endocarditis**, a less likely cause of FUO in this patient given **negative blood cultures** and the absence of a new **heart murmur**.- While culture-negative endocarditis exists, the overall presentation of diffuse myalgia and isolated elevated ALP is more consistent with a rheumatological condition like GCA.*Bone marrow aspiration and trephine*- **Bone marrow biopsy** is an invasive procedure typically reserved for cases where **hematological malignancy** or **granulomatous infection** (e.g., disseminated TB) is suspected and other less invasive tests have been inconclusive.- The **normocytic anemia** and **thrombocytosis** are non-specific findings often seen in conditions causing systemic inflammation and do not, in themselves, prioritize bone marrow examination as the most important next step.*Autoimmune screen including ANA, ANCA, and rheumatoid factor*- An **autoimmune screen** assesses for conditions like **SLE** or **ANCA-associated vasculitis**, which usually present with more specific organ system involvement (e.g., rash, arthritis, renal disease).- While useful in a broad FUO workup, these conditions are less likely to be the primary diagnosis in this elderly patient with classic GCA symptoms and high inflammatory markers, making the specific investigation for GCA more urgent.
Question 20: A 51-year-old woman presents with a 9-month history of widespread pain affecting her neck, back, shoulders, and hips bilaterally. She reports severe fatigue, non-restorative sleep despite 9 hours in bed, and difficulty concentrating. Pain scores 7/10 daily. She has tried paracetamol and ibuprofen with minimal benefit. Examination reveals multiple tender points but no synovitis or muscle weakness. Blood tests including FBC, CRP, ESR, TFTs, calcium, and vitamin D are normal. What is the most appropriate next management step?
A. Commence duloxetine and arrange cognitive behavioural therapy referral (Correct Answer)
B. Refer to rheumatology for specialist assessment
C. Start prednisolone 15mg daily for suspected polymyalgia rheumatica
D. Arrange MRI spine to exclude structural pathology
E. Prescribe amitriptyline for pain and sleep, with review in 2 weeks
Explanation: ***Commence duloxetine and arrange cognitive behavioural therapy referral***- This patient presents with classic **fibromyalgia** features, including chronic widespread pain, fatigue, **non-restorative sleep**, and cognitive dysfunction with normal inflammatory markers.- NICE guidelines for **chronic primary pain** recommend a multimodal approach using **SNRIs** (like duloxetine) and psychological therapies such as **Cognitive Behavioural Therapy (CBT)**.*Refer to rheumatology for specialist assessment*- **Fibromyalgia** is a clinical diagnosis that should ideally be managed in **primary care** once secondary causes are excluded by normal blood tests.- Specialist referral is typically reserved for diagnostic uncertainty or cases **refractory** to standard primary care interventions.*Start prednisolone 15mg daily for suspected polymyalgia rheumatica*- Although the age and proximal muscle involvement (shoulders/hips) may suggest **Polymyalgia Rheumatica (PMR)**, the 9-month history and **normal CRP/ESR** make this diagnosis unlikely.- PMR is an **inflammatory** condition characterized by elevated inflammatory markers and a rapid response to steroids, whereas fibromyalgia does not respond to corticosteroids.*Arrange MRI spine to exclude structural pathology*- Imaging is not indicated in this case as there are no **red flags** (e.g., focal neurological deficits, progressive motor weakness, cauda equina symptoms) or history of trauma to suggest structural spinal pathology.- Extensive imaging in suspected fibromyalgia can lead to the incidental finding of **degenerative changes** which may be irrelevant to the patient's centralized pain syndrome and cause unnecessary anxiety.*Prescribe amitriptyline for pain and sleep, with review in 2 weeks*- While low-dose **tricyclic antidepressants** like amitriptyline were historically used for fibromyalgia, current guidelines often prioritize **SNRIs** (duloxetine) or Gabapentinoids due to better tolerability profiles or specific mechanisms for neuropathic-like pain.- Two weeks is often insufficient to evaluate the full therapeutic benefit of antidepressants in chronic pain management, and a multimodal approach including **CBT** is generally preferred from the outset.
