General Medicine

Oliver Hart

Welcome to the General Medicine podcast. This episode aims to recap all of the important aspects of each topic so that you feel confident in your knowledge.

Alys Davies

We’ve split the episode into two parts. First, we will go through a topic breakdown. Then, we will move into our rapid-recall question round, a section where we test your knowledge on the topics we have covered in the episode.

Oliver Hart

There are five General Medicine topics to cover in this episode, with tips and reminders dotted throughout.

Alys Davies

If you are using this podcast as revision for upcoming exams, please look on official websites for specifics on question weighting and structure. In this podcast, we will be explaining each topic through realistic clinical scenarios and presentations. This is to help link up your knowledge within a topic. It may also simulate scenarios you’ll encounter in exams.

Oliver Hart

So, let’s get started.

Oliver Hart

Our first topic is allergy. We are going to cover it in three parts: the hypersensitivity classification that underpins all allergic disease, the specific conditions (allergies like food, drug, latex and venom), and then urticaria and angioedema.

Alys Davies

The Gell and Coombs classification divides hypersensitivity into four types. Type I is IgE-mediated: the immediate hypersensitivity reaction. The mechanism is mast cell degranulation triggered by IgE bound to an allergen. The clinical manifestations are urticaria, angioedema, and anaphylaxis. Onset is within minutes. Type IV is delayed, T-cell mediated, and drives contact dermatitis and certain serious drug reactions like Stevens-Johnson syndrome.

Oliver Hart

This classification determines the clinical presentation you expect and the treatment you reach for. Type I reactions respond to adrenaline and antihistamines. Type IV reactions do not.

Alys Davies

Starting with food allergy. IgE-mediated food allergy causes immediate onset within minutes to two hours. Non-IgE-mediated food allergy, such as Food Protein-Induced Enterocolitis Syndrome (known as FPIES), causes delayed gastrointestinal symptoms, typically vomiting two to four hours after ingestion. The delayed timing here distinguishes it from the immediate IgE-mediated reaction.

Oliver Hart

A key point in drug allergies is that most patients labelled as penicillin-allergic are not truly allergic. Only ten to fifteen per cent are confirmed allergic on formal testing. An incorrect allergy forces patients towards broader-spectrum antibiotics, which contributes to resistance and increases side effects.

Alys Davies

The drug reaction mechanisms map onto the same Gell and Coombs framework. Type I gives immediate urticaria or anaphylaxis. Type II, cytotoxic, causes haemolytic anaemia. Type III, immune complex, causes serum sickness and vasculitis. Type IV includes the severe cutaneous reactions: Stevens-Johnson Syndrome (SJS for short), the DRESS mnemonic, and fixed drug eruption.

Alys Davies

The DRESS mnemonic is Drug Reaction with Eosinophilia and Systemic Symptoms. The clinical picture is fever, a morbilliform rash, lymphadenopathy, eosinophilia, and internal organ involvement. It can be fatal. Onset is typically two to eight weeks after starting the drug, which makes it easy to miss the causative agent. The most commonly responsible drugs are allopurinol, carbamazepine, phenytoin, and sulphonamides.

Oliver Hart

Stevens-Johnson Syndrome (known as SJS) and Toxic Epidermal Necrolysis (known as TEN), sit at the most severe end of the cutaneous drug reaction spectrum. The distinction between them is the extent of skin involvement. SJS affects less than ten per cent of body surface area. TEN affects more than thirty per cent. Overlap is between ten and thirty per cent. Both are dermatological emergencies: stop the causative drug, provide supportive care, and refer urgently to dermatology and burns specialists.

Alys Davies

A latex allergy is IgE-mediated. The associated phenomenon worth knowing is latex-fruit syndrome: cross-reactivity between latex proteins and certain foods. A venom allergy, from bee or wasp stings, is also IgE-mediated. A systemic allergic reaction to venom is an indication for venom immunotherapy, which is the only treatment that modifies the underlying allergy rather than just treating the acute reaction.

Oliver Hart

Urticaria is the skin manifestation of mast cell degranulation. It produces wheals that resolve within twenty-four hours without leaving bruising or hyperpigmentation. That resolution is what distinguishes urticaria from other rashes. Acute urticaria lasts less than six weeks and is usually IgE-mediated or triggered by a non-immune stimulus. Chronic urticaria lasts more than six weeks, and the vast majority of cases are chronic spontaneous urticaria, or CSU, which has an autoimmune mechanism.

Alys Davies

The treatment ladder for CSU follows a clear sequence. Start with standard-dose non-sedating antihistamines, such as cetirizine or loratadine. Before adding a second agent, step up to high-dose antihistamines: up to four times the standard dose is permitted. If symptoms persist, add omalizumab, the anti-IgE monoclonal antibody, for refractory cases.

Oliver Hart

Angioedema is deep tissue swelling involving the dermis, subcutaneous tissue, and submucosa. It often occurs alongside urticaria, but the critical distinction for management is the underlying mechanism. Histaminergic angioedema is driven by mast cell degranulation (the same mechanism as urticaria), and it responds to antihistamines and adrenaline. Bradykinin-mediated angioedema does not respond to either of those treatments.

Alys Davies

The two main causes of bradykinin-mediated angioedema are Hereditary Angioedema and ACE inhibitor therapy. HAE is autosomal dominant and caused by C1-inhibitor deficiency or dysfunction. The screening test is a persistently low C4. Triggers include trauma, oestrogen (including the oral contraceptive pill), and ACE inhibitors. ACE inhibitor-induced angioedema is also bradykinin-mediated because ACEi blocks the breakdown of bradykinin. In both cases, the management is to stop the trigger and use a bradykinin-targeted treatment: icatibant (a bradykinin B2 receptor antagonist) or C1-inhibitor concentrate.

Oliver Hart

Remember. ACE inhibitor-induced angioedema is bradykinin-mediated, so antihistamines and adrenaline will NOT work. Stop the ACEi and use icatibant or C1-inhibitor concentrate.

Oliver Hart

Topic two covers three related conditions: rhinitis, sinusitis, and eosinophilic disease. The link between them is that all three involve the upper airway and share some overlapping symptoms, so being able to classify them correctly determines the management.

Alys Davies

Rhinitis is inflammation of the nasal mucosa, and the first step is to classify it as allergic or non-allergic, because the treatment differs. Allergic rhinitis is IgE-mediated. Within that, the classification is seasonal versus perennial. Seasonal rhinitis, or hay fever, is caused by outdoor allergens. Perennial rhinitis is year-round, often driven by indoor allergens.

Oliver Hart

The symptoms are the same across both types, which is why the history of timing and triggers is so important. Treatment follows a stepladder. For moderate to severe disease, intranasal corticosteroids, such as fluticasone or mometasone, are the most effective treatment for nasal symptoms. Oral non-sedating antihistamines work better for predominantly ocular symptoms or mild disease, and the two can be combined. For severe uncontrolled disease, allergen immunotherapy is the next step.

Alys Davies

Non-allergic rhinitis is not IgE-mediated, so skin prick testing will be negative. The main subtypes are vasomotor rhinitis (triggered by temperature change, strong smells, alcohol, and perfume), occupational rhinitis from workplace exposures, and rhinitis medicamentosa, which is rebound congestion caused by overuse of topical nasal decongestants like xylometazoline. That last one is iatrogenic and common: the decongestant that was meant to help becomes the cause of the problem.

Oliver Hart

Sinusitis often follows rhinitis or a viral upper respiratory tract infection. The important clinical point is that most acute sinusitis is viral and self-limiting, so antibiotics are not indicated routinely. They should be reserved for specific situations: symptoms lasting more than ten days without improvement, severe symptoms, or an immunocompromised patient. The most common bacterial causes are Streptococcus pneumoniae and Haemophilus influenzae. First-line antibiotic is amoxicillin or doxycycline.

Alys Davies

Moving from the upper airway to conditions characterised by eosinophilic infiltration: these are distinct conditions, but the eosinophilia is the thread linking them. The two conditions that come up most often are Eosinophilic Oesophagitis and EGPA.

Oliver Hart

Eosinophilic Oesophagitis, or EoE, is defined by dense eosinophilic infiltration of the oesophageal epithelium: fifteen or more eosinophils per high-power field on biopsy. The presentation is dysphagia, food bolus obstruction, and heartburn refractory to proton pump inhibitors. EoE is not acid-related, so it does not respond to PPIs the way GORD does. Endoscopy shows characteristic features: rings (sometimes described as trachealization), longitudinal furrows, and exudates. Treatment starts with a PPI trial to exclude GORD. If symptoms persist, topical steroids, such as swallowed fluticasone or orodispersible budesonide, are used. Dietary elimination therapy, particularly the six-food elimination diet, is also effective.

Alys Davies

Eosinophilic Granulomatosis with Polyangiitis (also known as EGPA, previously called Churg-Strauss syndrome) is at the severe end of eosinophilic disease. It is an ANCA-associated vasculitis, and its clinical triad is severe asthma, blood eosinophilia above ten per cent, and granulomatous vasculitis affecting small vessels. A characteristic feature is peripheral neuropathy, specifically mononeuritis multiplex. ANCA is positive in approximately forty per cent of cases, usually MPO-ANCA, also known as pANCA. Treatment is high-dose prednisolone, with cyclophosphamide added for severe organ-threatening disease.

Oliver Hart

Remember. In EoE, symptoms overlap with GORD but it is NOT acid-related. PPIs may not help, and diagnosis requires biopsy showing fifteen or more eosinophils per high-power field.

Oliver Hart

Topic three is antimicrobial resistance and stewardship. We will cover the four main mechanisms by which bacteria develop resistance, apply them to the organisms that matter clinically, and then look at C. difficile, which is a direct consequence of antibiotic misuse.

Alys Davies

There are four key mechanisms. The first is enzymatic inactivation: the bacterium produces an enzyme that destroys the antibiotic before it can act. The most important example clinically is beta-lactamases, which hydrolyse the beta-lactam ring. ESBLs, or Extended-Spectrum Beta-Lactamases, are the most common type in clinical practice, found mainly in E. coli and Klebsiella. They confer resistance to penicillins and most cephalosporins. ESBL infections are treated with carbapenems: meropenem or ertapenem.

Oliver Hart

Carbapenemase-producing organisms, or CPOs, are at the top of the resistance hierarchy. The main carbapenemases are KPC, NDM-1, and OXA-48. These organisms are resistant to carbapenems, which leaves very few treatment options: colistin, ceftazidime-avibactam, or aztreonam-avibactam, depending on the carbapenemase type.

Alys Davies

The second mechanism is target site modification: the bacterium changes the structure of the target so the antibiotic can no longer bind. The key example is MRSA, which carries the mecA gene encoding PBP2a, a modified penicillin-binding protein with low affinity for all beta-lactam antibiotics. MRSA is therefore resistant to virtually all beta-lactams, and vancomycin is first-line treatment. VRSA and VRE extend this further by acquiring resistance to vancomycin. Treatment then switches to linezolid or daptomycin.

Oliver Hart

The third mechanism is efflux pumps: membrane transport proteins that actively export antibiotics out of the bacterial cell before they can act. This is a key mechanism in Pseudomonas aeruginosa. The fourth is reduced permeability: bacteria lose or downregulate outer membrane porin channels, reducing antibiotic entry into the cell. This is also important in Pseudomonas and Acinetobacter.

Alys Davies

Knowing MRSA's resistance mechanism explains its management. Because it is resistant to all beta-lactams, decolonisation and treatment require agents from different drug classes. MRSA decolonisation is required before elective surgery in known carriers: the protocol is nasal mupirocin ointment for five days, plus chlorhexidine body wash. For established MRSA infection, vancomycin IV is first-line, and trough levels must be monitored. Alternatives depending on infection site include teicoplanin, linezolid, and daptomycin.

Oliver Hart

Clostridioides difficile ( known as C. Diff for short) is a bacterium that causes severe inflammation of the colon and is a direct consequence of antibiotic disruption of the normal gut flora, which is why it sits naturally in this topic. It is a Gram-positive anaerobic spore-forming bacillus, and the clinical context is almost always recent antibiotic use. The highest-risk antibiotics are clindamycin, cephalosporins, and fluoroquinolones. PPIs and hospitalisation are additional risk factors.

Alys Davies

C. diff produces two toxins: Toxin A, enterotoxin. And Toxin B, cytotoxin. Together they cause pseudomembranous colitis, with yellow plaques on the colonic mucosa visible at colonoscopy. Diagnosis uses GDH antigen plus toxin EIA, or stool PCR. Treatment has recently changed: for a first episode, fidaxomicin is now first-line. Oral vancomycin is the alternative if fidaxomicin is unavailable. Metronidazole is no longer first-line for any severity of C. diff infection. This is a recent guideline change from NICE NG199, which may appear in exams.

Oliver Hart

For severe or complicated disease, use IV metronidazole plus oral vancomycin. For recurrent infection, fidaxomicin again, or faecal microbiota transplant (FMT), which has strong evidence for preventing further recurrence.

Alys Davies

Antimicrobial stewardship is the clinical practice that sits alongside the science of resistance. It means prescribing the right drug, at the right dose, by the right route, for the right duration. In practice: de-escalate based on culture results, switch from IV to oral when the patient is absorbing medication and improving clinically, and review every antibiotic prescription at forty-eight to seventy-two hours. These habits reduce selection pressure and preserve the efficacy of the drugs we have.

Oliver Hart

Remember. Metronidazole is no longer first-line for any severity of infection. Fidaxomicin or oral vancomycin are now first-line per NICE and PHE guidance on C. Diff infections.

Oliver Hart

Topic four is bacterial meningitis and encephalitis. We are going to cover the organisms by age group, the clinical presentation, the critical decision about whether to scan before treating, the empirical treatment, CSF findings, and then encephalitis as a distinct condition that shares some features but requires a different approach.

Alys Davies

The organism responsible for bacterial meningitis varies significantly by age, and knowing this guides empirical treatment. In neonates: Group B Streptococcus, E. coli, and Listeria monocytogenes. In children and young adults: Neisseria meningitidis is the most common organism in under-25s. In adults overall: Streptococcus pneumoniae is the most common cause and carries the highest mortality. In the elderly and immunocompromised: Listeria re-emerges as a significant pathogen. This age-related pattern explains why ampicillin is added to empirical treatment in certain groups: it covers Listeria, which ceftriaxone does not.

Oliver Hart

The classic triad of bacterial meningitis is neck stiffness, photophobia, and fever. Fewer than fifty per cent of patients present with all three, so the absence of one feature does not exclude the diagnosis. Altered consciousness, or a reduced GCS, is a poor prognostic sign and warrants urgent action. A non-blanching petechial or purpuric rash indicates meningococcal septicaemia. This is a medical emergency requiring immediate IV benzylpenicillin or ceftriaxone without waiting for anything else.

Alys Davies

Kernig's sign (inability to extend the knee with the hip flexed at ninety degrees) and Brudzinski's sign (involuntary knee flexion on passive neck flexion) are the classic examination findings, but their sensitivity is modest. A negative sign does not exclude the diagnosis.

Oliver Hart

The most important decision in managing bacterial meningitis is whether to perform the lumbar puncture immediately or obtain a CT first. LP is safe to perform without CT if all five criteria are met: no focal neurological signs, no papilloedema, GCS above twelve, no immunocompromise, and no seizure in the preceding week. If any one of those criteria is not met, CT should be done first.

Alys Davies

The rule that overrides everything else is this: antibiotics must not be delayed for CT or LP. If there is any doubt, give the antibiotic first. Imaging and lumbar puncture follow. Every minute of delay increases mortality and the risk of permanent neurological damage. Culture results are still useful even after one or two doses of antibiotic, so starting treatment does not make the diagnosis impossible.

Oliver Hart

Empirical treatment for adults is ceftriaxone two grams IV twice daily. Dexamethasone, 0.15 milligrams per kilogram four times daily for four days, is added alongside antibiotics. It reduces hearing loss and neurological sequelae, and the benefit is most clearly demonstrated in pneumococcal meningitis. In patients over sixty, the immunocompromised, or pregnant women, add ampicillin to cover Listeria monocytogenes, which ceftriaxone does not cover.

Alys Davies

CSF analysis confirms the diagnosis and distinguishes bacterial from viral meningitis. In bacterial meningitis: cloudy fluid, neutrophilia above one thousand cells per microlitre, protein above one gram per litre, and glucose below 2.2 millimoles per litre, or a CSF to blood glucose ratio below 0.6. In viral meningitis: the fluid is clear, there are lymphocytes rather than neutrophils, protein is mildly raised, and glucose is normal.

Oliver Hart

Encephalitis is inflammation of the brain parenchyma itself, distinct from meningitis, which is inflammation of the meninges. The clinical picture includes fever, altered consciousness, and focal neurological signs or psychiatric symptoms. HSV encephalitis is the most common treatable cause. It characteristically involves the temporal lobes; MRI shows high signal in the temporal and frontal lobes. The rule is to treat empirically with IV aciclovir ten milligrams per kilogram three times daily without waiting for the PCR result. Time is brain tissue.

Alys Davies

Anti-NMDA receptor encephalitis is an autoimmune cause that is increasingly recognised. It typically affects young women and presents with psychiatric symptoms (psychosis, behavioural change) before the neurological syndrome becomes apparent. It is strongly associated with ovarian teratoma. Diagnosis is by detecting anti-NMDA receptor antibodies in CSF. Treatment is immunotherapy (steroids, IVIG, or plasma exchange) plus surgical removal of the teratoma if present.

Oliver Hart

Remember. Do not delay antibiotics for CT in bacterial meningitis. The antibiotic must be given first. Every minute of delay increases mortality and the risk of permanent neurological damage.

Oliver Hart

Topic five is infective endocarditis, referred to as IE in this episode. We are going to cover the diagnostic criteria, the organism by clinical context, the peripheral signs, blood cultures and treatment, and surgical indications.

Alys Davies

The Modified Duke Criteria provide the diagnostic framework for IE. Definite IE requires: two major criteria, OR one major plus three minor criteria, OR five minor criteria. Major criteria are: positive blood cultures with a typical organism (Streptococcus viridans, Staphylococcus aureus, Enterococcus, or the HACEK group) OR echocardiographic evidence of endocarditis, defined as vegetation, abscess, or new valvular regurgitation.

Oliver Hart

Minor criteria include: predisposing cardiac condition or IV drug use, fever above thirty-eight degrees Celsius, vascular phenomena including septic emboli and Janeway lesions, immunological phenomena including Osler's nodes, Roth spots, and a positive rheumatoid factor, and microbiological evidence that does not meet major criteria.

Alys Davies

The organism responsible varies predictably with the clinical context, and knowing this pattern helps both diagnosis and empirical treatment. Native valve community-acquired IE: Streptococcus viridans, also called Strep oralis or Strep sanguis, is the classic organism. It enters the bloodstream from dental procedures. Acute native valve IE: Staphylococcus aureus, typically from a skin source, causes a more aggressive course. Prosthetic valve IE within two months of surgery is usually nosocomial: Staphylococcus epidermidis or MRSA. Prosthetic valve IE more than two months post-surgery: the organism profile shifts back towards Strep viridans. IE in IV drug users: Staphylococcus aureus is dominant, and the tricuspid valve is most commonly affected because venous blood flows to the right heart first.

Oliver Hart

The peripheral signs of IE arise from two processes: immune complex deposition and septic microemboli. Understanding which mechanism causes which sign helps you remember them. Osler's nodes are painful nodules on the finger and toe pulps. They are caused by immune complex deposition, so they are painful because the immune system is actively responding. Janeway lesions are painless erythematous macules on the palms and soles. They are caused by septic microemboli, small infected clots lodging in capillaries. Splinter haemorrhages are linear haemorrhages under the nail, also embolic. Roth spots are retinal haemorrhages with a pale centre, visible on fundoscopy. Finger clubbing and microscopic haematuria are also associated features.

Alys Davies

The key distinction is painful versus painless. Osler's nodes are painful: immune complex mediated. Janeway lesions are painless: embolic. The mechanism explains the symptom.

Oliver Hart

Blood cultures must be taken before antibiotics are started. This is the most important practical rule in IE. Take three sets from different venepuncture sites. Ten per cent of IE cases are culture-negative. The main causes are Coxiella burnetii (Q fever), Bartonella, and Tropheryma whipplei. These require serology and molecular diagnostics rather than standard culture.

Alys Davies

Empirical antibiotic treatment. For native valve IE without MRSA risk: amoxicillin plus low-dose gentamicin. If there is MRSA risk or a penicillin allergy use vancomycin. For prosthetic valve IE: vancomycin plus gentamicin plus rifampicin. Rifampicin is added because of its activity against biofilm-associated organisms, which is relevant for prosthetic material.

Oliver Hart

Surgery is indicated in specific circumstances: heart failure caused by valvular destruction, intracardiac abscess or fistula, persistent bacteraemia after seven to ten days of appropriate antibiotics, large vegetation above ten millimetres with high embolic risk, and prosthetic valve dehiscence. These indications reflect situations where antibiotics alone cannot control the infection or its cardiac consequences.

Alys Davies

Remember. Blood cultures MUST be taken BEFORE antibiotics. Antibiotics before cultures greatly increases the chance of culture-negative IE and delays the correct microbiological diagnosis.

Oliver Hart

Let’s move on to our rapid-recall.

Alys Davies

This section is all about what you know, and quickly!

Oliver Hart

We’ll ask you a question, give you a couple of seconds to answer, then give you the correct answer. Just try to shout out your answer in time!

Alys Davies

Question one: What is the key treatment difference between histaminergic angioedema and hereditary angioedema?

Oliver Hart

HAE is bradykinin-mediated and does not respond to antihistamines or adrenaline. It requires C1-inhibitor concentrate or icatibant.

Alys Davies

Question two: What is first-line treatment for moderate to severe allergic rhinitis?

Oliver Hart

Intranasal corticosteroids.

Alys Davies

Question three: Name one of the three antibiotic classes most associated with triggering a Clostridioides difficile infection?

Oliver Hart

You could have answered: Clindamycin, cephalosporins, or fluoroquinolones.

Alys Davies

Question four: What is no longer a recommended treatment for a first episode of C. difficile infection?

Oliver Hart

Metronidazole is no longer recommended as per NICE NG199 guidelines.

Alys Davies

Question five: In bacterial meningitis, name one of the five criteria needed before performing an LP, prior to or without a CT.

Oliver Hart

The five criteria are: no focal neurological signs, no papilloedema, GCS above twelve, no immunocompromise, and no seizure in the preceding week.

Alys Davies

Question six: What is the empirical antibiotic for bacterial meningitis in adults, and which steroid is added?

Oliver Hart

IV Ceftriaxone, typically two grams twice daily.

Alys Davies

Question seven: Which antibiotic is added for patients over sixty or immunocompromised, and why?

Oliver Hart

Ampicillin is added to cover Listeria monocytogenes, which ceftriaxone does not cover.

Alys Davies

Question eight: How many major Duke criteria are needed to diagnose definite infective endocarditis?

Oliver Hart

The answer is two major criteria. However, you can also diagnose with a combination of one major plus three minor, or five minor criteria.

Alys Davies

Question nine: In an IV drug user with infective endocarditis, which valve is most commonly affected?

Oliver Hart

The tricuspid valve is most commonly affected.

Alys Davies

Question ten: What does EGPA stand for?

Oliver Hart

EGPA stands for Eosinophilic Granulomatosis with Polyangiitis.

Alys Davies

That is your General Medicine rapid recall done.

Oliver Hart

Thank you for joining us for this episode.

Alys Davies

If you have any questions or would like to recap any of the topics we have gone through today, take a moment to look back over the module.

Oliver Hart

We will see you in the next episode. Bye!