GC071 It Is Red And Painful
A clinical approach to the differential diagnosis of a red, painful eye, encompassing conditions such as acute angle-closure glaucoma, anterior uveitis, keratitis, episcleritis, and scleritis that require urgent evaluation.
It Is Red and Painful — Cutaneous Infections (Bacterial, Viral, Fungal) & Blistering Diseases
This lecture, delivered by Prof. Henry H Chan, is a comprehensive tour of cutaneous infections and selected blistering diseases — conditions that present as "red, swollen, and painful" skin. It is a high-yield GC lecture because dermatology questions in HKUMed summative exams frequently test:
- Pattern recognition (spot diagnosis) of skin infections and blisters
- Clinical differentiation between conditions that look alike but carry very different prognoses (e.g., cellulitis vs. necrotising fasciitis)
- Pharmacology of antifungals and antivirals — mechanism of action, side effects, and drug selection
- Dermatological emergencies — necrotising fasciitis, SSSS, pemphigus
The lecture naturally divides into three infection categories (bacterial → viral → fungal), then pivots to blistering diseases (pemphigus vs. pemphigoid). Think of the lecture as answering: "The skin is red and painful — what's the organism, what's the depth, what's the danger, and how do I treat it?"
Cutaneous infections are classified by organism: Bacterial, Viral, Fungal [1]
This is the organising principle. Within each category, the depth of infection determines severity and management.
SECTION 1: CUTANEOUS BACTERIAL INFECTIONS
Due to Staphylococcus or Streptococcus. Vesicles or pustules that arise on erythematous base with crusting formation. In skin damaged by previous minor trauma such as scratching. [1]
Why it matters: Impetigo is the most superficial bacterial skin infection — it sits in the subcorneal layer (beneath the stratum corneum). Because the split is so superficial, blisters are flaccid and rupture easily, leaving the classic honey-coloured crust.
- Pathogenesis: Bacteria (usually S. aureus or Group A Strep) enter through micro-breaks in skin (scratching, insect bites, eczema). They produce exfoliative toxins that cleave desmoglein 1 in the granular layer → subcorneal split.
- Clinical features:
- Vesicles/pustules on erythematous base → rapid rupture → golden-yellow crusting
- Typically on face (perioral, perinasal) in children
- Non-bullous form (most common) vs. bullous form (S. aureus toxin-mediated)
- Diagnosis: Clinically and skin swab [1]
- Treatment: Oral cloxacillin and ampicillin, topical antibiotic [1]
- Why cloxacillin? It is a penicillinase-resistant penicillin → covers S. aureus.
- Why ampicillin? Covers Group A Strep.
- Topical agents (e.g., fusidic acid, mupirocin) for localised disease.
Exam Tip
Impetigo produces a subcorneal blister. This is the same level as the blistering classification table later in the lecture. If asked "at what level does the blister form in impetigo?" → subcorneal.
Erysipelas involves dermal lymphatics. Cellulitis involves deep dermis and subcutaneous tissue. Organisms: Streptococcus, Staphylococcus, Haemophilus influenzae. [1]
Why the distinction matters: Erysipelas is more superficial (dermis/lymphatics) and therefore has a sharply demarcated, raised, palpable border — you can feel the edge because the infection tracks along superficial lymphatic channels. Cellulitis is deeper (deep dermis + subcutaneous fat), so the border is poorly defined and diffuse.
| Feature | Erysipelas | Cellulitis |
|---|---|---|
| Depth | Superficial dermis + lymphatics | Deep dermis + subcutaneous tissue |
| Border | Sharply demarcated, raised, "step-off" edge | Poorly demarcated, diffuse |
| Surface | Peau d'orange (lymphatic obstruction → oedema around hair follicles) | Smooth erythema |
| Common organism | Group A Strep (most classic) | S. aureus, Group A Strep, H. influenzae |
| Common site | Face, lower limbs | Lower limbs (most common) |
-
Site of entry: minor skin break from scratching or tinea infection [1]
- Key clinical pearl: Always examine the toe webs! Interdigital tinea pedis is the most common portal of entry for lower limb cellulitis. Treating the tinea prevents recurrence.
-
Systemic symptoms common (fever, lymphadenitis) [1]
-
IV antibiotics: Ampicillin/Cloxacillin or Cephalosporin/Cloxacillin [1]
- Why this combination? Ampicillin covers Strep; Cloxacillin covers Staph. A first-generation cephalosporin (e.g., cefazolin) can substitute for ampicillin as it covers both.
High Yield
Tinea pedis is the most common portal of entry for lower limb cellulitis/erysipelas. Always check the toe webs.
Folliculitis: inflammation of hair follicle. Furuncles: follicular staphylococcal infection with pustule formation. Carbuncles: multiple furuncles grouped together to form abscess. [1]
Think of this as a spectrum of increasing severity centred on the hair follicle:
| Condition | What it is | Depth |
|---|---|---|
| Folliculitis | Superficial infection/inflammation of the hair follicle ostium | Epidermis only |
| Furuncle (boil) | Deeper infection of the entire hair follicle → abscess formation | Dermis |
| Carbuncle | Coalescence of multiple furuncles → large abscess with multiple draining sinuses | Dermis + subcutaneous |
-
Recurrent infection: need to rule out immunocompromised (i.e., DM) [1]
- Why DM? Hyperglycaemia impairs neutrophil chemotaxis, phagocytosis, and oxidative burst → recurrent staph infections. Also consider other immunocompromised states: HIV, steroid use, haematological malignancy.
-
Management:
Corynebacterium minutissimum. Involves intertriginous areas such as axilla, groins, and toe webs. Slight brown erythematous scaly patch. Pink under Wood's light. Rx: oral erythromycin, topical Whitfield's ointment. [1]
Why it's tested: Erythrasma is a great mimicker of tinea — both present in intertriginous areas with scaly patches. The discriminator is Wood's light examination:
| Feature | Erythrasma | Tinea |
|---|---|---|
| Organism | Corynebacterium minutissimum (bacterium) | Dermatophyte (fungus) |
| Wood's light | Coral-pink fluorescence (due to coproporphyrin III) | No fluorescence (except T. schoenleinii – pale green) |
| KOH microscopy | Negative for hyphae | Positive for hyphae |
| Treatment | Erythromycin (it's a bacterium!) | Antifungals |
Exam Trap
The lecture says "Pink under Wood's light" [1]. Many textbooks say "coral-red." In exams, "coral-pink" or "coral-red" fluorescence under Wood's lamp = erythrasma. Do NOT confuse with tinea versicolor (which fluoresces yellow-green due to Malassezia).
1.5 Necrotising Subcutaneous Infection (Necrotising Fasciitis)
This is the dermatological emergency of the lecture, illustrated by a dramatic case history.
19F with preceding sore throat → painful right hip → no cutaneous abnormalities initially → next day: severe pain, K 2.4, WBC 12 → shock → fever, WBC 20, ecchymosis spreading rapidly → diagnosis: necrotising fasciitis → perineal involvement → died 30 hours after admission. [1]
Teaching points from this case:
- The initial presentation was deceptively benign — normal skin, normal joint movement. NF can begin with pain out of proportion to findings.
- Hypokalaemia (K 2.4) is a clue to severe sepsis (catecholamine surge → intracellular potassium shift).
- Rapidly rising WBC and ecchymosis are late signs — by then, tissue necrosis is advanced.
- Perineal involvement = Fournier's gangrene (a specific variant of NF) [7].
Infections producing necrosis of the subcutaneous tissues that may include the fascia. Organisms: Streptococcus / mixture of aerobic and anaerobic. Common sites: limbs and perineum. Complication of cutaneous infection or preceding surgery. [1]
Fever, systemic toxicity, severe local pain. Marked tenderness, oedema. Skin becomes violaceous, bullae formation, crepitus, gangrene. Rapid progression with mortality 6 to 67%. Treatment: Surgical exploration + IV antibiotic (gentamicin, Fortum [ceftazidime]). [1]
Classification:
| Type | Organism | Context |
|---|---|---|
| Type I (polymicrobial) | Mixed aerobic + anaerobic (e.g., E. coli, Bacteroides, Clostridium) | Post-surgical, diabetic, perineal (Fournier's) |
| Type II (monomicrobial) | Group A Streptococcus (or S. aureus) | Young, otherwise healthy; can follow trivial trauma or pharyngitis |
The case history (19F, preceding sore throat) is classic Type II — GAS pharyngitis → haematogenous seeding or direct invasion.
Features to differentiate cellulitis from NF: [1]
- Oedema beyond the apparent limit of infection
- Development of bullae and ecchymoses
- Dermal gangrene
- Numbness in infected area (nerve destruction)
- Crepitus (gas-forming organisms)
- Severe pain disproportionate to the clinical finding
- Poor response to antibiotics
- MRI: allows early diagnosis of NF
High Yield — Discriminating NF from Cellulitis
The single most important discriminator is "pain out of proportion to clinical findings" — if the patient is screaming in pain but the skin looks only mildly erythematous, think NF. Numbness (paradoxically) can then develop as cutaneous nerves are destroyed.
| Feature | Cellulitis | Necrotising Fasciitis |
|---|---|---|
| Pain | Proportionate to erythema | Disproportionate (severe pain early, then numbness) |
| Skin changes | Erythema, warmth | Violaceous/dusky, bullae, ecchymosis, gangrene |
| Crepitus | Absent | May be present (gas-forming organisms) |
| Systemic toxicity | Mild-moderate | Severe (septic shock) |
| Response to antibiotics | Good | Poor |
| Oedema | Confined to erythema | Extends beyond visible erythema |
| Investigation | Clinical diagnosis | MRI (fascial thickening, fluid tracking along fascial planes) |
| Management | IV antibiotics alone | Surgical debridement + IV antibiotics (surgical emergency) |
Management of NF:
- Surgical exploration is the definitive treatment — all necrotic tissue must be debrided [1]
- IV antibiotics: Broad-spectrum covering Gram-positives, Gram-negatives, and anaerobes
- Lecture mentions: gentamicin + Fortum (ceftazidime) [1]
- Modern regimens often include: carbapenem or piperacillin-tazobactam + clindamycin (for toxin suppression in GAS)
- Repeat debridement often needed (look-and-re-debride at 24-48 hours)
- Mortality remains high (6-67%) [1]
Past paper relevance: The 2022 Fourth Summative MCQ tested Fournier's gangrene (Q27): "68M, diabetic, painful perineal swelling, 39°C, crepitus → Fournier's gangrene" [7]. This directly maps to this lecture section.
Less than 5 [years old]. Exfoliative toxin. Fever, tender erythematous skin, exfoliation. Positive Nikolsky sign. Diagnosis: Tzanck smear, culture. Rx: systemic antibiotics. Mortality: 4% in newborn. [1]
Pathogenesis: Certain strains of S. aureus produce exfoliative toxins (ETA and ETB) that cleave desmoglein 1 (a desmosomal cadherin concentrated in the superficial epidermis/granular layer). This causes a subcorneal/granular layer split → widespread superficial desquamation.
-
Why children < 5? Neonates and young children have:
- Immature renal clearance → cannot clear the toxin
- Lack of anti-toxin antibodies
-
Nikolsky sign positive: Gentle lateral pressure on normal-appearing skin causes epidermis to shear off. This happens because the subcorneal split is extensive.
-
Differentiation from TEN (Toxic Epidermal Necrolysis):
| Feature | SSSS | TEN |
|---|---|---|
| Age | < 5 years | Any age (adults more common) |
| Cause | S. aureus exfoliative toxin | Drug reaction |
| Level of split | Subcorneal/granular layer | Dermoepidermal junction (full-thickness epidermal necrosis) |
| Biopsy | Superficial cleavage, no epidermal necrosis | Full-thickness epidermal necrosis |
| Mucous membranes | Spared | Involved |
| Mortality | ~4% in neonates | 20-40% |
| Treatment | Systemic antibiotics (target S. aureus) | Stop offending drug, supportive care, ?IVIG |
High Yield — SSSS vs TEN
In SSSS, the split is subcorneal (superficial) and mucous membranes are spared. In TEN, the split is at the dermoepidermal junction (deep) and mucous membranes are involved. This is because desmoglein 1 (target in SSSS) is not expressed in mucous membranes, where desmoglein 3 predominates.
Classification: [1]
- Exogenous: Primary inoculation TB, Tuberculosis verrucosa cutis
- Endogenous: Lupus vulgaris, Scrofuloderma, Metastatic TB abscess, Acute miliary TB, Orificial TB
- TB due to BCG
- Tuberculids: Lichen scrofulosorum, Papulonecrotic tuberculid
- Facultative tuberculids: Erythema nodosum (EN), Erythema induratum (EI)
- Others: Lupus miliaris disseminatus faciei
This is a classification slide — know the categories rather than deep details for the exam. Key points:
- Lupus vulgaris is the most common form of cutaneous TB in previously sensitised individuals — presents as "apple-jelly nodules" on diascopy.
- Scrofuloderma = TB of skin overlying an infected lymph node (direct extension) → draining sinuses.
- EN and EI are listed as "facultative tuberculids" — they are reactive processes, not direct infection.
SECTION 2: CUTANEOUS VIRAL INFECTIONS
Viral exanthems: chickenpox, Coxsackie, infectious mononucleosis, rubella. Viral infections: warts, herpes, molluscum contagiosum. [1]
Due to HPV. Transmitted by contact. Genital wart: sexually transmitted. Wart lesions with blood vessels beneath surface. Painful in sole. Genital wart can be associated with neoplastic changes. Treated by salicylic acid, cryotherapy and cauterisation. [1]
-
Pathogenesis: HPV infects keratinocytes → viral replication → epidermal hyperplasia (verrucous growth)
-
Types:
- Common warts (verruca vulgaris) — hands, fingers
- Plantar warts (verruca plantaris) — painful because weight-bearing compresses them inward
- Flat warts (verruca plana) — face, dorsal hands
- Genital warts (condylomata acuminata) — HPV 6, 11 (low risk); HPV 16, 18 associated with cervical, anal, penile neoplasia
-
"Blood vessels beneath surface" — when you pare down a wart, you see thrombosed capillaries as black dots (pathognomonic). This helps distinguish from corns/calluses.
-
Treatment options:
- Salicylic acid (keratolytic — dissolves keratin)
- Cryotherapy (liquid nitrogen — causes epidermal cell death)
- Cauterisation (electrosurgery)
- Imiquimod (immune response modifier — for genital warts)
Pox virus. Transmitted by contact, common in children. Can be sexually transmitted. Skin-coloured dome-shaped umbilicated papules. Sometimes itchy. Treated by salicylic acid, cryotherapy and cauterisation. [1]
- Key diagnostic feature: Umbilicated papule — the central dimple (dell/umbilication) is pathognomonic.
- Why umbilicated? The virus replicates in the central core of the papule, causing necrosis → central depression.
- In immunocompromised patients (especially HIV), molluscum can be widespread and giant.
- If molluscum is found in the genital area in an adult → consider as an STI.
Highly contagious due to varicella-zoster herpes virus. Usually children. Erythema macules that quickly develop into vesicles and pustules. Associated with systemic symptoms. IP: 14 days. [1]
-
Key clinical features:
- Rash appears in "crops" → lesions at different stages simultaneously ("stars in the sky" appearance)
- Centripetal distribution (trunk > extremities) — opposite to smallpox (centrifugal)
- Vesicles are described as "dewdrop on a rose petal" — superficial, clear vesicle on erythematous base
- Systemic: fever, malaise, pruritus
-
Complications: Secondary bacterial infection, pneumonia (especially in adults and immunocompromised), encephalitis, cerebellar ataxia, hepatitis
-
Incubation period: 14 days [1] (range 10-21 days)
2.4 Herpes Zoster (Shingles)
Reactivation of latent varicella-zoster virus. Dermatomal distribution. Usually elderly. Presented with painful erythematous eruption followed by vesicle and pustule formation that clustered into a herpetiform arrangement. If involved V1 can affect eye. [1]
Note: The slide says "V5" but this appears to be a slide error — cranial nerve V (trigeminal) has 3 divisions (V1/V2/V3); involvement of the ophthalmic division (V1) causes herpes zoster ophthalmicus.
-
Pathogenesis: After primary varicella, VZV remains latent in dorsal root ganglia (or cranial nerve ganglia). Reactivation occurs with declining cell-mediated immunity (aging, immunosuppression) → virus travels down the sensory nerve → dermatomal eruption.
-
Clinical features:
- Prodrome: Pain, burning, tingling in the dermatome 1-5 days before rash
- Rash: Grouped vesicles on erythematous base in a dermatomal distribution that does NOT cross the midline
- Pain: Often severe and can precede rash (can be misdiagnosed as MI, appendicitis, etc.)
Can be multidermatomal/disseminated if immunocompromised. [1] Post-herpetic neuralgia: main complication. [1] Ramsay-Hunt syndrome: ipsilateral VII and VIII nerves involvement. [1]
| Complication | Mechanism | Features |
|---|---|---|
| Post-herpetic neuralgia (PHN) | Nerve damage → chronic neuropathic pain | Pain persisting > 90 days after rash onset. Risk increases with age. |
| Herpes zoster ophthalmicus | V1 dermatome → cornea, conjunctiva, uvea | Hutchinson's sign (vesicles on tip of nose = nasociliary nerve involvement → high risk of ocular disease) |
| Ramsay-Hunt syndrome | VZV in geniculate ganglion of CN VII | Ipsilateral facial palsy + vesicles in ear canal/pinna + sensorineural hearing loss/vertigo (CN VIII involvement) |
| Disseminated zoster | Immunosuppression → viraemia | > 20 vesicles outside primary dermatome; visceral involvement (pneumonia, hepatitis, encephalitis) |
Clinical, viral culture, Tzanck smear, EM (electron microscopy), PCR, viral antigen detection [1]
- Tzanck smear: Scraping the base of a vesicle, staining → shows multinucleated giant cells (balloon cells). This confirms herpesvirus but does NOT distinguish HSV from VZV.
- PCR is the gold standard for definitive identification.
Systemic antiviral agents if less than 72 hours. Other supportive measures: 1. Pain control 2. Topical antibiotic [1]
Why < 72 hours? Antivirals work by inhibiting viral DNA replication. They are most effective when given early during active viral replication. After 72 hours, viral replication has largely subsided, and the benefit diminishes (though treatment may still be offered if new vesicles are appearing or in immunocompromised patients).
Acyclovir/valaciclovir/famciclovir: Guanosine analogue. Selectively phosphorylated by HSV and VZV thymidine kinases. Interferes with viral DNA synthesis by inhibiting viral DNA polymerase. Valaciclovir/famciclovir have better oral bioavailability. [1]
Mechanism (from first principles):
- Acyclovir enters virus-infected cells
- Viral thymidine kinase (not present in uninfected human cells) monophosphorylates acyclovir → acyclovir monophosphate
- Host cell kinases further phosphorylate → acyclovir triphosphate
- Acyclovir triphosphate competes with dGTP for incorporation into viral DNA by viral DNA polymerase
- Once incorporated, it acts as a chain terminator (lacks the 3'-OH needed for the next nucleotide) → stops viral DNA synthesis
Why is it selective? Because step 2 (initial phosphorylation) requires viral thymidine kinase, which human cells lack → minimal toxicity to uninfected cells.
| Drug | Pro-drug of | Oral bioavailability | Dosing convenience |
|---|---|---|---|
| Acyclovir | — | Low (~15-30%) | 5× daily (inconvenient) |
| Valaciclovir | L-valine ester of acyclovir | ~55% | 3× daily |
| Famciclovir | Pro-drug of penciclovir | ~77% | 3× daily |
High Yield — Antiviral Mechanism
Acyclovir is a guanosine analogue selectively activated by viral thymidine kinase → chain terminator of viral DNA polymerase. Valaciclovir and famciclovir have better oral bioavailability.
SECTION 3: CUTANEOUS FUNGAL INFECTIONS
Fungal infection classification: Superficial, Subcutaneous, Deep [1]
Superficial fungal infection: Dermatophytes and Yeast [1]
Types of superficial dermatophyte infection: [1]
- Onychomycosis (nail)
- Tinea pedis (feet)
- Tinea cruris (groin)
- Tinea corporis (trunk)
- Tinea manuum (hands)
- Tinea capitis (scalp)
Pathogenesis: Dermatophytes (Trichophyton, Microsporum, Epidermophyton) infect keratinised tissue (stratum corneum, hair, nails) by producing keratinases. They cannot invade living tissue or mucous membranes.
Clinical clue: Annular lesions with central clearing and active, scaly, raised border ("ringworm" — nothing to do with actual worms).
Can be associated with immunocompromised (DM). Affects mucocutaneous areas: oral, vaginal, intertrigo. Housewife dermatitis with loss of nail cuticle can lead to candidiasis paronychia. Anti-fungal therapy useful. [1]
- Candida is a yeast (not a dermatophyte) → it CAN affect mucous membranes (unlike dermatophytes)
- Risk factors: DM, immunosuppression, antibiotics (disrupt normal flora), chronic moisture (occlusion, wet work)
- "Housewife dermatitis" — chronic wet work → loss of cuticle seal → Candida colonises the proximal nail fold → chronic paronychia (swollen, red, tender proximal nail fold)
3.3 Antifungal Pharmacology
This is a heavily tested pharmacology section in this lecture.
Against dermatophyte, yeast, or both. Works by inhibiting various enzymes needed for sterol synthesis in the fungal cell membrane. Should be used after skin scraping for fungal microscopy and culture. [1]
Why scrape first? Once topical antifungal is applied, it kills surface organisms → subsequent scraping will be false-negative. Always take samples BEFORE starting treatment.
Types of topical antifungal: [1]
- Keratolytic (Whitfield's ointment) — salicylic acid + benzoic acid; not truly antifungal but removes infected stratum corneum
- Undecanoate (acid zinc salt in Mycota powder)
- Thiocarbamates (tolnaftate)
- Morpholines (amorolfine) — nail lacquer for onychomycosis
- Imidazole (miconazole, clotrimazole, ketoconazole)
- Allylamines (terbinafine cream)
Fungal cell membrane contains ergosterol (equivalent to cholesterol in human cells). [1]
The ergosterol synthesis pathway is the key pharmacology concept:
Squalene → (squalene epoxidase) → Lanosterol → (14α-demethylase) → Fecosterol → (Δ14-reductase, Δ-fecosterol isomerase) → Episterol → Ergosterol [1]
| Enzyme Target | Drug Class | Example |
|---|---|---|
| Squalene epoxidase | Allylamines, Thiocarbamates | Terbinafine, Tolnaftate |
| 14α-demethylase (CYP51) | Azoles | Ketoconazole, Itraconazole, Fluconazole |
| Δ14-reductase and Δ-fecosterol isomerase | Morpholines | Amorolfine |
Why target ergosterol? Human cell membranes use cholesterol, not ergosterol. The enzymes in the ergosterol pathway are sufficiently different from human enzymes → selective toxicity. However, azoles' binding to CYP enzymes is not perfectly selective → they also inhibit human CYP450 → drug interactions and hepatotoxicity.
Squalene
↓ ← Allylamines (terbinafine) BLOCK HERE
↓ Thiocarbamates (tolnaftate) BLOCK HERE
Squalene epoxide
↓
Lanosterol
↓ ← Azoles (itraconazole, fluconazole) BLOCK HERE
14α-demethylase
↓
Fecosterol
↓ ← Morpholines (amorolfine) BLOCK HERE
Δ14-reductase / Δ-fecosterol isomerase
↓
Episterol → Ergosterol3.3.3 Systemic Antifungals
Indications for systemic antifungal: Scalp, Nail, Extensive tinea infection, Immunosuppression [1]
Why systemic for these? Topical agents cannot penetrate to the nail matrix, hair follicle root, or widespread disease adequately.
Systemic antifungals: Griseofulvin, Azoles, Allylamines [1]
Bind to cytochrome P-450. Fungistatic. Ketoconazole, itraconazole, fluconazole. Ketoconazole no longer used because of liver toxicity. Effective against yeast AND dermatophytes. Stay in tissue after systemic clearance: intermittent therapy useful. [1]
| Feature | Detail |
|---|---|
| Mechanism | Inhibit lanosterol 14α-demethylase (CYP51) → ↓ergosterol → destabilised fungal membrane |
| Spectrum | Yeast + dermatophytes |
| Action | Fungistatic (inhibits growth, doesn't kill) |
| Key property | Persist in keratin after systemic clearance → allows pulse/intermittent dosing (especially itraconazole for onychomycosis) |
| Major concern | CYP450 interaction → hepatotoxicity + drug interactions |
Terbinafine. Fungicidal. Effective against dermatophytes. Minimal side effects: GI upset, loss of taste, rarely rash and liver impairment. [1]
| Feature | Detail |
|---|---|
| Mechanism | Inhibit squalene epoxidase → squalene accumulation (toxic) + ↓ergosterol |
| Spectrum | Dermatophytes (less effective against yeast) |
| Action | Fungicidal (kills the fungus) |
| Side effects | GI upset, loss of taste (dysgeusia), rarely hepatotoxicity |
High Yield — Terbinafine vs Itraconazole
Terbinafine is fungicidal (kills), effective primarily against dermatophytes. Itraconazole is fungistatic (inhibits growth), effective against both dermatophytes AND yeast. For onychomycosis, terbinafine has superior cure rates (LION study). For Candida, itraconazole/fluconazole is preferred.
LION study (Evans, BMJ 1999): Compared continuous terbinafine 250mg daily for 12-16 weeks vs. intermittent itraconazole 200mg BD for 1 week every 4 weeks for 12-16 weeks. 35 centres, 496 patients. [1]
Results — Mycological cure after 72 weeks: [1]
- Terbinafine 12 weeks: 75.7%, 16 weeks: 80.8%
- Itraconazole 12 weeks: 38.3%, 16 weeks: 49.1%
Extended LION study: 4 extra weeks of oral terbinafine may further improve cure rate. [1]
Take-home: Terbinafine is superior to itraconazole for onychomycosis. This is because terbinafine is fungicidal and accumulates in keratin with high concentrations.
Side effects of anti-fungal: GI, taste, liver, skin eruption, headache [1]
Hepatotoxicity: Occurs with all anti-fungals. Develops 4-6 weeks after start of medication. One death in HK as an indirect event. Should monitor liver function before and 4 weeks afterward among active hepatitis B [patients]. [1]
This directly relates to the counselling scenario in the lecture:
"Elderly patient died, coroner ruled anti-fungal drug to be indirectly related." Your father with tinea pedis and onychomycosis was due to take a course of systemic anti-fungal. He is concerned. What will you do? [1]
Counselling approach:
- Acknowledge the concern
- Explain that hepatotoxicity is rare but can occur with ALL systemic antifungals
- Baseline LFT before starting treatment
- Repeat LFT at 4-6 weeks
- Assess for risk factors: active hepatitis B, liver disease, concurrent hepatotoxic drugs
- If low risk, benefits of treating onychomycosis (preventing cellulitis portal of entry, quality of life) outweigh small risk
- Choose terbinafine (lower hepatotoxicity profile than ketoconazole, which is no longer used)
Exam Tip — Drug Counselling OSCE
If asked to counsel a patient about systemic antifungal therapy, always mention: (1) check baseline LFT, (2) repeat at 4-6 weeks, (3) stop if symptoms of hepatitis (jaundice, dark urine, nausea, RUQ pain), (4) avoid ketoconazole, (5) drug interactions if on other medications.
SECTION 4: BLISTERING DISEASES
Blistering disease classification by level of split: [1]
- Subcorneal: Impetigo
- Intraepidermal: Acute dermatitis, herpes, friction, erythema multiforme, pemphigus
- Subepidermal: Bullous pemphigoid, dermatitis herpetiformis, porphyria
Why does the level of split matter?
- Subcorneal/intraepidermal → flaccid blisters (the roof is thin → ruptures easily → erosions/crusts)
- Subepidermal → tense blisters (the entire epidermis forms the roof → more robust → blisters stay intact)
This is a fundamental principle that lets you clinically distinguish pemphigus (flaccid) from pemphigoid (tense).
4th-6th decade. Intraepidermal blister. Autoantibody against keratinocytes. Flaccid blisters in skin and mucosa. Normal skin in between lesions. Affects trunk and face, extremities spared. [1]
Nikolsky sign: positive. Skin biopsy and IMF. Serum antibody (IDIMF): against keratinocytes — level correlates with disease activity. Disease is more severe and before systemic steroid, mortality rate was 80%. [1]
Pathogenesis (from first principles):
- Autoantibodies (IgG) target desmogleins (desmoglein 3 in pemphigus vulgaris, desmoglein 1 in pemphigus foliaceus) — these are the adhesion molecules holding keratinocytes together
- Loss of cell-cell adhesion → acantholysis (individual keratinocytes separate from each other) → intraepidermal cleft → flaccid blister
- Desmoglein compensation theory:
- Oral mucosa has abundant desmoglein 3 but little desmoglein 1 → anti-Dsg3 alone causes oral erosions
- Skin has both Dsg1 and Dsg3 → need anti-Dsg1 (or both) for skin blisters
- This explains why mucosal involvement is often the FIRST manifestation of PV
Key Clinical Features:
| Feature | Detail |
|---|---|
| Age | 4th-6th decade |
| Blister type | Flaccid (intraepidermal split) |
| Distribution | Trunk, face; extremities spared |
| Mucous membranes | Commonly involved (often first site) |
| Nikolsky sign | Positive (lateral pressure on normal skin → blister) |
| Between lesions | Normal skin (no urticarial base) |
Investigations:
- Skin biopsy: Intraepidermal acantholysis (suprabasal cleft with "tombstoning" — basal keratinocytes remain attached to basement membrane like tombstones)
- Direct IMF (DIF): "Fishnet"/intercellular IgG and C3 deposition around keratinocytes
- Indirect IMF (IDIMF): Circulating anti-desmoglein antibodies; level correlates with disease activity [1] → useful for monitoring
Management:
- Systemic corticosteroids (mainstay) + steroid-sparing immunosuppressants (azathioprine, mycophenolate)
- Before steroids, mortality was 80% — this underscores the severity of untreated pemphigus
- Rituximab increasingly used in refractory cases
High Yield — Pemphigus
Pemphigus = intraepidermal, flaccid blisters, mucosal involvement, anti-keratinocyte antibodies (anti-desmoglein), Nikolsky positive, antibody level correlates with disease activity, mortality 80% without steroids.
More common in elderly. Autoantibody against basement membrane. Large intact blisters arise from urticarial base. Thigh, groin, axilla. Mucosal involvement less common. Less severe than pemphigus. [1]
Skin biopsy and IMF. IDIMF: level does NOT correlate with disease activity. [1]
Pathogenesis:
- Autoantibodies (IgG) target BP antigens (BP180/BPAg2 and BP230/BPAg1) at the dermoepidermal junction (hemidesmosomes)
- Antibody binding → complement activation → neutrophil and eosinophil infiltration → protease release → destruction of the dermoepidermal junction → subepidermal split → tense blister
Key Clinical Features:
| Feature | Detail |
|---|---|
| Age | Elderly (> 60 years) |
| Blister type | Tense, large, intact (full epidermis as roof) |
| Base | Urticarial (erythematous/oedematous) |
| Distribution | Flexural — thigh, groin, axilla |
| Mucous membranes | Less commonly involved (unlike pemphigus) |
| Nikolsky sign | Negative (subepidermal split → harder to separate) |
| Severity | Less severe than pemphigus |
Investigations:
- Skin biopsy: Subepidermal blister with eosinophilic infiltrate
- Direct IMF: Linear IgG and C3 at the basement membrane zone
- Indirect IMF: Circulating anti-BMZ antibodies, but level does NOT correlate with disease activity [1]
Management:
- Potent topical steroids (clobetasol) for localised disease — often sufficient
- Systemic steroids for widespread disease
- Steroid-sparing agents: doxycycline, dapsone, azathioprine, mycophenolate
| Feature | Pemphigus | Pemphigoid |
|---|---|---|
| Age | 4th-6th decade | Elderly |
| Level of split | Intraepidermal (acantholysis) | Subepidermal |
| Blister character | Flaccid | Tense |
| Base appearance | Normal skin between lesions | Urticarial base |
| Mucosal involvement | Common (often first) | Less common |
| Nikolsky sign | Positive | Negative |
| Target antigen | Desmoglein (keratinocyte) | BP180/BP230 (BMZ) |
| DIF pattern | Intercellular "fishnet" IgG + C3 | Linear IgG + C3 at BMZ |
| Antibody level vs activity | Correlates | Does NOT correlate |
| Severity | More severe (80% mortality without Rx) | Less severe |
| Treatment | Systemic steroids + immunosuppressants | Topical/systemic steroids |
Exam Trap — Nikolsky Sign
Nikolsky sign is positive in pemphigus (and SSSS) but negative in pemphigoid. Don't confuse! Both pemphigus and SSSS involve intraepidermal/subcorneal splits (fragile epidermis), while pemphigoid's subepidermal split means the whole epidermis is still intact.
SECTION 5: CLINICAL APPROACH — "IT IS RED AND PAINFUL"
When a patient presents with a red, painful skin lesion:
- Onset and duration: Acute (hours-days) vs. subacute vs. chronic
- Progression: Static vs. rapidly spreading (cellulitis vs. NF)
- Pain character: Proportionate vs. disproportionate (NF red flag)
- Systemic symptoms: Fever, rigors, malaise (suggests deeper infection)
- Predisposing factors:
- Skin break, trauma, surgery
- Tinea pedis (portal of entry)
- Diabetes mellitus / immunosuppression
- Recent medications (drug eruption)
- Sexual history: If genital lesion — warts, herpes, molluscum
- Contacts: Varicella, impetigo (school contacts)
- Distribution: Dermatomal (zoster), flexural (erythrasma, candida), intertriginous (tinea cruris)
- Morphology: Macule, papule, vesicle, bulla, pustule, erosion, ulcer, crust
- Configuration: Grouped (herpes), annular (tinea), linear (contact), dermatomal (zoster)
- Distribution: Localised vs. generalised
- Blister characteristics: Flaccid (pemphigus) vs. tense (pemphigoid)
- Special signs:
- Nikolsky sign
- Hutchinson's sign (nose tip vesicles in HZ ophthalmicus)
- Crepitus (NF)
- Wood's lamp (erythrasma — coral-pink)
- Depth assessment: Superficial (subcorneal) vs. deep (subcutaneous)
- Surrounding tissue: Oedema beyond erythema, bullae, ecchymosis (NF)
| Investigation | When to use | What it shows |
|---|---|---|
| Skin swab/culture | Impetigo, cellulitis, abscess | Organism identification, sensitivity |
| KOH/fungal scraping | Suspected tinea, candida | Hyphae (dermatophytes), pseudohyphae (candida) |
| Wood's lamp | Erythrasma, tinea capitis | Coral-pink (erythrasma), green (Microsporum) |
| Tzanck smear | Herpes, VZV, pemphigus | Multinucleated giant cells (herpes/VZV), acantholytic cells (pemphigus) |
| Viral PCR | Herpes, VZV | Definitive identification |
| Skin biopsy + DIF/IMF | Blistering disease | Level of split, antibody pattern |
| Blood cultures | NF, septic arthritis, systemic sepsis | Organism identification |
| MRI | Suspected NF | Fascial thickening, fluid tracking, gas |
Exam Intelligence
-
Spot diagnosis (EMQ/MCQ): Photo of lesion → identify condition
- Honey-crusted lesion on face → Impetigo
- Dermatomal vesicles → Herpes zoster
- Umbilicated papules → Molluscum contagiosum
- Annular scaly plaque → Tinea corporis
- Coral-pink fluorescence → Erythrasma
- Flaccid blisters with oral erosions → Pemphigus
-
Clinical scenario (SAQ): Differentiate cellulitis from NF → list features [1]
-
Pharmacology (MCQ/SAQ): Mechanism of acyclovir, terbinafine vs. itraconazole, site of action in ergosterol pathway
-
Management (SAQ): How to treat herpes zoster (< 72 hours, antiviral, pain control, topical antibiotics)
-
Counselling (OSCE): Systemic antifungal risks, LFT monitoring
| Trap | Correct Answer |
|---|---|
| Confusing erythrasma with tinea | Erythrasma = bacteria (Corynebacterium), coral-pink Wood's lamp |
| Saying "V5" causes eye involvement in zoster | It's V1 (ophthalmic division) — the slide appears to contain an error |
| Calling SSSS and TEN the same thing | SSSS = subcorneal (superficial), mucosa spared, treat with antibiotics; TEN = dermoepidermal, mucosa involved, stop drug |
| Saying pemphigoid antibody levels correlate with disease | They do NOT — only pemphigus antibody levels correlate |
| Forgetting to scrape before applying antifungal | Always sample BEFORE treatment |
-
SAQ: List 5 features that differentiate necrotising fasciitis from cellulitis.
- Pain disproportionate to findings, oedema beyond erythema, bullae/ecchymosis, crepitus, dermal gangrene, numbness, poor antibiotic response, MRI showing fascial thickening [1]
-
MCQ: A 3-year-old presents with fever, diffuse tender erythema, and superficial skin peeling. Nikolsky sign is positive. What is the most likely diagnosis?
- SSSS (age < 5, exfoliative toxin, subcorneal split) [1]
-
MCQ: Which antifungal is fungicidal and most effective against dermatophytes?
- Terbinafine [1]
-
SAQ: Describe the mechanism of action of acyclovir.
- Guanosine analogue → phosphorylated by viral thymidine kinase → inhibits viral DNA polymerase → chain termination [1]
-
EMQ: Brown scaly patch in groin with coral-pink fluorescence under Wood's lamp → Erythrasma (Corynebacterium minutissimum) [1]
-
SAQ: Compare pemphigus and pemphigoid — level of split, blister type, Nikolsky sign, antibody target, correlation with disease activity.
- See comparison table above [1]
-
MCQ: An elderly patient on itraconazole for onychomycosis. When should you check LFT?
- Baseline and at 4-6 weeks [1]
-
SAQ: What investigation allows early diagnosis of necrotising fasciitis?
- MRI [1]
-
MCQ: In herpes zoster, systemic antiviral should ideally be started within how many hours?
- 72 hours [1]
-
SAQ: A patient has recurrent furuncles. What underlying condition must you exclude?
- Diabetes mellitus / immunocompromised state [1]
High Yield Summary
Bacterial: Impetigo (subcorneal, Staph/Strep, honey crust, cloxacillin+ampicillin) → Erysipelas/Cellulitis (dermal/subcutaneous, sharp vs. diffuse border, tinea pedis as portal) → Furuncle/Carbuncle (I&D + antibiotics, rule out DM) → Erythrasma (Corynebacterium, coral-pink Wood's lamp, erythromycin) → NF (surgical emergency, pain disproportionate, MRI, mortality up to 67%) → SSSS (< 5yo, exfoliative toxin, Nikolsky+, subcorneal split, mucosa spared).
Viral: Warts (HPV, black dots, salicylic acid/cryo) → Molluscum (poxvirus, umbilicated papules) → Varicella (IP 14 days, crops, centripetal) → Herpes zoster (dermatomal, antiviral < 72h, PHN main complication, Ramsay-Hunt = VII+VIII).
Fungal: Dermatophytes (annular, KOH+) → Candida (mucocutaneous, DM risk) → Antifungals: Allylamines (terbinafine = fungicidal, dermatophytes), Azoles (fungistatic, dermatophytes+yeast, CYP450, hepatotoxicity), scrape before treating, LFT at baseline and 4 weeks.
Blistering: Pemphigus (intraepidermal, flaccid, mucosal, Nikolsky+, anti-desmoglein, level correlates, 80% mortality without steroids) vs. Pemphigoid (subepidermal, tense, urticarial base, elderly, less mucosal, Nikolsky−, anti-BMZ, level does NOT correlate, less severe).
Active Recall - It Is Red and Painful
[1] Lecture slides: GC 071. It is red and painful.pdf (all pages cited throughout) [2] Senior notes: Block A - It is red and painful (bacterial and viral skin infections).pdf [3] Senior notes: Block A - Dermatology PBL 2.pdf (p6 — SSSS, dermatological emergencies) [4] Lecture slides: GC 022. Visual Spot Diagnoses - Survival Guide for Primary Care.pdf [5] Senior notes: Ryan Ho Opthalmology.pdf (p16-20 — red eye differential for context) [6] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (p20 — Gram-positive organisms) [7] Past papers: 2022 Fourth Summative MCQ.pdf (Q27 — Fournier's gangrene) [8] Past papers: 2019 Fourth Summative MCQ.pdf (p2 — dermatological EMQ) [9] Past papers: 2025 Fourth Summative MCQ.pdf (Q82 — drug allergy workup after blistering eruption)
GC070 Is This The Best Drug For Me
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GC074 Multiple Joint Pain
Multiple joint pain (polyarthralgia) is the simultaneous or sequential occurrence of pain in several joints, arising from inflammatory, degenerative, autoimmune, infectious, or metabolic causes that require systematic clinical evaluation to identify the underlying etiology.