GC090 Treatments For Skin Diseases
Treatments for skin diseases encompass a range of therapeutic modalities including topical agents (corticosteroids, retinoids, antifungals, antibiotics), systemic medications (immunosuppressants, biologics, antihistamines), phototherapy, and procedural interventions used to manage dermatological conditions.
Treatments for Skin Diseases
This lecture, delivered by Professor Henry H. Chan (HKU Division of Dermatology), is a comprehensive treatment-focused session covering three major dermatological conditions—eczema (atopic dermatitis), psoriasis, and chronic urticaria—plus the autoimmune blistering diseases pemphigus and bullous pemphigoid. [1]
The organising principle is a severity-, site-, comorbidity- and response-based ladder. Start with skin care and appropriate topical treatment when disease is limited; escalate to phototherapy or systemic treatment when severity, high-impact sites, joint disease, quality-of-life impairment, or failure of topical therapy justifies it. The slides contain important landmark trials, but several treatment ladders are historical and are explicitly updated below.
I. Autoimmune Blistering Diseases
A. Pemphigus — Treatment
High Yield: Previous first-line treatment for pemphigus was high-dose systemic steroid, with mycophenolate, azathioprine, cyclophosphamide, cyclosporin, plasmapheresis, and IVIG as adjuncts. More recently, biologic therapy (rituximab) has become the standard. [1]
Pemphigus is caused by IgG autoantibodies against desmogleins (Dsg1 and Dsg3) on keratinocytes, produced by autoreactive B cells. By depleting the B-cell pool, you eliminate the source of pathogenic antibodies.
Rituximab (MabThera®) is a mouse/human chimeric monoclonal antibody. The murine variable regions bind specifically to the CD20 antigen on B lymphocytes. The human IgG1 Fc domain works in synergy with human effector mechanisms. [1]
CD20 antigen is expressed on > 90% of non-Hodgkin's lymphoma B cells but NOT on stem cells or normal tissues other than B cells. This allows effective eradication of CD20+ cells without excessive toxicity because: (1) stem cells continue to differentiate into normal B cells, and (2) unaffected plasma cells continue to maintain serum immunoglobulin levels. [1]
This is critical: rituximab depletes CD20-positive B-lineage cells, while haematopoietic stem cells and mature plasma cells lack CD20. That explains both later B-cell repopulation and persistence of some pre-existing antibody production. It does not mean immunoglobulins can never fall: repeated treatment can cause hypogammaglobulinaemia and serious infection, so baseline infection risk, hepatitis B status, vaccination timing, immunoglobulins and subsequent clinical monitoring matter. [8]
The lecture slide shows the developmental sequence and where CD20 is expressed:
Stem B-cell → Pro-B-cell → Pre-B-cell → Immature B-cell → Mature B-cell → Activated B-cell → Blast B-cell → Plasma cell
| Marker | Expression Span |
|---|---|
| CD34 | Stem B-cell only |
| CD19 | Pro-B-cell → Blast B-cell |
| CD20 | Pre-B-cell → Blast B-cell (absent on stem B-cells and plasma cells) |
Maturation is divided into antigen-independent (stem → immature B-cell) and antigen-dependent (mature → plasma cell) phases. Surface immunoglobulin appears from the pre-B-cell stage (intracellular μ), with IgM and IgD co-expressed on mature and activated B cells. Plasma cells secrete immunoglobulin but lose CD20, explaining why rituximab does not deplete existing antibody-producing plasma cells. [1]
| Mechanism | Detail |
|---|---|
| Complement-Dependent Cytotoxicity (CDC) | Initiates lysis of circulating B cells via complement cascade |
| Antibody-Dependent Cellular Cytotoxicity (ADCC) | Human antibody component interacts with immune effector cells (NK cells, macrophages), leading to cytolysis of CD20+ target cells |
| Direct Apoptosis | Binding to CD20 directly triggers apoptotic pathways in B cells |
The slide's rapid-depletion statistic is best read as pharmacodynamic evidence, not a bedside treatment target: clinical response and adverse effects—not a desired numerical fall in circulating B cells—guide care.
This is the trial that changed practice. The lecture goes through it in detail, suggesting it is examinable:
| Feature | Detail |
|---|---|
| Design | Prospective, multicentre, parallel-group, open-label RCT across 25 French dermatology departments |
| Population | Newly diagnosed pemphigus patients aged 18-80, treated for the first time (not relapse) |
| Arms | 1:1 randomisation: (1) Prednisone alone 1.0-1.5 mg/kg/day tapered over 12-18 months vs. (2) Rituximab 1000 mg IV on days 0 and 14, 500 mg at months 12 and 18, combined with short-term prednisone 0.5-1.0 mg/kg/day tapered over 3-6 months |
| Stratification | Disease severity (severe vs moderate, Harman's criteria) |
| Primary endpoint | Complete remission off-therapy at month 24 (ITT analysis) |
| Key result | 89% of rituximab+prednisone group vs. 34% of prednisone-alone group achieved complete remission off-therapy at month 24 (p < 0.0001) |
| NNT | 1.82 (only ~2 patients need to be treated with rituximab+prednisone rather than prednisone alone for one additional complete remission) |
| Safety | No deaths. MORE severe AEs (grade 3-4) in prednisone-alone group (53 events in 29 patients) vs rituximab+prednisone (27 events in 16 patients, p = 0.0021) |
| Common AEs | Diabetes/endocrine disorder, myopathy, bone disorders |
Interpretation: First-line use of rituximab plus short-term prednisone for pemphigus is more effective than prednisone alone, with fewer adverse events. [1]
On June 7, 2018, the FDA approved Rituxan (rituximab) for moderate-to-severe pemphigus vulgaris—the first FDA-approved treatment for PV in more than 60 years. Rituximab received Priority Review, Breakthrough Therapy Designation, and Orphan Drug Designation for PV. [1]
Exam Tip
If asked "What is the current first-line treatment for pemphigus?" the answer per this lecture is rituximab combined with short-term prednisone, not high-dose steroid monotherapy. This is a paradigm shift. The old answer of "high-dose systemic steroid" is now outdated but may still appear as a distractor.
Bullous pemphigoid is common in older, frail patients, but it is not automatically "mild": extensive disease, infection and treatment toxicity can be life-threatening. EADV guidance recommends high-potency/superpotent topical corticosteroids as the mainstay whenever feasible. Oral prednisone (often about 0.5 mg/kg/day initially) is an alternative when topical whole-body treatment is impractical. Methotrexate, azathioprine or mycophenolate can be steroid-sparing options; doxycycline or dapsone may be considered in selected patients, but are less reliably effective for blister control. Since the guideline, dupilumab became FDA-approved for adult BP in 2025 on the basis of a steroid-taper trial; availability/licensing elsewhere varies. B-cell depletion/IVIG remain refractory specialist options. [9] [16]
The slide's "minocycline + topical steroid first" is therefore a historical local simplification, not a universal current first-line rule. The pragmatic BLISTER trial used doxycycline rather than minocycline and found it less effective for short-term blister control but safer than prednisolone over one year—useful when treatment toxicity is the dominant concern. [9]
Pemphigus vs BP Treatment Comparison
| Feature | Pemphigus | Bullous Pemphigoid |
|---|---|---|
| Severity | Potentially life-threatening; mucosal disease common | Also potentially serious; usually older/frailer patients and treatment toxicity matters greatly |
| First-line (current) | Rituximab + short-term prednisone for moderate–severe disease | Superpotent topical corticosteroid where feasible; individualized oral alternative |
| Targeted biologic role | Rituximab is established first-line for moderate–severe disease | Dupilumab is FDA-approved for adults; rituximab/IVIG are selected refractory options |
| Escalation | Specialist immunomodulation according to response/risk | Steroid-sparing immunosuppressant; selected doxycycline/dapsone; refractory biologic/IVIG options |
II. Eczema (Atopic Dermatitis) — Treatment Ladder
First-Line Management
The slide lists avoidance, emollients, topical steroids, antihistamines, potassium permanganate and treatment of secondary infection. A safer modern translation is: regular leave-on emollient + appropriate anti-inflammatory topical treatment + avoidance of demonstrated irritants/allergens + treatment of clinically infected eczema. Oral antihistamines do not treat the underlying eczema; a short sedating course is sometimes used for severely sleep-disrupting itch. Potassium permanganate is a short, supervised option for acutely wet/weeping lesions—not routine maintenance. [10] [11]
Reduce clear, patient-specific aggravators: harsh soaps/detergents, fragranced products, friction, overheating and occupational wet work are common examples. The slide's blanket advice to avoid spicy food, fruit, alcohol or all "biological" washing products is not evidence-based for every patient. Do not impose broad diets without a reproducible history and appropriate allergy/dietetic assessment.
Mechanistic anchor: impaired barrier lipids/filaggrin, higher transepidermal water loss and type-2 inflammation create an itch–scratch–barrier-damage loop. Trigger reduction helps only if the trigger is real; moisturising and controlling inflammation repair the loop directly.
The lecture references a key study on S. aureus suppression in AD:
Huang et al. (Pediatrics, 2009): RCT of 31 children (age 6 months–17 years) with moderate-to-severe AD and clinical signs of secondary bacterial infection. After 14 days of oral cephalexin, patients were randomised to intranasal mupirocin + dilute sodium hypochlorite (bleach) baths vs. intranasal petrolatum + plain water baths for 3 months. The bleach bath group showed significantly greater reductions in EASI scores at 1 and 3 months. [1]
The image sequence describes a very dilute bath (about 0.005% sodium hypochlorite), brief soak, rinse/pat dry, then immediate prescribed topical treatment and emollient. This is not a DIY concentration to guess: household products vary and undiluted bleach causes chemical injury. Current guidelines treat bleach baths as a conditional adjunct for selected moderate–severe, infection-prone AD—not a treatment for colonisation in every patient. Topical or systemic antibiotics are reserved for clinically infected eczema rather than routine decolonisation. [10] [11]
Emollients are important to treat the dryness in eczema. They are safe but allergic reactions can occur. They act by either preventing water loss by evaporation or addition of water-binding substances. [1]
Choose a leave-on product the patient will use frequently: ointments are more occlusive; creams are often more acceptable; humectants such as urea may sting inflamed skin. Brand lists date quickly. Bath emollient additives have not shown extra clinical benefit over standard care, and paraffin-containing emollients contaminate clothing/bedding and create a serious fire risk. After a short lukewarm bath, gently pat dry and apply medication and leave-on emollient as directed; separate applications if needed to avoid dilution/spread of the prescribed drug. [10] [11]
Antiseptic bath, probiotics, aeroallergen avoidance, food allergy assessment. [1]
Probiotics and prevention (historical slide evidence):
Zuccotti et al. (Allergy 2015): Systematic review and meta-analysis of 17 RCTs (4755 children). Probiotic supplementation during pregnancy/early infancy significantly reduced eczema risk (RR 0.78, 95% CI 0.69–0.89, p = 0.0003). Mixed-strain probiotics showed the greatest effect (RR 0.54, 95% CI 0.43–0.68, p < 0.00001). No significant effect on asthma, wheezing, or rhinoconjunctivitis. [1]
Early peanut introduction (LEAP trial, from lecture):
Du Toit et al. (NEJM 2015): 640 infants (age 4–11 months) with severe eczema and/or egg allergy randomised to consume or avoid peanuts until 60 months. Among those with negative baseline skin-prick test: peanut allergy prevalence was 1.9% (consumption) vs. 13.7% (avoidance), p < 0.001. Among those with positive SPT (1–4 mm wheal): 10.6% vs. 35.3%, p = 0.004. Early peanut introduction significantly decreased peanut allergy development and modulated immune responses (↑ peanut-specific IgG4 in consumption group). [1]
The probiotic meta-analysis suggested a modest reduction in incident eczema, but heterogeneity in strain, timing and population means probiotics are not a treatment for established AD and are not a universal prevention prescription. Routine house-dust-mite avoidance has inconsistent benefit. Investigate food allergy when the history suggests an immediate reaction, growth is poor, or severe eczema remains refractory despite optimized treatment. Skin-prick/specific-IgE tests show sensitisation, not necessarily clinical allergy; supervised oral food challenge is the diagnostic reference standard. Avoid unsupervised broad elimination diets. [10] [12]
The LEAP slides are about peanut-allergy prevention, not eczema treatment. For infants with severe eczema and/or egg allergy, NIAID guidance supports assessment and age-appropriate peanut introduction at around 4–6 months rather than avoidance, once developmentally ready. Never give whole peanuts to infants because of choking risk. [12]
Common Exam Trap
Positive skin-prick or specific-IgE tests indicate sensitisation, not clinical allergy. Diagnosis requires concordant history and, when needed, a medically supervised oral food challenge; do not use an unsupervised "open rechallenge" when an IgE-mediated reaction is possible.
Topical steroids interact with cell nucleus affecting mRNA expression. They are anti-inflammatory, cause vasoconstriction, have immunosuppressive action, and are anti-proliferative. [1]
UK-style classification (four named potency bands):
| Band | Common examples | Practical use |
|---|---|---|
| Mild | Hydrocortisone 0.5–1% | Thin/sensitive sites or young children when appropriate |
| Moderate | Clobetasone butyrate 0.05% | Moderate inflammation; short, site-appropriate courses |
| Potent | Betamethasone valerate 0.1%, mometasone furoate 0.1%, fluticasone propionate 0.05% | Thicker skin or more severe flares; avoid casual long use on face/folds |
| Very potent | Clobetasol propionate 0.05% | Short specialist-directed courses for severe/thick disease |
Adverse Effects of Topical Steroids (comprehensive list from lecture):
Hypopigmentation, increased hair growth, skin atrophy, telangiectasia, easy bruising, stretch marks, acne, perioral dermatitis, infection, rebound, tachyphylaxis, contact dermatitis, Cushing syndrome, pituitary-adrenal suppression. [1]
The adverse-effect slide deliberately juxtaposes local dose/site effects (atrophy, telangiectasia, striae, bruising, hypertrichosis, acneiform/perioral eruption, infection masking) with systemic effects (HPA-axis suppression/Cushing syndrome), which are uncommon with appropriate courses but become more plausible with very potent preparations, large areas, prolonged use, occlusion or infancy. Apparent "tachyphylaxis" often reflects undertreatment, poor adherence, wrong diagnosis or contact allergy rather than proven receptor exhaustion. Relapse of the underlying disease after stopping is common; true topical-steroid withdrawal is uncommon and follows prolonged inappropriate use. Do not escalate potency automatically—reassess diagnosis, site, quantity and technique.
Key recommendations from the AAD Guidelines (Eichenfield et al., JAAD 2014), as presented in the lecture: [1]
- TCS are recommended for AD patients who fail good skin care and regular emollients alone
- Consider patient age, body site, degree of xerosis, patient preference, and cost when choosing a TCS
- Once-daily treatment is often sufficient for many modern preparations; follow the product and local guideline rather than assuming twice daily is always better
- Proactive intermittent maintenance therapy (1–2 times/week) on commonly flaring areas is recommended to prevent relapses and is more effective than emollients alone
- Monitor for cutaneous side effects during long-term potent steroid use
- Address patient fears of TCS side effects ("steroid phobia") to improve adherence and avoid undertreatment
| Drug | Key Features |
|---|---|
| Mometasone furoate (Elomet) | Low systemic resorption, rapid breakdown in liver, 6 weeks therapy local effect similar to 1% HC, potency equivalent to Betnovate |
| Fluticasone (Cutivate) | Rapidly broken down in liver, potent steroid equivalent to class III, local safety with short-term use |
| Methylprednisolone aceponate (Advantan) | Once daily, fast inactivation within the circulation, low risk of systemic and cutaneous adverse effects, approved for age 4 months to 14 years |
The slides emphasize rapid systemic metabolism, but these are still potent topical corticosteroids, not risk-free "soft" drugs. Safety depends on age, body site, amount, duration and occlusion; paediatric age licences differ by jurisdiction. A fingertip unit is a useful counselling measure, and proactive once- or twice-weekly application to repeatedly flaring sites can reduce relapse after control. [10] [11]
Topical Calcineurin Inhibitors: In the US, second-line treatment. Tacrolimus (Protopic) and Pimecrolimus (Elidel). [1]
| Feature | Tacrolimus (Protopic) | Pimecrolimus (Elidel) |
|---|---|---|
| Indicated population | Moderate-severe AD | Mild-moderate AD |
| Mechanism | Immunosuppressant similar to cyclosporin; inhibits calcineurin → blocks T-cell activation. 10-100× more potent than cyclosporin in inhibiting T cells. | Anti-inflammatory macrolactam; blocks synthesis of both Th1 and Th2 type cytokines in target cells |
| Potency | 0.1% as effective as mid-potency topical steroid; 0.03% less than mid-potency but more than low-potency steroid | Less than mid-potency steroid |
| Key advantage over steroids | Does not cause skin atrophy | Does not cause skin atrophy |
| Side effects | Mild burning sensation (topical); in most cases undetectable plasma levels | Burning/stinging (transient) |
| Long-term concern | FDA boxed warning remains; large observational data have not demonstrated the causal cancer signal originally feared | Same regulatory warning/evidence context |
Why TCIs are important for the face/flexures: thin and occluded sites are especially susceptible to steroid adverse effects. TCIs provide anti-inflammatory control without steroid-induced atrophy. Transient burning/stinging is common; do not apply to clinically infected skin. The slide's exact "42% eyelid absorption" figure is not needed for safe prescribing.
Guideline Recommendations for TCI Use in AD
Key recommendations from the AAD Guidelines, as presented in the lecture: [1]
- TCIs are recommended for acute, chronic, and maintenance treatment in adults and children with AD
- TCIs are recommended as a steroid-sparing agent on actively affected areas
- For patients < 2 years: off-label use of 0.03% tacrolimus or 1% pimecrolimus can be recommended
- Proactive intermittent TCI maintenance (2–3 times/week) on commonly flaring areas helps prevent relapses while reducing TCS need
- No consistent increase in cutaneous viral infections with continuous or intermittent TCI use for up to 5 years
- Routine blood monitoring of tacrolimus/pimecrolimus levels is not recommended
- Clinicians should be aware of the FDA black-box warning and discuss as warranted
Wet wraps: rehydrate the skin, enhance absorption of topical ointment, reduce the dose of topical steroid, prevent scratching. [1]
Visual sequence: short bath → prescribed anti-inflammatory/emollient to the appropriate sites → damp tubular garment/bandage → dry outer garment. The paired arm-and-leg garments in the slides show how the wet layer hydrates and cools while the dry layer retains it and prevents scratching.
Pilot study (Tang & Chan, 1999): 12 patients with refractory AD received wet wrap therapy using mometasone (1/10) ointment for 2 weeks. Well-tolerated; plasma cortisol was not depressed. 60-85% reduction in objective and subjective scores. [1]
Pei & Chan (Pediatr Dermatol 2001): 40 children randomized to wet wraps with 1/10 Elomet vs. Cutivate ointment. Significant improvement from baseline during first 2 weeks of open application (p=0.043). Wet wraps further improved severity and extent after week 2 (p < 0.05). Both mometasone furoate and fluticasone propionate ointments effective for wet wrap dressing. [1]
Occlusion increases, rather than neutralizes, topical-steroid absorption. A fixed 1:10 home dilution is not a universal recipe and mixing can give uneven dosing. Wet wraps are a short rescue intervention for severe flares under an eczema-trained clinician's instructions; choose potency/quantity deliberately, monitor children or extensive treatment for systemic absorption, and avoid wrapping untreated infection. Sedating antihistamine is not a mandatory component. The small studies and rising line graphs show short-term improvement but do not establish long-term safety or superiority of one diluted potent steroid. [10] [11]
Third-Line: Systemic & Phototherapy
The slide's third-line list predates modern targeted treatment. Current AAD guidance strongly recommends adult systemic options including biologics and oral JAK inhibitors; phototherapy, methotrexate, mycophenolate, azathioprine and ciclosporin are conditional options. Routine systemic corticosteroids are recommended against because benefit is brief and rebound/toxicity is substantial. [10]
The lecture's triangular interchange diagram (steroid + azathioprine ↔ ciclosporin → phototherapy) reflects an older era of cycling broad immunosuppression. A current decision map is:
Choice is individualized by age, comorbidity, pregnancy potential, access, speed required and monitoring burden. [10]
The slide's old Hong Kong incidence counts and ethnic generalisation should not be used to declare phototherapy "safe" for an entire group. Assess phenotype, photosensitivity, prior skin cancer/phototherapy, immunosuppression and cumulative exposure individually. Systemic steroid cover is not routinely required, and supervised phototherapy can be used in selected children as well as adults. [10] [11]
Narrow-band UVB (311 nm): like other forms of phototherapy, induces immunosuppression by altering cutaneous antigen-presenting cells. Increases non-Langerhans cell APCs which stimulate suppressor T8 cells. Three times a week therapy. [1]
NB-UVB vs. Broadband UVB:
| Feature | NB-UVB | BB-UVB |
|---|---|---|
| Spectrum | Around 311–313 nm | Wider UVB spectrum |
| Practical position | Usually preferred because useful wavelengths are concentrated and treatment is effective | Less commonly used |
| Risks | Erythema/burn, photoageing and uncertain cumulative long-term cancer risk; protect eyes/genitals and record dose | Similar UVB precautions; do not infer a simple fixed cancer-risk ratio |
| Clinical efficacy | Effective for selected widespread AD/psoriasis | Generally less convenient/effective than NB-UVB |
NB-UVB vs. PUVA:
| Feature | NB-UVB | PUVA |
|---|---|---|
| Carcinogenicity | Less carcinogenic | More carcinogenic |
| Use in pregnancy/children | May be considered with specialist precautions | Avoid oral psoralen in pregnancy; paediatric use is uncommon and specialist-led |
| Efficacy in chronic plaque psoriasis | Slightly inferior (not statistically significant) | Slightly superior |
| Eye protection | During exposure | During exposure and, after systemic psoralen, UVA-blocking eyewear for the instructed period |
| Drug | Mechanism/role | Safety focus |
|---|---|---|
| Mycophenolate | Inhibits inosine-monophosphate dehydrogenase and lymphocyte purine synthesis; off-label conventional option | CBC, renal/liver review, infection and major pregnancy/teratogenic precautions; the slide's ten-patient series cannot define a universal dose |
| Azathioprine | Purine antimetabolite; slow-onset off-label option | CBC/LFT, infection and drug interactions; TPMT/NUDT15 testing helps identify severe myelotoxicity risk but does not replace blood monitoring |
| Ciclosporin | Rapid calcineurin inhibition; useful when fast control is needed | BP, creatinine/eGFR, electrolytes, interactions and infection; generally a short-term/bridging rather than indefinite strategy |
| Systemic corticosteroid | Rapid broad suppression | Avoid routinely; exceptional short bridge only under specialist care because rebound and cumulative toxicity outweigh durable benefit |
TPMT and NUDT15 Before Azathioprine
Check TPMT and NUDT15 genotype/activity according to local practice, especially where relevant variants are prevalent, before azathioprine. A normal result does not eliminate later marrow toxicity: continue CBC/LFT monitoring. Allopurinol/febuxostat can cause profound toxicity unless the azathioprine dose and monitoring are deliberately specialist-adjusted. [6]
Biologic Therapy for AD: Dupilumab
The lecture presents three linked visual stages:
- Uninvolved skin in AD: Langerhans cells, mast cells with surface IgE, CD4+ T cells present but quiescent
- Acute AD skin: Allergen exposure → Th0 cells differentiate into Th2 cells under IL-4 drive → Th2 cells produce IL-4, IL-5, IL-13 → IgE production → mast cell degranulation → histamine release
- Chronic AD skin: repeated scratching/barrier injury → lichenification and epidermal hyperplasia; microbial products and additional immune axes join the persistent type-2 circuit
The acute-versus-chronic diagram is pedagogic, not a binary switch from "Th2 disease" to "Th1 disease." Type-2 signalling remains central in both phases, while chronic lesions recruit additional Th1/Th17/Th22 activity. The older drawing also over-centres IgE/histamine: AD itch and inflammation are not simply an immediate allergy, which is why routine antihistamines and blanket allergen avoidance do not control the disease.
Dupilumab is a fully human monoclonal antibody against IL-4Rα, thereby inhibiting signalling from both IL-4 and IL-13. [10]
Why block both IL-4 AND IL-13? Dupilumab targets the IL-4 receptor alpha subunit, which is shared by both the IL-4 receptor and the IL-13 receptor. IL-4 drives Th2 differentiation and IgE class switching. IL-13 promotes mucus production, fibrosis, and barrier dysfunction. Blocking both simultaneously addresses multiple pathogenic pathways.
12-week monotherapy study: 85% of dupilumab group vs. 35% of placebo had ≥50% reduction in EASI score (p < 0.001). 40% of dupilumab group vs. 7% of placebo had IGA 0-1 (clear/near-clear) (p < 0.001). Pruritus scores decreased 55.7% vs. 15.1% (p < 0.001). [1]
Phase 3 study design (R668-AD-1416):
- Eligibility: IGA 3 (moderate) or 4 (severe), or inadequate response/intolerance to topical AD medications
- Randomisation: 1:1:1 — dupilumab 600mg loading then 300mg weekly : 600mg loading then 300mg biweekly : placebo
- Treatment period: 16 weeks
- Primary endpoint: IGA 0 or 1, OR EASI 75 at week 16, not on rescue therapy
The 2014 proof-of-concept and 2016 phase-3 slides document how dupilumab moved from "new direction" to routine therapy. The photographed flexural plaques become much less erythematous/scaly/lichenified after treatment; residual pigment change does not necessarily mean active eczema. Exact 2017 price and adolescent-only approval statements are historical: indications now include younger children and vary by regulator. Dupilumab commonly causes injection-site and ocular-surface problems and is not a general immunosuppressant requiring routine laboratory monitoring. [10]
AD Treatment Summary from the Lecture
The slide conclusion is historical. Current AAD guidance strongly recommends topical corticosteroids and calcineurin inhibitors, alongside newer non-steroidal topicals where licensed. For moderate–severe disease it strongly recommends several targeted systemic classes: IL-4/13-pathway biologics (dupilumab, tralokinumab, lebrikizumab), IL-31-pathway treatment (nemolizumab with topical therapy), and selected oral JAK inhibitors; patient age/licensing and boxed-warning risks differ. Conventional immunosuppressants and phototherapy remain conditional options, and systemic corticosteroids are strongly discouraged. [10] [11]
The 2026 Derm General Clerkship slides confirm the same three-tier structure and add JAK inhibitors and tralokinumab (anti-IL-13) as additional systemic options. [7]
III. Psoriasis — Treatment
Psoriasis is a chronic immune-mediated disease of skin and often joints. The chromosome diagram places the major PSORS1 susceptibility region within the MHC at 6p21; HLA-C*06:02 is the best-known association, but genetics are polygenic and the slide's fixed "50%" attribution should not be treated as an individual risk calculation.
The "Vicious Cycle" of psoriatic plaque development:
- Genetic predisposition + trigger → dendritic cell activation
- Activated dendritic cells produce TNF and IL-23, sustaining pathogenic type-17 cells
- IL-17A/F and IL-22 activate keratinocytes; TNF amplifies the circuit (IL-12/Th1 is contributory but not the main modern treatment axis)
- Keratinocytes proliferate and release cytokines/chemokines → further dendritic/T-cell/neutrophil recruitment and angiogenesis
- This self-amplifying loop produces a plaque; successful biologics interrupt TNF, IL-17 or IL-23 at different nodes
Reading the labelled histology slide: A is regular psoriasiform epidermal hyperplasia/acanthosis with elongated rete ridges; B is a dilated superficial dermal capillary (basis of Auspitz bleeding); C/D mark dermal and epidermal inflammatory cells; E marks epidermal/stratum-corneum neutrophils. Add parakeratosis with reduced granular layer and Munro microabscesses to the classic pattern. Histology supports a clinical diagnosis but is not required in a typical plaque.
Important Cytokines in Psoriasis
| Cytokine | Proposed Role |
|---|---|
| IFN-γ | ↑ keratinocyte proliferation |
| IL-2 | ↑ T-cell growth |
| TNF-α | ↑ vascular adhesion molecules, ↑ macrophage cytokines/chemokines |
| TGF-α, Amphiregulin | EGF-R ligand → keratinocyte proliferation |
| IL-6 | ↑ angiogenesis |
| IL-8 | Neutrophil attractant |
| IL-1 | ↑ vascular permeability |
| IL-12 | ↑ Th1 differentiation |
| IL-23 | ↑ Th17 differentiation |
The slide's exact fold-risks come from older heterogeneous observational cohorts and the "seven-fold MI" figure should not be counselled as a fixed patient risk. The durable clinical message is to screen for psoriatic arthritis, obesity, smoking, hypertension, diabetes/dyslipidaemia, cardiovascular disease, depression/suicidality, alcohol misuse and inflammatory bowel disease, and coordinate preventive care. Association does not prove psoriasis alone caused each comorbidity. [13] [14]
Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation (Yiu, Yeung, Chan et al., Br J Dermatol 2011) [1]
Why the link matters: systemic inflammation, shared metabolic risk factors, smoking and treatment effects all contribute. The arterial-stiffness paper on the slide supports association with inflammatory activity; it does not prove a specific psoriasis drug will prevent cardiovascular events or that severe psoriasis is universally "equivalent to diabetes."
Topical agents: Tar, steroid, keratolytic, Vitamin D analogue, dithranol, emollient. [1]
| Agent | Mechanism/Use | Drawbacks |
|---|---|---|
| Tar | Mechanism not known; used as shampoo, bath, in combination with other agents | Messy, irritation, phototoxic |
| Dithranol | Antiproliferative and anti-inflammatory; applied as short-contact therapy | Messy, irritation, stains skin |
| Calcipotriol (Daivonex) | Vitamin D analogue; normalizes keratinocyte differentiation; often combined with a topical corticosteroid | Irritation; respect maximum weekly dose/calcium-disorder cautions |
| Topical steroids | Potent anti-inflammatory; select vehicle/potency by site | Atrophy/striae with misuse; use a planned maintenance or steroid-sparing strategy rather than indefinite unreviewed treatment |
| Keratolytics (e.g., salicylic acid) | Remove thick scale to allow penetration of other agents | Irritation |
| Emollients | Maintain hydration, reduce scaling | — |
2nd line for psoriasis: Phototherapy. 308 nm UVB excimer laser can be used for localized lesions. [1]
NB-UVB is a common whole-body option; 308-nm excimer treatment is useful for localized resistant plaques. PUVA has greater cumulative phototoxic/carcinogenic burden and is selected less often. Phototherapy requires calibrated dosing, eye protection and cumulative-exposure review—not tanning beds.
Psoriasis Treatment Algorithm (AAD Guidelines)
The slide reproduces a 2011 "healthy adult male" algorithm that includes now-obsolete alefacept and potentially hazardous combinations of systemic immunosuppressants. Do not use it as a current prescribing flowchart. A safer current structure is: [13] [14]
Systemic Therapy for Psoriasis
The slide's "third-line" list predates contemporary oral targeted drugs and biologics. Hydroxyurea is not a routine approved psoriasis treatment. Current options include methotrexate, ciclosporin, acitretin, apremilast, deucravacitinib and biologics, with availability and licensing varying by jurisdiction. [13] [14]
Consider systemic therapy when optimized topical treatment is inadequate or impractical, disease is extensive, function/QoL is substantially impaired, psoriatic arthritis is active, or high-impact sites (scalp, face, genitals, palms/soles, nails) make otherwise low-BSA disease severe. Generalized pustular psoriasis and erythroderma require urgent specialist assessment.
Rule of Tens — High Yield
The Rule of Tens (BSA > 10%, PASI > 10 or DLQI > 10) is a memorable historical threshold for severe disease and remains exam-relevant, but it does not automatically "qualify" or exclude a patient. PASI is mainly a trial tool; a painful genital/palmoplantar/nail phenotype or PsA may justify systemic treatment below 10% BSA. [13] [14]
Historical trial reading: In an older RCT comparing MTX with ciclosporin:
- MTX 15 mg/week: 60% achieved PASI 75 at week 16
- Ciclosporin 3 mg/kg/day: 71% achieved PASI 75 at week 16
These week-16 response proportions do not establish a universal ranking; dosing, population and outcomes differ from modern head-to-head studies.
Historical local snapshot: the slide's 80-patient QMH cohort was mostly PASI < 10 and had low biologic use. It describes practice at that time, not today's prescribing distribution or a recommended treatment mix. [1]
Local survey/trial context: public belief that traditional Chinese medicine is effective is not evidence of efficacy. The AAD evidence review found insufficient or conflicting evidence to recommend herbal/alternative therapies; ask specifically about products because hepatotoxicity, adulteration and interactions are possible. [13]
| Agent | Useful clinical role | Monitoring/cautions |
|---|---|---|
| Methotrexate | Skin plus peripheral joint disease; slower and generally less skin clearance than modern biologics | Weekly dosing only; CBC, renal/liver assessment, interactions, folate and pregnancy prevention; use non-invasive fibrosis assessment rather than an automatic cumulative-dose liver biopsy rule |
| Ciclosporin | Rapid rescue for severe/recalcitrant, erythrodermic or generalized pustular disease | BP, creatinine/eGFR, electrolytes, interactions; short-term use because nephrotoxicity/hypertension accumulate |
| Acitretin | Non-immunosuppressive; useful for pustular/hyperkeratotic phenotypes and with phototherapy | Highly teratogenic with prolonged post-treatment pregnancy avoidance; lipids/LFT and mucocutaneous toxicity |
| Apremilast | Oral PDE4 inhibitor with modest skin/joint efficacy and low laboratory burden | GI effects, weight and mood; renal dose adjustment |
| Deucravacitinib | Oral selective TYK2 inhibitor for plaque psoriasis where licensed | Screen/monitor according to product label; do not assume class warnings/dosing are identical to JAK1/2/3 inhibitors |
The slide uses obsolete FDA letter pregnancy categories (A/B/C/D/X), replaced by narrative Pregnancy and Lactation Labeling Rule sections. Methotrexate and acitretin are contraindicated when pregnancy is possible without effective prevention; exact washout requirements and safer alternatives require the current local label/guideline. [14]
Biologic Therapy for Psoriasis
The slide's European wording required failure/intolerance/contraindication to conventional systemic therapy. Access rules vary: current selection is based on disease severity, previous therapy, efficacy, safety, psoriatic arthritis/IBD and other comorbidity, pregnancy plans, patient preference and local funding/label. [14]
| Target | Examples | Visual/mechanistic anchor |
|---|---|---|
| TNF | adalimumab, certolizumab pegol, etanercept, infliximab | Interrupts a broad inflammatory amplifier; monoclonal antibodies and receptor fusion proteins are not interchangeable across IBD/PsA |
| IL-12/23 p40 | ustekinumab | Blocks the shared p40 subunit; the older slide calls this the bridge between Th1 and Th17 pathways |
| IL-17A/F pathway | secukinumab, ixekizumab, brodalumab (IL-17RA), bimekizumab (IL-17A/F) | Acts downstream and often rapidly on the keratinocyte–neutrophil circuit |
| IL-23 p19 | guselkumab, risankizumab, tildrakizumab | Selectively suppresses maintenance of pathogenic type-17 cells |
Evolution of therapeutic targets: MTX → anti-TNF → anti-IL-12/23 → anti-IL-17 → anti-IL-23p19. Each generation achieves higher PASI responses:
The slide's rising arrows summarize separate trials, not randomized head-to-head comparisons. Modern IL-17/IL-23 agents often yield more PASI90/100 responses than older classes, but there is substantial drug-level variation and selection cannot be based on this graphic alone. [14]
Activated T cells stimulate macrophages and fibroblasts to secrete TNF-α. Adalimumab, infliximab and etanercept inhibit TNF-α-induced joint damage. [1]
| Drug | Type |
|---|---|
| Adalimumab | Fully human anti-TNF monoclonal antibody |
| Infliximab | Chimeric (mouse/human) anti-TNF monoclonal antibody |
| Etanercept | Soluble TNF receptor fusion protein (decoy receptor) |
Why distinguish these? Infliximab can trigger anti-drug antibodies (immunogenicity) more readily due to its chimeric nature. Etanercept, being a fusion protein rather than an antibody, binds TNF differently and is less effective for Crohn's disease (a common exam trap). All three are effective for psoriasis and psoriatic arthritis.
The two indication-grid slides are time-stamped snapshots and several cells have changed. The enduring interpretation is:
| Clinical context | Treatment-selection implication |
|---|---|
| Active psoriatic arthritis | Coordinate rheumatology care; choose an agent proven for the relevant peripheral/axial/enthesitis phenotype rather than treating skin alone |
| Inflammatory bowel disease | Prefer a class effective for both diseases where possible; avoid or use IL-17-pathway agents cautiously because they can exacerbate/newly trigger IBD |
| Demyelinating disease or significant heart failure | Avoid TNF inhibitors in important scenarios; use a different mechanism |
| Pregnancy plans | Drug-specific placental transfer and washout matter; certolizumab has minimal Fc-mediated placental transfer, but decisions remain specialist-led |
| Recurrent/latent infection | Screen and manage TB/HBV and update vaccines before immunomodulation; choice depends on pathogen, class and local guidance |
Do not infer approval from a lecture grid: always check the current Hong Kong/local product label. [14]
| Category | Adverse Events |
|---|---|
| All classes | Serious infection risk varies by agent; hypersensitivity/injection reactions and immunogenicity can occur; withhold live vaccines and individualize cancer-history decisions |
| TNF inhibitors | TB/HBV reactivation, serious infection, infusion reaction (infliximab), lupus-like disease; avoid/caution in demyelination and moderate–severe heart failure |
| IL-12/23 and IL-23 inhibitors | Infection/hypersensitivity; still perform class- and jurisdiction-appropriate infection screening |
| IL-17-pathway inhibitors | Mucocutaneous candidiasis and inflammatory-bowel-disease caution; neutropenia is uncommon |
| Brodalumab | US boxed warning/REMS for suicidal ideation and behaviour; assess psychiatric history, while recognizing causality is uncertain and labelling differs by jurisdiction |
Before treatment: history/exam, TB and hepatitis B assessment, hepatitis C/HIV testing according to risk/local protocol, vaccines, pregnancy plans, malignancy history and baseline tests dictated by the chosen drug. HBV and TB are the classic reactivation hazards; the slide's blanket "hepatitis C reactivation" label is too crude. [14]
Anti-IL-17 and IBD — Exam Trap
IL-17-pathway agents can worsen or newly trigger IBD and are generally avoided in active IBD. Do not turn that into a universal unsupervised drug rule: select an agent with gastroenterology/dermatology input and current indication data; several TNF, IL-12/23 and IL-23 agents treat both diseases, but not every member of a target class has the same GI licence.
Highly efficacious treatments combined with a treat-to-target approach to achieve and maintain skin clearance is pivotal to maximizing long-term health-related QoL. Target: PGA of clear or nearly clear. Involves: appropriate treatment selection, monitoring of treatment response, treatment optimization (dose adjustment, switching). [1]
The final lecture ladder is now substantially outdated. The 2026 international algorithm is: [15]
- A modern second-generation H1 antihistamine, usually taken regularly for chronic spontaneous urticaria (CSU).
- If uncontrolled, up-dose one agent to as much as fourfold (off-label in many jurisdictions); do not exceed fourfold or routinely mix several H1 antihistamines.
- Add omalizumab for disease uncontrolled by high-dose H1 antihistamine. Current guideline alternatives/additions include dupilumab or the oral BTK inhibitor remibrutinib where licensed/appropriate; approval differs by country.
- Ciclosporin is an off-label specialist option only for severe disease refractory to licensed treatment or where it is unavailable, because monitoring and adverse effects are substantial.
Reassess control and ongoing need every 3–6 months. Chronic urticaria is mast-cell driven; extensive allergy panels and restrictive diets are not routine without a history suggesting a specific trigger.
Second-generation antihistamines listed:
Fexofenadine, cetirizine, loratadine, desloratadine, levocetirizine. [1]
Why modern second-generation agents first? First-generation drugs (e.g., chlorpheniramine, hydroxyzine) cross the blood–brain barrier and cause sedation, impaired driving/learning and anticholinergic effects. Modern agents generally cause much less CNS impairment, though cetirizine and some others can still sedate an individual patient—ask about driving/work and do not call every agent completely "non-sedating." [15]
Why up-dose to fourfold? It is better supported than mixing several agents, but it remains off-label in many settings and requires attention to sedation, renal/hepatic function, pregnancy and drug-specific QT considerations. Doses above fourfold are not recommended. [15]
What fell out of the main ladder? H2 blockers have too little evidence for a recommendation. Montelukast provides at most modest adjunctive benefit and carries a neuropsychiatric warning; it is not the default third line. Ciclosporin acts partly by reducing mast-cell mediator release, not simply by treating a T-cell disease. [15]
Steroids are rescue, not maintenance
Do not treat CSU with prolonged or depot systemic corticosteroids. A brief course (up to about 10 days in the international guideline) can be considered only for a severe acute exacerbation; evidence is limited and cumulative toxicity is high. Topical steroids do not treat ordinary urticaria. [15]
The 1996/1998 Hong Kong counts on the slides are historical epidemiology and should not be used as current incidence or mortality.
SCC age-adjusted incidence: Australia 250/100,000; USA 30-154/100,000; Japanese in Hawaii 23/100,000 (45× that of Japanese in Japan). Sun exposure and skin colour are important for the lower prevalence of non-melanoma skin cancer in Chinese populations. [1]
Why it appears here: the lecturer used background skin-cancer incidence to discuss phototherapy. Lower population incidence does not remove individual UV risk. Skin phenotype, past skin cancer, photosensitising disease/drugs, immunosuppression and cumulative UV/PUVA exposure determine suitability; every skin tone can develop UV injury and cancer.
VI. Exam Intelligence
| Likely Stem | Expected Answer Points |
|---|---|
| "List the stepwise management of moderate atopic dermatitis" | Regular leave-on emollient + patient-specific trigger reduction → site/potency-appropriate topical anti-inflammatory → supervised wet wraps for selected severe flares and treat proven infection → phototherapy or systemic targeted/conventional treatment if inadequately controlled; avoid routine systemic steroid |
| "What is the current first-line treatment for pemphigus?" | Rituximab (anti-CD20) + short-term prednisone (Ritux 3 trial) |
| "Name 3 adverse effects of topical corticosteroids" | Atrophy, telangiectasia, striae, easy bruising, hypertrichosis, acneiform/perioral eruption, infection masking; HPA suppression with high cumulative exposure |
| "What is the 'Rule of Tens' in psoriasis?" | Historical severity mnemonic: BSA > 10%, PASI > 10 or DLQI > 10; supplement with special sites, symptoms, PsA and patient impact |
| "List the targets of biologic agents used in psoriasis" | TNF; IL-12/23 p40; IL-17A/F or IL-17RA; IL-23 p19 |
| "What is dupilumab and how does it work?" | Fully human monoclonal antibody targeting IL-4Rα subunit, blocking both IL-4 and IL-13. FDA-approved breakthrough therapy for moderate-severe AD |
| "What is the treatment ladder for chronic urticaria?" | Modern second-generation H1 antihistamine → up-dose one agent to ≤4-fold → add omalizumab; current targeted alternatives depend on licence → specialist ciclosporin only if severe refractory/unavailable licensed options; brief systemic steroid only for an acute flare |
| "Why are topical calcineurin inhibitors preferred for facial eczema?" | They do not cause skin atrophy (unlike steroids), making them safer for thin-skinned areas like eyelids |
| "What checks are needed before starting azathioprine?" | TPMT enzyme activity, NUDT15 (especially in Asian populations), check for concomitant xanthine oxidase inhibitors (allopurinol) |
| "Name 2 side effects specific to IL-17 inhibitors" | Candidiasis, exacerbation/new onset of IBD |
- Treating the slide's BP line as current: BP usually starts with a superpotent topical corticosteroid where feasible; doxycycline is a selected safety-first alternative, not a universal substitute.
- Using antihistamines as anti-eczema therapy: they do not treat AD inflammation; a sedating agent is only a short sleep/itch adjunct in selected patients.
- Calling a positive specific IgE "food allergy": it proves sensitisation; clinical history and sometimes supervised challenge establish allergy.
- Treating the Rule of Tens as a gatekeeper: special-site disease or PsA can justify systemic treatment below 10% BSA.
- Reading the biologic efficacy graphic as head-to-head evidence: it compares separate trials and cannot by itself select a drug.
- Repeating the old CSU third line: current default after fourfold H1 treatment is omalizumab, not H2 blockade/leukotriene treatment.
High Yield Summary
-
Eczema treatment ladder
- Regular leave-on emollient and demonstrated-trigger reduction → site/potency-appropriate topical corticosteroid or steroid-sparing topical → short supervised wet wraps for selected severe flares → phototherapy/systemic treatment when inadequately controlled. IL-4/13, IL-13 and IL-31 biologics and oral JAK inhibitors have transformed moderate–severe disease; routine systemic steroid is discouraged.
-
Psoriasis
- Topical corticosteroid ± vitamin-D analogue for limited plaque disease → phototherapy or systemic treatment when extent, special sites, QoL or PsA warrants. Systemic choices include conventional/oral targeted agents and TNF, IL-12/23, IL-17 or IL-23 biologics. Let PsA, IBD, infection, pregnancy plans and patient preference choose the class; screen cardiometabolic and mental-health comorbidity.
-
Pemphigus
- Rituximab (anti-CD20) + short-term prednisone is first-line for moderate–severe pemphigus (Ritux 3: 89% vs 34% complete remission off therapy). Bullous pemphigoid: superpotent topical corticosteroid is the mainstay where feasible; individualize oral/steroid-sparing alternatives for frail patients.
-
Chronic urticaria
- Modern 2nd-generation H1 antihistamine → up-dose one agent to ≤4× → add omalizumab; use other licensed targeted options by jurisdiction and reserve ciclosporin for severe refractory disease. Steroid is brief rescue only.
Active Recall - Treatments for Skin Diseases
[1] Lecture slides: GC 090. Treatments for skin diseases.pdf (all pages referenced throughout) [2] Past papers: 2019 Fourth Summative MCQ.pdf (EMQ sections on dermatological conditions and drugs in inflammatory arthritis) [3] Past papers: 2021 Fourth Summative SAQ.pdf (Q7 on skin pathology and treatment) [4] Senior notes: Ryan Ho Fundamentals.pdf (p419-420, steroid ladder in HK, topical treatments) [5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p404, approach to management of AD) [6] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p45, TPMT/NUDT15 and azathioprine) [7] Medicine lecture slides: Derm General Clerkship 2026 Part1.pdf (p14, treatment tiers for AD including JAK inhibitors) [8] Joly P, et al. Updated EADV S2K guideline for pemphigus vulgaris and foliaceus. J Eur Acad Dermatol Venereol. 2020. [9] Borradori L, et al. Updated EADV S2K guideline for bullous pemphigoid. J Eur Acad Dermatol Venereol. 2022. [10] American Academy of Dermatology. Atopic dermatitis clinical guidelines: topical, phototherapy and systemic therapy; 2025 focused update. [11] American Academy of Dermatology. 2026 pediatric atopic dermatitis guideline highlights. [12] NIAID-sponsored Expert Panel. Addendum guidelines for prevention of peanut allergy. [13] American Academy of Dermatology/National Psoriasis Foundation. Psoriasis clinical guidelines. [14] European Dermatology Forum. Living EuroGuiDerm guideline for systemic treatment of psoriasis vulgaris, partial update February 2025. [15] Zuberbier T, et al. International guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2026. [16] U.S. Food and Drug Administration. Dupilumab prescribing information: bullous pemphigoid indication and ADEPT trial. 2025.
GC089 Syncope And Irregular Heart Beat
Syncope is a transient loss of consciousness due to cerebral hypoperfusion, and irregular heartbeat (arrhythmia) refers to abnormal cardiac rhythm disturbances, which together represent a clinical presentation where cardiac dysrhythmias may cause hemodynamic compromise leading to fainting episodes.
GC091 Unsteady Gait Cerebellar Lesions; Movement Disorders; Parkinsonism
Unsteady gait is a disturbance in walking stability that can arise from cerebellar lesions causing ataxia, movement disorders such as dystonia or chorea, or parkinsonism characterized by shuffling steps, festination, and postural instability.