Allergic Skin Disorders (25 marks)

1. Definition and classification

1. Urticaria and angioedema
2. Atopic dermatitis (eczema)
3. Allergic contact dermatitis
4. Cutaneous drug eruptions
5. Others: photoallergic dermatitis, id reaction, papular urticaria, food- and insect-related reactions

2. Urticaria and angioedema

• Acute: less than 6 weeks. Causes are foods, drugs, infections and stings.
• Chronic: 6 weeks or more.
  • Chronic spontaneous urticaria: often autoimmune, with IgG against FcεRI or IgE.
  • Chronic inducible urticaria: dermographism, cold, cholinergic, pressure, solar, aquagenic.

• Immunologic triggers: IgE-mediated (penicillin and other β-lactams, foods, venom) and complement-mediated.
• Non-immunologic triggers: aspirin and NSAIDs (altered prostaglandin metabolism enhances mast cell degranulation), radiocontrast, opiates, tubocurarine and polymyxin B (Andrews' Diseases of the Skin, p. 143-144).
• Drug points from the same text:
  • Penicillin urticaria is IgE-mediated.
  • Third-generation cephalosporins cross-react less than first- or second-generation agents.
  • Bupropion can cause urticaria with a serum-sickness-like picture.
  • Cetirizine and hydroxyzine can paradoxically induce urticaria.
  • ACE inhibitors and angiotensin II antagonists cause angioedema, and Black patients have about 5 times the risk of White patients.

• Mostly clinical.
• Chronic urticaria: FBC, ESR/CRP, TSH and thyroid autoantibodies, with further tests guided by history.
• Provocation tests for inducible types.
• Skin prick test or specific IgE (RAST) when an IgE-mediated cause is suspected.
• C4 and C1 esterase inhibitor levels if there is angioedema without wheals, to exclude hereditary angioedema.

1. Identify and avoid triggers, and stop culprit drugs.
2. Non-sedating H1 antihistamines (cetirizine, fexofenadine, loratadine). If the response is poor, increase the dose up to 4 times the standard dose.
3. Omalizumab (anti-IgE) for refractory chronic spontaneous urticaria. Ciclosporin is another option.
4. Short oral prednisolone course for severe acute attacks or angioedema. Avoid long-term use.
5. Anaphylaxis: intramuscular adrenaline 0.5 mg (1:1000), airway support, IV fluids, antihistamine and steroid.
6. Hereditary angioedema: does not respond to antihistamines, steroids or adrenaline. Treat with C1 inhibitor concentrate, icatibant or ecallantide.

3. Atopic dermatitis (atopic eczema)

• Genetic: filaggrin gene loss-of-function mutations cause barrier failure and transepidermal water loss.
• Immune: Th2 skew (IL-4, IL-5, IL-13, IL-31), raised IgE, and eosinophilia.
• Environmental: house dust mite, soaps, heat, sweat, stress, and Staphylococcus aureus colonisation.

• Flexural involvement.
• Personal history of asthma or hay fever.
• Generalised dry skin.
• Onset before age 2.
• Visible flexural dermatitis.

1. General measures: avoid irritants and harsh soaps, use soap substitutes, keep nails short, wear cotton clothing.
2. Emollients: liberal and frequent, applied within minutes of bathing.
3. Topical corticosteroids matched to site and severity. Examples are 1% hydrocortisone for the face and flexures, and a moderate to potent steroid for the trunk and limbs. Ointments are most effective (Tintinalli's).
4. Topical calcineurin inhibitors (tacrolimus, pimecrolimus) for the face, flexures and steroid-sparing use. Topical crisaborole and ruxolitinib are other options.
5. Wet wraps and bandaging for severe flares.
6. Sedating antihistamines at night help with sleep only, not with the eczema itself.
7. Treat infection: flucloxacillin or cephalexin for bacterial infection, and IV aciclovir for eczema herpeticum.
8. Phototherapy (narrowband UVB) for moderate disease.
9. Systemic therapy for severe disease: ciclosporin, methotrexate, azathioprine, short courses of prednisolone.
10. Biologics and small molecules: dupilumab (anti-IL-4Rα), tralokinumab and lebrikizumab (anti-IL-13), and JAK inhibitors (upadacitinib, abrocitinib, baricitinib).

4. Allergic contact dermatitis (ACD)

• Nickel (jewellery, buckles).
• Chromate (cement, leather).
• Rubber chemicals.
• Fragrances.
• Preservatives (methylisothiazolinone, formaldehyde releasers).
• Neomycin.
• Hair dye (p-phenylenediamine).
• Plant resins: urushiol in poison ivy, parthenium in India.
• Topical drugs.

• Acute: well-marginated erythema and oedema confined to the contact area, with papules and vesicles. Bullae can occur in severe reactions.
• Linear lesions suggest poison ivy. Geographic lesions suggest nickel.
• Chronic: lichenified, scaly, with postinflammatory pigment change.
• Later it may spread beyond the contact site, and chronic ACD is often misdiagnosed as endogenous eczema (Tintinalli's).

• Identify and avoid the allergen. This is the key step.
• Topical steroids (potency by site and severity).
• Emollients and barrier creams.
• For severe or widespread disease, oral prednisolone tapered over about 3 weeks. Starting dose in adults is 40 to 60 mg/day, and in children 1 to 2 mg/kg up to 40 mg/day (Tintinalli's).
• Antihistamines at night may help with sleep.
• Treat secondary infection.

5. Allergic (hypersensitivity) drug eruptions

• Stop the suspected drug immediately.
• Give supportive care and topical steroids.
• SJS/TEN: admit to a burns or ICU unit with fluid and wound care. Specialist-guided options include ciclosporin, IVIG, or etanercept.
• DRESS: systemic steroids.
• Document the allergy, and test (skin or challenge) where appropriate.

6. Other allergic and related conditions

• Photoallergic dermatitis: a type IV reaction to a photo-activated sensitiser (sunscreens, NSAIDs), appearing in sun-exposed areas.
• Id (autoeczematisation) reaction: distant vesicular eruption after a primary eczema, tinea or stasis dermatitis.
• Papular urticaria: hypersensitivity to insect bites in children.
• Urticarial vasculitis: wheals lasting more than 24 hours that leave bruising or pigmentation.
• Food allergy: pollen-food syndrome, and oral allergy syndrome.

7. Summary points for the examiner

• Type I causes urticaria and angioedema. Type IV causes allergic contact dermatitis and most delayed drug eruptions.
• Atopic dermatitis combines a barrier defect (filaggrin) with Th2 inflammation. Itching is the key feature, and emollients and topical steroids are the foundation of treatment.
• Patch testing is the gold standard for ACD. Allergen avoidance is the cure.
• Stop the culprit drug in any suspected drug allergy. Recognise SJS/TEN and DRESS early because they are life-threatening.
• Anaphylaxis is treated with IM adrenaline first.

Autoimmune Skin Disorders (13 marks)

1. Definition

2. Classification

3. Pemphigus vulgaris (the main example)

• Flaccid, easily ruptured bullae on normal skin, which leave painful erosions.
• Oral mucosal erosions are often the first sign.
• Nikolsky sign positive and Asboe-Hansen sign positive.
• Middle-aged adults are most commonly affected.

• Biopsy from the edge of a lesion: suprabasal split with acantholysis ("tombstone" basal cells).
• Perilesional direct immunofluorescence: intercellular IgG and C3 ("chicken-wire" pattern). This is the gold standard.
• Indirect immunofluorescence and ELISA for anti-Dsg1 and anti-Dsg3.
• Tzanck smear shows acantholytic cells.

• Systemic corticosteroids (prednisolone 1 mg/kg/day) with a steroid-sparing agent such as azathioprine or mycophenolate.
• Rituximab (anti-CD20) is now first-line for moderate to severe disease. It depletes B cells and lowers anti-desmoglein antibody levels (Dermatology 5e).
• Other options: IVIG, plasmapheresis, dapsone, methotrexate.
• Supportive care: wound care, infection control, fluid and nutrition, and monitoring for steroid side effects.

4. Bullous pemphigoid

• Typically affects elderly patients.
• Autoantibodies (IgG, and sometimes IgE) target BP180 (collagen XVII, NC16A domain) and BP230 in the hemidesmosome (Fitzpatrick's Dermatology, pathophysiology of subepidermal blistering).
• Presents with tense bullae on an urticarial or erythematous base, mainly on flexures and limbs. Itching is prominent. The mouth is usually spared.
• Biopsy shows a subepidermal split with eosinophils. DIF shows linear IgG and C3 along the basement membrane zone.
• Treatment: potent topical steroids (clobetasol), or oral prednisolone for extensive disease. Doxycycline and steroid-sparing agents (azathioprine, methotrexate) are alternatives. Dupilumab and rituximab are used in refractory disease.

5. Cutaneous lupus erythematosus (CLE)

• Types: acute (malar "butterfly" rash), subacute (annular or psoriasiform, anti-Ro/SSA), and chronic discoid lupus (scarring plaques with follicular plugging and atrophy).
• Diagnosis: ANA, anti-dsDNA, anti-Ro/La, and complement in systemic disease. Skin biopsy shows interface dermatitis. The lupus band test is positive (granular IgG/IgM at the dermoepidermal junction).
• Treatment: strict photoprotection, topical steroids or calcineurin inhibitors, hydroxychloroquine as first-line systemic therapy, and methotrexate, mycophenolate or belimumab for severe disease. Smoking cessation improves response.

6. Dermatomyositis and scleroderma (brief)

• Dermatomyositis: heliotrope rash, Gottron papules, shawl sign, and proximal muscle weakness. Antibodies include anti-Mi-2, anti-MDA5 and anti-TIF1γ. Screen for associated malignancy. Treat with steroids and immunosuppressants (methotrexate, IVIG).
• Systemic sclerosis: skin thickening, Raynaud's phenomenon, sclerodactyly, and telangiectasia. Antibodies are anti-centromere (limited disease) and anti-Scl-70 (diffuse disease).
• Morphea: localised sclerosis of the skin without systemic involvement. Treat with topical steroids or calcipotriol, phototherapy (UVA1), and methotrexate for extensive disease.

7. Organ-specific autoimmune conditions

• Vitiligo: autoimmune destruction of melanocytes, causing depigmented macules. It is associated with thyroid disease and type 1 diabetes. Treat with topical steroids or tacrolimus, narrowband UVB, and topical JAK inhibitors (e.g. ruxolitinib cream).
• Alopecia areata: T-cell attack on hair follicles, causing patchy, non-scarring hair loss with exclamation-mark hairs. Treat with intralesional triamcinolone, topical agents, and JAK inhibitors (baricitinib) for severe disease.
• Lichen planus: the 6 P's are purple, polygonal, pruritic, papules and plaques. Wickham striae are characteristic. Treat with potent topical steroids or systemic therapy.

8. General principles of management

1. Confirm the diagnosis with biopsy and immunofluorescence.
2. Control the disease with immunosuppression.
3. Monitor for steroid complications. Give bone protection, GI prophylaxis, and screen for infection.
4. Look for associated systemic disease and malignancy.
5. Offer counselling and psychological support.

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