Topic map

1. Paraneoplastic dermatoses: list, plus one in detail (for example acanthosis nigricans, Sweet syndrome, dermatomyositis, paraneoplastic pemphigus, Leser-Trélat sign or acquired ichthyosis)
2. Psoriasis: IL-23/Th17 pathogenesis, classification of biologics, and one agent in detail (mechanism, dosing, screening)
3. Hypocomplementemic urticarial vasculitis syndrome (HUVS): management
4. Pyoderma gangrenosum: pathogenesis, clinical variants, therapy
5. Premalignant skin lesions in the elderly: list, plus management of one (for example actinic keratosis)
6. Pregnancy-specific dermatoses: list, plus management of polymorphic eruption of pregnancy (PEP)
7. Laboratory diagnosis of autoimmune connective tissue diseases: ANA patterns, ENA, anti-dsDNA, complement, direct immunofluorescence (lupus band test), myositis antibodies
8. Dyslipidaemias: WHO (Fredrickson) classification, then tuberous xanthoma
9. Short notes: (a) fixed drug eruption, (b) acrodermatitis enteropathica, (c) delusional parasitosis

Brief overview of the key points

• Q1: Paraneoplastic dermatoses fall into three groups. The obligate or strong markers are acanthosis nigricans (malignant type), tripe palms, Bazex syndrome, necrolytic migratory erythema, paraneoplastic pemphigus, Sweet syndrome and erythema gyratum repens. Other associations include dermatomyositis, hypertrichosis lanuginosa acquisita, Leser-Trélat sign and acquired ichthyosis. Cutaneous markers of genetic cancer syndromes, such as Cowden and Peutz-Jeghers, are a separate group.
• Q2: Dendritic cells release IL-23, which sustains Th17 cells that make IL-17A/F, IL-22 and TNF. These act on keratinocytes to cause hyperproliferation and chemokine release, and the loop is amplified through the IL-36 pathway. The biologics are TNF inhibitors (etanercept, infliximab, adalimumab, certolizumab), IL-12/23 inhibitors (ustekinumab), IL-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab) and IL-23 inhibitors (guselkumab, tildrakizumab, risankizumab). Screening before starting includes TB (IGRA or Mantoux and chest X-ray), hepatitis B and C, HIV, pregnancy status and vaccination review.
• Q3: HUVS is treated with steroids plus steroid-sparing agents (dapsone, hydroxychloroquine, azathioprine, mycophenolate, methotrexate). Rituximab, IVIG, plasmapheresis and cyclophosphamide are used in severe or organ-threatening disease. Patients also need screening for anti-C1q antibodies, SLE overlap and the pulmonary, renal and ocular complications.
• Q4: Pyoderma gangrenosum is a neutrophilic dermatosis with IL-1, IL-17 and TNF dysregulation. The variants are ulcerative (classic), bullous, pustular, vegetative (superficial granulomatous) and peristomal. Treatment is topical or intralesional steroids and calcineurin inhibitors for mild disease. Systemic steroids and cyclosporine are first line for moderate to severe disease, and infliximab or adalimumab are the main biologics.
• Q5: The main premalignant lesions in the elderly are actinic keratosis, actinic cheilitis, cutaneous horn, Bowen disease, leukoplakia, radiation keratosis and arsenical keratosis. Lentigo maligna and erythroplasia of Queyrat also belong here.
• Q6: Pregnancy-specific dermatoses are PEP (PUPPP), pemphigoid gestationis, intrahepatic cholestasis of pregnancy and atopic eruption of pregnancy. PEP is managed with emollients, antihistamines and topical steroids, with short oral steroids for severe cases. It is self-limiting, usually resolves after delivery and has no fetal risk.
• Q7: The core tests are ANA by IIF on HEp-2 cells with pattern interpretation, then ENA (Ro, La, Sm, RNP, Scl-70, centromere, Jo-1). Anti-dsDNA, complement levels, antiphospholipid antibodies, myositis-specific antibodies and skin biopsy with lupus band test complete the panel.
• Q8: The WHO/Fredrickson types are I, IIa, IIb, III, IV and V. Tuberous xanthomas are classically seen in type III (familial dysbetalipoproteinaemia) and in familial hypercholesterolaemia. Treatment is a statin, ezetimibe, a fibrate and lifestyle change, with surgery for large lesions.
• Q9: The three short notes cover fixed drug eruption (a recurrent, well-defined, hyperpigmented lesion at the same site), acrodermatitis enteropathica (zinc deficiency from a SLC39A4 mutation, treated with zinc) and delusional parasitosis (a monodelusional disorder treated with pimozide or atypical antipsychotics).

Topic map

1. Paraneoplastic dermatoses: list, plus one in detail (for example acanthosis nigricans, Sweet syndrome, dermatomyositis, paraneoplastic pemphigus, Leser-Trélat sign or acquired ichthyosis)
2. Psoriasis: IL-23/Th17 pathogenesis, classification of biologics, and one agent in detail (mechanism, dosing, screening)
3. Hypocomplementemic urticarial vasculitis syndrome (HUVS): management
4. Pyoderma gangrenosum: pathogenesis, clinical variants, therapy
5. Premalignant skin lesions in the elderly: list, plus management of one (for example actinic keratosis)
6. Pregnancy-specific dermatoses: list, plus management of polymorphic eruption of pregnancy (PEP)
7. Laboratory diagnosis of autoimmune connective tissue diseases: ANA patterns, ENA, anti-dsDNA, complement, direct immunofluorescence (lupus band test), myositis antibodies
8. Dyslipidaemias: WHO (Fredrickson) classification, then tuberous xanthoma
9. Short notes: (a) fixed drug eruption, (b) acrodermatitis enteropathica, (c) delusional parasitosis

Brief overview of the key points

• Q1: Paraneoplastic dermatoses fall into three groups. The obligate or strong markers are acanthosis nigricans (malignant type), tripe palms, Bazex syndrome, necrolytic migratory erythema, paraneoplastic pemphigus, Sweet syndrome and erythema gyratum repens. Other associations include dermatomyositis, hypertrichosis lanuginosa acquisita, Leser-Trélat sign and acquired ichthyosis. Cutaneous markers of genetic cancer syndromes, such as Cowden and Peutz-Jeghers, are a separate group.
• Q2: Dendritic cells release IL-23, which sustains Th17 cells that make IL-17A/F, IL-22 and TNF. These act on keratinocytes to cause hyperproliferation and chemokine release, and the loop is amplified through the IL-36 pathway. The biologics are TNF inhibitors (etanercept, infliximab, adalimumab, certolizumab), IL-12/23 inhibitors (ustekinumab), IL-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab) and IL-23 inhibitors (guselkumab, tildrakizumab, risankizumab). Screening before starting includes TB (IGRA or Mantoux and chest X-ray), hepatitis B and C, HIV, pregnancy status and vaccination review.
• Q3: HUVS is treated with steroids plus steroid-sparing agents (dapsone, hydroxychloroquine, azathioprine, mycophenolate, methotrexate). Rituximab, IVIG, plasmapheresis and cyclophosphamide are used in severe or organ-threatening disease. Patients also need screening for anti-C1q antibodies, SLE overlap and the pulmonary, renal and ocular complications.
• Q4: Pyoderma gangrenosum is a neutrophilic dermatosis with IL-1, IL-17 and TNF dysregulation. The variants are ulcerative (classic), bullous, pustular, vegetative (superficial granulomatous) and peristomal. Treatment is topical or intralesional steroids and calcineurin inhibitors for mild disease. Systemic steroids and cyclosporine are first line for moderate to severe disease, and infliximab or adalimumab are the main biologics.
• Q5: The main premalignant lesions in the elderly are actinic keratosis, actinic cheilitis, cutaneous horn, Bowen disease, leukoplakia, radiation keratosis and arsenical keratosis. Lentigo maligna and erythroplasia of Queyrat also belong here.
• Q6: Pregnancy-specific dermatoses are PEP (PUPPP), pemphigoid gestationis, intrahepatic cholestasis of pregnancy and atopic eruption of pregnancy. PEP is managed with emollients, antihistamines and topical steroids, with short oral steroids for severe cases. It is self-limiting, usually resolves after delivery and has no fetal risk.
• Q7: The core tests are ANA by IIF on HEp-2 cells with pattern interpretation, then ENA (Ro, La, Sm, RNP, Scl-70, centromere, Jo-1). Anti-dsDNA, complement levels, antiphospholipid antibodies, myositis-specific antibodies and skin biopsy with lupus band test complete the panel.
• Q8: The WHO/Fredrickson types are I, IIa, IIb, III, IV and V. Tuberous xanthomas are classically seen in type III (familial dysbetalipoproteinaemia) and in familial hypercholesterolaemia. Treatment is a statin, ezetimibe, a fibrate and lifestyle change, with surgery for large lesions.
• Q9: The three short notes cover fixed drug eruption (a recurrent, well-defined, hyperpigmented lesion at the same site), acrodermatitis enteropathica (zinc deficiency from a SLC39A4 mutation, treated with zinc) and delusional parasitosis (a monodelusional disorder treated with pimozide or atypical antipsychotics).

Q1. Paraneoplastic dermatoses: enumeration, and paraneoplastic pemphigus (PNP) in detail

Part A. Enumeration of paraneoplastic dermatoses

• The cancer and the dermatosis start together.
• They follow a parallel course.
• Neither is a common disorder.
• There is a statistical association.
• There is a genetic link, where one exists.

1. Obligate paraneoplastic dermatoses (almost always indicate cancer)

2. Facultative dermatoses (sometimes signal malignancy)

• Dermatomyositis, especially in patients over 40. It is associated with ovarian, lung, pancreatic and GI cancers and with nasopharyngeal carcinoma in Asians. Anti-TIF1-gamma and anti-NXP2 antibodies mark higher risk.
• Sweet syndrome (acute febrile neutrophilic dermatosis), associated with AML and MDS.
• Pyoderma gangrenosum, bullous type, associated with myeloid malignancy.
• Paraneoplastic acquired ichthyosis, associated with Hodgkin and other lymphomas.
• Exfoliative erythroderma, associated with cutaneous T-cell lymphoma and other lymphoproliferative disease.
• Pityriasis rotunda, associated with hepatocellular carcinoma.
• Palmoplantar keratoderma (late-onset, non-hereditary), associated with oesophageal carcinoma.
• Multicentric reticulohistiocytosis and palmar fasciitis with polyarthritis, associated with ovarian and other carcinomas.
• Pruritus, associated with Hodgkin disease, polycythaemia vera and other cancers.
• Cutaneous vasculitis, erythromelalgia and paraneoplastic urticaria, associated with myeloproliferative and lymphoid neoplasms.
• Nodular fat necrosis (pancreatic panniculitis), associated with pancreatic carcinoma.
• Extramammary Paget disease (marker of underlying adnexal or visceral carcinoma).
• Eruptive xanthomas, acquired palmoplantar keratoderma, pachydermoperiostosis and cutaneous amyloidosis (primary systemic AL type, with myeloma).

3. Genodermatoses with internal malignancy (not strictly paraneoplastic)

• Peutz-Jeghers, Cowden, Gardner and Muir-Torre syndromes.
• Birt-Hogg-Dubé syndrome.
• Neurofibromatosis.
• Tuberous sclerosis.
• Howel-Evans syndrome (tylosis with oesophageal cancer).

Part B. Paraneoplastic pemphigus (PNP)

Definition

Aetiology and associated neoplasms

• Non-Hodgkin lymphoma, CLL, Castleman disease (especially in children), thymoma, Waldenström macroglobulinaemia, AML and sarcoma.
• Some patients have no identifiable neoplasm (Andrews' Diseases of the Skin, Paraneoplastic Pemphigus).
• Most common are haematological neoplasms, and most reported patients die of their tumour or of bronchiolitis obliterans.

Pathogenesis

1. The tumour produces antigens or cytokines (such as IL-6) that drive a breakdown of tolerance.
2. Both humoral and cell-mediated immunity are involved.
3. Autoantibodies target plakin family proteins in desmosomes and hemidesmosomes:
   • Desmoplakin I (250 kD) and desmoplakin II.
   • Envoplakin (210 kD) and periplakin (190 kD).
   • BP antigen 1 (230 kD) and plectin.
   • Often a 170 kD antigen, identified as alpha-2-macroglobulin-like-1 (A2ML1).
   • Desmoglein 3 (and sometimes Dsg1) and desmocollins.
4. The IgG is mainly IgG1 and IgG2, unlike pemphigus vulgaris, which is IgG4 dominant.
5. Dsg3 epitopes are spread across the whole extracellular domain, not just the N-terminus as in pemphigus vulgaris.
6. Cytotoxic T cells and interface/lichenoid inflammation explain the dyskeratosis and the lichenoid and erythema multiforme-like lesions.
7. There is a significant HLA-DRB1*03 association.
8. Antibodies to epithelia other than skin, such as respiratory epithelium, cause bronchiolitis obliterans.

Clinical features

• Mucosal lesions are the hallmark, and they are often the first sign.
  • There is severe, persistent, painful stomatitis with erosions of the tongue and lips.
  • Hemorrhagic crusting of the lips can mimic Stevens-Johnson syndrome.
  • Lesions are resistant to treatment.
• Skin lesions are polymorphic:
  • Erythematous macules and lichenoid papules.
  • Erythema multiforme-like target lesions.
  • Flaccid bullae and erosions typical of pemphigus.
  • Tense, deep-set bullae resembling pemphigoid.
  • Graft-versus-host-like eruptions.
  • Palms and soles are commonly involved, which is unusual in other pemphigus types.
• Ocular disease is conjunctival, with cicatrising conjunctivitis, symblepharon and corneal melting.
• Other mucosae (nasopharynx, oesophagus, genitalia, anus) may be involved.
• Pulmonary involvement is bronchiolitis obliterans. It presents with cough, dyspnoea and fixed obstruction that does not respond to bronchodilators. It carries the worst prognosis, because it can progress even when the skin disease and tumour are controlled.

Investigations

Differential diagnosis

• Pemphigus vulgaris.
• Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Erosive lichen planus.
• Bullous pemphigoid and mucous membrane pemphigoid.
• Graft-versus-host disease.
• Erythema multiforme major.

Treatment

• The tumour comes first. Benign tumours such as a localised Castleman tumour or thymoma are resected, and the skin disease often improves. Malignant tumours are treated according to their type.
• Immunosuppression is balanced against the tumour treatment, and the textbook lists these options:
  • High-dose systemic corticosteroids (prednisolone 1 to 2 mg/kg/day).
  • Rituximab, and alemtuzumab in CLL.
  • Cyclosporine, and cyclophosphamide (high-dose without stem cell rescue).
  • IVIG, plasmapheresis and immunoapheresis.
• Supportive care covers mouth care, topical anaesthetics, ocular lubricants and ophthalmology review, nutrition, and infection control.
• Bronchiolitis obliterans is treated with immunosuppression and, in selected cases, lung transplantation. It often responds poorly even when the other disease is controlled.

Prognosis

Exam tips

• Draw the table of paraneoplastic dermatoses, with the obligate group first.
• Write the antigens as a list (envoplakin, periplakin, desmoplakin, BPAG1, plectin, Dsg3, A2ML1).
• State clearly that bronchiolitis obliterans is the main cause of death.
• Add a labelled diagram of the plakin family in the desmosome.

Dermatology Theory Paper: Answers to Q2 to Q9 (10-mark format)

Q2. Psoriasis: IL-23/Th17 axis, biologic classification, and secukinumab

A. Pathogenesis of psoriasis (IL-23/Th17 axis)

• PSORS1 (HLA-Cw6, HLA-C*06:02) is the strongest association.
• Other susceptibility genes: IL23R, IL12B, IL23A, TRAF3IP2, TNFAIP3, CARD14.
• Triggers: trauma (Koebner phenomenon), streptococcal infection, drugs (lithium, beta-blockers, antimalarials), stress, alcohol, smoking.

1. Initiation. Keratinocyte injury releases self-DNA/RNA and the antimicrobial peptide LL-37. LL-37 complexes with nucleic acids and activates plasmacytoid dendritic cells through TLR7/9, causing interferon-alpha release.
2. Dendritic cell activation. Myeloid (inflammatory) dendritic cells release IL-23 (p19/p40), IL-12 and TNF-alpha. IL-12 drives Th1 cells, which make IFN-gamma and TNF.
3. IL-23 action. IL-23 binds IL-23R on Th17, Tc17, gamma-delta T cells and ILC3. It does not start Th17 differentiation (IL-6, TGF-beta, IL-1beta do that). It maintains, expands and stabilises the Th17 population.
4. Effector cytokines. Th17 cells release IL-17A and IL-17F, IL-22, TNF-alpha and IL-21.
5. Keratinocyte response.
   • IL-17 and IL-22 cause hyperproliferation, parakeratosis, acanthosis and loss of the granular layer.
   • Keratinocytes release chemokines (CXCL1, CXCL8, CCL20) that recruit neutrophils (Munro microabscesses) and more Th17 cells.
   • They also release antimicrobial peptides (beta-defensins, S100A7/8/9) and IL-36 cytokines.
6. Positive feedback loop. Keratinocyte products (IL-1, IL-6, IL-36, CCL20) further stimulate dendritic cells and Th17 cells.
7. Vascular changes. VEGF produces dilated, tortuous papillary capillaries, which explains the Auspitz sign.
8. Memory. Tissue-resident memory T cells persist in healed skin, which explains recurrence at the same sites.

• Blocking TNF breaks the early loop.
• Blocking IL-23 or IL-17 acts on the central axis.
• IL-23 blockade is more upstream, with fewer candida infections and less frequent dosing.
• IL-17 blockade acts faster.

B. Classification of approved biologics for moderate-to-severe plaque psoriasis

C. Secukinumab in detail

• 300 mg SC (two 150 mg injections) at weeks 0, 1, 2, 3 and 4.
• Then 300 mg every 4 weeks.
• 150 mg may be used in some patients, and a lower-weight patient may do well on it. Heavier patients (more than 90 kg) may need the 300 mg dose.
• Typical onset is rapid, with PASI improvement by week 2 to 4. Assess response at week 12 to 16.

• Detailed history and examination.
• Look for active or latent TB:
  • Tuberculin test (Mantoux) or IGRA, plus a chest X-ray.
  • Treat latent TB before starting, and consider annual re-screening in high-burden countries like India.
• HBsAg, anti-HBc and anti-HBs; anti-HCV; HIV.
• CBC with differential, liver function tests, renal function tests.
• Pregnancy test, and contraception counselling.
• Ask about IBD (Crohn disease, ulcerative colitis). Secukinumab can worsen it, so it is avoided in active IBD.
• Ask about recurrent candidiasis or other chronic infections.
• Vaccination review: update inactivated vaccines before starting, and avoid live vaccines during treatment.
• Baseline severity scores: PASI, BSA, DLQI.

Q3. Management of hypocomplementemic urticarial vasculitis syndrome (HUVS)

Definition

• Major (both required): chronic urticaria (for 6 months or more) and hypocomplementemia.
• Minor (at least 2): venulitis on biopsy, arthralgia or arthritis, glomerulonephritis, uveitis or episcleritis, recurrent abdominal pain, positive C1q precipitin test (anti-C1q).

Evaluation before treatment

• Skin biopsy of a lesion less than 24 to 48 hours old: leukocytoclastic vasculitis with fibrinoid necrosis.
• Complement: C3, C4, CH50, C1q levels, anti-C1q antibodies.
• ANA, anti-dsDNA, ENA, to look for SLE overlap.
• Hepatitis B and C, cryoglobulins, serum protein electrophoresis.
• Urine routine and protein/creatinine ratio, renal function.
• Chest X-ray and spirometry for obstructive lung disease (COPD), which is a frequent systemic complication.
• Ophthalmology review (uveitis, episcleritis, conjunctivitis).
• Abdominal evaluation if there is pain.

Treatment (stepwise)

• Antihistamines (H1 blockers). These are often ineffective for the vasculitic lesions.
• NSAIDs. Indomethacin is noted as particularly effective.
• Colchicine 0.5 mg twice daily.
• Dapsone 50 to 100 mg/day (check G6PD first). The textbook notes that adding pentoxifylline to dapsone may help.
• Hydroxychloroquine 200 to 400 mg/day (ophthalmology screening).

• Prednisolone 0.5 to 1 mg/kg/day, tapered once control is achieved.
• Steroid-sparing agents: azathioprine, mycophenolate mofetil, methotrexate, cyclosporine. The textbook names prednisone with MMF, azathioprine, rituximab and canakinumab.

• Rituximab.
• IL-1 blockade: canakinumab, anakinra.
• IVIG.
• Cyclophosphamide (for severe renal disease).
• Plasmapheresis.
• Omalizumab has been used in case reports.

Q4. Pyoderma gangrenosum (PG): pathogenesis, clinical variants, therapy

Definition

Pathogenesis

• Innate immune dysregulation: overactivity of the inflammasome with raised IL-1beta, IL-8 (CXCL8), IL-36, TNF-alpha, and neutrophil chemotaxis.
• Th17 axis: raised IL-17 and IL-23.
• Genetic:
  • PAPA syndrome (pyogenic arthritis, PG, acne): PSTPIP1 mutations.
  • PASH (PG, acne, suppurative hidradenitis) and PAPASH.
  • Gene variants in IL-1 and neutrophil pathways.
• Pathergy: minor trauma or surgery induces new lesions.
• Immune complexes and abnormal neutrophil chemotaxis have also been described.
• Associated diseases (in about 50% of cases):
  • Inflammatory bowel disease.
  • Inflammatory arthritis (rheumatoid arthritis, seronegative arthropathy).
  • Haematological disease (MGUS, myeloma, AML, MDS).
  • Hepatitis C, Takayasu arteritis, SLE.
  • Drugs: isotretinoin, G-CSF, propylthiouracil, sunitinib.

Clinical variants

Diagnosis

• Major: biopsy of the ulcer edge shows neutrophilic infiltrate.
• Minor:
  • Exclusion of infection.
  • Pathergy.
  • History of IBD or inflammatory arthritis.
  • Papule, pustule or vesicle ulcerating within 4 days of appearing.
  • Peripheral erythema, undermined border and tenderness at the ulcer site.
  • Multiple ulcers, at least one on the anterior lower leg.
  • Cribriform scars at healed sites.
  • Decrease in ulcer size within 1 month of starting immunosuppression.

Therapeutic options

• Super-potent topical steroids (clobetasol).
• Tacrolimus 0.1% ointment.
• Intralesional triamcinolone to the ulcer edge.

• Prednisolone 0.5 to 1 mg/kg/day (some use pulse methylprednisolone for fast control).
• Cyclosporine 3 to 5 mg/kg/day. The STOP-GAP trial found similar efficacy to prednisolone. The textbook notes it is efficacious off-label in PG (Fitzpatrick's Dermatology, Cyclosporine).

• Dapsone, colchicine, minocycline, clofazimine.
• Mycophenolate mofetil, azathioprine, methotrexate.
• IVIG.

• Infliximab. This is the best-supported biologic, with an RCT showing benefit.
• Adalimumab, etanercept.
• Ustekinumab, secukinumab, ixekizumab, guselkumab.
• IL-1 blockers: anakinra, canakinumab.
• JAK inhibitors (tofacitinib, baricitinib), apremilast.

Q5. Premalignant skin lesions in the elderly, and management of actinic keratosis

A. List of premalignant lesions

B. Management of actinic keratosis (AK)

• Cryotherapy (liquid nitrogen, 5 to 10 seconds freeze per lesion, 1 to 2 cycles). Best for isolated lesions.
• Curettage with or without electrodesiccation.
• Shave or surgical excision for hypertrophic or suspicious lesions.
• Laser ablation (CO2, Er:YAG).

• Topical 5-fluorouracil. 5% cream twice daily for 2 to 4 weeks (up to 4 weeks on the face). Expect marked erythema and erosion, which signals response.
• Imiquimod. 5% cream three times a week for 4 weeks (repeat the cycle if needed), or the 3.75% cream daily in 2-week cycles.
• Diclofenac 3% in hyaluronic acid gel. Twice daily for 60 to 90 days. Mild reactions, suited to mild lesions.
• Tirbanibulin 1% ointment. Once daily for 5 days over a 25 cm2 area.
• Photodynamic therapy. ALA or methyl-ALA with red light. Good cosmetic result. Pain during illumination is the main problem.
• Chemical peels (TCA).
• Ingenol mebutate was withdrawn in Europe because of concern about skin tumours.

• Nicotinamide 500 mg twice daily reduces new non-melanoma skin cancers in high-risk patients.
• Oral retinoids (acitretin) in organ transplant recipients and others with many lesions.
• Daily broad-spectrum sunscreen (SPF 30 or higher), protective clothing, and avoiding midday sun.
• Regular skin examination, every 6 to 12 months or more often if high risk.

• Few lesions: cryotherapy.
• Multiple lesions or field change: 5-FU, imiquimod, PDT or tirbanibulin.
• Immunosuppressed: combine field treatment with retinoids, and a low threshold for biopsy.
• Hypertrophic lesions: debulk first, then give field therapy.

Q6. Pregnancy-specific dermatoses, and management of polymorphic eruption of pregnancy (PEP)

A. Pregnancy-specific dermatoses (revised classification)

1. Pemphigoid gestationis (gestational pemphigoid). Autoimmune blistering disease (anti-BP180, mainly NC16A).
2. Polymorphic eruption of pregnancy (PUPPP).
3. Atopic eruption of pregnancy (AEP). Includes eczema of pregnancy, prurigo of pregnancy and pruritic folliculitis of pregnancy.
4. Intrahepatic cholestasis of pregnancy (pruritus gravidarum). Itch without a primary lesion, with raised serum bile acids.

B. Polymorphic eruption of pregnancy (PEP)

• About 1 in 160 to 200 pregnancies.
• Primigravidas, third trimester, multiple pregnancy (twins or triplets), excessive maternal weight gain, male fetus.

• Abdominal wall distension damages connective tissue in the striae and exposes antigens.
• Fetal DNA (Y-chromosome material) has been found in lesional skin.
• Hormonal factors.

• Urticarial papules and plaques that start in the abdominal striae.
• Sparing of the periumbilical area (a useful sign).
• Spreads to thighs, buttocks, and sometimes arms.
• Later polymorphism: target-like lesions, vesicles, eczematous change.
• Face, palms and soles are usually spared.
• Usually resolves in 4 to 6 weeks, and within days of delivery.
• Rarely recurs in later pregnancies.

• Biopsy: non-specific perivascular infiltrate with dermal oedema, sometimes spongiosis.
• DIF: negative (separates it from pemphigoid gestationis).
• Serum bile acids and liver function: normal.
• Tests for scabies and drug eruptions if needed.

1. Counsel and reassure. Explain it is harmless to the baby, self-limiting, and rarely recurs.
2. Emollients and cool compresses, and avoid hot baths.
3. Topical corticosteroids. Moderate to potent (for example betamethasone valerate or mometasone) for 1 to 2 weeks gives relief in most patients.
4. Oral antihistamines. Sedating H1 blockers (chlorpheniramine) at night are acceptable. Cetirizine or loratadine are alternatives.
5. Systemic corticosteroids. A short course of oral prednisolone (about 0.5 mg/kg/day, tapered) for severe, unresponsive pruritus, using the lowest effective dose.
6. Induction of labour is not needed for PEP alone.
7. Follow-up until resolution. Re-examine and consider DIF if blisters appear (pemphigoid gestationis).

Q7. Laboratory diagnosis of autoimmune cutaneous connective tissue diseases

Overview

1. Non-specific tests

2. Skin histopathology

3. Direct immunofluorescence: lupus band test

• Granular deposits of IgG, IgM and C3 at the dermoepidermal junction.
• Positive in lesional skin of DLE (about 90%), and in non-lesional sun-exposed skin of active SLE.
• A non-lesional, sun-protected skin positive result indicates SLE, usually with renal involvement.

4. Antinuclear antibody (ANA)

• Indirect immunofluorescence on HEp-2 cells is the reference method. Titre of 1:80 or higher is clinically significant (2019 EULAR/ACR SLE criteria use ANA 1:80 or higher as the entry criterion).
• Sensitive for SLE (over 95%) but not specific (positive in many other diseases and in healthy people).

5. Extractable nuclear antigens (ENA) and specific antibodies

6. Complement and other immunology

• C3, C4, CH50: low in active SLE (consumption). Low C4 may appear early; hereditary C2 or C4 deficiency predisposes to lupus.
• Anti-C1q antibodies: lupus nephritis and HUVS.
• Antiphospholipid antibodies: lupus anticoagulant, anticardiolipin, anti-beta2 glycoprotein I.
• Direct Coombs test, rheumatoid factor, anti-CCP, cryoglobulins.

7. Organ-specific investigations

• Kidney: urine protein/creatinine, renal biopsy if abnormal.
• Muscle: CK, aldolase, EMG, MRI, muscle biopsy.
• Lung: HRCT, pulmonary function tests (especially in SSc and dermatomyositis).
• Nailfold capillaroscopy: dilated loops and dropout in SSc and dermatomyositis.
• Schirmer test, salivary gland biopsy (Sjogren).

8. Interpretation points

• A negative ANA makes SLE unlikely, but anti-Ro antibodies can be present with a negative ANA.
• Anti-dsDNA and anti-Sm are specific; other antibodies are not.
• Always match results to clinical features.
• Repeat tests during flares and for monitoring (anti-dsDNA, C3, C4, urine).

Q8. WHO dyslipidaemia classification and tuberous xanthoma

A. WHO (Fredrickson) classification

B. Tuberous xanthoma

• They occur in familial hypercholesterolaemia (Fredrickson type II) and familial dysbetalipoproteinaemia (type III, "broad beta disease"). The textbook states they are seen in these hypercholesterolaemic states (Dermatology 5e, Tuberous/Tuberoeruptive Xanthomas).
• Heterozygous FH: about 1 in 250 to 500 people. Homozygous FH: about 1 in 300,000 to 1,000,000.
• Familial dysbetalipoproteinaemia (FDBL): ApoE2/E2 genotype is common (about 1% of the population), but disease expression is rare (about 1 in 5,000 to 10,000), because a second metabolic hit (obesity, diabetes, hypothyroidism, alcohol, oestrogen deficiency) is needed. Usually autosomal recessive.
• Tuberous xanthomas are more frequent and appear earlier in homozygous FH than in heterozygous FH.
• Onset: adulthood in FDBL, childhood in homozygous FH.

• Firm, painless, round yellow-red nodules, 0.5 to 3 cm or larger, which may coalesce into multilobulated masses.
• Sites: extensor surfaces of elbows and knees, buttocks, fingers and heels.
• They are slow to regress after treatment, unlike eruptive xanthomas (Dermatology 5e).
• Associated signs:
  • Tendon xanthomas (Achilles, extensor tendons of the hands) in FH.
  • Palmar crease (plane) xanthomas in FDBL, which are almost pathognomonic. The textbook notes they occur in about two-thirds of FDBL patients.
  • Xanthelasma, corneal arcus before age 45.
  • Premature coronary, peripheral and carotid atherosclerosis.

1. Fasting lipid profile: total cholesterol, LDL-C, HDL-C, triglycerides, non-HDL-C. Lipoprotein(a).
2. FDBL specifics: raised cholesterol and TG together, VLDL-C/TG ratio above 0.30 (ultracentrifugation), beta-VLDL, ApoE genotyping, apoB measurement.
3. FH: LDL-C above 190 mg/dL, family history, genetic testing (LDLR, APOB, PCSK9). Use the Dutch Lipid Clinic Network score.
4. Secondary causes: fasting glucose or HbA1c, TSH, liver function (cholestasis), urine protein and albumin (nephrotic syndrome), serum protein electrophoresis (paraproteinaemia).
5. Cardiovascular assessment: ECG, echocardiography, stress test, carotid ultrasound, coronary calcium score or CT angiography.
6. Skin biopsy if the diagnosis is uncertain.
7. Family cascade screening.

1. Lifestyle. Low saturated fat and low sugar diet, weight loss, exercise, no alcohol, and smoking cessation. Control diabetes and hypothyroidism.
2. Drug therapy for FH.
   • High-intensity statin (atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg).
   • Add ezetimibe 10 mg.
   • Add a PCSK9 inhibitor (evolocumab, alirocumab) or inclisiran, or bempedoic acid, if LDL target is not reached.
   • Homozygous FH: lomitapide, evinacumab, and LDL apheresis.
3. FDBL. Fibrate (fenofibrate) is first line, often combined with a statin. Treat the second hit (diabetes, hypothyroidism, obesity).
4. Targets. LDL-C below 70 mg/dL, or below 55 mg/dL in very high-risk patients. Aim for at least a 50% reduction.
5. Local treatment of the xanthomas. Surgical excision, CO2 laser, or trichloroacetic acid for cosmetic or functional reasons. Recurrence is common if lipids remain uncontrolled.
6. Family screening and cardiovascular risk follow-up.

Q9. Short notes

(a) Fixed drug eruption (FDE)

• One or more sharply demarcated, round or oval erythematous or dusky violaceous plaques. A bulla or erosion may develop in the centre.
• Residual slate-grey to brown pigmentation after the acute phase.
• Favoured sites: lips, genitalia (glans penis), hands, feet and perianal area. Mucosal involvement is common.
• A refractory period follows each episode.
• With repeated exposure, lesions increase in number and size.

• History of the same site recurring on drug re-exposure.
• Skin biopsy: interface dermatitis, necrotic keratinocytes, dermal melanophages and eosinophils.
• Patch testing on a previously affected (residual) site, applied with the suspected drug, can confirm the culprit.
• Oral provocation under supervision is rarely needed.

• Stop the culprit drug and any cross-reacting drug.
• Topical corticosteroids, oral antihistamines.
• Wound care and antiseptics for erosions.
• Systemic corticosteroids for extensive or bullous disease.
• Fading of pigmentation is slow. Sun protection helps.
• Educate the patient to avoid the drug and carry a warning card.

(b) Acrodermatitis enteropathica (AE)

• Onset in infancy, typically a few weeks after weaning from breast milk. Human milk contains zinc-binding ligands that make zinc more available.
• Classic triad: acral and periorificial dermatitis, alopecia, and diarrhoea.
• Skin lesions: well-demarcated, erythematous, scaly, vesiculobullous or crusted-erosive patches around the mouth, nose, eyes, anus and genitalia, and on the hands, feet, elbows and knees.
• Secondary candidal or bacterial infection, paronychia, nail dystrophy, glossitis, stomatitis, photophobia.
• Failure to thrive, irritability, delayed wound healing.

• Low serum or plasma zinc (below about 50 to 60 micrograms/dL). Low serum alkaline phosphatase (a zinc-dependent enzyme) supports the diagnosis.
• Histology: confluent parakeratosis, pallor and vacuolation of the upper epidermis, keratinocyte necrosis.
• Genetic testing for SLC39A4 is possible but is not always positive. Textbook note: only about 40% of diagnosed patients are identified as homozygotes or complex heterozygotes (Yamada's Textbook of Gastroenterology).
• Response to zinc is itself diagnostic.

• Oral elemental zinc, usually 1 to 3 mg/kg/day (zinc sulphate, gluconate or acetate), in divided doses.
• Diarrhoea and irritability improve within days, and skin within 1 to 2 weeks.
• Inherited AE needs lifelong zinc. The dose is adjusted by serum zinc and clinical response. Acquired forms need zinc only until the cause is corrected.
• Monitor zinc, copper (excess zinc causes copper deficiency), and alkaline phosphatase.
• Treat secondary infection. Without treatment, the disease can be fatal (infection, failure to thrive).

(c) Delusional parasitosis (delusional infestation, Ekbom syndrome)

• Primary: an isolated delusional disorder (monosymptomatic hypochondriacal psychosis).
• Secondary: due to another condition, including:
  • Psychiatric (schizophrenia, depression, dementia, OCD).
  • Medical and neurological (vitamin B12 deficiency, diabetes, hypothyroidism, HIV, stroke, renal or hepatic failure).
  • Substances (cocaine, amphetamines, alcohol withdrawal) and drugs (dopamine agonists).
• Folie a deux: the delusion is shared by a close relative or partner.

• Patients report crawling, biting or burrowing sensations (formication), and insist on parasites in the skin.
• Specimen sign (matchbox, bag or tissue-paper sign): they bring debris, skin flakes, hair or lint as "proof".
• Self-inflicted excoriations, ulcers, scars. The "butterfly sign" is sparing of the mid-upper back where the patient cannot reach.
• Excessive cleaning, use of insecticides and harsh chemicals, and frequent doctor visits.
• Otherwise, the personality and function are preserved.

• Careful examination, dermoscopy and skin scraping to exclude scabies and lice.
• Examine the specimens under a microscope.
• CBC, glucose, thyroid function, B12 and folate, liver and renal function, HIV, VDRL, urine drug screen.
• Neuroimaging if there is a neurological or dementia concern.

• Build rapport. Be empathic and non-confrontational. Do not tell the patient the belief is false, and do not endorse it either.
• Examine the specimens seriously and offer a skin-focused explanation.
• Rule out true infestation and organic causes, and treat them.
• Liaise with psychiatry, but patients often refuse referral, so dermatologists commonly start treatment.
• Antipsychotics:
  • Risperidone 0.5 to 1 mg at night, titrated to 2 to 4 mg/day. Textbook discussion covers its use in delusional infestation (Dermatology 5e, Use of Risperidone in Dermatology).
  • Olanzapine, aripiprazole, or amisulpride as alternatives.
  • Pimozide 0.5 to 1 mg at night, increased to 2 to 4 mg/day, was the traditional choice. It needs a baseline ECG for QT prolongation and awareness of drug interactions.
• Check for extrapyramidal side effects (AIMS scale) and for metabolic effects. Drug interactions with CYP2D6 and CYP3A4 inhibitors are important (Dermatology 5e).
• Continue treatment for at least 6 to 12 months after remission, then taper slowly. Relapse is common if stopped early.
• Treat secondary causes and depression (SSRIs where needed).

Exam tips

• Draw a flow diagram for Q2 (dendritic cell, IL-23, Th17, IL-17/IL-22, keratinocyte) and label where each drug acts.
• Use tables for the classification questions (Q2, Q6, Q8) and for the antibody lists (Q7).
• Open Q3, Q4 and Q5 with the definition and close with a stepwise algorithm.

Topic map

1. Bone involvement in leprosy: mechanisms, clinical manifestations, radiological features and management guidelines
2. Cardiovascular syphilis: pathophysiology, clinical spectrum, diagnosis and current treatment guidelines
3. Lymphogranuloma venereum (LGV): clinical spectrum, diagnostic pitfalls and management
4. Paediatric leprosy and its relevance to the National Leprosy Eradication Programme (NLEP)
5. HIV life cycle in the CD4+ lymphocyte, with each step mapped to its antiretroviral drug class
6. Non-pharmacological management of leprosy, with emphasis on prevention and care of insensitive hands and feet
7. NACO syndromic management of urethral discharge syndrome, and a stepwise approach to persistent or recurrent urethritis
8. Ridley-Jopling classification: a table of the five polar and borderline states (clinical features, histopathology, bacteriological index, lepromin), with WHO operational correlation
9. Short notes: (A) HPV vaccines, (B) silent neuritis in leprosy, (C) pediculosis pubis

Brief overview

• Leprosy (Q1, 4, 6, 8, 9B): Leprosy is a chronic infection with Mycobacterium leprae that affects skin and peripheral nerves, and the immune response sets the spectrum. Bone involvement is either specific (direct bacillary invasion, mainly in lepromatous disease) or non-specific. The non-specific form is the commoner one, and it comes from neuropathy, trauma, infection and neurotrophic resorption. The Ridley-Jopling spectrum runs TT, BT, BB, BL, LL, and the WHO operational system reduces it to paucibacillary and multibacillary. Paediatric leprosy is a marker of ongoing transmission and a key indicator in NLEP (child cases and grade 2 disability in children). Care of insensitive hands and feet rests on self-care, protective footwear, wound management and early detection of nerve damage, including silent neuritis.
• Syphilis and LGV (Q2, 3): Cardiovascular syphilis is a tertiary manifestation appearing 10 to 30 years after infection. It causes obliterative endarteritis of the vasa vasorum, leading to ascending aortitis, aortic regurgitation, aneurysm and coronary ostial stenosis. Treatment is penicillin-based, along with cardiac care. LGV is caused by Chlamydia trachomatis L1 to L3. It presents as a transient genital ulcer, then inguinal syndrome (buboes) or anorectal syndrome (proctocolitis). The main pitfalls are misdiagnosis as Crohn disease or other ulcer causes, and relying on tests that do not identify the L-serovars. Doxycycline for 21 days is the standard treatment.
• HIV and genital infections (Q5, 7, 9A, 9C): HIV enters the CD4 cell and goes through six steps, each with a drug class: attachment and fusion (fusion, attachment and CCR5 inhibitors), reverse transcription (NRTIs and NNRTIs), integration (INSTIs), and maturation (protease inhibitors). The NACO syndromic approach to urethral discharge treats for both gonorrhoea and chlamydia. Persistent or recurrent urethritis needs a check of adherence and reinfection, then consideration of Trichomonas vaginalis, Mycoplasma genitalium and resistant gonorrhoea. HPV vaccines (bivalent, quadrivalent, nonavalent) prevent cervical and anogenital disease. Pediculosis pubis is treated with permethrin 1% and screening for other STIs.

Topic map

1. Paraneoplastic dermatoses: list, plus one in detail (for example acanthosis nigricans, Sweet syndrome, dermatomyositis, paraneoplastic pemphigus, Leser-Trélat sign or acquired ichthyosis)
2. Psoriasis: IL-23/Th17 pathogenesis, classification of biologics, and one agent in detail (mechanism, dosing, screening)
3. Hypocomplementemic urticarial vasculitis syndrome (HUVS): management
4. Pyoderma gangrenosum: pathogenesis, clinical variants, therapy
5. Premalignant skin lesions in the elderly: list, plus management of one (for example actinic keratosis)
6. Pregnancy-specific dermatoses: list, plus management of polymorphic eruption of pregnancy (PEP)
7. Laboratory diagnosis of autoimmune connective tissue diseases: ANA patterns, ENA, anti-dsDNA, complement, direct immunofluorescence (lupus band test), myositis antibodies
8. Dyslipidaemias: WHO (Fredrickson) classification, then tuberous xanthoma
9. Short notes: (a) fixed drug eruption, (b) acrodermatitis enteropathica, (c) delusional parasitosis

Brief overview of the key points

• Q1: Paraneoplastic dermatoses fall into three groups. The obligate or strong markers are acanthosis nigricans (malignant type), tripe palms, Bazex syndrome, necrolytic migratory erythema, paraneoplastic pemphigus, Sweet syndrome and erythema gyratum repens. Other associations include dermatomyositis, hypertrichosis lanuginosa acquisita, Leser-Trélat sign and acquired ichthyosis. Cutaneous markers of genetic cancer syndromes, such as Cowden and Peutz-Jeghers, are a separate group.
• Q2: Dendritic cells release IL-23, which sustains Th17 cells that make IL-17A/F, IL-22 and TNF. These act on keratinocytes to cause hyperproliferation and chemokine release, and the loop is amplified through the IL-36 pathway. The biologics are TNF inhibitors (etanercept, infliximab, adalimumab, certolizumab), IL-12/23 inhibitors (ustekinumab), IL-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab) and IL-23 inhibitors (guselkumab, tildrakizumab, risankizumab). Screening before starting includes TB (IGRA or Mantoux and chest X-ray), hepatitis B and C, HIV, pregnancy status and vaccination review.
• Q3: HUVS is treated with steroids plus steroid-sparing agents (dapsone, hydroxychloroquine, azathioprine, mycophenolate, methotrexate). Rituximab, IVIG, plasmapheresis and cyclophosphamide are used in severe or organ-threatening disease. Patients also need screening for anti-C1q antibodies, SLE overlap and the pulmonary, renal and ocular complications.
• Q4: Pyoderma gangrenosum is a neutrophilic dermatosis with IL-1, IL-17 and TNF dysregulation. The variants are ulcerative (classic), bullous, pustular, vegetative (superficial granulomatous) and peristomal. Treatment is topical or intralesional steroids and calcineurin inhibitors for mild disease. Systemic steroids and cyclosporine are first line for moderate to severe disease, and infliximab or adalimumab are the main biologics.
• Q5: The main premalignant lesions in the elderly are actinic keratosis, actinic cheilitis, cutaneous horn, Bowen disease, leukoplakia, radiation keratosis and arsenical keratosis. Lentigo maligna and erythroplasia of Queyrat also belong here.
• Q6: Pregnancy-specific dermatoses are PEP (PUPPP), pemphigoid gestationis, intrahepatic cholestasis of pregnancy and atopic eruption of pregnancy. PEP is managed with emollients, antihistamines and topical steroids, with short oral steroids for severe cases. It is self-limiting, usually resolves after delivery and has no fetal risk.
• Q7: The core tests are ANA by IIF on HEp-2 cells with pattern interpretation, then ENA (Ro, La, Sm, RNP, Scl-70, centromere, Jo-1). Anti-dsDNA, complement levels, antiphospholipid antibodies, myositis-specific antibodies and skin biopsy with lupus band test complete the panel.
• Q8: The WHO/Fredrickson types are I, IIa, IIb, III, IV and V. Tuberous xanthomas are classically seen in type III (familial dysbetalipoproteinaemia) and in familial hypercholesterolaemia. Treatment is a statin, ezetimibe, a fibrate and lifestyle change, with surgery for large lesions.
• Q9: The three short notes cover fixed drug eruption (a recurrent, well-defined, hyperpigmented lesion at the same site), acrodermatitis enteropathica (zinc deficiency from a SLC39A4 mutation, treated with zinc) and delusional parasitosis (a monodelusional disorder treated with pimozide or atypical antipsychotics).# Q1. Paraneoplastic dermatoses: enumeration, and paraneoplastic pemphigus (PNP) in detail

Part A. Enumeration of paraneoplastic dermatoses

• The cancer and the dermatosis start together.
• They follow a parallel course.
• Neither is a common disorder.
• There is a statistical association.
• There is a genetic link, where one exists.

1. Obligate paraneoplastic dermatoses (almost always indicate cancer)

2. Facultative dermatoses (sometimes signal malignancy)

• Dermatomyositis, especially in patients over 40. It is associated with ovarian, lung, pancreatic and GI cancers and with nasopharyngeal carcinoma in Asians. Anti-TIF1-gamma and anti-NXP2 antibodies mark higher risk.
• Sweet syndrome (acute febrile neutrophilic dermatosis), associated with AML and MDS.
• Pyoderma gangrenosum, bullous type, associated with myeloid malignancy.
• Paraneoplastic acquired ichthyosis, associated with Hodgkin and other lymphomas.
• Exfoliative erythroderma, associated with cutaneous T-cell lymphoma and other lymphoproliferative disease.
• Pityriasis rotunda, associated with hepatocellular carcinoma.
• Palmoplantar keratoderma (late-onset, non-hereditary), associated with oesophageal carcinoma.
• Multicentric reticulohistiocytosis and palmar fasciitis with polyarthritis, associated with ovarian and other carcinomas.
• Pruritus, associated with Hodgkin disease, polycythaemia vera and other cancers.
• Cutaneous vasculitis, erythromelalgia and paraneoplastic urticaria, associated with myeloproliferative and lymphoid neoplasms.
• Nodular fat necrosis (pancreatic panniculitis), associated with pancreatic carcinoma.
• Extramammary Paget disease (marker of underlying adnexal or visceral carcinoma).
• Eruptive xanthomas, acquired palmoplantar keratoderma, pachydermoperiostosis and cutaneous amyloidosis (primary systemic AL type, with myeloma).

3. Genodermatoses with internal malignancy (not strictly paraneoplastic)

• Peutz-Jeghers, Cowden, Gardner and Muir-Torre syndromes.
• Birt-Hogg-Dubé syndrome.
• Neurofibromatosis.
• Tuberous sclerosis.
• Howel-Evans syndrome (tylosis with oesophageal cancer).

Part B. Paraneoplastic pemphigus (PNP)

Definition

Aetiology and associated neoplasms

• Non-Hodgkin lymphoma, CLL, Castleman disease (especially in children), thymoma, Waldenström macroglobulinaemia, AML and sarcoma.
• Some patients have no identifiable neoplasm (Andrews' Diseases of the Skin, Paraneoplastic Pemphigus).
• Most common are haematological neoplasms, and most reported patients die of their tumour or of bronchiolitis obliterans.

Pathogenesis

1. The tumour produces antigens or cytokines (such as IL-6) that drive a breakdown of tolerance.
2. Both humoral and cell-mediated immunity are involved.
3. Autoantibodies target plakin family proteins in desmosomes and hemidesmosomes:
   • Desmoplakin I (250 kD) and desmoplakin II.
   • Envoplakin (210 kD) and periplakin (190 kD).
   • BP antigen 1 (230 kD) and plectin.
   • Often a 170 kD antigen, identified as alpha-2-macroglobulin-like-1 (A2ML1).
   • Desmoglein 3 (and sometimes Dsg1) and desmocollins.
4. The IgG is mainly IgG1 and IgG2, unlike pemphigus vulgaris, which is IgG4 dominant.
5. Dsg3 epitopes are spread across the whole extracellular domain, not just the N-terminus as in pemphigus vulgaris.
6. Cytotoxic T cells and interface/lichenoid inflammation explain the dyskeratosis and the lichenoid and erythema multiforme-like lesions.
7. There is a significant HLA-DRB1*03 association.
8. Antibodies to epithelia other than skin, such as respiratory epithelium, cause bronchiolitis obliterans.

Clinical features

• Mucosal lesions are the hallmark, and they are often the first sign.
  • There is severe, persistent, painful stomatitis with erosions of the tongue and lips.
  • Hemorrhagic crusting of the lips can mimic Stevens-Johnson syndrome.
  • Lesions are resistant to treatment.
• Skin lesions are polymorphic:
  • Erythematous macules and lichenoid papules.
  • Erythema multiforme-like target lesions.
  • Flaccid bullae and erosions typical of pemphigus.
  • Tense, deep-set bullae resembling pemphigoid.
  • Graft-versus-host-like eruptions.
  • Palms and soles are commonly involved, which is unusual in other pemphigus types.
• Ocular disease is conjunctival, with cicatrising conjunctivitis, symblepharon and corneal melting.
• Other mucosae (nasopharynx, oesophagus, genitalia, anus) may be involved.
• Pulmonary involvement is bronchiolitis obliterans. It presents with cough, dyspnoea and fixed obstruction that does not respond to bronchodilators. It carries the worst prognosis, because it can progress even when the skin disease and tumour are controlled.

Investigations

Differential diagnosis

• Pemphigus vulgaris.
• Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Erosive lichen planus.
• Bullous pemphigoid and mucous membrane pemphigoid.
• Graft-versus-host disease.
• Erythema multiforme major.

Treatment

• The tumour comes first. Benign tumours such as a localised Castleman tumour or thymoma are resected, and the skin disease often improves. Malignant tumours are treated according to their type.
• Immunosuppression is balanced against the tumour treatment, and the textbook lists these options:
  • High-dose systemic corticosteroids (prednisolone 1 to 2 mg/kg/day).
  • Rituximab, and alemtuzumab in CLL.
  • Cyclosporine, and cyclophosphamide (high-dose without stem cell rescue).
  • IVIG, plasmapheresis and immunoapheresis.
• Supportive care covers mouth care, topical anaesthetics, ocular lubricants and ophthalmology review, nutrition, and infection control.
• Bronchiolitis obliterans is treated with immunosuppression and, in selected cases, lung transplantation. It often responds poorly even when the other disease is controlled.

Prognosis

Exam tips

• Draw the table of paraneoplastic dermatoses, with the obligate group first.
• Write the antigens as a list (envoplakin, periplakin, desmoplakin, BPAG1, plectin, Dsg3, A2ML1).
• State clearly that bronchiolitis obliterans is the main cause of death.
• Add a labelled diagram of the plakin family in the desmosome.

Q2. Psoriasis: IL-23/Th17 axis, biologic classification, and secukinumab

A. Pathogenesis of psoriasis (IL-23/Th17 axis)

• PSORS1 (HLA-Cw6, HLA-C*06:02) is the strongest association.
• Other susceptibility genes: IL23R, IL12B, IL23A, TRAF3IP2, TNFAIP3, CARD14.
• Triggers: trauma (Koebner phenomenon), streptococcal infection, drugs (lithium, beta-blockers, antimalarials), stress, alcohol, smoking.

1. Initiation. Keratinocyte injury releases self-DNA/RNA and the antimicrobial peptide LL-37. LL-37 complexes with nucleic acids and activates plasmacytoid dendritic cells through TLR7/9, causing interferon-alpha release.
2. Dendritic cell activation. Myeloid (inflammatory) dendritic cells release IL-23 (p19/p40), IL-12 and TNF-alpha. IL-12 drives Th1 cells, which make IFN-gamma and TNF.
3. IL-23 action. IL-23 binds IL-23R on Th17, Tc17, gamma-delta T cells and ILC3. It does not start Th17 differentiation (IL-6, TGF-beta, IL-1beta do that). It maintains, expands and stabilises the Th17 population.
4. Effector cytokines. Th17 cells release IL-17A and IL-17F, IL-22, TNF-alpha and IL-21.
5. Keratinocyte response.
   • IL-17 and IL-22 cause hyperproliferation, parakeratosis, acanthosis and loss of the granular layer.
   • Keratinocytes release chemokines (CXCL1, CXCL8, CCL20) that recruit neutrophils (Munro microabscesses) and more Th17 cells.
   • They also release antimicrobial peptides (beta-defensins, S100A7/8/9) and IL-36 cytokines.
6. Positive feedback loop. Keratinocyte products (IL-1, IL-6, IL-36, CCL20) further stimulate dendritic cells and Th17 cells.
7. Vascular changes. VEGF produces dilated, tortuous papillary capillaries, which explains the Auspitz sign.
8. Memory. Tissue-resident memory T cells persist in healed skin, which explains recurrence at the same sites.

• Blocking TNF breaks the early loop.
• Blocking IL-23 or IL-17 acts on the central axis.
• IL-23 blockade is more upstream, with fewer candida infections and less frequent dosing.
• IL-17 blockade acts faster.

B. Classification of approved biologics for moderate-to-severe plaque psoriasis

C. Secukinumab in detail

• 300 mg SC (two 150 mg injections) at weeks 0, 1, 2, 3 and 4.
• Then 300 mg every 4 weeks.
• 150 mg may be used in some patients, and a lower-weight patient may do well on it. Heavier patients (more than 90 kg) may need the 300 mg dose.
• Typical onset is rapid, with PASI improvement by week 2 to 4. Assess response at week 12 to 16.

• Detailed history and examination.
• Look for active or latent TB:
  • Tuberculin test (Mantoux) or IGRA, plus a chest X-ray.
  • Treat latent TB before starting, and consider annual re-screening in high-burden countries like India.
• HBsAg, anti-HBc and anti-HBs; anti-HCV; HIV.
• CBC with differential, liver function tests, renal function tests.
• Pregnancy test, and contraception counselling.
• Ask about IBD (Crohn disease, ulcerative colitis). Secukinumab can worsen it, so it is avoided in active IBD.
• Ask about recurrent candidiasis or other chronic infections.
• Vaccination review: update inactivated vaccines before starting, and avoid live vaccines during treatment.
• Baseline severity scores: PASI, BSA, DLQI.

Q3. Management of hypocomplementemic urticarial vasculitis syndrome (HUVS)

Definition

• Major (both required): chronic urticaria (for 6 months or more) and hypocomplementemia.
• Minor (at least 2): venulitis on biopsy, arthralgia or arthritis, glomerulonephritis, uveitis or episcleritis, recurrent abdominal pain, positive C1q precipitin test (anti-C1q).

Evaluation before treatment

• Skin biopsy of a lesion less than 24 to 48 hours old: leukocytoclastic vasculitis with fibrinoid necrosis.
• Complement: C3, C4, CH50, C1q levels, anti-C1q antibodies.
• ANA, anti-dsDNA, ENA, to look for SLE overlap.
• Hepatitis B and C, cryoglobulins, serum protein electrophoresis.
• Urine routine and protein/creatinine ratio, renal function.
• Chest X-ray and spirometry for obstructive lung disease (COPD), which is a frequent systemic complication.
• Ophthalmology review (uveitis, episcleritis, conjunctivitis).
• Abdominal evaluation if there is pain.

Treatment (stepwise)

• Antihistamines (H1 blockers). These are often ineffective for the vasculitic lesions.
• NSAIDs. Indomethacin is noted as particularly effective.
• Colchicine 0.5 mg twice daily.
• Dapsone 50 to 100 mg/day (check G6PD first). The textbook notes that adding pentoxifylline to dapsone may help.
• Hydroxychloroquine 200 to 400 mg/day (ophthalmology screening).

• Prednisolone 0.5 to 1 mg/kg/day, tapered once control is achieved.
• Steroid-sparing agents: azathioprine, mycophenolate mofetil, methotrexate, cyclosporine. The textbook names prednisone with MMF, azathioprine, rituximab and canakinumab.

• Rituximab.
• IL-1 blockade: canakinumab, anakinra.
• IVIG.
• Cyclophosphamide (for severe renal disease).
• Plasmapheresis.
• Omalizumab has been used in case reports.

Q4. Pyoderma gangrenosum (PG): pathogenesis, clinical variants, therapy

Definition

Pathogenesis

• Innate immune dysregulation: overactivity of the inflammasome with raised IL-1beta, IL-8 (CXCL8), IL-36, TNF-alpha, and neutrophil chemotaxis.
• Th17 axis: raised IL-17 and IL-23.
• Genetic:
  • PAPA syndrome (pyogenic arthritis, PG, acne): PSTPIP1 mutations.
  • PASH (PG, acne, suppurative hidradenitis) and PAPASH.
  • Gene variants in IL-1 and neutrophil pathways.
• Pathergy: minor trauma or surgery induces new lesions.
• Immune complexes and abnormal neutrophil chemotaxis have also been described.
• Associated diseases (in about 50% of cases):
  • Inflammatory bowel disease.
  • Inflammatory arthritis (rheumatoid arthritis, seronegative arthropathy).
  • Haematological disease (MGUS, myeloma, AML, MDS).
  • Hepatitis C, Takayasu arteritis, SLE.
  • Drugs: isotretinoin, G-CSF, propylthiouracil, sunitinib.

Clinical variants

Diagnosis

• Major: biopsy of the ulcer edge shows neutrophilic infiltrate.
• Minor:
  • Exclusion of infection.
  • Pathergy.
  • History of IBD or inflammatory arthritis.
  • Papule, pustule or vesicle ulcerating within 4 days of appearing.
  • Peripheral erythema, undermined border and tenderness at the ulcer site.
  • Multiple ulcers, at least one on the anterior lower leg.
  • Cribriform scars at healed sites.
  • Decrease in ulcer size within 1 month of starting immunosuppression.

Therapeutic options

• Super-potent topical steroids (clobetasol).
• Tacrolimus 0.1% ointment.
• Intralesional triamcinolone to the ulcer edge.

• Prednisolone 0.5 to 1 mg/kg/day (some use pulse methylprednisolone for fast control).
• Cyclosporine 3 to 5 mg/kg/day. The STOP-GAP trial found similar efficacy to prednisolone. The textbook notes it is efficacious off-label in PG (Fitzpatrick's Dermatology, Cyclosporine).

• Dapsone, colchicine, minocycline, clofazimine.
• Mycophenolate mofetil, azathioprine, methotrexate.
• IVIG.

• Infliximab. This is the best-supported biologic, with an RCT showing benefit.
• Adalimumab, etanercept.
• Ustekinumab, secukinumab, ixekizumab, guselkumab.
• IL-1 blockers: anakinra, canakinumab.
• JAK inhibitors (tofacitinib, baricitinib), apremilast.

Q5. Premalignant skin lesions in the elderly, and management of actinic keratosis

A. List of premalignant lesions

B. Management of actinic keratosis (AK)

• Cryotherapy (liquid nitrogen, 5 to 10 seconds freeze per lesion, 1 to 2 cycles). Best for isolated lesions.
• Curettage with or without electrodesiccation.
• Shave or surgical excision for hypertrophic or suspicious lesions.
• Laser ablation (CO2, Er:YAG).

• Topical 5-fluorouracil. 5% cream twice daily for 2 to 4 weeks (up to 4 weeks on the face). Expect marked erythema and erosion, which signals response.
• Imiquimod. 5% cream three times a week for 4 weeks (repeat the cycle if needed), or the 3.75% cream daily in 2-week cycles.
• Diclofenac 3% in hyaluronic acid gel. Twice daily for 60 to 90 days. Mild reactions, suited to mild lesions.
• Tirbanibulin 1% ointment. Once daily for 5 days over a 25 cm2 area.
• Photodynamic therapy. ALA or methyl-ALA with red light. Good cosmetic result. Pain during illumination is the main problem.
• Chemical peels (TCA).
• Ingenol mebutate was withdrawn in Europe because of concern about skin tumours.

• Nicotinamide 500 mg twice daily reduces new non-melanoma skin cancers in high-risk patients.
• Oral retinoids (acitretin) in organ transplant recipients and others with many lesions.
• Daily broad-spectrum sunscreen (SPF 30 or higher), protective clothing, and avoiding midday sun.
• Regular skin examination, every 6 to 12 months or more often if high risk.

• Few lesions: cryotherapy.
• Multiple lesions or field change: 5-FU, imiquimod, PDT or tirbanibulin.
• Immunosuppressed: combine field treatment with retinoids, and a low threshold for biopsy.
• Hypertrophic lesions: debulk first, then give field therapy.

Q6. Pregnancy-specific dermatoses, and management of polymorphic eruption of pregnancy (PEP)

A. Pregnancy-specific dermatoses (revised classification)

1. Pemphigoid gestationis (gestational pemphigoid). Autoimmune blistering disease (anti-BP180, mainly NC16A).
2. Polymorphic eruption of pregnancy (PUPPP).
3. Atopic eruption of pregnancy (AEP). Includes eczema of pregnancy, prurigo of pregnancy and pruritic folliculitis of pregnancy.
4. Intrahepatic cholestasis of pregnancy (pruritus gravidarum). Itch without a primary lesion, with raised serum bile acids.

B. Polymorphic eruption of pregnancy (PEP)

• About 1 in 160 to 200 pregnancies.
• Primigravidas, third trimester, multiple pregnancy (twins or triplets), excessive maternal weight gain, male fetus.

• Abdominal wall distension damages connective tissue in the striae and exposes antigens.
• Fetal DNA (Y-chromosome material) has been found in lesional skin.
• Hormonal factors.

• Urticarial papules and plaques that start in the abdominal striae.
• Sparing of the periumbilical area (a useful sign).
• Spreads to thighs, buttocks, and sometimes arms.
• Later polymorphism: target-like lesions, vesicles, eczematous change.
• Face, palms and soles are usually spared.
• Usually resolves in 4 to 6 weeks, and within days of delivery.
• Rarely recurs in later pregnancies.

• Biopsy: non-specific perivascular infiltrate with dermal oedema, sometimes spongiosis.
• DIF: negative (separates it from pemphigoid gestationis).
• Serum bile acids and liver function: normal.
• Tests for scabies and drug eruptions if needed.

1. Counsel and reassure. Explain it is harmless to the baby, self-limiting, and rarely recurs.
2. Emollients and cool compresses, and avoid hot baths.
3. Topical corticosteroids. Moderate to potent (for example betamethasone valerate or mometasone) for 1 to 2 weeks gives relief in most patients.
4. Oral antihistamines. Sedating H1 blockers (chlorpheniramine) at night are acceptable. Cetirizine or loratadine are alternatives.
5. Systemic corticosteroids. A short course of oral prednisolone (about 0.5 mg/kg/day, tapered) for severe, unresponsive pruritus, using the lowest effective dose.
6. Induction of labour is not needed for PEP alone.
7. Follow-up until resolution. Re-examine and consider DIF if blisters appear (pemphigoid gestationis).

Q7. Laboratory diagnosis of autoimmune cutaneous connective tissue diseases

Overview

1. Non-specific tests

2. Skin histopathology

3. Direct immunofluorescence: lupus band test

• Granular deposits of IgG, IgM and C3 at the dermoepidermal junction.
• Positive in lesional skin of DLE (about 90%), and in non-lesional sun-exposed skin of active SLE.
• A non-lesional, sun-protected skin positive result indicates SLE, usually with renal involvement.

4. Antinuclear antibody (ANA)

• Indirect immunofluorescence on HEp-2 cells is the reference method. Titre of 1:80 or higher is clinically significant (2019 EULAR/ACR SLE criteria use ANA 1:80 or higher as the entry criterion).
• Sensitive for SLE (over 95%) but not specific (positive in many other diseases and in healthy people).

5. Extractable nuclear antigens (ENA) and specific antibodies

6. Complement and other immunology

• C3, C4, CH50: low in active SLE (consumption). Low C4 may appear early; hereditary C2 or C4 deficiency predisposes to lupus.
• Anti-C1q antibodies: lupus nephritis and HUVS.
• Antiphospholipid antibodies: lupus anticoagulant, anticardiolipin, anti-beta2 glycoprotein I.
• Direct Coombs test, rheumatoid factor, anti-CCP, cryoglobulins.

7. Organ-specific investigations

• Kidney: urine protein/creatinine, renal biopsy if abnormal.
• Muscle: CK, aldolase, EMG, MRI, muscle biopsy.
• Lung: HRCT, pulmonary function tests (especially in SSc and dermatomyositis).
• Nailfold capillaroscopy: dilated loops and dropout in SSc and dermatomyositis.
• Schirmer test, salivary gland biopsy (Sjogren).

8. Interpretation points

• A negative ANA makes SLE unlikely, but anti-Ro antibodies can be present with a negative ANA.
• Anti-dsDNA and anti-Sm are specific; other antibodies are not.
• Always match results to clinical features.
• Repeat tests during flares and for monitoring (anti-dsDNA, C3, C4, urine).

Q8. WHO dyslipidaemia classification and tuberous xanthoma

A. WHO (Fredrickson) classification

B. Tuberous xanthoma

• They occur in familial hypercholesterolaemia (Fredrickson type II) and familial dysbetalipoproteinaemia (type III, "broad beta disease"). The textbook states they are seen in these hypercholesterolaemic states (Dermatology 5e, Tuberous/Tuberoeruptive Xanthomas).
• Heterozygous FH: about 1 in 250 to 500 people. Homozygous FH: about 1 in 300,000 to 1,000,000.
• Familial dysbetalipoproteinaemia (FDBL): ApoE2/E2 genotype is common (about 1% of the population), but disease expression is rare (about 1 in 5,000 to 10,000), because a second metabolic hit (obesity, diabetes, hypothyroidism, alcohol, oestrogen deficiency) is needed. Usually autosomal recessive.
• Tuberous xanthomas are more frequent and appear earlier in homozygous FH than in heterozygous FH.
• Onset: adulthood in FDBL, childhood in homozygous FH.

• Firm, painless, round yellow-red nodules, 0.5 to 3 cm or larger, which may coalesce into multilobulated masses.
• Sites: extensor surfaces of elbows and knees, buttocks, fingers and heels.
• They are slow to regress after treatment, unlike eruptive xanthomas (Dermatology 5e).
• Associated signs:
  • Tendon xanthomas (Achilles, extensor tendons of the hands) in FH.
  • Palmar crease (plane) xanthomas in FDBL, which are almost pathognomonic. The textbook notes they occur in about two-thirds of FDBL patients.
  • Xanthelasma, corneal arcus before age 45.
  • Premature coronary, peripheral and carotid atherosclerosis.

1. Fasting lipid profile: total cholesterol, LDL-C, HDL-C, triglycerides, non-HDL-C. Lipoprotein(a).
2. FDBL specifics: raised cholesterol and TG together, VLDL-C/TG ratio above 0.30 (ultracentrifugation), beta-VLDL, ApoE genotyping, apoB measurement.
3. FH: LDL-C above 190 mg/dL, family history, genetic testing (LDLR, APOB, PCSK9). Use the Dutch Lipid Clinic Network score.
4. Secondary causes: fasting glucose or HbA1c, TSH, liver function (cholestasis), urine protein and albumin (nephrotic syndrome), serum protein electrophoresis (paraproteinaemia).
5. Cardiovascular assessment: ECG, echocardiography, stress test, carotid ultrasound, coronary calcium score or CT angiography.
6. Skin biopsy if the diagnosis is uncertain.
7. Family cascade screening.

1. Lifestyle. Low saturated fat and low sugar diet, weight loss, exercise, no alcohol, and smoking cessation. Control diabetes and hypothyroidism.
2. Drug therapy for FH.
   • High-intensity statin (atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg).
   • Add ezetimibe 10 mg.
   • Add a PCSK9 inhibitor (evolocumab, alirocumab) or inclisiran, or bempedoic acid, if LDL target is not reached.
   • Homozygous FH: lomitapide, evinacumab, and LDL apheresis.
3. FDBL. Fibrate (fenofibrate) is first line, often combined with a statin. Treat the second hit (diabetes, hypothyroidism, obesity).
4. Targets. LDL-C below 70 mg/dL, or below 55 mg/dL in very high-risk patients. Aim for at least a 50% reduction.
5. Local treatment of the xanthomas. Surgical excision, CO2 laser, or trichloroacetic acid for cosmetic or functional reasons. Recurrence is common if lipids remain uncontrolled.
6. Family screening and cardiovascular risk follow-up.

Q9. Short notes

(a) Fixed drug eruption (FDE)

• One or more sharply demarcated, round or oval erythematous or dusky violaceous plaques. A bulla or erosion may develop in the centre.
• Residual slate-grey to brown pigmentation after the acute phase.
• Favoured sites: lips, genitalia (glans penis), hands, feet and perianal area. Mucosal involvement is common.
• A refractory period follows each episode.
• With repeated exposure, lesions increase in number and size.

• History of the same site recurring on drug re-exposure.
• Skin biopsy: interface dermatitis, necrotic keratinocytes, dermal melanophages and eosinophils.
• Patch testing on a previously affected (residual) site, applied with the suspected drug, can confirm the culprit.
• Oral provocation under supervision is rarely needed.

• Stop the culprit drug and any cross-reacting drug.
• Topical corticosteroids, oral antihistamines.
• Wound care and antiseptics for erosions.
• Systemic corticosteroids for extensive or bullous disease.
• Fading of pigmentation is slow. Sun protection helps.
• Educate the patient to avoid the drug and carry a warning card.

(b) Acrodermatitis enteropathica (AE)

• Onset in infancy, typically a few weeks after weaning from breast milk. Human milk contains zinc-binding ligands that make zinc more available.
• Classic triad: acral and periorificial dermatitis, alopecia, and diarrhoea.
• Skin lesions: well-demarcated, erythematous, scaly, vesiculobullous or crusted-erosive patches around the mouth, nose, eyes, anus and genitalia, and on the hands, feet, elbows and knees.
• Secondary candidal or bacterial infection, paronychia, nail dystrophy, glossitis, stomatitis, photophobia.
• Failure to thrive, irritability, delayed wound healing.

• Low serum or plasma zinc (below about 50 to 60 micrograms/dL). Low serum alkaline phosphatase (a zinc-dependent enzyme) supports the diagnosis.
• Histology: confluent parakeratosis, pallor and vacuolation of the upper epidermis, keratinocyte necrosis.
• Genetic testing for SLC39A4 is possible but is not always positive. Textbook note: only about 40% of diagnosed patients are identified as homozygotes or complex heterozygotes (Yamada's Textbook of Gastroenterology).
• Response to zinc is itself diagnostic.

• Oral elemental zinc, usually 1 to 3 mg/kg/day (zinc sulphate, gluconate or acetate), in divided doses.
• Diarrhoea and irritability improve within days, and skin within 1 to 2 weeks.
• Inherited AE needs lifelong zinc. The dose is adjusted by serum zinc and clinical response. Acquired forms need zinc only until the cause is corrected.
• Monitor zinc, copper (excess zinc causes copper deficiency), and alkaline phosphatase.
• Treat secondary infection. Without treatment, the disease can be fatal (infection, failure to thrive).

(c) Delusional parasitosis (delusional infestation, Ekbom syndrome)

• Primary: an isolated delusional disorder (monosymptomatic hypochondriacal psychosis).
• Secondary: due to another condition, including:
  • Psychiatric (schizophrenia, depression, dementia, OCD).
  • Medical and neurological (vitamin B12 deficiency, diabetes, hypothyroidism, HIV, stroke, renal or hepatic failure).
  • Substances (cocaine, amphetamines, alcohol withdrawal) and drugs (dopamine agonists).
• Folie a deux: the delusion is shared by a close relative or partner.

• Patients report crawling, biting or burrowing sensations (formication), and insist on parasites in the skin.
• Specimen sign (matchbox, bag or tissue-paper sign): they bring debris, skin flakes, hair or lint as "proof".
• Self-inflicted excoriations, ulcers, scars. The "butterfly sign" is sparing of the mid-upper back where the patient cannot reach.
• Excessive cleaning, use of insecticides and harsh chemicals, and frequent doctor visits.
• Otherwise, the personality and function are preserved.

• Careful examination, dermoscopy and skin scraping to exclude scabies and lice.
• Examine the specimens under a microscope.
• CBC, glucose, thyroid function, B12 and folate, liver and renal function, HIV, VDRL, urine drug screen.
• Neuroimaging if there is a neurological or dementia concern.

• Build rapport. Be empathic and non-confrontational. Do not tell the patient the belief is false, and do not endorse it either.
• Examine the specimens seriously and offer a skin-focused explanation.
• Rule out true infestation and organic causes, and treat them.
• Liaise with psychiatry, but patients often refuse referral, so dermatologists commonly start treatment.
• Antipsychotics:
  • Risperidone 0.5 to 1 mg at night, titrated to 2 to 4 mg/day. Textbook discussion covers its use in delusional infestation (Dermatology 5e, Use of Risperidone in Dermatology).
  • Olanzapine, aripiprazole, or amisulpride as alternatives.
  • Pimozide 0.5 to 1 mg at night, increased to 2 to 4 mg/day, was the traditional choice. It needs a baseline ECG for QT prolongation and awareness of drug interactions.
• Check for extrapyramidal side effects (AIMS scale) and for metabolic effects. Drug interactions with CYP2D6 and CYP3A4 inhibitors are important (Dermatology 5e).
• Continue treatment for at least 6 to 12 months after remission, then taper slowly. Relapse is common if stopped early.
• Treat secondary causes and depression (SSRIs where needed).

Exam tips

• Draw a flow diagram for Q2 (dendritic cell, IL-23, Th17, IL-17/IL-22, keratinocyte) and label where each drug acts.
• Use tables for the classification questions (Q2, Q6, Q8) and for the antibody lists (Q7).
• Open Q3, Q4 and Q5 with the definition and close with a stepwise algorithm.

Topic map

1. Bone involvement in leprosy: mechanisms, clinical manifestations, radiological features and management guidelines
2. Cardiovascular syphilis: pathophysiology, clinical spectrum, diagnosis and current treatment guidelines
3. Lymphogranuloma venereum (LGV): clinical spectrum, diagnostic pitfalls and management
4. Paediatric leprosy and its relevance to the National Leprosy Eradication Programme (NLEP)
5. HIV life cycle in the CD4+ lymphocyte, with each step mapped to its antiretroviral drug class
6. Non-pharmacological management of leprosy, with emphasis on prevention and care of insensitive hands and feet
7. NACO syndromic management of urethral discharge syndrome, and a stepwise approach to persistent or recurrent urethritis
8. Ridley-Jopling classification: a table of the five polar and borderline states (clinical features, histopathology, bacteriological index, lepromin), with WHO operational correlation
9. Short notes: (A) HPV vaccines, (B) silent neuritis in leprosy, (C) pediculosis pubis

Brief overview

• Leprosy (Q1, 4, 6, 8, 9B): Leprosy is a chronic infection with Mycobacterium leprae that affects skin and peripheral nerves, and the immune response sets the spectrum. Bone involvement is either specific (direct bacillary invasion, mainly in lepromatous disease) or non-specific. The non-specific form is the commoner one, and it comes from neuropathy, trauma, infection and neurotrophic resorption. The Ridley-Jopling spectrum runs TT, BT, BB, BL, LL, and the WHO operational system reduces it to paucibacillary and multibacillary. Paediatric leprosy is a marker of ongoing transmission and a key indicator in NLEP (child cases and grade 2 disability in children). Care of insensitive hands and feet rests on self-care, protective footwear, wound management and early detection of nerve damage, including silent neuritis.
• Syphilis and LGV (Q2, 3): Cardiovascular syphilis is a tertiary manifestation appearing 10 to 30 years after infection. It causes obliterative endarteritis of the vasa vasorum, leading to ascending aortitis, aortic regurgitation, aneurysm and coronary ostial stenosis. Treatment is penicillin-based, along with cardiac care. LGV is caused by Chlamydia trachomatis L1 to L3. It presents as a transient genital ulcer, then inguinal syndrome (buboes) or anorectal syndrome (proctocolitis). The main pitfalls are misdiagnosis as Crohn disease or other ulcer causes, and relying on tests that do not identify the L-serovars. Doxycycline for 21 days is the standard treatment.
• HIV and genital infections (Q5, 7, 9A, 9C): HIV enters the CD4 cell and goes through six steps, each with a drug class: attachment and fusion (fusion, attachment and CCR5 inhibitors), reverse transcription (NRTIs and NNRTIs), integration (INSTIs), and maturation (protease inhibitors). The NACO syndromic approach to urethral discharge treats for both gonorrhoea and chlamydia. Persistent or recurrent urethritis needs a check of adherence and reinfection, then consideration of Trichomonas vaginalis, Mycoplasma genitalium and resistant gonorrhoea. HPV vaccines (bivalent, quadrivalent, nonavalent) prevent cervical and anogenital disease. Pediculosis pubis is treated with permethrin 1% and screening for other STIs.

Dermatology Theory Paper: Answers to Q1 to Q9 (10-mark format)

Q1. Bone involvement in leprosy

Mechanisms

1. Specific (direct bacillary invasion)
   • Bacilli reach bone through the blood or from adjacent skin and mucosa, mainly in lepromatous disease.
   • The result is leprous osteitis and periostitis.
2. Non-specific neuropathic changes (the commonest)
   • Sensory loss causes repeated unnoticed trauma, ulcers and fractures.
   • Autonomic loss causes hyperaemia and anhidrosis, with osteoclast-mediated resorption.
   • Motor loss causes muscle imbalance, claw deformity and abnormal joint stress.
3. Secondary infection: plantar ulcers spreading to bone, giving osteomyelitis.
4. Reactions and disuse: osteitis and arthritis in type 2 reaction (ENL), and osteoporosis from disuse or long-term steroids.

Clinical manifestations

Radiological features

• Hands and feet (neuropathic, non-specific):
  • Concentric tapering of phalanges ("licked candy stick", "pencil-in-cup" appearance).
  • Resorption of the distal phalanges and metatarsal heads.
  • Osteoporosis, subluxation, and loss of joint space.
  • Tarsal disintegration and Charcot change.
  • Periosteal reaction and neuropathic fractures.
• Specific leprous osteitis: small punched-out cystic lesions, periostitis, and cortical erosion.
• Nasal and maxillary: atrophy of the anterior nasal spine and alveolar process, widened nasal aperture.
• Osteomyelitis: sequestrum, involucrum, cortical destruction, soft-tissue swelling.
• Further imaging: MRI separates osteomyelitis from Charcot change. Bone scan and ultrasound help in selected cases. An Indian study of clinico-radiological correlation of bone changes in disabled leprosy patients exists (Mohammad et al., Indian J Lepr 2016).

Management

1. Treat the infection: multidrug therapy (MDT) according to the NLEP schedule.
2. Treat reactions: prednisolone for nerve function impairment, and thalidomide or clofazimine for ENL.
3. Prevent trauma and deformity (see Q6): self-care, protective footwear, splints, and early nerve decompression where indicated.
4. Ulcer and osteomyelitis care: rest, debridement, off-loading (total contact cast), culture-directed antibiotics, and removal of the sequestrum. Amputation is needed in advanced cases.
5. Reconstructive surgery: tendon transfers, arthrodesis, and corrective footwear, done once reactions are quiet.
6. Rehabilitation: physiotherapy, occupational therapy and vocational support under the NLEP disability prevention and medical rehabilitation (DPMR) programme.

Q2. Cardiovascular syphilis

Pathophysiology

• It is a tertiary manifestation, appearing 10 to 30 years after untreated infection.
• T. pallidum reaches the adventitia of the thoracic aorta and lodges around the vasa vasorum.
• Perivascular lymphocytes and plasma cells infiltrate, causing obliterative endarteritis.
• Ischaemia of the media destroys elastic fibres and smooth muscle. Healing by scarring leaves a wrinkled "tree-bark" intima.
• The weakened wall dilates, producing aortic root dilatation (aortic regurgitation) and saccular aneurysm. Scarring around coronary ostia narrows them.
• Histologically, syphilitic aortitis is mononuclear with plasma cells. The only definitive pathological finding is identification of T. pallidum by immunohistochemistry (Henry's Clinical Diagnosis, Pathology).

Clinical spectrum

Diagnostic approach

1. Serology:
   • Non-treponemal (VDRL, RPR): titre may be low or negative in late disease.
   • Treponemal (TPHA, TPPA, FTA-ABS, EIA): remain reactive for life.
   • Diagnosis needs reactive tests of both types.
2. Chest X-ray: linear calcification of the ascending aorta, widened mediastinum.
3. Echocardiography, CT or MR angiography: aortic root and aneurysm size, valve function.
4. Coronary angiography when ostial disease is suspected.
5. CSF examination: recommended in tertiary syphilis (Harrison's, Tertiary Syphilis) to exclude neurosyphilis.
6. HIV test and screening for other STIs.
7. Differential diagnosis: atherosclerotic aneurysm, Marfan syndrome, Takayasu arteritis, giant cell aortitis, bicuspid aortic valve.

Treatment (current guidelines)

• Penicillin is the drug of choice. If the CSF is normal, benzathine penicillin G 7.2 million units total (2.4 million units IM weekly for 3 weeks) (Harrison's; Goldman-Cecil, Penicillin treatment for syphilis, which groups cardiovascular syphilis with late disease).
• If the CSF is abnormal, treat as neurosyphilis (aqueous crystalline penicillin G IV for 10 to 14 days).
• Penicillin allergy: desensitise where possible (especially in pregnancy or neurosyphilis). Doxycycline 100 mg twice daily for about 28 to 30 days is the usual alternative.
• Some centres give a short course of prednisolone before the first dose to limit the Jarisch-Herxheimer reaction. This is practice, not a strict guideline.
• Cardiac management:
  • Treat heart failure.
  • Control blood pressure.
  • Aortic valve replacement or Bentall procedure for severe aortic regurgitation.
  • Surgical or endovascular repair for aneurysm.
  • Revascularisation for ostial stenosis.
• Penicillin does not reverse structural damage, so it mainly halts progression.
• Serological follow-up at 6, 12 and 24 months.

Q3. Lymphogranuloma venereum (LGV)

Aetiology and epidemiology

Clinical spectrum

1. Primary stage (3 to 30 days): small painless papule, shallow ulcer or herpetiform lesion, or urethritis. It is often missed because it heals in days.
2. Secondary stage (weeks later):
   • Inguinal syndrome (usually in men with penile infection): unilateral, painful inguinal and femoral lymphadenopathy. The "groove sign" (nodes above and below the inguinal ligament) occurs in some. Nodes coalesce into a bubo that may suppurate and drain through multiple sinuses.
   • Anogenital or anorectal syndrome: proctitis or proctocolitis after receptive anal sex or in women with cervicitis. Rectal pain, bleeding, tenesmus, mucopurulent discharge, diarrhoea. Often mimics inflammatory bowel disease.
   • Systemic symptoms: fever, malaise, arthralgia.
3. Tertiary stage:
   • Rectal strictures and fistulae, rectovaginal fistula.
   • Genital elephantiasis and esthiomene (chronic ulcerating genital lymphoedema).
   • Chronic lymphoedema.

Diagnostic pitfalls

• Misdiagnosis as Crohn disease, herpes proctitis, other proctitis, chancroid, syphilis, donovanosis, tuberculous adenitis, lymphoma or cat-scratch disease.
• Silent rectal infection in MSM.
• A standard C. trachomatis NAAT does not distinguish L1 to L3 from the non-LGV serovars (D to K). Non-LGV proctitis is usually asymptomatic (Goldman-Cecil, Proctitis). L-serovar identification needs ompA genotyping or a specific PCR.
• Serology (complement fixation, microimmunofluorescence): cross-reacts with other chlamydial infections. A high titre supports but does not prove the diagnosis. The Frei skin test is obsolete.
• Culture is difficult, and rectal culture is unreliable.
• Co-infection with HIV, syphilis, gonorrhoea and hepatitis C is common. HIV-positive patients can have prolonged or atypical disease.
• Beware of incision and drainage of buboes, which causes sinus formation.

Management

• First line: doxycycline 100 mg twice daily for 21 days (NACO 2024 lists this for anorectal discharge when LGV is suspected or confirmed).
• Alternatives: azithromycin 1 g orally once weekly for 3 weeks, or erythromycin 500 mg four times daily for 21 days. Use azithromycin or erythromycin in pregnancy.
• Bubo: aspirate through normal skin with a wide-bore needle. Do not incise.
• Late disease: surgery for strictures, fistulae, and lymphoedema, plus antibiotics.
• Test for HIV, syphilis, gonorrhoea and hepatitis B and C.
• Treat sexual partners from the 60 days before onset, presumptively, and advise abstinence until treatment ends.
• Follow up until resolution of symptoms.
• Recent evidence: two 2024 observational studies (PMIDs 38465962 and 39102506) suggest a 7-day doxycycline course may work in rectal LGV. These are not randomised trials, so the guideline duration remains 21 days.

Q4. Paediatric leprosy and its relevance to NLEP

Definition

Why it matters

• It is a sentinel indicator of ongoing community transmission, since children have short incubation and were recently exposed, usually from a household contact.
• The child proportion among new cases is an NLEP monitoring indicator. It fell from 9.04% (2014-15) to 4.68% (2024-25) according to the NLEP and PIB data. The NLEP roadmap 2023-27 targets about 2% child cases by 2026-27 (DGHS NLEP page).
• National figures: prevalence rate 0.57 per 10,000, and Grade 2 disability (G2D) per million population fell from 4.48 to 1.31 (2014-15 to 2024-25). A news report cites 3,832 child cases in 2025-26, of which 37 had G2D at diagnosis (I could not verify this against a primary source). G2D in a child indicates delayed diagnosis and is an alarm indicator.
• India reached elimination as a public health problem (prevalence below 1 per 10,000) in March 2005, and the goal now is zero transmission, with interruption of transmission by 2027.

Clinical features in children

• Mostly paucibacillary: a single hypopigmented or erythematous patch, TT or BT type.
• Nerve involvement and deformity are less frequent than in adults, but disability does occur if diagnosis is late.
• Lesions are on the face, trunk, buttocks and limbs.
• Differentials: pityriasis alba, tinea, vitiligo, post-inflammatory hypopigmentation, eczema, nevus anaemicus.
• Sensory testing is difficult in small children, so repeated examination and a high index of suspicion are needed.

Diagnosis and treatment

• Cardinal signs: hypopigmented or reddish patch with definite sensory loss, thickened nerve, and AFB on slit-skin smear.
• Slit-skin smear and, where needed, biopsy.
• MDT with paediatric blister packs (children 10 to 14 years have reduced doses; younger children are dosed by weight or age). PB: 6 months. MB: 12 months. Check the current NLEP schedule for doses.
• Treat reactions with prednisolone, and monitor nerve function.
• Educate on self-care, and maintain school attendance without stigma.

NLEP measures relevant to children

• Contact survey and tracing of household and neighbourhood contacts, and the single-dose rifampicin post-exposure prophylaxis (SDR-PEP) for eligible contacts. WHO age-based doses: 2 to 5 years 150 mg, 6 to 9 years 300 mg, 10 to 14 years 450 mg, 15 years and older 600 mg. Infants under 2 years and contacts with active disease or TB are excluded.
• Active case detection through the Leprosy Case Detection Campaign (LCDC), and school health screening (RBSK).
• Sparsh Leprosy Awareness Campaign (around 30 January) to reduce stigma.
• ASHA incentives for case detection and treatment completion.
• Case reporting through the Nikusth portal, and disability prevention and medical rehabilitation (DPMR) services.
• Surveillance of child cases and G2D in children at district level.

Q5. HIV life cycle in a CD4+ lymphocyte and ART drug classes

• India's NACO first-line regimen is TLD: tenofovir 300 mg + lamivudine 300 mg + dolutegravir 50 mg, once daily.
• Ritonavir and cobicistat are pharmacokinetic boosters that inhibit CYP3A4. They have no direct antiviral action in this role.
• Combination of at least three drugs from two or more classes suppresses viral replication and prevents resistance.
• Check for baseline resistance and HLA-B*57:01 before abacavir.

Q6. Non-pharmacological management of leprosy: care of insensitive hands and feet

General non-drug measures

• Health education and counselling: nature of the disease, curability, treatment adherence, reactions, and early reporting.
• Reducing stigma: community education, self-help groups, and anti-discrimination support.
• Contact examination and prophylaxis education.
• Nutrition and general health, including management of anaemia.
• Psychosocial support and counselling for depression.
• Rehabilitation: medical (surgery and physiotherapy), social, and economic (vocational training, loans, colony support). NLEP provides MCR footwear and self-care training (Park's Textbook of Preventive and Social Medicine).
• Regular nerve function assessment: sensory testing (monofilament, ballpoint pen) and voluntary muscle testing at every visit.
• Eye care: blink exercises, lubricants, sunglasses, protection from dust.

Principles of care of insensitive hands and feet

1. Inspect hands and feet daily for cuts, blisters, redness, swelling and thorns. Use a mirror for the soles.
2. Soak in plain water for 20 to 30 minutes.
3. Scrape off callus and dead skin gently with a stone or file.
4. Oil (coconut or petroleum jelly) to keep the skin supple and prevent cracks.

• Avoid heat, sharp objects and rough tools. Use a thick cloth to hold hot pots, padded or larger handles, and protective gloves.
• Do not hold cigarettes or work near fire without protection.
• Rest any hand with a wound.
• Perform daily passive and active exercises to prevent contractures and claw deformity.
• Splinting for nerve palsy (for example a night splint for ulnar claw).
• Surgical tendon transfer when appropriate.

• Protective footwear: microcellular rubber (MCR) footwear with a cushioned insole, closed toe, wide fit and a firm sole. Shake out the footwear and check inside for foreign bodies before wearing.
• Never walk barefoot.
• Avoid long walks, and rest regularly to limit repetitive pressure.
• Correct footwear modification for foot drop (an ankle-foot orthosis).

• Rest the part and avoid pressure (off-loading).
• Clean daily, remove dead tissue, and use moist non-adherent dressings.
• Plaster of Paris or total contact cast for plantar ulcers.
• Antibiotics for infection, and tetanus prophylaxis.
• Elevate the limb for oedema.

Q7. NACO urethral discharge (UD) syndrome and persistent or recurrent urethritis

A. NACO syndromic management (National Technical Guidelines on STI and RTI, 2024)

• Condom use and partner notification.
• HIV and syphilis testing and counselling (offered to every patient).
• Treat all partners whose last contact with the patient was within 60 days before onset or diagnosis, on the same lines.
• Abstain until patient and partners are cured.
• Return visit after 7 days.

B. Persistent or recurrent urethritis (stepwise)

1. Confirm objective urethritis (visible discharge, Gram stain with at least 2 PMN per oil immersion field, or first-void urine pyuria). Symptoms alone are not enough.
2. Check adherence and reinfection: was the full course taken, was the partner treated, and was there re-exposure? If non-adherence or reinfection is likely, repeat the original regimen and treat the partner.
3. Send laboratory tests where available: Gram stain, NAAT for N. gonorrhoeae, C. trachomatis, M. genitalium and T. vaginalis, and gonococcal culture with sensitivity if treatment failure is suspected.
4. Consider the causes, by frequency:
   • Mycoplasma genitalium is the commonest cause of persistent non-gonococcal urethritis, especially after doxycycline (Red Book 2021, Table 4.4).
   • Trichomonas vaginalis.
   • Resistant gonorrhoea.
   • Other: Ureaplasma urealyticum, HSV, adenovirus, anaerobes, urethral stricture, foreign body, prostatitis or epididymitis, and non-infectious causes.
5. Treatment:
   • Trichomonas coverage: metronidazole 2 g orally in a single dose (or tinidazole 2 g).
   • M. genitalium:
     • If the initial regimen was doxycycline, give azithromycin 1 g single dose (or 500 mg then 250 mg daily for 4 days).
     • If azithromycin failed, give moxifloxacin 400 mg once daily for 7 days (Smith and Tanagho's General Urology; Red Book 2021).
     • Where resistance testing exists, macrolide-sensitive disease is treated with doxycycline for 7 days, then azithromycin 1 g, then azithromycin 500 mg daily for 3 days (Harriet Lane Handbook).
   • Gonorrhoea failure: ceftriaxone, with culture-guided therapy.
6. NACO regimen for persistent discharge. The NACO 2024 summary I retrieved lists a regimen reserved for persistent urethral discharge, "ceftriaxone 250 mg IM + azithromycin 2 g (single dose)" to cover gonorrhoea and chlamydia in addition to T. vaginalis. That text appears to be the earlier column of the table, and the 2024 document raised the ceftriaxone dose to 500 mg. I could not confirm the exact current persistent-discharge row, so please verify it in the NACO 2024 technical guidelines before writing a dose in the exam.
7. Refer if still persistent: urology review (stricture, prostatitis), cystoscopy, and expert opinion.
8. Partners: treat and test. Retest for HIV and syphilis.

Q8. Ridley-Jopling classification

• Indeterminate leprosy is an early stage, outside the five groups.
• The BI uses Ridley's logarithmic scale (0 to 6+).
• Lepromin is a classification and prognostic tool, not a diagnostic test.
• Borderline groups are unstable and can shift (reversal reaction upgrades, ENL or downgrading in untreated disease).

Correlation with the WHO operational classification

Q9. Short notes

A. HPV vaccines

• Type and composition: non-infectious virus-like particles made from recombinant L1 major capsid protein. They contain no viral DNA.
• Available vaccines:
  • Bivalent (Cervarix): HPV 16 and 18 (about 70% of cervical cancers). Licensed in 2009 (Yamada's Textbook of Gastroenterology).
  • Quadrivalent (Gardasil, Cervavac): adds 6 and 11, which cause genital warts. The quadrivalent vaccine was later licensed for males (Yamada's).
  • Nonavalent (Gardasil 9): adds 31, 33, 45, 52 and 58 (Harrison's, Vaccines and Cancer Prevention).
  • India has an indigenous quadrivalent vaccine (Cervavac).
• Schedule:
  • Age 9 to 14 years: 2 doses (0 and 6 months).
  • 15 years and older, or immunocompromised: 3 doses (0, 1 to 2 and 6 months).
  • WHO now permits a single-dose schedule in this age group.
• Efficacy: over 90% against persistent infection, CIN2+, and genital warts in HPV-naive recipients. It works best before sexual debut.
• Safety: injection-site pain and fever are common. It is not given in pregnancy (not harmful if given inadvertently), and it is contraindicated after a severe reaction to a previous dose.
• Limits: it does not treat existing infection or lesions, and cervical screening is still needed.
• Dermatology relevance: prevention of anogenital warts and anogenital cancer, and possible use as an adjunct in recalcitrant warts (off-label).
• India's national programme status has been announced for girls aged 9 to 14, and the current rollout status should be checked.

B. Silent neuritis in leprosy

• Definition: progressive sensory or motor nerve function impairment without pain, paraesthesia or nerve tenderness and without signs of a lepra reaction. It is also called "quiet nerve paralysis" (Harrison's, Nerve Function Impairment; Park's Textbook).
• Pathogenesis: Schwann cell infection with demyelination and endoneurial inflammation (a form of cell-mediated nerve damage), occurring before, during or after MDT.
• Clinical relevance: it presents as new numbness, weakness, claw hand or foot drop, and is a major cause of disability. It may be the first sign of a severe reversal reaction (Park's lists it among signs of severe reaction).
• Detection: regular nerve function assessment (monofilament sensory testing and voluntary muscle testing) at each visit, and during and after treatment. Nerve conduction studies and high-resolution ultrasound can help.
• Treatment: the same as for type 1 reaction. High-dose prednisolone is the drug of choice (Harrison's), typically 40 mg/day, tapered over about 24 weeks in the NLEP schedule. Prognosis for recovery is good if started shortly after onset. Nerve decompression is used by some, but there is no randomised evidence (Harrison's).
• Continue MDT, protect the limb, and give physiotherapy and self-care education.

C. Pediculosis pubis (phthiriasis)

• Cause: the crab louse Pthirus pubis, about 1 to 2 mm long, with broad body and large claws for coarse hair.
• Transmission: mainly sexual contact. Fomites (clothes, bedding, towels) are less common (Campbell-Walsh Urology, Infestation). Infestation in children is on eyelashes, and sexual abuse should be considered.
• Life cycle: eggs (nits) cemented to the hair shaft hatch in about 7 days, then three nymphal stages, with an adult life of about 3 to 4 weeks. Lice survive about 1 to 2 days off the host.
• Clinical features:
  • Pubic itching, worse at night.
  • Visible lice and nits on pubic hair; blood-tinged specks in underwear.
  • Maculae ceruleae (bluish-grey macules from bites) on the thighs and lower abdomen.
  • Excoriation and secondary pyoderma.
  • May involve axilla, chest, beard, eyebrows and eyelashes.
• Diagnosis: finding live lice or nits on naked eye, magnifying glass or dermoscopy. Screen for other STIs (HIV, syphilis, gonorrhoea, chlamydia).
• Treatment:
  • Permethrin 1% cream rinse, applied to the affected area and washed off after 10 minutes (Rosen's Emergency Medicine). Permethrin 5% cream can be used overnight, repeated after 1 week (Campbell-Walsh, Fitzpatrick's).
  • Alternatives: pyrethrins with piperonyl butoxide, malathion 0.5%, and oral ivermectin 200 micrograms/kg, two doses 7 to 14 days apart.
  • Remove nits mechanically. Shaving is optional.
  • Eyelashes: petrolatum applied twice daily for about 10 days, plus mechanical removal. Avoid permethrin near the eyes.
  • Wash clothing and bedding in hot water (at least 50 to 60 °C) and dry on high heat.
  • Treat sexual partners and avoid sexual contact until treatment is complete.
  • Follow up at 1 week.

Exam tips

• Q8: draw the table in full, and add a spectrum arrow from TT to LL showing immunity falling and BI rising.
• Q5: a labelled life-cycle diagram with the drug at each step is worth marks.
• Q7: write the NACO first-line regimen exactly, and say that dual therapy continues when laboratory tests are unavailable.
• Q2 and Q3: state the penicillin schedule and the 21-day doxycycline course clearly.