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What's Covered - Structure at a Glance

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1. Pathogenesis of Leprosy

Introduction

The Organism

• M. leprae is the only bacterium that parasitizes peripheral nerves (Schwann cells)
• Generation time: 12-14 days (slowest of any known bacterial pathogen)
• Cannot be cultured in vitro; grown in armadillo footpads experimentally
• Optimal growth temperature: 27-30°C, explaining predilection for cooler body parts (skin, peripheral nerves, anterior eye, testes, nasal mucosa)
• Cell wall contains unique PGL-1 (phenolic glycolipid-1) - key virulence factor

Route of Entry and Initial Events

1. Bacilli enter via the respiratory route (nasal droplets/secretions from lepromatous patients) - primary mode
2. Less commonly through skin abrasions or mucous membranes
3. After entry, bacilli migrate toward neural tissue and enter Schwann cells via the PGL-1 / laminin-2 binding mechanism
4. Bacteria also found in macrophages, endothelial cells, and smooth muscle cells
5. During early multiplication, the person remains entirely asymptomatic (subclinical infection)
6. Only a small proportion of those infected develop clinical disease - M. leprae has low pathogenicity

Role of Immunity - The Spectrum Concept (Ridley-Jopling)

• Paucibacillary (PB): 1-5 skin patches, smear negative
• Multibacillary (MB): >5 skin patches, or smear positive

Immunopathological Mechanisms

In Tuberculoid Leprosy (Strong CMI):

• Dominant Th1 response: IL-2, IFN-γ, TNF-β predominate
• Activated macrophages efficiently destroy bacilli
• Well-formed epithelioid cell granulomas with Langhans giant cells
• Lymphocytes abundant at lesion periphery
• Near-absent bacilli; strong lepromin (Mitsuda) reaction
• Nerve damage from compact granulomatous inflammation - few nerves affected, but severely damaged

In Lepromatous Leprosy (Defective CMI):

• Dominant Th2 response: IL-4, IL-5, IL-10 predominate
• CD8+ suppressor T cells outnumber CD4+ helper T cells
• Specific anergy to M. leprae antigens (normal response to other antigens retained)
• Macrophages fail to kill bacilli → transform into Virchow cells (Lepra cells): foamy, vacuolated macrophages stuffed with bacilli
• Globi: packets of bacilli within macrophages/foamy cells
• High antibody titers (anti-PGL-1) but these are ineffective - humoral immunity does not protect
• Diffuse bacillary infiltration; negative lepromin reaction
• Nerve damage from bacillary infiltration - many nerves involved, slow and symmetric

Key Virulence Molecules:

• PGL-1 (Phenolic Glycolipid-1): unique surface antigen of M. leprae; mediates binding to laminin-α2 on Schwann cells; scavenges reactive oxygen species protecting bacillus from oxidative killing
• LAM (Lipoarabinomannan): suppresses macrophage activation; inhibits IFN-γ signalling
• HSP65: contributes to immunological evasion

Nerve Pathology - Central to Leprosy Pathogenesis

• M. leprae is uniquely neurotropic - the only known pathogen to infect Schwann cells
• PGL-1 binds laminin-α2 of the basal lamina → entry into Schwann cells
• Schwann cell infection → demyelination → axonal degeneration
• Superficial peripheral nerves most vulnerable: ulnar, median, common peroneal, posterior tibial, facial, greater auricular, radial cutaneous
• Results in: anaesthesia, anhidrosis, motor paralysis, trophic ulcers, and deformity

Lepra Reactions (Immunological Flares)

Type 1 Reaction (Reversal Reaction):

• Occurs in borderline spectrum (BT, BB, BL)
• Mechanism: Delayed hypersensitivity (Type IV) - sudden upgrade or downgrade in CMI
• Triggers: MDT commencement, pregnancy, intercurrent infection
• Features: erythema and edema of existing skin lesions; acute nerve function impairment (neuritis); pain and tenderness over nerve trunks
• Treatment: Prednisolone (starting 40-60 mg/day, tapered over 3-6 months)

Type 2 Reaction (Erythema Nodosum Leprosum - ENL):

• Occurs in BL and LL types
• Mechanism: Immune complex deposition (Type III) + neutrophilic infiltration; complement activation
• Features: tender erythematous papules/nodules (ENL), fever, systemic involvement - iritis, orchitis, neuritis, nephritis, lymphadenitis
• Treatment: Thalidomide (drug of choice - 100-400 mg/day), Clofazimine, Prednisolone

Lucio Phenomenon:

• Occurs in diffuse, non-nodular LL (Lucio leprosy; Mexico/Central America)
• Mechanism: vasculitis; ischaemic necrosis of skin
• Features: haemorrhagic infarcts, skin necrosis, high mortality

Summary of Pathogenesis

Inhalation of M. leprae → entry into Schwann cells via PGL-1/laminin → slow bacillary multiplication (silent phase) → immune recognition → if CMI strong → tuberculoid granuloma, bacillary clearance (TT, BT, controlled disease) → if CMI defective → unchecked bacillary proliferation, foamy Virchow cells, diffuse infiltration (LL) → nerve damage, deformities, disabilities. Immune fluctuations during treatment or spontaneously → Lepra reactions → accelerated nerve and tissue damage → permanent disability.

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2. Bone Involvement in Leprosy - Pathogenesis

Introduction

Classification of Bone Involvement

A. Specific (Direct) Bone Involvement - from Bacillary Invasion

1. Leprous Periostitis / Osteitis

• M. leprae directly invades periosteum, cortex, and marrow via haematogenous spread
• Most prominent in LL and BL types (high bacillary load)
• Granulomatous inflammation → osteoclast activation → osteolysis
• Sites: small bones of hands and feet, tibia, fibula, radius, ulna
• Radiologically: periosteal reaction, cortical erosions, medullary infiltration

2. Concentric Bone Atrophy (Periosteal Osteolysis)

• Uniform periosteal erosion causing tapering of phalanges
• "Licked candy-stick" / "sucked candy" appearance on X-ray
• Pathognomonic of leprosy
• Proximal phalanges most often affected

3. Leprous Dactylitis

• Endosteal proliferation + medullary granulomata within the bone
• Spindle-shaped (ballooning) expansion of the phalanx on X-ray
• Occurs in MB leprosy; phalanges of hands more than feet
• Cystic radiolucencies within the medullary cavity

4. Nasal Bone Involvement

• Direct bacillary infiltration of nasal submucosa → turbinate atrophy and mucosal ulceration
• Progressive destruction of anterior nasal spine, vomer, nasal septum cartilage
• Consequences: septal perforation → loss of support → collapse
• Saddle nose deformity - characteristic and disfiguring feature of lepromatous leprosy
• Preceded by chronic rhinitis, epistaxis, nasal obstruction

5. Facies Leonina

• Diffuse bacillary infiltration of facial skin and underlying periosteum
• Supraorbital ridges, zygomata, and alveolar processes infiltrated and thickened
• Coarse leonine (lion-like) facies; madarosis accompanies this

B. Secondary (Indirect / Neuropathic) Bone Involvement

1. Neuropathic (Charcot) Arthropathy

• Loss of protective pain sensation from peripheral nerve damage → repeated unrecognised trauma to joints
• Progressive painless joint destruction, disorganisation, and fragmentation
• "Bag of bones" appearance on X-ray
• Affects: foot (tarsometatarsal, midfoot, ankle), hand (wrist, MCP)
• Charcot midfoot collapse → rocker-bottom foot deformity

2. Disuse Osteoporosis

• Immobility from paralysis, contractures, and plantar ulcers → generalised bone mineral loss
• Diffuse osteoporosis → pathological fractures from trivial trauma
• Compounded by hypovitaminosis D (limited sun exposure, malnutrition)

3. Plantar Ulcer - Secondary Osteomyelitis

• Plantar anaesthesia (posterior tibial nerve) → pressure ulcers over metatarsal heads
• Secondary bacterial infection → osteomyelitis of metatarsals and phalanges
• Progressive metatarsal resorption → "squared-off" or pencil-shaped stumps
• Repeated cycles: ulcer → infection → osteolysis → digit shortening

4. Absorption of Phalanges (Acroosteolysis) - Primary Mechanism of Digit Loss

• NOT from direct leprous invasion - this is the commonest mechanism of finger/toe loss
• Sequential pathology: trophic ulcer → secondary bacterial infection → osteomyelitis → osteolysis → pathological fracture → absorption → digit shortening
• Ultimately leads to mutilation with complete loss of digits

5. Muscle Imbalance and Periarticular Erosions

• Paralysis of intrinsic muscles (ulnar, median, peroneal nerve) → imbalance between flexors and extensors
• Repeated abnormal mechanical stress on joints → periarticular erosions, subluxations, fixed deformities

C. Bone Changes in Lepra Reactions

• ENL (Type 2): periostitis, acute arthritis; osteolytic lesions during florid reactions; painful periosteal swelling
• Reversal Reaction (Type 1): acute severe neuritis → rapid onset motor deficit → accelerated deformity progression

Radiological Features Summary

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3. Disabilities and Deformities in Leprosy

Introduction

WHO Disability Grading (2016)

Mechanism of Nerve Damage

• M. leprae invades Schwann cells → demyelination → axonal degeneration
• Loss of all three nerve fibre functions:
  • Sensory: anaesthesia (loss of pain, temperature, touch)
  • Motor: muscle paralysis → deformity
  • Autonomic: anhidrosis → dry, cracked skin → portal of entry for infection → trophic ulcer
• Nerves affected (in order of frequency): ulnar > common peroneal > posterior tibial > median > facial > greater auricular > radial cutaneous > trigeminal

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Disabilities and Deformities - By Nerve

1. Ulnar Nerve (Most Commonly Affected in Leprosy)

• Site of compression: ulnar groove at elbow (medial epicondyle)
• Motor loss: intrinsic muscles of hand - hypothenar muscles, all interossei, medial 2 lumbricals, adductor pollicis
• Deformity: Claw Hand (Main en Griffe)
  • Hyperextension at MCP joints + flexion at IP joints of ring and little fingers
  • Mechanism: lumbricals flex MCP + extend IPs; their loss allows EDC to hyperextend MCPs, leaving long flexors to flex IPs unopposed
  • "Ulnar claw" - ring and little finger predominantly affected
• Sensory loss: medial 1.5 fingers, medial palm, hypothenar eminence

2. Median Nerve

• Site: carpal tunnel/wrist
• Motor loss: thenar muscles (opponens pollicis, abductor pollicis brevis, flexor pollicis brevis), lateral 2 lumbricals
• Deformity: Ape Thumb (Simian Hand)
  • Thumb lies flat in the plane of the palm - loss of opposition and abduction
  • Thenar wasting prominent
  • Index and middle finger claw (lateral 2 lumbricals lost)
• Combined ulnar + median palsy: Complete Claw Hand - all four fingers clawed
• Sensory loss: lateral 3.5 fingers, thenar eminence, lateral palm

3. Radial Nerve / Posterior Interosseous Nerve

• Wrist drop: loss of wrist and finger extensors (uncommon in leprosy but can occur)
• Radial cutaneous nerve is more commonly affected in leprosy: anaesthesia of dorsal hand/thumb web

4. Common Peroneal (Lateral Popliteal) Nerve

• Site: neck of fibula
• Motor loss: tibialis anterior, extensor digitorum longus, extensor hallucis longus, peronei
• Deformity: Foot Drop (Drop Foot)
  • Inability to dorsiflex the foot
  • Foot drags during walking → steppage gait (high-stepping to clear foot)
  • Fixed equinovarus deformity if contracture occurs
• Sensory loss: dorsum of foot, lateral lower leg

5. Posterior Tibial Nerve

• Site: behind medial malleolus (tarsal tunnel)
• Motor loss: all intrinsic muscles of foot (interossei, lumbricals, flexor digitorum brevis, abductor hallucis)
• Deformity: Claw Toes - hyperextension at MTP joints, flexion at IP joints
• Most dangerous consequence: Plantar Anaesthesia
  • Loss of protective sensation on weight-bearing surface
  • Pressure necrosis → plantar trophic ulcers (perforating ulcers)
  • At pressure points: first and fifth metatarsal heads, heel
  • Secondary infection → osteomyelitis → digit/foot loss
• Anhidrosis of sole → dry, fissured skin → portal for infection

6. Facial Nerve

• Site: around the ear, parotid region
• Motor loss: orbicularis oculi (zygomatic branch most commonly affected)
• Deformity: Lagophthalmos - incomplete eye closure
• Consequences: exposure keratitis, corneal ulceration, corneal scarring → blindness
• Combined with trigeminal sensory loss ("Paralytic + Anaesthetic Cornea") → devastating ocular outcome

7. Trigeminal Nerve (Ophthalmic Division)

• Sensory loss of cornea (anaesthetic cornea) and face
• Foreign bodies, trauma go unnoticed → corneal ulceration → opacity → blindness
• Corneal anaesthesia alone (without lagophthalmos) is a significant blinding risk

8. Greater Auricular Nerve

• Thickened, visible, palpable over the sternomastoid - classic physical sign of leprosy
• No major functional disability but diagnostically important

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Specific Deformities

Hand Deformities:

1. Claw hand (ulnar and/or median nerve palsy)
2. Ape thumb / Simian hand (median nerve palsy)
3. Wrist drop (radial nerve)
4. Z-deformity of thumb (thenar wasting + adductor contracture)
5. Absorption of fingers (trophic ulcer → osteomyelitis → resorption)
6. Mutilation - progressive loss of digits; "mitten hand"

Foot Deformities:

1. Foot drop (common peroneal nerve palsy)
2. Claw toes (posterior tibial nerve palsy)
3. Plantar trophic ulcers - at pressure points (metatarsal heads, heel)
4. Absorption of toes
5. Rocker-bottom foot (Charcot neuropathic midfoot)
6. Callosities over pressure areas

Facial Deformities:

1. Saddle nose (destruction of nasal cartilage and bone in LL)
2. Facies leonina (lion face: diffuse lepromatous infiltration, skin thickening, loss of normal contours)
3. Madarosis (loss of lateral eyebrows and eyelashes) - pathognomonic of LL
4. Lagophthalmos (facial nerve palsy)
5. Gynecomastia + testicular atrophy (LL bacillary infiltration of testes → hypogonadism)
6. Loss of ear lobule architecture (LL infiltration)

Eye Complications (Major Cause of Blindness in Leprosy):

1. Lagophthalmos → exposure keratitis → corneal ulceration → blindness
2. Uveitis (Iridocyclitis) - in LL and during ENL reactions; chronic leads to cataract, glaucoma, phthisis bulbi → blindness
3. Scleritis / Episcleritis during lepra reactions
4. Corneal anaesthesia (trigeminal nerve involvement)
5. Superficial punctate keratitis and corneal opacities from lepromatous infiltration
6. Cataract secondary to chronic uveitis

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Prevention of Disabilities (POD) - The 3 Pillars

1. Early Diagnosis and MDT

• Prevents progression of nerve damage before it becomes permanent
• MDT (Multi-Drug Therapy) kills bacilli and prevents new nerve invasion

2. Neuritis Management (Preserve Nerve Function)

• Prompt prednisolone for Type 1 reactions and acute neuritis
• Starting dose: 40-60 mg/day; taper over 3-6 months
• Protects against permanent nerve function impairment (NFI)
• Regular Voluntary Muscle Testing (VMT) and sensory testing (Semmes-Weinstein monofilaments)

3. Rehabilitation

• Physiotherapy: prevent contractures, maintain joint mobility, muscle strengthening
• Special footwear: Microcellular rubber (MCR) sandals - redistribute plantar pressure; custom moulded insoles
• Eye care: lubricating drops (methylcellulose), protective spectacles, taping of eye at night
• Wound care: regular soaking, debridement of trophic ulcers; elevation

Reconstructive Surgery:

• Tendon transfers for claw hand: Zancolli lasso procedure; Brand tendon transfer (extensor to flexor)
• Tendon transfer for foot drop: ECRB or peroneus longus transfer; tibialis posterior transfer (Bridle procedure)
• Tarsorrhaphy (lateral): for lagophthalmos not responding to conservative measures
• Neurolysis: decompression of thickened, compressed nerve (e.g. ulnar nerve at elbow, tibial nerve at tarsal tunnel)

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4. HIV Skin Manifestations

Introduction

1. Infectious (viral, bacterial, fungal, parasitic)
2. Inflammatory / non-infectious dermatoses
3. Neoplastic
4. Drug reactions
5. HIV-specific / HAART-associated

CD4 Count - Cutaneous Disease Correlation

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A. Viral Infections

1. Herpes Simplex Virus (HSV)

• CD4 <200: chronic, ulcerative, non-healing perianal, genital, or orolabial lesions
• Large, deep, necrotic, extremely painful ulcers (rather than typical grouped vesicles)
• Diagnostic pearl: Mucocutaneous HSV ulcer persisting >1 month = AIDS-defining illness
• Treatment: Acyclovir 400 mg TDS for 7-10 days; valacyclovir; IV acyclovir for severe/disseminated; lifelong suppressive therapy for recurrent disease

2. Herpes Zoster (VZV)

• Multi-dermatomal, bilateral, or disseminated zoster strongly suggests HIV
• May occur even at CD4 counts >200 - often an early warning sign
• Complications: postherpetic neuralgia, ocular zoster, dissemination, necrosis
• Treatment: Acyclovir 800 mg 5 times/day x 7-10 days; IV acyclovir for disseminated or ophthalmic zoster

3. Molluscum Contagiosum

• Giant molluscum (>1 cm diameter): virtually pathognomonic of advanced HIV (CD4 <100)
• Disseminated - hundreds of lesions on face, neck, genitals, trunk
• Facial giant molluscum: common AIDS-defining presentation
• Atypical presentations mimic histoplasmosis and cryptococcosis (always biopsy atypical lesions)
• Treatment: cryotherapy, curettage, cantharadin; best response with HAART (immune restoration)

4. Human Papillomavirus (HPV) / Warts

• Extensive, recalcitrant, large, multiple warts (verruca vulgaris, condylomata acuminata, flat warts)
• Florid oral warts (uncommon in immunocompetent)
• Epidermodysplasia verruciformis-like eruptions with HPV 5, 8 in advanced HIV
• High-grade anal and cervical dysplasia and invasive SCC - dramatically increased risk
• Treatment: ablative therapies (laser, cryo, TCA); imiquimod; HAART reduces recurrence

5. Oral Hairy Leukoplakia (EBV)

• White, corrugated, "hairy" plaques on the lateral borders of the tongue
• Cannot be scraped off (unlike oral candidiasis which leaves bleeding base)
• EBV-driven; occurs almost exclusively in HIV-infected individuals
• WHO clinical stage 2 marker
• No specific treatment needed; acyclovir can temporarily reduce lesions; resolves with HAART

6. Cytomegalovirus (CMV) - CD4 <50

• Painful perianal/genital ulcers; haemorrhagic skin lesions at orifices
• CMV retinitis is the most feared manifestation (blindness)
• Perivascular "brushfire" retinal lesions on fundoscopy
• Treatment: Ganciclovir IV (induction) followed by valganciclovir maintenance

7. Acute HIV Exanthem (Primary HIV / Acute Retroviral Syndrome)

• 2-4 weeks after initial HIV infection; coincides with peak viraemia
• Morbilliform (maculopapular) eruption on trunk, face, and arms
• Associated with fever, sore throat, lymphadenopathy, oral ulcers, myalgia - "glandular fever-like" illness
• Resolves spontaneously in 1-2 weeks
• Clinically important - window period for diagnosis; NAAT (HIV RNA) positive, antibody tests may be negative

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B. Bacterial Infections

1. Bacillary Angiomatosis (BA)

• Caused by Bartonella henselae (cat scratch) or B. quintana (body louse); CD4 <100
• AIDS-defining opportunistic infection
• Bright red, dome-shaped, friable vascular papules and nodules resembling Kaposi sarcoma or pyogenic granuloma
• Bleeds profusely when cut; responds to antibiotics (unlike KS)
• Also causes bacillary peliosis (liver, spleen), bacteraemia, lymphadenopathy
• Diagnosis: Warthin-Starry silver stain of biopsy shows bacilli; PCR confirmation
• Treatment: Erythromycin 500 mg QID or Doxycycline 100 mg BD x 8-12 weeks (long course to prevent relapse)

2. Staphylococcal Infections

• Extensive folliculitis, furunculosis, carbuncles, ecthyma
• MRSA soft tissue infections increasingly common in HIV/MSM
• Diffuse impetigo, cellulitis, and bacteraemia risk higher with breach of skin barrier

3. Syphilis (Co-infection - Treponema pallidum)

• Very high prevalence in MSM co-infected with HIV
• Lues maligna: ulceronecrotic secondary syphilis - papules with haemorrhagic crusts that break down to deep punched-out ulcers; HIV-specific accelerated presentation
• Atypical presentations: noduloulcerative, psoriasiform ("corona veneris")
• Rapid progression to tertiary syphilis; neurosyphilis more common in HIV
• Serological titers may be unreliable (false negative prozone, or unusually high)
• Treatment: Benzathine penicillin 2.4 MU IM; may need longer courses; LP to exclude neurosyphilis

4. Mycobacterial Infections

• MAC (Mycobacterium avium complex): CD4 <50; skin abscesses, draining sinuses, pustules
• M. tuberculosis: lupus vulgaris, scrofuloderma, miliary TB skin lesions
• Atypical mycobacteria (M. chelonae, M. fortuitum): papules, nodules, abscesses

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C. Fungal Infections

1. Oropharyngeal / Esophageal Candidiasis

• Most common HIV-associated mucosal infection
• Pseudomembranous (thrush): white curd-like plaques that scrape off leaving erythematous base - oral/pharyngeal
• Erythematous (atrophic): smooth red patches on palate or tongue
• Esophageal candidiasis = AIDS-defining illness (CD4 <100) - dysphagia, odynophagia
• Treatment: Fluconazole 150-200 mg daily; clotrimazole troches for mild oral disease

2. Dermatophytoses (Tinea)

• Extensive, inflammatory, proximal, palmar, or unusual-pattern tinea
• Tinea faciei (unusual in immunocompetent adults)
• Proximal subungual onychomycosis (PSO): dermatophyte infects the proximal nail fold → "white islands" under proximal nail plate; virtually diagnostic of HIV in an adult
• Treatment: Terbinafine or itraconazole; longer courses essential; nail avulsion may be needed

3. Cryptococcus neoformans

• Disseminated cryptococcosis; CD4 <50; blood-borne spread to skin
• Skin: Umbilicated papules - virtually indistinguishable from molluscum contagiosum (always culture/biopsy)
• Also: nodules, plaques, cellulitis-like, pustules
• Meningitis is primary concern; skin lesions = marker of life-threatening dissemination
• Diagnosis: India ink; cryptococcal antigen (CrAg); skin biopsy + mucicarmine stain (encapsulated yeasts)
• Treatment: Amphotericin B + flucytosine (induction 2 weeks) → fluconazole 400 mg/day (consolidation 8 weeks) → fluconazole 200 mg/day (maintenance)

4. Histoplasma capsulatum

• Endemic in Americas and South-East Asia
• Umbilicated papules, necrotic plaques - mimic molluscum and cryptococcosis
• Disseminated: fever, hepatosplenomegaly, pancytopenia
• Treatment: Amphotericin B → itraconazole

5. Talaromyces (Penicillium) marneffei - Talaromycosis / Penicilliosis

• Endemic in South-East Asia and North-East India (bamboo rat associated)
• Umbilicated papules with central necrotic umbilication on face and trunk - hallmark
• Systemic dissemination: fever, weight loss, lymphadenopathy, hepatosplenomegaly
• Diagnosis: Giemsa stain of peripheral blood smear, skin biopsy; culture (produces red pigment)
• Treatment: Amphotericin B → itraconazole maintenance

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D. Parasitic / Ectoparasitic

1. Norwegian (Crusted) Scabies

• CD4 <200; Sarcoptes scabiei
• Massive hyperkeratotic, crusted, grey-white plaques on hands, feet, scalp, trunk, face
• Thousands to millions of mites (highly infectious - causes ward outbreaks)
• Pruritus may be absent or mild (immune deficit)
• Treatment: Oral Ivermectin (200 mcg/kg) on days 1, 2, 8, 9, 15 + topical 5% Permethrin x multiple applications; treat all contacts; decontaminate environment

2. Demodex Folliculitis

• Demodex folliculorum proliferation on face → pruritic follicular papulopustules
• Responds to permethrin 5%, azelaic acid, oral ivermectin, topical metronidazole

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E. Inflammatory / Non-Infectious Dermatoses

1. Seborrheic Dermatitis

• Most common inflammatory skin condition in HIV (prevalence 30-83%)
• Severity correlates with falling CD4 count - useful clinical marker
• Severe, widespread involvement: nasolabial folds, eyebrows, glabella, central chest (V-area), axillae, groin
• Driven by Malassezia yeast proliferation + immune dysregulation
• Treatment: Ketoconazole 2% shampoo/cream; ciclopirox; low-potency topical corticosteroids; responds to HAART

2. Psoriasis

• New-onset psoriasis or dramatic exacerbation of pre-existing psoriasis; aggressive course
• Inverse (flexural), erythrodermic, or pustular forms common in HIV
• Associated with psoriatic arthritis
• Treatment: Acitretin preferred retinoid (avoid methotrexate, ciclosporin - immunosuppressive); NB-UVB phototherapy; HAART significantly improves psoriasis

3. Eosinophilic Folliculitis (HIV-Associated EF)

• Pruritic, sterile folliculitis predominantly on upper trunk, face, scalp, neck
• Occurs at CD4 <200; intensely pruritic papulopustules
• Histology: eosinophilic infiltration of follicular infundibulum; no infectious organism
• Peripheral eosinophilia; elevated IgE
• Treatment: NB-UVB phototherapy (first line); permethrin; itraconazole; antihistamines; isotretinoin; HAART reduces severity

4. Papular Pruritic Eruption (PPE)

• WHO clinical stage 3 marker for HIV disease
• Symmetrical, chronic, pruritic urticarial papules on extensor surfaces of limbs and trunk
• May represent hypersensitivity to insect bites (hypersensitive reaction in the context of immune dysregulation)
• Treatment: HAART (primary), antihistamines, NB-UVB, topical corticosteroids

5. Xerosis / Acquired Ichthyosis

• Generalised dry skin; acquired ichthyosis (fish-scale appearance) at CD4 <100
• Treatment: Emollients, 5-10% urea preparations, lactic acid

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F. Neoplasms

1. Kaposi Sarcoma (KS)

• Most common AIDS-defining malignancy
• Caused by HHV-8 (Human Herpesvirus 8 / KSHV)
• Classic Features:
  • Violaceous/purple/dark brown non-blanching patches, plaques, and nodules
  • In AIDS: begins on face, oral mucosa, genitals, and lower extremities
  • Oral KS: purple/red plaques on hard palate and gingiva - often first site in AIDS-KS
  • Non-tender; painless unless extensive or involving extremities (lymphoedema)
  • Visceral KS: GIT (leading cause of GI bleeding), lung (respiratory failure) - life-threatening
• Histology: spindle cells, slit-like vascular spaces, extravasated RBCs, PAS-positive hyaline globules
• Staging: ACTG staging system (T - tumour extent, I - immune status, S - systemic illness)
• Treatment:
  • HAART - often leads to significant or complete regression of limited KS
  • Local: cryotherapy, radiotherapy (highly radiosensitive), intralesional vinblastine
  • Systemic chemotherapy for advanced/visceral KS: Liposomal doxorubicin (first line) or paclitaxel

2. Non-Hodgkin's Lymphoma (NHL)

• Diffuse large B-cell lymphoma or Burkitt's lymphoma; EBV-driven
• Skin: violaceous nodules, ulcerated plaques; can mimic KS
• Primary cutaneous vs secondary (systemic with skin involvement)

3. Squamous Cell Carcinoma (SCC)

• HPV-driven; dramatically increased in HIV (especially HPV 16, 18)
• Anogenital SCC, oropharyngeal SCC
• Screen high-risk HIV patients with anal cytology (analogous to Pap smear)

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G. Drug Reactions (Highly Common in HIV)

• SJS/TEN from cotrimoxazole and nevirapine is a leading cause of drug-related mortality in HIV patients
• All HIV patients on cotrimoxazole prophylaxis should be monitored for cutaneous reactions

H. Immune Reconstitution Inflammatory Syndrome (IRIS) - Cutaneous

• Occurs 2-12 weeks after HAART initiation; paradoxical worsening or unmasking
• Zoster IRIS: severe, disseminated, necrotising zoster
• Molluscum IRIS: explosive increase in lesions
• KS IRIS: rapid increase in size and number of KS lesions
• Leprosy IRIS: reversal reactions, new skin patches, neuritis
• Management: Continue HAART; add corticosteroids for severe IRIS; treat underlying infection

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5. Lymphogranuloma Venereum (LGV): Clinical Features, Complications, and Management

Introduction

Etiology and Pathogenesis

• C. trachomatis L1-L3: obligate intracellular Gram-negative bacterium
• Two morphological forms: Elementary body (EB) - metabolically inert, extracellular infectious form; Reticulate body (RB) - intracellular replicating form
• L serovars penetrate epithelial surfaces → infect regional macrophages → spread to regional lymph nodes → granulomatous lymphadenitis → lymphatic obstruction → fibrosis and scarring
• Incubation period: 3-30 days (average 7-12 days)

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Clinical Stages (Classical Heterosexual Pattern)

Stage 1: Primary Inoculation Stage

• Appears 3-12 days after sexual contact
• Small, painless, transient papule, vesicle, or shallow ulcer at the site of inoculation
• Sites: glans, prepuce, urethra (male); posterior fourchette, vaginal wall, labia, cervix (female)
• Self-limiting - disappears spontaneously in 3-5 days without scarring
• Frequently unnoticed, especially in women and in urethral/cervical sites
• May present as non-specific urethritis or cervicitis

Stage 2: Regional Lymphadenopathy (Inguinal / Bubo Stage)

• Appears 2-6 weeks after the primary lesion
• Painful unilateral (70%) or bilateral (30%) inguinal lymphadenopathy (BUBO)
• Initially tender, discrete, rubbery nodes → become matted, periadenitis develops (skin adherent and erythematous) → fluctuant bubo

Groove Sign (Pathognomonic) / Greenblatt's Sign:

• Double genitocrural fold created by simultaneous enlargement of nodes both above and below the inguinal ligament
• Inguinal nodes + femoral nodes both enlarge, with the inguinal ligament creating a groove between them
• Present in approximately 15-20% of cases
• Virtually pathognomonic of LGV
• Overlying skin: purple-red, hot, tense, adherent
• Spontaneous rupture → multiple sinuses discharging thick yellowish-green pus
• Systemic features accompany the bubo stage: fever, chills, malaise, headache, arthralgias, nausea, hepatosplenomegaly, meningoencephalitis (rare)
• In women: inguinal adenopathy is less prominent because the lymphatic drainage of the upper vagina and cervix is to iliac and perirectal nodes → presents as lower abdominal/back pain, parametritis, pelvic mass
• In MSM (anorectal LGV): Absent inguinal bubo; presents primarily as proctitis / proctocolitis

Stage 3: Genitoanorectal Syndrome (Esthiomene Stage) - Chronic Untreated

• Late stage; results from chronic lymphatic obstruction, fibrosis, and scarring

Esthiomene:

• Chronic indolent ulceration + lymphoedema + fibrosis of the external genitalia
• In women: elephantiasis and ulceration of the vulva, labia, and clitoris
• In men: "saxophone deformity" - lymphoedema of the penis and scrotum with firm fibrotic thickening
• Irreversible if established

Rectal and Perirectal Involvement:

• Perirectal and pelvic lymphatic fibrosis → rectal strictures (circumferential fibrotic narrowing)
• Constipation, tenesmus, ribbon-like stools progressing to complete obstruction
• Rectovaginal fistulas, rectovesical fistulas, perineal fistulas, ischiorectal fistulas
• "Frozen pelvis" from massive pelvic fibrosis

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Anorectal LGV (MSM / Women - Now the Predominant Presentation in Developed Countries)

• Proctocolitis: tenesmus, bloody/mucoid rectal discharge, rectal pain, constipation, fever
• Clinically and histologically mimics Crohn's disease - granulomatous inflammation, transmural involvement, crypt abscesses on rectal biopsy
• Rectal ulcers, perianal ulcers, rectal mass (simulating carcinoma)
• Key diagnostic clue: young MSM, history of receptive anal intercourse, STI history
• NAAT of rectal swab = essential for diagnosis in this group

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Complications of LGV

Acute Complications:

1. Bubo rupture with sinus formation and secondary bacterial infection
2. Acute urethritis, cervicitis, or endometritis
3. Acute proctocolitis (haemorrhagic)
4. Perihepatitis (Fitz-Hugh-Curtis syndrome equivalent)
5. Reactive arthritis (particularly HLA-B27 positive patients)
6. Meningoencephalitis (rare)
7. Pneumonitis, pleuritis

Chronic / Late Complications:

1. Elephantiasis genitalis (Esthiomene): irreversible genital lymphoedema; major cause of psychosexual morbidity
2. Rectal strictures: fibrotic circumferential narrowing; may require surgery
3. Genital fistulas: rectovaginal, vesicovaginal, urethrorectal, perineal
4. Chronic inguinal sinuses
5. Squamous cell carcinoma: rare malignant transformation of chronic LGV lesions
6. Frozen pelvis with infertility
7. Lymphatic obstruction → chylous discharge

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Diagnosis of LGV

1. Clinical Diagnosis:

• Groove sign + painful fluctuant bubo + history of STI exposure in endemic region or MSM

2. Laboratory Investigations:

3. Differential Diagnosis:

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Management of LGV

Recommended Treatment Regimens (WHO / CDC / IUSTI):

Doxycycline 100 mg orally twice daily for 21 days (minimum)

• Should be extended until complete resolution of all symptoms and signs
• Effective against all serovars; prevents ongoing tissue damage

• Erythromycin base 500 mg orally four times daily for 21 days
• Azithromycin 1 g orally once weekly for 3 weeks (convenient but less evidence; used where adherence is a concern)
• Tetracycline 500 mg QID x 21 days

• Pregnancy: Erythromycin 500 mg QID x 21 days (doxycycline and tetracycline are absolutely contraindicated)
• HIV co-infection: Same first-line regimen (doxycycline 21 days); may require extended duration; close clinical follow-up; higher complication risk
• Children: Erythromycin based on weight

Management of Buboes:

• Needle aspiration through adjacent normal, intact skin - preferred management
• Prevents inguinal/femoral ulceration from spontaneous rupture
• Repeat aspiration as required for re-accumulation
• Incision and drainage (I&D) is avoided - leads to chronic non-healing sinus formation
• Antibiotics started early can prevent bubo development entirely

Partner Notification and Treatment:

• All sexual contacts within 60 days before symptom onset should be evaluated, tested, and treated
• Empirical treatment for partners (even if asymptomatic):
  • Doxycycline 100 mg BD x 7 days, OR
  • Azithromycin 1 g single dose
• Screen for co-existing STIs in all partners: syphilis, gonorrhoea, HIV, hepatitis B and C

Management of Complications:

1. Rectal strictures: Gentle progressive dilatation; stricturoplasty; loop colostomy for complete obstruction
2. Elephantiasis / Esthiomene: Surgical reduction; lymphatic bypass procedures (limited efficacy)
3. Fistulas: Surgical repair after infection fully controlled with antibiotics
4. Chronic sinuses: Keep clean with dressings; antibiotics; surgical excision of sinus tracts if persistent

Follow-up:

• Continue until complete clinical resolution of all signs and symptoms
• Test of cure: Repeat NAAT 3-4 weeks after completing therapy
• Repeat STI screening at 3 months
• Annual HIV testing if ongoing risk behaviour

Counseling:

• Consistent condom use and reduction of sexual partners
• Abstain from sexual contact until treatment completed and symptoms fully resolved
• HIV testing and pre-exposure prophylaxis (PrEP) counseling where indicated
• Contact tracing and notification

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Summary Table - High-Yield Exam Points