---

1. Pathogenesis of Leprosy

Introduction

The Organism

• M. leprae is the only bacterium that parasitizes peripheral nerves (Schwann cells)
• Has a very slow generation time: 12-14 days (longest of any known bacterial pathogen)
• Cannot be cultured in vitro; grown in armadillo footpads
• Optimal growth temperature: 27-30°C, explaining predilection for cooler body parts (skin, peripheral nerves, anterior eye, testes, nasal mucosa)

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
3. After entry, bacilli migrate toward neural tissue and enter Schwann cells via the PGL-1 (phenolic glycolipid-1) - laminin binding mechanism
4. Bacteria are also found in macrophages, endothelial cells, and smooth muscle cells
5. During early multiplication, the person remains asymptomatic (subclinical infection)

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

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

Immunopathological Mechanism

In Tuberculoid Leprosy:

• Strong Th1 response: IL-2, IFN-γ, TNF-β predominate
• Macrophages are activated and destroy bacilli efficiently
• Well-formed epithelioid cell granulomas with Langhans giant cells
• Lymphocytes abundant at lesion periphery
• Near-absent bacilli; strong lepromin reaction
• Nerve damage is from granulomatous inflammation - few nerves, severe damage

In Lepromatous Leprosy:

• Defective CMI: Th2 response predominates (IL-4, IL-5, IL-10)
• CD8+ suppressor T cells predominate over CD4+ helper T cells
• Specific anergy to M. leprae antigens
• Macrophages fail to kill bacilli (foam cells/Virchow cells)
• Virchow cells (lepra cells): macrophages stuffed with bacilli, vacuolated foamy cytoplasm
• Globi: packets of bacilli within macrophages
• High antibody titers (anti-PGL-1) but ineffective (humoral immunity does not protect)
• Diffuse infiltration; negative lepromin reaction
• Nerve damage is from bacillary infiltration - many nerves, slow symmetric damage

Key Molecules:

• PGL-1 (Phenolic Glycolipid-1): unique to M. leprae, mediates binding to laminin-2 on Schwann cells, scavenges reactive oxygen species
• LAM (Lipoarabinomannan): suppresses macrophage activation, inhibits IFN-γ signaling
• NDO-BSA / ML2055: used in serodiagnosis

Nerve Pathology (Central to Leprosy)

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

Lepra Reactions (Immunological Flares)

• Borderline spectrum (BT, BB, BL)
• Delayed hypersensitivity (Type IV): sudden upgrade in CMI
• Triggered by: MDT, pregnancy, intercurrent infection
• Features: erythema, edema of existing lesions; acute nerve function impairment
• Treatment: Prednisolone

• BL and LL types
• Immune complex deposition (Type III hypersensitivity) + neutrophilic infiltration
• Tender erythematous nodules, fever, systemic involvement (iritis, orchitis, neuritis, nephritis)
• Treatment: Thalidomide (drug of choice), Clofazimine, Prednisolone

• Diffuse LL (Lucio leprosy - Mexico/Central America)
• Ischemic skin necrosis; vasculitis; high mortality

Summary of Pathogenesis

Inhalation of M. leprae → entry into Schwann cells via PGL-1/laminin → slow bacillary multiplication → immune recognition → if CMI strong → tuberculoid granuloma (TT, BT, controlled disease) → if CMI defective → unchecked bacillary proliferation, foam cells, diffuse infiltration (LL) → nerve damage, deformities, disabilities. Immune fluctuations → Lepra reactions → accelerated nerve/tissue damage.

---

2. Bone Involvement in Leprosy - Pathogenesis

Introduction

Classification of Bone Involvement

A. Specific (Direct) Bone Involvement

1. Bacillary Invasion of Bone

• M. leprae directly invades periosteum, cortex, and marrow
• Most common in LL and BL types (high bacillary load)
• Radiologically: periostitis, cortical erosions, medullary infiltration

2. Leprous Osteitis/Periostitis

• Periosteum of small bones of hands and feet, tibia, fibula, radius
• Bacilli incite granulomatous inflammation → osteoclast activation → osteolysis
• Concentric bone atrophy: uniform periosteal erosion → pencil-like tapering of phalanges → "licked candy-stick" or "sucked candy" appearance on X-ray
• Cystic lesions in bones - oval radiolucencies in phalanges
• Whittling of phalanges: progressive dissolution from distal to proximal

3. Leprous Dactylitis

• Endosteal proliferation + medullary granulomata
• Ballooning of phalanx on X-ray (spindle-shaped expansion of shaft)
• Occurs in MB leprosy; phalanges of hands > feet

4. Nasal Bone Involvement

• Direct bacillary infiltration of nasal submucosa → nasal turbinate atrophy
• Destruction of anterior nasal spine and nasal septum cartilage
• Saddle nose deformity - characteristic facial disfigurement of LL
• Rhinitis, septal perforation precede bony collapse

5. Facies Leonina

• Diffuse bacillary infiltration of the facial skin and periosteum
• Supraorbital ridges, zygomata, and alveolar processes infiltrated
• Loss of eyebrows/eyelashes (madarosis) accompanies this

B. Secondary (Indirect/Neuropathic) Bone Involvement

1. Neuropathic (Charcot) Arthropathy

• Repeated trauma to anesthetic limbs → painless joint destruction
• Loss of protective pain sensation → unrecognized fractures, dislocations
• Disorganized joint architecture, "bag of bones" appearance on X-ray
• Occurs in foot (tarsometatarsal, ankle), hand (wrist, MCP)

2. Disuse Osteoporosis

• Immobility from paralysis and plantar ulcers → diffuse osteoporosis
• Pathological fractures from trivial trauma

3. Plantar Ulcer - Bone Erosion

• Plantar ulcers secondary to anesthesia, pressure, and trauma
• Secondary bacterial infection → osteomyelitis of metatarsals/phalanges
• Progressive metatarsal resorption → "squared-off" stumps

4. Absorption of Phalanges (Main Mechanism of Digit Loss)

• Sequential: trophic ulcer → secondary infection → osteomyelitis → osteolysis → pathological fracture → digit shortening
• NOT from direct leprous invasion - this is the commonest mechanism of digit loss

5. Muscle Imbalance and Joint Deformity

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

C. Lepra Reaction and Bone

• ENL (Type 2): periostitis, arthritis; osteolysis during florid reactions
• Reversal reaction: acute neuritis can cause rapid onset of motor deficit → accelerated deformity

Radiological Features Summary

---

3. Disabilities and Deformities in Leprosy

Introduction

WHO Disability Grading (WHO 2016)

Mechanism of Nerve Damage

• M. leprae invades Schwann cells → demyelination → axonal degeneration
• Nerves affected: ulnar, median, radial cutaneous, common peroneal, posterior tibial, facial, greater auricular, trigeminal
• Damage leads to: loss of sensation, loss of motor function, loss of autonomic function (anhidrosis → dry skin → fissuring → entry for infection)

Disabilities and Deformities - By Nerve

1. Ulnar Nerve (Most Commonly Affected)

• Motor loss: intrinsic muscles of hand (hypothenar, interossei, medial 2 lumbricals)
• Deformity: Claw hand (main en griffe)
  • Hyperextension at MCP, flexion at IP joints of ring and little fingers
  • Called "ulnar claw" - ring + little finger most affected
  • Mechanism: Loss of lumbrical function → no MCP flexion → EDC pulls MCP into extension; long flexors flex IPs
• Sensory loss: medial 1.5 fingers, medial palm

2. Median Nerve

• Motor loss: thenar muscles (opponens, APB, flexor pollicis brevis), lateral 2 lumbricals
• Deformity: Ape thumb (simian hand) / "Pointing index"
  • Thumb lies in plane of palm - loss of opposition
  • Index, middle finger claw (lateral 2 lumbricals lost)
• Combined ulnar + median: "Complete claw hand" - all fingers clawed
• Sensory loss: lateral 3.5 fingers, thenar eminence

3. Radial Nerve / Posterior Interosseous Nerve

• Wrist drop (rare in leprosy, but can occur with radial nerve leprous neuritis)
• Loss of wrist extensors and finger extensors

4. Common Peroneal (Lateral Popliteal) Nerve

• Motor loss: tibialis anterior, toe extensors, peronei
• Deformity: Foot drop (drop foot)
  • Inability to dorsiflex foot → foot drags during walking
  • Steppage gait (high-stepping to avoid foot drag)
  • Leads to equinovarus deformity if not treated

5. Posterior Tibial Nerve

• Motor loss: intrinsic muscles of foot (interossei, lumbricals)
• Deformity: Claw toes - hyperextension at MTP, flexion at IP joints
• Sensory loss: plantar anesthesia - most dangerous for trophic ulcer development
• Anhidrosis of sole → cracks → entry for secondary infection → plantar ulcer → osteomyelitis

6. Facial Nerve

• Motor loss: orbicularis oculi
• Deformity: Lagophthalmos - inability to close eye completely
• Consequences: exposure keratitis, corneal ulceration, blindness (leading cause of leprosy blindness)
• Combined with trigeminal nerve involvement (anesthetic cornea) → "Paralytic + anesthetic cornea" = devastating

7. Trigeminal Nerve

• Sensory loss of cornea and face
• Anesthetic cornea: unaware of foreign bodies, injury → corneal ulceration → blindness

8. Greater Auricular Nerve

• Thickened, visible, palpable - a classic sign of leprosy
• No major functional disability but diagnostically important

Specific Deformities

Hand Deformities:

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

Foot Deformities:

1. Foot drop (common peroneal nerve palsy)
2. Claw toes (posterior tibial nerve palsy)
3. Plantar ulcers (trophic ulcers) - on pressure points (metatarsal heads)
4. Absorption of toes
5. Rocker-bottom foot (Charcot neuropathy of midfoot)

Facial Deformities:

1. Saddle nose (destruction of nasal cartilage/bone in LL)
2. Facies leonina (leonine face: diffuse infiltration, thickening of facial skin)
3. Madarosis (loss of lateral eyebrows and eyelashes) - pathognomonic of LL
4. Lagophthalmos (facial nerve palsy)
5. Loss of ear lobule architecture

Eye Complications (Major cause of blindness):

1. Lagophthalmos → exposure keratitis
2. Uveitis (iridocyclitis) - in LL and during ENL - chronic, leads to cataract, glaucoma, blindness
3. Scleritis / episcleritis - during lepra reactions
4. Corneal anesthesia (trigeminal nerve)
5. Lepromatous infiltration of cornea - "fleshy" corneal infiltrates in LL

Other Deformities:

1. Gynecomastia + testicular atrophy - bacillary infiltration of testes (LL); leads to hypogonadism
2. Hoarse voice - laryngeal involvement
3. Nasal collapse - saddle nose
4. Anhidrosis - autonomic nerve involvement

Prevention of Disabilities (POD)

1. Early diagnosis and treatment with MDT - prevent nerve damage
2. Neuritis management - prompt prednisolone for reactions to arrest nerve damage
3. Rehabilitation - surgical correction, physiotherapy, special footwear

• Regular sensory testing (Semmes-Weinstein monofilaments)
• Eye care: lubricating drops, protective glasses, corrective surgery (tarsorrhaphy for lagophthalmos)
• Footwear: microcellular rubber (MCR) sandals to redistribute pressure
• Physiotherapy: prevent contractures, maintain muscle strength
• Reconstructive surgery: tendon transfers (e.g., Burkhalter's for claw hand, ECRB transfer for foot drop), arthrodesis

---

4. HIV Skin Manifestations

Introduction

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

Staging Correlation

• Primary HIV infection: Acute retroviral syndrome rash
• CD4 200-500: Mucocutaneous herpes, seborrheic dermatitis, oral hairy leukoplakia, tinea
• CD4 <200: Kaposi sarcoma, cryptococcosis, molluscum, extensive warts, CMV
• CD4 <50: Disseminated MAC, advanced Kaposi, CMV retinitis

---

A. Viral Infections

1. Herpes Simplex Virus (HSV)

• CD4 <200: chronic, ulcerative, non-healing perianal/genital/orolabial lesions
• Large, necrotic, painful ulcers (rather than typical grouped vesicles)
• Diagnostic pearl: Ulcer persisting >1 month = AIDS-defining illness
• Treatment: Acyclovir (400 mg TDS for 5-10 days); valacyclovir; suppressive therapy for recurrent cases

2. Herpes Zoster (VZV)

• Multi-dermatomal, bilateral, or disseminated zoster suggests HIV
• May occur at CD4 counts >200
• Complications: postherpetic neuralgia, dissemination, ophthalmic zoster
• Treatment: Acyclovir 800 mg 5x/day x 7-10 days; IV acyclovir for disseminated/ophthalmic

3. Molluscum Contagiosum

• Giant molluscum (>1 cm): pathognomonic of advanced HIV (CD4 <100)
• Disseminated, hundreds of lesions on face, neck, genitals
• Facial giant molluscum = common AIDS-defining presentation in Africa
• Atypical: may mimic histoplasmosis, cryptococcus (biopsy needed)
• Treatment: cryotherapy, curettage; responds to HAART

4. Human Papillomavirus (HPV) / Warts

• Extensive, recalcitrant, large warts (verruca vulgaris, condylomata acuminata)
• Oral warts (florid)
• High-grade anal/cervical dysplasia and invasive carcinoma in HIV
• Epidermodysplasia verruciformis-like eruptions with HPV 5, 8

5. Oral Hairy Leukoplakia (EBV)

• White corrugated plaques on lateral borders of tongue
• Cannot be scraped off (unlike oral candidiasis)
• EBV-driven; almost exclusive to HIV
• No treatment needed usually; responds to acyclovir; improves with HAART

6. Cytomegalovirus (CMV)

• CD4 <50
• Painful perianal ulcers, hemorrhagic skin lesions, ulcers in GIT
• Retinitis (most feared - blindness)
• Skin: ulcerative lesions at orifices

---

B. Bacterial Infections

1. Bacillary Angiomatosis (Bartonella henselae / quintana)

• AIDS-defining at CD4 <100
• Bright red, dome-shaped, friable vascular papules/nodules resembling Kaposi sarcoma or pyogenic granuloma
• Distinguish from KS: BA bleeds profusely when cut; seen in immunocompromised; responds to antibiotics
• Diagnosis: Warthin-Starry silver stain shows bacilli; PCR
• Treatment: Erythromycin or doxycycline x 8-12 weeks

2. Staphylococcal Infections

• Extensive folliculitis, furunculosis, ecthyma
• MRSA skin infections common
• Diffuse impetigo, cellulitis

3. Syphilis (Co-infection)

• Highly prevalent in MSM with HIV
• Lues maligna: ulceronecrotic syphilis with papules that break down - HIV-specific presentation
• Unusual presentations: noduloulcerative, psoriasiform; rapid progression to tertiary
• Treatment: Benzathine penicillin; may need prolonged courses; neurosyphilis more common

4. Mycobacterial infections

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

---

C. Fungal Infections

1. Oropharyngeal / Esophageal Candidiasis

• Most common HIV-associated mucosal infection
• Pseudomembranous (white plaques, scrape off leaving erythema) or erythematous
• Esophageal candidiasis = AIDS-defining (CD4 <100)
• Treatment: Fluconazole

2. Dermatophytoses (Tinea)

• Extensive, proximal, palmar, unusual-pattern tinea corporis/cruris/pedis
• Tinea faciei (unusual in immunocompetent)
• Proximal subungual onychomycosis (PSO): virtually diagnostic of HIV
  • Dermatophyte entering from proximal nail fold - opposite to usual pattern
• Treatment: Terbinafine, itraconazole; longer courses needed

3. Cryptococcus neoformans

• Disseminated cryptococcosis (CD4 <50)
• Skin: Umbilicated papules mimicking molluscum contagiosum
• Also: nodules, plaques, cellulitis-like
• Meningitis is the primary concern; skin lesion = marker of dissemination
• Diagnosis: India ink of CSF/skin biopsy
• Treatment: Amphotericin B + flucytosine → fluconazole maintenance

4. Histoplasma capsulatum

• Endemic in Americas, SE Asia
• Umbilicated papules, necrotic plaques, mimicking molluscum or cryptococcosis
• Treatment: Amphotericin B → itraconazole

5. Penicilliosis (Talaromyces marneffei)

• Bamboo rat-associated; endemic in Southeast Asia, NE India
• Umbilicated papules with necrotic centers on face and trunk - hallmark
• Fever, lymphadenopathy, hepatosplenomegaly
• Treatment: Amphotericin B → itraconazole

---

D. Parasitic / Ectoparasitic

1. Scabies

• Norwegian (Crusted) Scabies: CD4 <200
• Massive hyperkeratotic, crusted plaques on hands, feet, scalp, trunk
• Thousands to millions of mites (highly contagious - ward outbreaks)
• Pruritus may be absent due to immune deficit
• Treatment: Ivermectin (oral) + Permethrin; repeat doses needed

2. Demodex Folliculitis

• Demodex mite proliferation → pruritic folliculitis on face
• Responds to permethrin, azelaic acid

---

E. Inflammatory / Non-infectious Dermatoses

1. Seborrheic Dermatitis

• Most common inflammatory dermatosis in HIV (30-83%)
• Marker of disease progression
• Severe, widespread: nasiolabial folds, eyebrows, central chest, axillae, groin
• Pityrosporum ovale overgrowth
• Treatment: Ketoconazole shampoo/cream; hydrocortisone

2. Psoriasis

• New-onset psoriasis or dramatic worsening of pre-existing psoriasis
• Inverse pattern, erythrodermic, or pustular forms
• May be associated with psoriatic arthritis
• Treatment: Acitretin preferred (avoid immunosuppressants); HAART improves psoriasis

3. Eosinophilic Folliculitis (HIV-associated)

• Pruritic, sterile, eosinophilic folliculitis predominantly on upper trunk, face, scalp
• CD4 <200; intensely pruritic papules
• Treatment: Phototherapy (NB-UVB), antihistamines, itraconazole, permethrin

4. Prurigo Nodularis / Papular Pruritic Eruption (PPE)

• Papular pruritic eruption: WHO clinical stage 3 marker
• Symmetrical pruritic papules on extremities and trunk
• May represent hypersensitivity to insect bites
• Responds to HAART, antihistamines, phototherapy

5. Xerosis / Ichthyosis

• Generalized dry skin, acquired ichthyosis (CD4 <100)
• Emollients, keratolytics

---

F. Neoplasms

1. Kaposi Sarcoma (KS)

• Most common AIDS-defining malignancy
• Caused by HHV-8 (Human Herpesvirus 8 / KSHV)
• Classic features:
  • Violaceous/purple/brown patches, plaques, nodules
  • Begin on lower extremities (classic) or face/oral mucosa (AIDS-associated)
  • Non-blanching, non-tender
  • Oral KS: palate and gingiva - purple plaques
  • Visceral: GIT, lung (life-threatening)
• Histology: spindle cells, slit-like vascular spaces, extravasated RBCs, PAS+ hyaline globules
• Treatment: HAART (often leads to regression), local (cryotherapy, radiotherapy, intralesional vinblastine), systemic chemotherapy (liposomal doxorubicin, paclitaxel) for advanced/visceral KS

2. Non-Hodgkin's Lymphoma (NHL)

• Diffuse large B-cell lymphoma or Burkitt's
• Skin: violaceous nodules, ulcers
• Often EBV-driven

3. Squamous Cell Carcinoma / Anal Cancer

• HPV-driven; dramatically increased in HIV
• Anogenital, oropharyngeal SCC

---

G. Drug Reactions

• Stevens-Johnson Syndrome (SJS) / TEN especially with Cotrimoxazole (most common) and Nevirapine
• Morbilliform drug eruptions: very common with Cotrimoxazole, Efavirenz
• Nevirapine rash: >20% develop rash; Stevens-Johnson in severe cases
• Abacavir hypersensitivity: fever, rash, GI symptoms within first 6 weeks; HLA-B*5701 screening mandatory

H. Immune Reconstitution Inflammatory Syndrome (IRIS) - Skin

• Occurs 2-12 weeks after HAART initiation
• Paradoxical worsening of pre-existing infections or unmasking of new ones
• Zoster IRIS: severe, disseminated zoster after HAART
• KS IRIS: rapid increase in size/number of KS lesions after HAART
• Molluscum IRIS
• Leprosy IRIS: reversal reactions; new skin patches

---

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

Introduction

Etiology

• Chlamydia trachomatis serovars L1, L2, L2a, L2b, L3
• Obligate intracellular pathogen
• Two morphological forms: Elementary body (EB - infectious) and Reticulate body (RB - replicating intracellular)
• L serovars penetrate epithelium and infect regional lymphatics → systemic spread

Clinical Stages (Classical - Heterosexual Pattern)

Stage 1: Primary Lesion (Inoculation Stage)

• Appears 3-12 days after contact
• Small, transient, painless papule, vesicle, or shallow ulcer at site of inoculation
• Locations: glans, prepuce, posterior fourchette, vaginal wall, labia, cervix
• Disappears spontaneously in 3-5 days
• Often goes unnoticed (especially women)
• Urethritis or cervicitis may accompany

Stage 2: Inguinal/Femoral Lymphadenopathy (Bubo Stage)

• Appears 2-6 weeks after primary lesion
• Painful inguinal lymphadenopathy (bubo)
• Initially single, tender, discrete nodes → become matted, fluctuant
• Groove sign (Groove of Greenblatt): pathognomonic
  • Tender inguinal mass bisected by inguinal ligament (groove)
  • Due to simultaneous enlargement of inguinal AND femoral nodes on either side of the inguinal ligament
  • Present in ~20% of cases
• Buboes: unilateral in ~70%, bilateral in ~30%
• Overlying skin: red, hot, adherent → periadenitis
• Spontaneous rupture → single/multiple sinuses; sinus tracts discharge thick, yellowish pus
• Systemic features: fever, malaise, headache, arthralgias, hepatosplenomegaly
• Women: inguinal nodes less prominent; perirectal/pelvic lymph nodes more affected
• MSM: absent inguinal bubo; presents with proctitis/proctocolitis (anorectal LGV)

Stage 3: Genitoanorectal Syndrome (Esthiomene Stage)

• Late, untreated disease
• Esthiomene: chronic, indolent lymphedema/elephantiasis of genitalia
  • Female: swelling, ulceration, fibrosis of vulva/vagina → "saxophone penis" in men
• Rectal strictures (especially women, MSM): progressive fibrotic narrowing of rectum
• Fistulas: rectovaginal, rectovesical, perineal, ischiorectal fistulas
• Frozen pelvis from fibrotic lymphadenitis

Anorectal LGV (MSM Presentation)

• Proctitis/proctocolitis: tenesmus, rectal discharge (bloody/mucoid), rectal pain, constipation
• Mimics Crohn's disease clinically and histologically
• Rectal biopsy: granulomatous proctitis, crypt abscesses
• May present as rectal ulcers, rectal mass

Complications of LGV

Acute Complications:

1. Bubo rupture and sinus formation
2. Acute urethritis/cervicitis
3. Proctocolitis (especially MSM, women)
4. Perihepatitis (Fitz-Hugh-Curtis syndrome analogue)
5. Reactive arthritis (HLA-B27 positive patients)
6. Meningoencephalitis (rare)
7. Pneumonitis, pleuritis

Chronic/Late Complications:

1. Elephantiasis genitalis (Esthiomene): irreversible lymphedema; progressive vulvar/labial enlargement; "tapiroid" deformity of penis
2. Rectal strictures: fibrotic, circumferential narrowing of the rectum; may cause obstruction, tenesmus, constipation
3. Genital fistulas: rectovaginal, vesicovaginal, urethrorectal
4. Chronic sinuses of inguinal region
5. Carcinoma: rare - chronic LGV lesions may undergo malignant transformation (SCC)
6. Frozen pelvis
7. Lymphatic obstruction → chylous discharge, edema

Diagnosis

Clinical Diagnosis:

• Groove sign + bubo + history of STI exposure

Laboratory Diagnosis:

1. Frei's intradermal test (historical - no longer used; antigen withdrawn)
2. Complement Fixation Test (CFT): titer ≥1:64 suggestive; ≥1:128 diagnostic (genus-specific, not type-specific)
3. Microimmunofluorescence (MIF): species-specific; type-specific; most sensitive serological test; L serovar-specific antibodies
4. NAAT (PCR): Gold standard for definitive diagnosis; swab from bubo aspirate, rectal swab, urethral swab; OmpA typing distinguishes L1/L2/L3
5. Culture: C. trachomatis grown in McCoy/HeLa cells; technically demanding; not routinely done
6. Biopsy: granulomatous lymphadenitis; stellate abscess; not specific
7. Gram stain/smear: negative (to exclude gonorrhoea)

Key Differential Diagnoses:

• Chancroid (painful, multiple ulcers + bubo; H. ducreyi)
• Primary syphilis (painless ulcer; painless non-suppurating nodes)
• Donovanosis (painless, beafy red ulcer; no bubo)
• Inguinal hernia, filariasis (non-tender, reducible/chronic)
• Tuberculosis of lymph nodes
• Hodgkin's/NHL

Management of LGV

WHO / CDC Recommended Treatment:

Doxycycline 100 mg orally twice daily for 21 days (minimum 3 weeks)

• Erythromycin base 500 mg orally 4 times daily for 21 days
• Azithromycin 1 g orally once weekly for 3 weeks (data limited, convenience advantage)
• Tetracycline 500 mg QID x 21 days (alternative)

• Pregnancy: Erythromycin 500 mg QID x 21 days (doxycycline contraindicated)
• HIV co-infection: Same regimen but may require longer duration; close follow-up; higher rates of complications
• Macrolides (azithromycin) may be used

Management of Buboes:

• Needle aspiration through adjacent normal skin (not direct incision) - prevents fistula formation
• Aspiration preferred over incision and drainage (I&D may leave chronic sinus)
• Repeat aspiration if re-accumulation occurs
• Antibiotics alone can prevent fluctuant bubo progression if started early

Partner Notification and Treatment:

• All sexual contacts within 60 days prior to symptom onset should be evaluated and treated
• Treat partners even if asymptomatic: Doxycycline 100 mg BD x 7 days OR Azithromycin 1 g single dose
• Screen for other STIs: syphilis, gonorrhoea, HIV, hepatitis B/C

Management of Complications:

1. Rectal strictures: Gentle dilatation; surgery (stricturoplasty, colostomy for severe cases)
2. Elephantiasis/Esthiomene: Surgical reduction, lymphatic bypass procedures (limited success)
3. Fistulas: Surgical repair after infection controlled
4. Sinuses: Keep clean; antibiotics; surgical excision if persistent

Follow-up:

• Until complete resolution of clinical signs and symptoms
• Repeat STI screening at 3 months
• Test of cure: repeat NAAT 3 weeks after completion of therapy

Counseling:

• Safe sex practices; consistent condom use
• Abstain from sexual contact until treatment completed and symptoms resolved
• HIV testing and counseling

---

Summary Table: 5 Topics - High-Yield Points for Examination

---

What's Covered - Structure at a Glance

---

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.

---

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

---

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

---

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

---

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

---

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)

---

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

---

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

---

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

---

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

---

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

---

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

---

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)

---

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

---

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)

---

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

---

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

---

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

---

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:

---

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

---

Summary Table - High-Yield Exam Points