Quick Index

MD Dermatology — 3rd Year PG Theory Examination

Complete 10-Mark Answer Bank

A. PEMPHIGUS ERYTHEMATOSUS (PE) / SENEAR-USHER SYNDROME

Definition

Epidemiology

• Rare; occurs in adults; no sex predilection
• Drug-induced cases: penicillamine, captopril, propranolol, cefuroxime, heroin
• Reported association with myasthenia gravis and thymoma

Etiopathogenesis

• Autoantibodies: Anti-desmoglein 1 (Dsg1) - same as pemphigus foliaceus; anti-Dsg3 absent
• Additional autoantibodies may target BP230 (bullous pemphigoid antigen 1) and periplakin
• Antinuclear antibody (ANA) positive in ~30% of patients at low titers
• UV light triggers disease by upregulating Dsg1 expression and exposing autoantigens
• Overlap mechanism: IgG autoantibodies cause acantholysis in the subcorneal layer (PF pattern) + immune complex deposition at DEJ (LE pattern)
• HLA associations: HLA-DR4, HLA-DR14 (similar to LE)

Clinical Features

• Sites: Seborrheic/photo-exposed areas - nose, malar cheeks, ears (butterfly distribution), scalp, chest, upper back - resembling SLE/seborrheic dermatitis
• Lesions: Erythematous, thickly crusted plaques; may be bullous, vesicular, or hyperkeratotic
• Classic description: "Impetiginous lesions amid bullae on the scalp, chest and extremities"
• Nikolsky sign: Positive (lateral pressure → new blister)
• Mucous membrane involvement: typically ABSENT (as in PF)
• Systemic features: generally absent; course is indolent/benign compared to PV
• Pruritus variable; burning sensation common
• May worsen with UV exposure (photosensitive component)

Histopathology

• Same as pemphigus foliaceus:
  • Subcorneal/superficial intraepidermal acantholysis
  • Sparse inflammatory infiltrate
  • Eosinophilic spongiosis

Immunofluorescence (Hallmark)

• DIF (Diagnostic): IgG + C3 at TWO sites:
  1. Intercellular spaces of epidermis (pemphigus pattern - "chicken wire")
  2. DEJ - continuous granular deposits (lupus band pattern)
• IIF: Anti-intercellular antibody positive (as in PF); anti-BMZ negative
• Serology: ANA positive (low titer) in 30%; anti-dsDNA usually negative

Investigations

• DIF (key diagnostic test)
• IIF on monkey esophagus
• ELISA for anti-Dsg1 antibodies (positive; anti-Dsg3 negative)
• ANA, anti-dsDNA, complement levels
• Evaluate for underlying systemic lupus features

Differential Diagnosis

Treatment

1. Photoprotection: Strict sun avoidance + broad-spectrum SPF ≥50 (essential - reduces UV-triggered flares)
2. Topical corticosteroids: High potency (clobetasol) - often sufficient in mild cases
3. Systemic corticosteroids: Prednisolone 0.5–1 mg/kg/day if widespread; usually lower doses required than in PV
4. Immunosuppressants (steroid-sparing): Azathioprine 1–2 mg/kg/day; mycophenolate mofetil 2 g/day
5. Hydroxychloroquine: For lupus overlap component (200–400 mg/day)
6. Drug-induced PE: Withdraw offending drug; may resolve spontaneously

Prognosis

B. SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUS (SCLE)

Definition

Epidemiology

• Women > Men (approximately 3:1); Caucasians predominant
• Peak onset: 3rd–5th decade
• Accounts for ~10% of all LE patients

Etiopathogenesis

• Genetic susceptibility: HLA-DR3, HLA-B8, HLA-DQ2 (strongest HLA associations in LE)
• Central autoantibody: Anti-Ro/SSA (70–100%); Anti-La/SSB (30–40%)
• UV radiation → Ro/SSA antigen expression on keratinocyte surface → antibody-mediated complement activation + CD4+ cytotoxic T-cell attack → vacuolar interface dermatitis
• Drug-induced SCLE (important): ~33% of SCLE is drug-induced
  • Most common: terbinafine (most frequently identified in Swedish population study)
  • Others: TNF-α inhibitors, anti-epileptics, proton pump inhibitors (omeprazole), hydrochlorothiazide, CCBs, checkpoint inhibitors (pembrolizumab, nivolumab), ACE inhibitors
  • Cutaneous lesions may or may not clear after drug discontinuation

Clinical Features

1. Papulosquamous (psoriasiform) type (~50%): Scaly erythematous papules/plaques resembling psoriasis or eczema
2. Annular/polycyclic type (~50%): Annular lesions with raised erythematous borders, central clearing, fine scaling at periphery; may coalesce into polycyclic arcs

• Upper back, V of neck, shoulders, lateral aspects of face
• Midface characteristically SPARED (in contrast to DLE which prominently involves the nose/cheeks)
• Extensor upper extremities

• No scarring (hallmark)
• No follicular plugging
• No dermal atrophy
• Dyspigmentation (especially hypopigmentation) may occur as sequela

• Arthralgia/arthritis (~50%)
• Sicca symptoms (Sjögren's overlap)
• Serositis (pleuritis, pericarditis) - minority
• Renal involvement: <10% (contrast with SLE where >50%)
• ~10–15% fulfill ACR criteria for SLE

Investigations

• Anti-Ro/SSA: 70–100% (hallmark antibody)
• Anti-La/SSB: 30–40%
• ANA: Positive in 60–80% (low to moderate titer, speckled/cytoplasmic pattern)
• Anti-dsDNA: Negative or low titer (usually negative)
• Histopathology:
  • Interface dermatitis - vacuolar type (basal vacuolation)
  • Superficial perivascular lymphocytic infiltrate
  • Epidermal atrophy, melanin incontinence
  • Absent: follicular plugging, dermal mucin, scarring (all absent - differentiates from DLE)
• DIF: Lupus band (IgG, IgM, C3 at DEJ) in ~60%; less reliable than in DLE
• CBC (lymphopenia, anemia), urinalysis, complement (C3, C4), anti-dsDNA, ANA profile

Treatment

1. Photoprotection (cornerstone): Broad-spectrum SPF ≥50 applied daily; avoid UV-A/B; protective clothing
2. Topical: Potent corticosteroids; tacrolimus/pimecrolimus (for face; steroid-sparing)
3. Antimalarials (first-line systemic):
   • Hydroxychloroquine 200–400 mg/day (6.5 mg/kg/day max)
   • Add quinacrine 100 mg/day if inadequate response (combination)
4. Second-line:
   • Dapsone 50–100 mg/day
   • Thalidomide 50–100 mg/day (effective but teratogenic)
   • Acitretin/isotretinoin
5. Third-line/refractory:
   • Methotrexate 7.5–15 mg/week
   • Mycophenolate mofetil 1–3 g/day
   • Belimumab (anti-BLyS/BAFF monoclonal antibody)
6. Drug-induced SCLE: Withdraw causative drug; monitor for resolution

Prognosis

C. DRESS SYNDROME (Drug Reaction with Eosinophilia and Systemic Symptoms)

Definition

Epidemiology

• Incidence: 1/1000 to 1/10,000 drug exposures (for high-risk drugs)
• No strong sex predilection; all ages

Etiopathogenesis

• Genetic polymorphisms affecting drug detoxification - e.g., inability to detoxify toxic arene oxide metabolites of aromatic anticonvulsants (phenytoin, carbamazepine, phenobarbital) → reactive metabolite accumulation → immune activation
• Explains cross-reactivity between aromatic anticonvulsants

• HLA allele associations (drug-specific):
  • HLA-B*58:01 → allopurinol (Han Chinese, Thai, Korean)
  • HLA-B*57:01 → abacavir
  • HLA-A*31:01 → carbamazepine (European)
  • HLA-B*13:01 → dapsone (Chinese)
• IL-5 drives eosinophilia; drug-specific T cells activated in skin/internal organs

• Sequential herpesvirus reactivation is a hallmark:
  • HHV-6 most consistently implicated (~70% of DRESS); transmitted to skin-infiltrating CD4+ T cells
  • Also HHV-7, EBV, CMV
  • EBV-transformed B cells produce EBV when triggered by culprit drugs

• Aromatic anticonvulsants: carbamazepine, phenytoin, phenobarbital, lamotrigine
• Allopurinol (most common overall cause)
• Sulfonamides (cotrimoxazole, sulfasalazine)
• Dapsone (antibiotic + antileprotic)
• Abacavir, nevirapine (antiretrovirals)
• Minocycline, vancomycin, mexiletine, strontium ranelate

Clinical Features

• Onset: 2–8 weeks after drug initiation (long latency - key differentiator)
• Fever: High-grade (>38.5°C), early, often before rash

• Begins as morbilliform exanthem on face and upper trunk → spreads caudally
• Progresses to edematous, confluent, extensive eruption ± erythroderma
• Facial edema (periorbital, perioral) - HALLMARK of DRESS (distinguishes from other drug reactions)
• Less common: vesicles, follicular/non-follicular pustules (~20%, overlap with AGEP), purpuric lesions
• Mucosal involvement: mild if present (unlike SJS/TEN where mucosal ulceration is prominent)

• Lymphadenopathy: Generalized, tender (hepatic and lymph node involvement most common)
• Hepatitis (~80%): Most common and potentially life-threatening organ involvement; elevated ALT >100 U/L; may progress to fulminant hepatic failure
• Renal: Interstitial nephritis
• Pulmonary: Interstitial pneumonitis, ARDS
• Cardiac: Myocarditis (associated especially with carbamazepine, dapsone)
• Thyroid: Autoimmune thyroiditis - delayed manifestation occurring up to 2 years after DRESS (critical long-term monitoring point)
• Hematophagocytic lymphohistiocytosis (HLH): Rare but life-threatening complication

Diagnostic Criteria

• Fever >38.5°C
• Enlarged lymph nodes ≥2 sites
• Atypical lymphocytes
• Eosinophilia (≥700/mm³ or ≥10%)
• Skin rash >50% BSA + ≥2 skin features (edema, infiltration, purpura, desquamation)
• Organ involvement (liver, kidney, lung, heart, others)
• Resolution >15 days
• Exclusion of alternative diagnoses

1. Maculopapular rash >3 weeks after drug initiation
2. Prolonged symptoms after drug discontinuation
3. Fever >38°C
4. Liver abnormalities (ALT >100 U/L) or other organ involvement
5. Leukocyte abnormality (leukocytosis, atypical lymphocytes >5%, or eosinophilia >1.5×10⁹/L)
6. Lymphadenopathy
7. HHV-6 reactivation

Investigations

• CBC: eosinophilia, atypical lymphocytes, leukocytosis
• LFT, RFT, troponin (cardiac)
• HHV-6 IgM/PCR (serum, skin)
• Skin biopsy: interface dermatitis, superficial dermal edema, atypical lymphocytes, eosinophilic infiltrate
• Serial TSH/T4 at 3, 6, 12, 24 months (thyroid monitoring)

Treatment

1. Immediate drug withdrawal - most important step
2. Systemic corticosteroids (first-line):
   • Prednisolone 1 mg/kg/day
   • SLOW taper over 3–6 months (rapid taper causes rebound/flare - critical exam point)
   • IV methylprednisolone pulses for severe organ involvement (hepatitis, myocarditis)
3. IVIG (1–2 g/kg) for steroid-refractory cases or HLH
4. Cyclosporine 3–5 mg/kg/day for refractory cases
5. Antihistamines + emollients for symptom control
6. Long-term monitoring: Thyroid function every 3–6 months for 2 years
7. Cross-reactive drugs: Avoid entire class (all aromatic anticonvulsants cross-react); provide a drug alert card

Prognosis

D. MYCETOMA (Madura Foot / Maduromycosis)

Definition

1. Tumefaction (swelling/induration)
2. Draining sinuses
3. Grains (aggregates of causative organisms discharged from sinuses)

Classification

Epidemiology

• "Mycetoma Belt": 15°N–30°S latitude (Sudan, India, Mexico, Somalia, Yemen, Senegal)
• India: Madurella mycetomatis (eumycetoma) in south; Nocardia and Actinomadura (actinomycetoma) more common
• Predominantly males, outdoor workers (farmers, laborers), age 20–40 years
• Mode of infection: Penetrating injury by thorns, splinters (Acacia thorn - a vector); causative organisms are soil/plant saprophytes

Etiopathogenesis

• Organisms inoculated subcutaneously via penetrating trauma
• No underlying immunodeficiency required (unlike opportunistic fungi)
• Evasion of host defenses: Cell wall thickening and melanin deposition (in dark-grain fungi) prevent phagocytosis
• Organisms form grains within abscess cavities - protective aggregates
• Spreads by direct contiguous extension through fascial planes → involves muscle, tendon, bone
• Distant metastasis: exceptionally rare
• Results in chronic suppurative granulomatous inflammation → fibrosis → bone destruction

Clinical Features

1. Tumefaction: Firm to brawny swelling, progressive enlargement; initially painless
2. Draining sinuses: Multiple, open on skin surface; discharge seropurulent fluid + grains
3. Grains: Key pathognomonic feature - visible to naked eye in discharge

• Early: Firm, painless, subcutaneous nodule at site of inoculation
• Progressive: Papules, plaques; multiple draining sinus tracts; "peppered" surface appearance
• Advanced: Massive deformity, bone involvement (periosteal erosion, lytic lesions), destroyed joint architecture

• Foot/lower leg: most common (60-70%) - "Madura foot"
• Hand
• Back/chest wall (characteristic of Nocardia)
• Head and neck (unusual)

• Black/dark grains → ALWAYS fungi (e.g., Madurella mycetomatis)
• Red/pink grains → ALWAYS actinomycetes (e.g., Actinomadura pelletieri)
• White/pale grains → EITHER fungi OR actinomycetes (e.g., A. madurae = actino; Scedosporium, Fusarium = fungi)

Investigations

• Obtained from sinus discharge, squeezing sinus edges, or curettage
• Grains: 250–1000 μm, visible with naked eye
• KOH mount: Shows broad fungal hyphae (eumycetoma) vs. fine filaments (actinomycetoma - hard to see in KOH)

• Chronic suppurative granulomatous inflammation
• Neutrophil abscesses + scattered giant cells + fibrosis
• Grains in center of inflammation
• PAS and GMS (Grocott-Gomori) stains highlight fungal elements
• Gram stain/Fite stain for actinomycetes

• Multiple media: Sabouraud's dextrose agar, blood agar
• Morphologic + physiologic characteristics for species ID
• Molecular PCR for definitive identification

• X-ray: Periosteal erosion and proliferation, lytic lesions ("soap bubble" pattern), bone sclerosis
• MRI/CT: Detects soft tissue extent and bone involvement at early stage; "dot-in-circle" sign on MRI (grains surrounded by fibrous capsule - highly specific for mycetoma)
• USG: Hyperechoic dots (grains) within hypoechoic lesion

Differential Diagnosis

• Chronic osteomyelitis (bacterial or tuberculous)
• Actinomycosis (commensal sites - mouth, cecum)
• Botryomycosis (staphylococcal soft tissue infection with granules)
• Chromoblastomycosis (verrucous, no sinuses, no bone involvement, sclerotic bodies)
• Cutaneous TB, deep fungal infections

Treatment

• First-line: Dapsone 100 mg BD + streptomycin 14 mg/kg/day IM (Destombes-Mariat regimen) in 4-week cycles with 4-week rest periods
• Alternative: Cotrimoxazole (TMP-SMX) + rifampicin + streptomycin
• For Nocardia: Amikacin + imipenem; moxifloxacin for recalcitrant cases
• Treatment duration: months to years; outcomes generally good

• Itraconazole 400 mg/day (first-line; most studied)
• Voriconazole 200–400 mg/day (for resistant/unresponsive cases)
• Ketoconazole 200–400 mg/day
• Terbinafine: worth attempting
• Treatment response unpredictable; may slow progression but rarely curative with antifungals alone

• Wide surgical excision (with antifungal coverage) for localized eumycetoma
• Amputation may be necessary for advanced cases with massive bone destruction
• Early surgical intervention with drug cover gives best results
• Surgery alone has very high recurrence

Prognosis

E. LEG ULCERS — Causes, Etiopathogenesis, and Management of Venous Leg Ulcers

Definition

Causes of Leg Ulcers

Venous Leg Ulcers — Etiopathogenesis

1. Primary valve incompetence of saphenous veins (superficial)
2. Incompetence of perforating veins (Cockett perforators at medial gaiter region)
3. Deep vein incompetence or obstruction (post-DVT, primary valvular insufficiency)

• Dilated, incompetent veins → venous pooling → fluid transudation → edema

1. Fibrin cuff theory (Browse & Burnand, 1982):
   • Venous hypertension → increased capillary pressure → pericapillary fibrin deposition ("fibrin cuffs") → acts as barrier to oxygen and nutrient diffusion → tissue ischemia and necrosis
   • Not entirely confirmed
2. White cell trapping theory (Thomas et al.):
   • Venous hypertension → leukocyte (neutrophil) margination and trapping in capillaries → leukocyte activation → release of proteolytic enzymes (MMPs) + reactive oxygen species → endothelial damage + free radical-mediated tissue damage
   • Increased mast cells, monocytes, lymphocytes found in peri-ulcer tissue
3. Growth factor "trap" theory:
   • Plasma proteins (fibrin, albumin, alpha-2-macroglobulin) leak into tissues → "trap" growth factors (TGF-β, PDGF) → growth factors unavailable for wound healing → impaired repair
4. Senescent fibroblasts:
   • Fibroblasts in ulcer surrounds are in a "senescent" (non-proliferating) state → impaired healing
   • Proteolytic enzymes (MMPs) raised → degrade extracellular matrix
5. Haemosiderin toxicity:
   • RBC extravasation → haemosiderin deposition → brown pigmentation (lipodermatosclerosis/LDS pattern)
   • Haemosiderin itself may be directly injurious to tissue

Clinical Features of Venous Leg Ulcers

• Location: Medial gaiter region (between calf muscles and ankle); medial malleolus most common site (Cockett perforators)
• Morphology: Shallow, irregularly shaped ulcer with gently sloping edges; floor contains pink granulation tissue + variable slough + exudate; not punched-out (contrast with arterial ulcers)
• Surrounding skin: Haemosiderosis (brown pigmentation), lipodermatosclerosis (LDS) - thickening/induration/fibrosis of calf skin ("inverted champagne bottle" appearance), varicose eczema (varicose dermatitis)
• Symptoms: Aching, heaviness; mild pruritus before ulcer formation; ulcers often relatively painless (compare with arterial ulcers which are severely painful)
• Raised ulcer edge → biopsy to exclude Marjolin's ulcer (squamous cell carcinoma in chronic venous ulcer)
• Varicose veins may or may not be present

Investigations

1. Ankle-Brachial Pressure Index (ABPI): All new ulcers; ABPI ≥0.9 = adequate perfusion (venous); ABPI 0.5–0.8 = mixed; ABPI <0.5 = critical ischaemia (compression contraindicated)
2. Duplex ultrasound: Assess deep and superficial venous reflux, perforator incompetence; also excludes deep vein thrombosis
3. Biopsy: For non-healing or atypical ulcers to exclude carcinoma
4. Blood tests: CBC, glucose, HbA1c, ESR/CRP, ANA, ANCAs, ANCA (vasculitis workup), sickle cell test if applicable
5. Bacterial swab: Only if clinically infected (routine swabbing unhelpful)

Management of Venous Leg Ulcers

• Reduces venous hypertension - the pathological basis
• Ideal interface pressure for pure venous ulcer: 35–40 mmHg
• Multi-layer compression bandaging (4-layer - Charing Cross regimen):
  1. Layer 1 - Orthopaedic wool: distributes pressure, absorbs exudate, protects bony prominences
  2. Layer 2 - Cotton crepe: smooths wool, holds in place
  3. Layer 3 - Elastic bandage: first compressive layer (~1/3 of pressure)
  4. Layer 4 - Cohesive bandage: second compressive layer (~2/3 of pressure)
• Two-layer compression hosiery: Equally cost-effective
• Mixed ulcers (ABPI 0.5–0.8): Modified compression at 30 mmHg is safe and effective with monitoring
• Contraindicated: ABPI <0.5 (critical limb ischaemia)

• Debridement: Mechanical (sharp), autolytic (hydrogels), enzymatic (collagenase), larval (maggot) therapy for sloughy wounds
• Dressings: Non-adherent; choice based on exudate level:
  • Low exudate: hydrocolloid, hydrogel
  • High exudate: alginate, foam dressings
  • Infected ulcer: silver-containing dressings (Ag+), iodine dressings
• Antimicrobials: Only if clinically infected; avoid routine antibiotics (promotes resistance)

• Treatment of superficial venous incompetence accelerates healing and reduces recurrence
• Expeditious vascular surgery referral recommended
• Options: Endovenous laser ablation (EVLA), radiofrequency ablation (RFA), foam sclerotherapy, conventional surgery (Trendelenburg/SAPHENA procedures)
• Early Venous Reflux in Non-Healing Leg Ulcers (EVRA trial): Early intervention group had faster healing and fewer recurrences

• Oxpentifylline (pentoxifylline) 400 mg TDS: Improves microvascular circulation; enhances healing when added to compression (Cochrane evidence)
• Aspirin 300 mg/day: May improve healing by reducing platelet aggregation
• Zinc supplementation (if deficient)
• Treat underlying conditions: Anaemia, hyperglycaemia, rheumatoid arthritis

• Split-thickness skin grafting (STSG): For large, non-healing ulcers
• Pinch grafting: Simple OPD technique for smaller ulcers
• Provides immediate wound cover; stimulates healing

• Compression hosiery (23–32 mmHg): Life-long use; most important for preventing recurrence
• Leg elevation at rest (above heart level)
• Regular walking and calf muscle exercise (enhances venous pump)
• Weight reduction in obese patients
• Treat underlying venous disease

F. MYCETOMA (Detailed/Repeat — see Topic D above for complete answer)

Quick Structured 10-Mark Framework for Mycetoma:

• Eumycetoma: Madurella mycetomatis (most common globally, dark grains), Scedosporium apiospermum (pale, temperate)
• Actinomycetoma: Nocardia brasiliensis (Central America), Actinomadura madurae, Streptomyces somaliensis (Sudan)

• Triad: tumefaction + sinuses + grains
• Black grains = always fungi; red = always actinomycetes; white = either
• Stages: painless nodule → draining sinuses → bone destruction + deformity
• Foot (60%) most common; chest = Nocardia

• KOH of grains; culture on Sabouraud's
• Histopathology: suppurative granulomatous inflammation; PAS/GMS stain; grains in center of abscesses
• X-ray: periosteal erosion, lytic lesions
• MRI: "dot-in-circle" sign (pathognomonic)

• Actinomycetoma: dapsone + streptomycin (Destombes-Mariat); co-trimoxazole + rifampicin; good prognosis
• Eumycetoma: itraconazole/voriconazole; surgery for localized; amputation for advanced; poor response
• Topical antifungals ineffective (deep infection)

Quick Reference Summary Table

High-yield exam points:

• PE: "Both ICS AND DEJ positive on DIF" - the only pemphigus with lupus band
• SCLE: terbinafine is now the most common drug cause (not hydrochlorothiazide)
• DRESS: 3-6 month steroid taper mandatory; thyroid monitoring for 2 years post-DRESS
• Mycetoma: black grains = always fungi; red grains = always actinomycetes; topical antifungals useless
• Venous ulcer: ABPI mandatory before compression; 4-layer bandage = 35-40 mmHg; early venous ablation reduces recurrence