Systemic Lupus Erythematosus (SLE)

Definition

Epidemiology

• Prevalence ~1 in 2500 in some populations
• Female predominance: F:M = 9:1 in reproductive age (17–55 years); 2:1 in childhood and post-65
• More prevalent/severe in African, Hispanic, and Asian individuals
• Peak onset: 20s–30s

Etiology & Pathogenesis

Autoantibodies — The Hallmark

Pathogenetic Mechanisms

1. Genetic factors: HLA-DR2, HLA-DR3 associations; defects in complement genes (C1q, C2, C4) → impaired clearance of apoptotic cells/immune complexes
2. Defective clearance of apoptotic cells → persistence of nuclear antigens (dsDNA, histones, ribonucleoproteins) → stimulate autoreactive B and T lymphocytes
3. TLR dysregulation: Self nucleic acids engage Toll-like receptors (TLR7, TLR9) on B cells and dendritic cells → overproduction of Type I interferons (IFN-α) → amplify autoimmune response
4. Environmental triggers: UV light induces apoptosis + enhances DNA immunogenicity; drugs (hydralazine, procainamide, isoniazid)
5. Sex hormones: Estrogen promotes disease (explains female dominance)

Tissue Injury — Mechanisms

• Type III hypersensitivity (immune complex deposition) — responsible for most systemic lesions: glomerulonephritis, vasculitis, serositis
• Type II hypersensitivity — autoantibodies against RBCs, platelets, neutrophils → hemolytic anemia, thrombocytopenia, leukopenia

LE Cell & Hematoxylin Bodies

• LE body (hematoxylin body): Nuclear material of damaged cells reacted with ANAs → loses chromatin pattern, becomes homogeneous, stains with hematoxylin
• LE cell: A phagocytic neutrophil/monocyte that has engulfed a denatured nucleus (LE body) — historically used as a diagnostic test, now superseded by ANA testing

Morphology (Organ Lesions)

1. Kidney (most important — lupus nephritis)

• Glomerular changes — classified by WHO/ISN-RPS (Class I–VI):
  • Class I: Minimal mesangial LN
  • Class II: Mesangial proliferative LN
  • Class III: Focal LN (<50% glomeruli)
  • Class IV: Diffuse LN (>50% glomeruli) — most common and severe; "wire loop" lesions on LM; granular (lumpy-bumpy) deposits on IF; subendothelial deposits on EM
  • Class V: Membranous LN
  • Class VI: Advanced sclerosing LN
• Wire-loop lesion: Thickened glomerular capillary walls due to massive subendothelial immune complex deposition

2. Skin

• Butterfly (malar) rash over nose and cheeks
• Photosensitivity
• Discoid lupus: Erythematous patches with follicular plugging
• Histology: Liquefaction degeneration of basal layer, edema, mononuclear infiltrate; IF → immunoglobulin + complement deposition at dermoepidermal junction ("lupus band test" — positive even in uninvolved skin)

3. Joints

• Non-erosive synovitis; no pannus formation (unlike RA)

4. Heart

• Libman-Sacks endocarditis: Small, sterile, warty vegetations on both surfaces of the mitral valve (pathognomonic); caused by immune complex deposition
• Pericarditis (most common cardiac manifestation)
• Myocarditis

5. Blood Vessels

• Acute necrotizing vasculitis; perivascular fibrosis ("onion-skin lesion") in the spleen — periarteriolar fibrosis

6. Serosal Surfaces

• Fibrinous pleuritis, pericarditis, peritonitis (serositis)

7. Lungs

• Pleuritis, diffuse alveolar damage

8. CNS

• Microinfarcts, cerebritis (due to vasculitis and antineuronal antibodies)

9. Blood

• Hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia

Clinical Features (ACR/SLICC Criteria Mnemonic: DOPAMINE RASH)

Antiphospholipid Syndrome in SLE

Drug-Induced Lupus

• Drugs: Hydralazine, Procainamide, Isoniazid, D-penicillamine, Anti-TNF agents
• Key difference from classic SLE:
  • Anti-histone antibodies (not anti-dsDNA)
  • Renal and CNS involvement uncommon
  • Resolves on stopping the drug

Laboratory Diagnosis

Prognosis

• 10-year survival >90% with treatment
• Main causes of death: Renal failure, infections (from immunosuppression), cardiovascular disease (accelerated atherosclerosis)
• Disease activity monitored by anti-dsDNA titers and complement levels

Primary Tuberculosis

Definition

Pathogenesis

Step-by-Step Sequence

Inhalation of M. tuberculosis droplet nuclei
            ↓
Bacilli deposit in distal alveoli (lower upper lobe / upper lower lobe)
            ↓
Phagocytosed by alveolar macrophages → bacilli survive & multiply inside
(escape killing via inhibition of phagolysosome fusion)
            ↓
Macrophages carry bacilli via lymphatics → hilar/tracheobronchial LN
(Bacteremia may occur → seeding of liver, spleen, kidneys, meninges, bone)
            ↓
~ 3–8 weeks: Cell-mediated immunity (CMI) develops
Th1 cells activated → secrete IFN-γ
            ↓
IFN-γ activates macrophages → produce:
 • Reactive nitrogen intermediates (NO)
 • TNF → recruits more macrophages
            ↓
Activated macrophages transform into EPITHELIOID CELLS
+ Fuse to form LANGHANS GIANT CELLS
→ GRANULOMA formation (TUBERCLE)
            ↓
Central CASEOUS NECROSIS develops
(due to DTH — Type IV hypersensitivity)
            ↓
95% → Fibrosis + Calcification → GHON COMPLEX → RANKE COMPLEX
5% → Progressive primary TB (in immunocompromised)

Key Immune Mechanisms

Loss of tuberculin positivity (anergy) = ominous sign of failing immunity and severe disease.

Common Sites

Primary TB — Site of Implantation

Sites of Hematogenous Seeding (during primary bacteremia)

• Apices of lungs (Simon foci)
• Liver, spleen
• Kidneys
• Vertebrae (Pott's disease potential)
• Meninges
• Adrenal glands
• Epididymis/fallopian tubes

Primary Complex (Ghon Complex)

┌─────────────────────────────────────────────────────────────┐
│                   GHON COMPLEX                              │
│                                                             │
│  1. GHON FOCUS (Ghon's focus / Primary focus)              │
│     • 1–1.5 cm gray-white area of consolidation            │
│     • In lung parenchyma (subpleural)                       │
│     • Center = caseous necrosis                             │
│                                                             │
│  2. LYMPHANGITIS                                            │
│     • Lymphatic vessel inflammation                         │
│     • Connects Ghon focus to hilar nodes                    │
│                                                             │
│  3. HILAR / TRACHEOBRONCHIAL LYMPHADENOPATHY               │
│     • Draining lymph nodes enlarged + caseous               │
│     • Often larger than the Ghon focus itself               │
└─────────────────────────────────────────────────────────────┘

Ranke Complex = Calcified Ghon Complex (seen on chest X-ray as calcified parenchymal nodule + calcified hilar node)

Schematic Diagram — Evolution of the Tubercle

Evolution of the Tubercle — Detailed Description

Stage 1: Non-specific Pneumonia

• Bacilli inhaled → alveolar exudate
• PMNs + macrophages → non-specific acute inflammation
• No granuloma yet

Stage 2: Epithelioid Cell Granuloma (Early Tubercle)

• Macrophages activated by IFN-γ → transform into epithelioid cells (elongated, pale, abundant cytoplasm)
• Multiple epithelioid cells fuse → Langhans giant cells (nuclei arranged in horseshoe/peripheral pattern)
• Surrounded by a rim of lymphocytes
• No necrosis yet → non-caseating granuloma

Stage 3: Caseating Granuloma (Classic Tubercle)

• Central caseous necrosis develops (firm, cheesy material — coagulative necrosis with cell outlines lost)
• Caused by DTH (Type IV hypersensitivity) to mycobacterial antigens
• Structure from inside out:

  Central caseous necrosis
       ↓ surrounded by
  Epithelioid cells + Langhans giant cells
       ↓ surrounded by
  Lymphocytes + plasma cells
       ↓ surrounded by
  Fibroblasts (outer collar)
  

• Tubercle = the characteristic granuloma of TB

Stage 4: Fate / Evolution

              CASEATING TUBERCLE
                     │
         ┌───────────┴───────────┐
         ▼                       ▼
   HEALING (95%)           PROGRESSION (5%)
         │                       │
  Fibrosis → Calcification   Liquefaction of caseous centre
  (Fibro-calcific nodule)         │
  Ranke complex on X-ray    ┌────┴────┐
                            ▼         ▼
                         CAVITY    Spread
                    (Thick fibrous   • Bronchogenic
                      wall; air       spread
                      crescent       • Miliary TB
                      sign)          • Lymphatic
                                     • Hematogenous

Radiological Correlates

Key Exam Points (Harsh Mohan Emphasis)