Infection Timeline Post-BMT

Phase I: Pre-engraftment (0-30 days)

• Earliest infection: Herpes Simplex Virus (HSV)
• Other pathogens: Bacteria, Candida, Aspergillus
• Risk factors: Neutropenia, mucositis, central lines

Phase II: Early post-engraftment (30-100 days)

• ~7th week (50 days): Interstitial Pneumonitis peak incidence
• Causes: CMV, Pneumocystis jirovecii, idiopathic
• GVHD: Acute graft-versus-host disease peak

Phase III: Late post-engraftment (>100 days)

• Chronic GVHD: Major concern
• Encapsulated bacteria: Due to functional asplenia
• Varicella-zoster virus: Reactivation common

Specific Infectious Complications

CMV Disease

• Timeline: 30-100 days post-BMT
• High risk: CMV+ recipient or donor
• Manifestations: Pneumonitis, gastroenteritis, retinitis

Interstitial Pneumonitis (IP)

• Peak incidence: ~7th week (50 days) post-BMT
• Types:
  • CMV pneumonitis (most common infectious cause)
  • Idiopathic IP
  • Pneumocystis pneumonia
• Mortality: High, especially CMV pneumonitis

Prophylactic Strategies

• Antibacterial: Fluoroquinolones
• Antifungal: Fluconazole or newer azoles
• Antiviral: Acyclovir for HSV/VZV
• PCP prophylaxis: Trimethoprim-sulfamethoxazole
• CMV monitoring: Pre-emptive therapy based on viral load

GVHD Prevention

• Immunosuppression: Methotrexate + calcineurin inhibitors
• T-cell depletion: In some protocols
• HLA matching: Reduces risk significantly

Stage I: Initial Lesion

• Cellular Infiltrate: Polymorphonuclear neutrophils (PMNs) present
• Timeframe: Develops within 2-4 days of plaque accumulation
• Characteristics: Subclinical changes, increased vascular permeability

Stage III: Established Lesion

• Duration: Develops after 2-3 weeks of continuous plaque exposure
• Cellular Changes: Plasma cell dominance, collagen destruction
• Clinical Features: Frank gingivitis with erythema, edema, and bleeding on probing

ANUG (Acute Necrotizing Ulcerative Gingivitis)

Microbiology

• Primary Organisms: Spirochetes and Prevotella species
• Pathogenesis: Opportunistic infection in compromised host defense

Demographics

• Primary Population: Young adults (20-30 years)
• Risk Factors: Stress, smoking, malnutrition, immunocompromise

Clinical Presentation

• Pathognomonic Sign: Crater-like depressions on interdental papilla
• Additional Features: Spontaneous bleeding, halitosis, lymphadenopathy
• Pain: Severe, spontaneous gingival pain

Staging System (7 Stages)

1. Stages 1-2: Necrotizing Ulcerative Gingivitis (NUG)
2. Stages 3-4: Necrotizing Ulcerative Periodontitis (NUP)
3. Stages 5-6: Necrotizing Stomatitis
4. Stage 7: Noma (cancrum oris) - life-threatening condition

Progression from Gingivitis to Periodontitis

The transition from gingivitis to periodontitis is a critical process in periodontal disease progression. This lecture will outline the key stages involved in this progression, highlighting the changes in microbial composition, host response, and tissue alterations.

Pathway of Progression

1. Establishment and Maturation of Supragingival Plaque:

   • The process begins with the formation of supragingival plaque, which is evident in gingivitis.
   • As this plaque matures, it becomes more complex and can lead to changes in the surrounding tissues.

2. Migration of Periodontopathogenic Bacteria:

   • When the microbial load overwhelms the local host immune response, pathogenic bacteria migrate subgingivally (below the gum line).
   • This migration establishes a subgingival niche that is conducive to the growth of periodontopathogenic bacteria.

Initial Lesion

• Timeline:
  • The initial lesion, characterized by subclinical gingivitis, appears approximately 2 to 4 days after the colonization of the gingival sulcus by bacteria.
• Clinical Manifestations:
  • Vasculitis: Inflammation of blood vessels in the gingival tissue.
  • Exudation of Serous Fluid: Increased flow of gingival crevicular fluid (GCF) from the gingival sulcus.
  • Increased PMN Migration: Polymorphonuclear neutrophils (PMNs) migrate into the sulcus in response to the inflammatory process.
  • Alteration of Junctional Epithelium: Changes occur at the base of the pocket, affecting the integrity of the junctional epithelium.
  • Collagen Dissolution: Perivascular collagen begins to dissolve, contributing to tissue breakdown.

Early Lesion

• Timeline:
  • The early lesion forms within 4 to 7 days after the initial lesion due to the continued accumulation of bacterial plaque.
• Characteristics:
  • Leukocyte Accumulation: There is a significant increase in leukocytes at the site of acute inflammation, indicating an ongoing immune response.
  • Cytopathic Alterations: Resident fibroblasts undergo cytopathic changes, affecting their function and viability.
  • Collagen Loss: Increased collagen loss occurs within the marginal gingiva, contributing to tissue destruction.
  • Proliferation of Basal Cells: The basal cells of the junctional epithelium proliferate in response to the inflammatory environment.

Hyperparathyroidism Laboratory Pattern

Hypercalcemia Causes

Malignancy

Breast cancer, Squamous cell lung cancer, Renal cell carcinoma, Multiple myeloma, Lymphoma

Endocrine

Hyperparathyroidism, Hyperthyroidism, Addison's disease, Pheochromocytoma, MEN-1

Others

• Drugs: Lithium, Thiazides
• Intoxications: Vitamin D, Vitamin A, Aluminum
• Milk-alkali syndrome
• Prolonged immobilization
• Sarcoidosis

Pathophysiology

• Enzyme defect: Glucose-6-phosphate dehydrogenase deficiency
• Result: Impaired NADPH production → reduced glutathione → oxidative damage
• Inheritance: X-linked recessive (affects males predominantly)

Key Clinical Features

• Heinz bodies: Characteristic finding (precipitated denatured hemoglobin)
• Hemolytic episodes: Triggered by oxidative stress
• Chronic hemolysis: Usually absent between episodes
• Neonatal jaundice: May be severe

Important Clinical Points

• Estrogen does NOT induce hemolysis (unlike other conditions)
• Favism: Hemolysis after eating fava beans
• Drug-induced: Most common trigger for hemolytic crisis

Oxidative Stressors to Avoid

Medications

• Antimalarials: Primaquine, chloroquine
• Antibiotics: Sulfonamides, nitrofurantoin, chloramphenicol
• Analgesics: Aspirin (high doses), phenazopyridine
• Others: Methylene blue, naphthalene (mothballs)

Infections

• Bacterial infections
• Viral hepatitis
• Pneumonia
• Typhoid fever

Other Triggers

• Fava beans (favism)
• Diabetic ketoacidosis
• Severe illness/stress