What are the characteristics and treatment options for sarcoidosis pathology?

Sarcoidosis Pathology and Treatment

Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating granulomas, primarily affecting the lungs and lymph nodes, with first-line treatment being glucocorticoids (prednisone 20-40 mg daily) for symptomatic disease, followed by steroid-sparing agents for refractory cases. 1

Pathological Features

Key Diagnostic Characteristics

• Granuloma Presence and Morphology:

  • Compact, tightly formed collections of "epithelioid" histiocytes and multinucleated giant cells
  • Granulomas tend to remain discrete
  • Nonnecrotic or with minimal ischemic necrosis
  • Fibrosis beginning at granuloma periphery with extension centrally 2

• Lesion Location:

  • Perilymphatic distribution
  • Around bronchovascular bundles and fibrous septa
  • Near visceral pleura
  • In necrotizing sarcoid angiitis: granulomatous angiitis with vascular wall invasion 2

• Distinguishing Features:

  • Sparse surrounding lymphocytic infiltrate
  • Negative microorganism stains and cultures
  • Intra- and extrathoracic involvement 2

Features Against Sarcoidosis Diagnosis

• Extensive necrosis
• "Dirty necrosis" containing nuclear debris
• Palisading granulomas
• Robust surrounding inflammatory infiltrate
• Secondary lymphoid follicles 2

Organ Involvement and Clinical Manifestations

Pulmonary Involvement

• Most common organ affected (90% of cases)
• Staging (Scadding):
  • Stage I: Bilateral hilar lymphadenopathy (BHL) - 75% remission rate
  • Stage II: BHL with pulmonary infiltrates - 65% remission rate
  • Stage III: Pulmonary infiltrates without BHL - 30% remission rate
  • Stage IV: Pulmonary fibrosis - no chance of resolution 3

Cardiac Involvement

• Present in 20-50% of patients at autopsy, but often clinically silent
• Can manifest as:
  • Conduction abnormalities
  • Ventricular tachycardia
  • Ventricular aneurysms
  • Reduced LVEF
  • Sudden cardiac death 2

Other Organ Systems

• Skin (erythema nodosum, lupus pernio)
• Eyes (uveitis, conjunctivitis)
• Nervous system (cranial nerve palsies, peripheral neuropathy)
• Liver and spleen
• Bones and joints 1

Treatment Approach

First-Line Therapy

• Glucocorticoids (prednisone):
  • Initial dose: 20-40 mg daily for 2 weeks to 2 months
  • Taper over 6-18 months if improvement occurs
  • Indicated for symptomatic disease with organ dysfunction 1, 3
  • FDA-approved indication for symptomatic sarcoidosis 4

Second-Line (Steroid-Sparing) Agents

• Methotrexate: 10-15 mg once weekly (most widely used)
• Azathioprine: 50-250 mg daily
• Leflunomide: 10-20 mg daily
• Mycophenolate mofetil: 500-1500 mg twice daily 1, 5

Third-Line Therapy

• Anti-TNF agents:
  • Infliximab: Most widely studied, effective for refractory sarcoidosis
  • Adalimumab: Alternative anti-TNF option 1, 5

Treatment for Cardiac Sarcoidosis

• Glucocorticoids as first-line therapy
• ICD implantation for:
  • High-risk patients
  • Survivors of sudden cardiac arrest
  • Sustained ventricular tachycardia
  • LVEF <35%
  • Patients requiring permanent pacemaker 2, 1
• Cardiac transplantation for end-stage heart failure 1

Monitoring and Follow-up

Assessment of Treatment Response

• Regular pulmonary function tests (FVC, FEV1, DLCO)
• Chest imaging (radiographs, CT)
• 6-minute walk test for exercise capacity
• Cardiac monitoring for those with cardiac involvement 1

High-Risk Features Requiring Aggressive Monitoring

• LVEF <35%
• Evidence of cardiac granulomas
• Pulmonary hypertension
• Progressive pulmonary fibrosis
• Neurological involvement 1

Prognosis and Outcomes

• Mortality rate approximately 7% over 5 years 3
• About 5% of patients die from sarcoidosis, primarily due to cardiac and pulmonary complications 1
• Relapse rates range from 13-75% depending on:
  • Disease stage
  • Number of organs involved
  • Socioeconomic status
  • Geographic location 3
• 10-40% of patients develop progressive pulmonary disease 3
• Stage IV fibrocystic sarcoidosis with significant impairment has >40% mortality at 5 years 3

Common Pitfalls in Management

• Underdiagnosing cardiac involvement (may be clinically silent but carries significant mortality risk)
• Overreliance on endomyocardial biopsy (low sensitivity due to patchy nature of lesions)
• Inadequate treatment duration (at least 50% of patients remain on treatment after 2 years)
• Failure to monitor for treatment complications
• Underestimating risk of sudden death even in patients with preserved LVEF 1

By understanding the pathological features and implementing appropriate treatment strategies based on organ involvement and disease severity, outcomes for patients with sarcoidosis can be significantly improved.