What is sarcoidosis?

What is Sarcoidosis?

Sarcoidosis is a chronic multi-system inflammatory disease of unknown etiology characterized by the formation of non-caseating granulomas that can affect multiple organs, most commonly the lungs and intrathoracic lymph nodes. 1

Definition and Pathophysiology

• Sarcoidosis involves the formation of well-formed, concentrically arranged layers of immune cells, with a central core of macrophage aggregates and multinucleated giant cells, surrounded by loosely organized lymphocytes 1
• The disease appears to be an exaggerated immune response to an unknown antigen, with various suggested triggers including infectious agents (mycobacteria, propionibacteria), chemicals (beryllium, zirconium), and environmental exposures (pine pollen, peanut dust) 1
• T cells play a central role with accumulation of CD4+ T cells, accompanied by release of IL-2 and formation of non-caseating granulomas 1
• Sarcoidosis granulomas are typically non-necrotic, though variants (particularly nodular pulmonary sarcoidosis) can present with a mixture of necrotic and non-necrotic granulomas 1

Epidemiology

• The age-adjusted incidence is approximately 11 cases per 100,000 in Caucasians, with higher prevalence in northern Europe (20/100,000) 1
• In the United States, sarcoidosis is more prevalent in African Americans than whites (35.5/100,000 versus 10.9/100,000) 1
• It is twice as common in women than men, with women experiencing higher morbidity, mortality, and extrapulmonary involvement 1
• Incidence peaks in the third to fourth decades, with a second peak in women between 45-65 years 1
• Mortality is significantly higher in some populations, with African American women having 2.4 times higher mortality compared to matched cohorts without sarcoidosis 1

Clinical Manifestations

Highly Probable Clinical Features for Diagnosis:

• Löfgren's syndrome (bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis) 1
• Lupus pernio (specific skin lesions) 1
• Uveitis and optic neuritis 1
• Bilateral hilar adenopathy on imaging (CXR, CT, PET) 1
• Perilymphatic nodules on chest CT 1

Common Organ Involvement:

• Pulmonary: Most commonly affected (>90% of cases), presenting with persistent dry cough, dyspnea, and chest pain 2
• Lymph nodes: Bilateral hilar lymphadenopathy is a classic finding 1
• Skin: Manifestations include lupus pernio, maculopapular lesions, erythema nodosum, and subcutaneous nodules 1
• Eyes: Uveitis, optic neuritis, scleritis, and retinitis 1
• Upper respiratory tract: Nasal involvement with blockage, crusting, and bleeding occurs in approximately 3-4% of patients with generalized disease 1
• Cardiac: Can present with cardiomyopathy, atrioventricular block, or ventricular tachycardia 1
• Musculoskeletal: Joint involvement occurs in 15-25% of cases, presenting as acute or chronic arthritis 3

Diagnosis

Diagnosis of sarcoidosis relies on three key criteria:

1. Compatible clinical and radiologic presentation 4

   • Bilateral hilar adenopathy, perilymphatic nodules, and upper lobe or diffuse infiltrates are highly suggestive 1
   • Specific clinical syndromes like Löfgren's syndrome may be diagnostic 1

2. Pathologic evidence of non-caseating granulomas 4

   • Histological evaluation often required due to nonspecific clinical manifestations 1
   • Granulomas typically show well-formed, concentrically arranged layers of immune cells 1

3. Exclusion of alternative causes of granulomatous inflammation 1

   • Must rule out infections (particularly tuberculosis), malignancy, berylliosis, and other granulomatous diseases 1
   • Blood lymphocyte proliferation test can diagnose chronic beryllium disease 1
   • BAL fluid analysis may help exclude infections or identify patterns suggestive of other conditions 1

Diagnostic Tests:

• High-resolution CT scan of the chest 1
• Tissue biopsy from affected organs 1
• Bronchoalveolar lavage showing lymphocytosis or elevated CD4:CD8 ratio 1
• Laboratory tests may show hypercalcemia (10-13%), hypercalciuria (~30%), elevated ACE levels (60-83%), and elevated alkaline phosphatase 1

Treatment

• Glucocorticoids are the first-line therapy for symptomatic sarcoidosis 5
• For patients with severe forms requiring long-term glucocorticoids and those intolerant or refractory to steroids, immunosuppressive drugs are used as sparing agents 5
• Management of extrathoracic sarcoidosis must be tailored to the specific organs involved 5
• Biological therapies, particularly anti-TNF agents, are emerging as promising options for refractory cases 5
• Many patients with asymptomatic bilateral hilar lymphadenopathy have self-limited disease and do not require treatment 1

Prognosis

• Prognosis is variable and depends on epidemiologic factors, mode of onset, initial clinical course, and specific organ involvement 4
• Sarcoidosis often undergoes spontaneous regression, but chronic forms can progressively damage involved organs through fibrotic changes 6
• Despite aggressive treatment, some patients may develop life-threatening pulmonary, cardiac, or neurologic complications 4
• End-stage disease may ultimately require lung or heart transplantation for eligible patients 4