27. Sarcoidosis

Question 1

Epidemiology of Sarcoidosis

Answer 1

• 2:1 ratio for Female:Male
• Much more common in African-American and Scandinavian individuals
• Average age of onset between 30-55

Question 2

Etiology of Sarcoidosis

Answer 2

Unknown but thought to occur in genetically predisposed individuals [HLA-linked] after exposure to granuloma causing agents [Beryillium and it’s salt; Mycobacteria]

Question 3

Pathophysiology of Sarcoidosis

Answer 3

It is a systemic disorder characterised by non-caseating granuloma formation in multiple organ mediated by immune system
- Inhalation of foreign antigen activating alveolar macrophages, Th1 cells recruitment, immune cell infiltration and inflammation of alveoli, granuloma formation in lungs and lymphatic system [epitheliod cells and multinucleated giant cells]
- Th1 cells forming Epitheliod cells and Multinucleated giant cells, which in turn recruit more lymphocytes and fibroblasts leading to Mature Granuloma and fibrosis
- Extensive fibrosis leads to organ damange and tissue damage
- Calcium dysregulation via alveolar macrophages, increased 1-alpha hydoxylase activity => increased Calcitriol formation => Hypervitaminosis D => Hypercalcemia and potential renal failure

In lungs we thus see Non-caseating Granuloma formation, hypercalcemia due to increased 1-alpha hydroxylase activity by alveolar macrophages and fibrosis from fibroblast recruitment by Epithelioid cells

Question 4

Clinical features

Answer 4

Sudden onset and spontaneous remission is common in 2/3 rd of patients
Can be classified as Pulmonary Sarcoidosis and Extra-Pulmonary Sarcoidosis

Signs and Symptoms:
- Constituitional [fever, malaise, weight loss, loss of appetite]
- Lymphadenopathy
- Pulmonary Sarcoidosis [Exertional dyspnea, cough, chest pain, Bilateral Hilar lymphadenophathy often symmetric; Interstitial fibrosis signs] in ~90% patients
- Extra-pulmonary Sarcoidosis [Arthritis, erythema nodosum, anterior uveitis]

Symptoms are GRUELING - Granuloma, aRthritis, Uveitis, Erythema nodosum, Lymphadenopathy, Interstitial lung fibrosis, Negative tb test, Gammaglobulinemia

Question 5

2 subtypes of Sarcoidosis in clinical settings

Answer 5

1. Lofgren Syndrome: Acute Fever + Migratory Polyarthritis + Erythema nodosum + Bilateral Hilar lymphadenopathy [Spontaneous remission of syndrome in 70-80% of patients]
2. Heerfordt Syndrome: Fever + Parotitis + Uveitis + Facial palsy

Question 6

Diagnosis of Sarcoidosis

Answer 6

It is a diagnosis of exclusion

Approach:
- Labs [CBC for leukocytopenia; Vit D, 1,25-OH levels; Calcium levels in urine; Comprehensive Metabolic Panel; TB screening; 12 lead EKG]
- CXR [Bilateral Hilar lymphadenopathy with/without pulmonary infiltrates; ground glass appearance; staging done to assess rate of spontaneous remission]
- HRCT [Extensive hilar and mediastinal lymphadenopathy; bronchocentric and perilymhatic micronodules; peribronchial thickening; fibrosis]
- PFTs [spirometry shows restrictive pattern; Decreased DLco]
- Biopsy [Gold standard]
- Broncho-Alveolar Lavage [supports diagnosis of Sarcoidosis if CD4:CD8 ratio > 3,5]

Cardiac Sarcoidosis can result in Sudden Cardiac Arrest

Ddx: Hodgkins and Non-Hodgkins Lymphoma, Pneumoconiosis, Tuberculosis, Histoplasmosis, Granulomatosis with Polyangitis

Question 7

Treatment of Pulmonary Sarcoidosis

Answer 7

Immunosuppresive Therapy:
- Glucocorticoids
- DMARDS if no response to glucocorticoids [Methotrexate or Azathioprine with/without glucocorticoids; Chloroquine; Biologics]

Supportive Therapy:
- Pain relief
- Supplemental oxygen
- Noninvasive ventilation

Transplantation of lung in unresponsive to therapy, progressing disease

Question 8

Complications of Sarcoidosis

Answer 8

• Have an increased risk of malignancies, especially Lung cancer and lymphomas
• Bronchiectasis
• PAH from fibrosis
• Aspergilloma
• Chronic renal failure [especially in increased calcium levels]