Sarcoidosis: Clinical features, Investigations and Management

Sarcoidosis is multisystem granulomatous disorder unknown etiology characterized by presence of non-caseating granuloma. Its etiology is unknown and associated with class II HLA genes.

It is less in smoker. 

Clinical features:

Cough, dyspnea on exertion, stridor.

Sarcoidosis is considered with other DPLD, as most of the cases affect lungs but the disease can involve any organ.

• Most common organ involved: Lungs > skin.
• Least common organ involved: Heart.

There is bilateral hilar lymphadenopathy and symptoms due to enlarged hilar lymph nodes are:

• Hoarseness of voice due to compression of recurrent laryngeal nerve.
• Chylous ascites due to compression of thoracic duct.

Night sweats, weight loss.

Often confused with Tuberculosis.

Lupus pernio, Erythema nodosum.

Lupus pernio is a rare cutaneous manifestation of Sarcoidosis. It is characterized by painless violaceous or erythematous, indurated plaques that are primarily distributed on the central face involving the nose and cheeks.

Lofgren Syndrome.

It is an acute illness that is characterized by erythema nodosum, peripheral arthropathy, uveitis, bilateral hilar lymphadenopathy, lethargy and occasionally fever. It is often seen in young women.

Cardiac manifestation:

Heart block, sudden death, Tachyarrhythmias, (PAH) Pulmonary artery hypertension (characterized by loud P2, decreased diffusion capacity for CO), Increased risk for ischemic heart disease.

• Most common cause of death in patient with sarcoidosis: Respiratory failure.
• Most common cause of sudden death in patient with sarcoidosis: Arrhythmias.

Bone marrow manifestation:

Lymphopenia is seen in bone marrow studies.

Endocrine manifestation:

• Hypercalcemia due to increased synthesis of Vit- D3 by macrophages from granuloma. As it is controlled by steroids, it is an example of steroid responsive hypercalcemia. The hypercalcemia may lead to nephrocalcinosis, hypercalciuria and renal stones.
• Diabetes insipidus.

Ocular manifestations:

• Optic neuritis due to second cranial nerve involvement.
• Anterior uveitis.
• Lacrimal gland enlargement.
• Sicca syndrome.

Parotid gland enlargement.

The enlarged parotid gland may compress the branches of facial nerve and so it can lead to bilateral facial nerve palsy.

CNS manifestations and neuropathy:

• Lymphocytic meningitis.
• Pachymeningitis.
• Space occupying lesion.
• Cranial nerve palsy (II^nd and VII^th nerve).
• Mononeuritis multiplex.
• Peripheral neuropathies.

Others.

• Granulomatous liver disease.
• Phalangeal bone cysts.
• Arthropathies, osteoporosis.
• Splenomegaly 

Investigations:

Chest X-ray (CXR):

Chest x-ray changes in sarcoidosis are:

• Stage I: Bilateral hilar lymphadenopathy. It is usually symmetrical, seen as eggshell calcifications, paratracheal nodes are often enlarged.
• Stage II: Bilateral hilar lymphadenopathy and parenchymal infiltrates.
• Stage III: Parenchymal infiltrates without bilateral hilar lymphadenopathy.
• Stage IV: Pulmonary fibrosis.

Hilar lymphadenopathy is early presentation and deterioration (fibrosis) is late presentation. Fibrosis can cause progression to ventilatory failure, pulmonary hypertension and cor pulmonale.

Blood investigations:

• Hypercalcemia, hypercalciuria (urine).
• Increases ACE.

Bronchoalveolar lavage (BAL).

Increased CD4: CD8 T cell ratio. CD4: CD8 T cell ratio is more than 3.5.

Bronchoscopy.

Cobblestone appearance of mucosa.

Bronchial biopsy.

It shows non caseating granuloma. Bronchial biopsy can be taken by two methods.

• Endobronchial: for enlarged lymph node.
• Transbronchial: for parenchymal involvement.

HRCT.

Shows reticulonodular shadowing. Galaxy sign.

Gallium-67 scan.

It is usually not done nowadays. It has historical importance in evaluation and follow up in sarcoidosis patients.

Treatment & Management:

NSAIDS and Glucocorticoids.

Patient with acute illness and erythema nodosum. Majority of patients have spontaneous remission. If there is no evidence of organ damage, systemic glucocorticoid therapy can be withheld for 6 months.

Prednisolone (started at lowest effective dose) is indicated immediately in presence of hypercalcemia, pulmonary impairment, renal impairment and uveitis. 

Topical Glucocorticoids are useful in cases of mild uveitis.

Inhaled glucocorticoids are used in asymptomatic parenchymal sarcoid to shorten the duration of systemic glucocorticoid use.

Chloroquine, Hydroxychloroquine, Thalidomide.

These are useful in cutaneous sarcoid with limited pulmonary involvement.

Immunosuppresser and Biologics.

In patients with severe disease; methotrexate, azathioprine and specific tumor necrosis factor alpha inhibitors are effective.

Lung Transplantation.

Selected patients may be referred for the consideration of lung transplantation.