Atlas of pathophysiology, 2 Edition

Part II - Disorders

Respiratory Disorders

Sarcoidosis

Sarcoidosis is a multisystem, granulomatous disorder that characteristically produces lymphadenopathy, pulmonary infiltration, and skeletal, liver, eye, or skin lesions.

Age Alert

Sarcoidosis affects twice as many women as men. Onset usually occurs between ages 30 and 50.

Causes

Exact cause unknown

Possible contributing factors

·         Hypersensitivity response (possibly from T-cell imbalance) to such agents as atypical mycobacteria, fungi, and pine pollen

·         Genetic predisposition (suggested by a slightly higher incidence of sarcoidosis within the same family)

·         Chemicals, such as zirconium and beryllium, which can lead to illnesses resembling sarcoidosis, suggesting an extrinsic cause for this disease

Pathophysiology

An excessive inflammatory process is initiated in the alveoli, bronchioles, and blood vessels of the lungs. Monocyte-macrophages accumulate in the target tissue, where they induce the inflammatory process. CD4+ T lymphocytes and sensitized immune cells form a ring around the inflamed area. Fibroblasts, mast cells, collagen fibers, and proteoglycans encase the inflammatory and immune cells, causing granuloma formation. Organ dysfunction results from the accumulation of T lymphocytes, mononuclear phagocytes, and nonsecreting epithelial granulomas, which distort normal tissue architecture, causing alveolitis.

Signs and symptoms

Initial symptoms of sarcoidosis include arthralgia (in the wrists, ankles, and elbows), fatigue, malaise, and weight loss. Sarcoidosis is characterized by formation of granulomatous tissue leading to pulmonary fibrosis. Other clinical features vary according to the extent and location of the fibrosis:

·         Respiratory—breathlessness, cough (usually nonproductive), and substernal pain; wheezing; pulmonary hypertension and cor pulmonale (in advanced pulmonary disease)

·         Cutaneous—erythema nodosum, subcutaneous skin nodules with maculopapular eruptions, and extensive nasal mucosal lesions

·         Ophthalmic—anterior uveitis (common) and glaucoma

·         Lymphatic—bilateral hilar and right paratracheal lymphadenopathy and splenomegaly

·         Musculoskeletal—muscle weakness, polyarthralgia, pain, and punched-out lesions on phalanges

·         Hepatic—granulomatous hepatitis (usually asymptomatic)

·         Genitourinary—hypercalciuria

·         Cardiovascular—arrhythmias and, rarely, cardiomyopathy

·         Central nervous system (CNS)—cranial or peripheral nerve palsies, basilar meningitis, seizures, and pituitary and hypothalamic lesions producing diabetes insipidus

Diagnostic test results

·         Arterial blood gas analysis shows a decreased partial pressure of arterial oxygen.

·         Chest X-rays show bilateral hilar and right paratracheal adenopathy, with or without diffuse interstitial infiltrates.

·         Lymph node, skin, or lung biopsy shows noncaseating granulomas with negative cultures for mycobacteria and fungi.

·         Pulmonary function tests show decreased total lung capacity and compliance and reduced diffusing capacity.

Clinical Tip

A positive Kveim-Stilzbach skin test supports the diagnosis. In this test, the patient receives an intradermal injection of an antigen prepared from human sarcoidal spleen or lymph nodes from patients with sarcoidosis. If the patient has active sarcoidosis, a granuloma develops at the injection site in 2 to 6 weeks.

Treatment

·         No treatment for asymptomatic sarcoidosis

·         With ophthalmic, respiratory, CNS, cardiovascular, or systemic symptoms or destructive skin lesions: systemic or topical steroids, usually for 1 to 2 years, but possibly lifelong

·         With hypercalcemia: low-calcium diet and avoidance of direct exposure to sunlight

P.111

LUNG CHANGES IN SARCOIDOSIS

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