Sarcoidosis

Question 1

What are the immunologic abnormalities observed in patients with sarcoidosis?

Answer 1

1. Intra-alveolar and interstitial accumulation of CD4+ Th1 cells
2. Oligoclonal expansion of T-cell subsets
3. Increases in T cell-derived Th1 cytokines such as IL-2 and IFN-γ
4. Increases in several cytokines in the local environment (IL-8, TNF, macrophage inflammatory protein 1α) that favor recruitment of additional T cells and monocytes and contribute to the formation of granulomas
5. Anergy to common skin test antigens such as Candida or purified protein derivative (PPD), that may result from pulmonary recruitment of CD4+ T cells and consequent peripheral depletion
6. Polyclonal hypergammaglobulinemia, another manifestation of Th1-cell dysregulation

Question 2

What is the major presenting manifestation in most cases of sarcoidosis?

Answer 2

Bilateral hilar lymphadenopathy or lung involvement (or both), visible on chest radiographs

Question 3

What putative “antigens” have been proposed as the inciting agent for sarcoidosis?

Answer 3

1. Viruses
2. Mycobacteria
3. Borrelia
4. Pollen

Question 4

What is the histopathologic sine qua non of sarcoidosis?

Answer 4

Noncaseating epithelioid granuloma (i.e., a discrete, compact collection of epithelioid cells rimmed by an outer zone of largely CD4+ T cells)

Question 5

What are the other two microscopic features sometimes seen in granulomas associated with sarcoidosis?

Answer 5

1. Schaumann bodies = laminated concretions composed of calcium and proteins
2. Asteroid bodies = stellate inclusions enclosed within giant cells

Question 6

Which organ is involved at some stage of the disease in 90% of patients?

Answer 6

The lungs. The granulomas predominantly involve the interstitium rather than airspaces. The bronchoalveolar lavage (BAL) contains abundant CD4+ T cells. In 5% to 15% of patients, the granulomas are eventually replaced by diffuse interstitial fibrosis resulting in a honeycomb lung.

Question 7

What does it mean for a lymph node to be “nonmatted”?

Answer 7

It means a node is nonadherent.

Question 8

Which clinical finding is the hallmark of acute sarcoidosis?

Answer 8

Erythema nodosum = raised, red, tender nodules on the anterior aspects of the legs

Question 9

Other than erythema nodosum, what is another characteristic skin lesion of sarcoidosis?

Answer 9

Indurated plaques associated with a violaceous discoloration in the region of the nose, cheeks, and lips (lupus pernio)

Question 10

In what percentage of patients with sarcoidosis does involvement of the eye and lacrimal glands occur?

Answer 10

In about one-fifth to one-half of patients. The ocular involvement takes the form of iritis or iridocyclitis and may be unilateral or bilateral. As a consequence, corneal opacities, glaucoma, and (less commonly) total loss of vision may develop. The posterior uveal tract is also affected, with resultant choroiditis, retinitis, and optic nerve involvement. These ocular lesions are frequently accompanied by inflammation in the lacrimal glands, with suppression of lacrimation (sicca syndrome). Unilateral or bilateral parotitis with painful enlargement of the parotid glands occurs in less than 10% of the individuals with sarcoidosis.

Question 11

What is the medical term for “dry mouth”?

Answer 11

xerostomia

Question 12

What eponymous name is used to describe the combined uveoparotid involvement observed in some patients with sarcoidosis?

Answer 12

Mikulicz syndrome

Question 13

In approximately 10% of patients with sarcoidosis, which organ becomes clinically enlarged?

Answer 13

The spleen.

Question 14

Which metabolic abnormalities may be observed in patients with sarcoidosis and why?

Answer 14

Sometimes there is hypercalcemia and hypercalciuria. This is not related to bone destruction but rather is caused by increased calcium absorption secondary to production of active vitamin D by the mononuclear phagocytes in the granulomas.

Question 15

What is the typical clinical course of symptomatic cases of sarcoidosis?

Answer 15

In about two-thirds of symptomatic cases there is gradual appearance of respiratory symptoms (shortness of breath, dry cough, or vague substernal discomfort) or constitutional signs and symptoms (fever, fatigue, weight loss, anorexia, night sweats).

Overall, 65% to 70% of affected individuals recover with minimal or no residual manifestations. Twenty percent develop permanent lung dysfunction or visual impairment. Of the remaining 10% to 15%, most succumb to progressive pulmonary fibrosis and cor pulmonale.