Nejm 2007;357:2153; Jama 2006;296:2133

Cause:Unknown, possibly infectious or toxin exposure plus genetic host factors

Pathophys:Probably an end result of immune responses to various ubiquitous environmental triggers. Activated T cells (also seen in Crohn’s disease, perhaps same pathophysiology) and macrophages, unclear why activated. Granuloma formation without necrosis or inflammation, often involves lung, skin, and RES; occasionally bone, kidney, eye, gi tract. Hypercalcemia due to increased vit D sensitivity

10-50/100 000/yr in US; black/white = 3:1; associated with regional enteritis; peak incidence at age 30 yr, rare over 50 yr

Sx:Fatigue, weight loss, fever/malaise, dyspnea, cough

Si:Rales; neurologic (Ann IM 1977;87:336); uveitis, anterior chamber tissue masses, corneal precipitant and band keratopathy; splenomegaly, lymphadenopathy; skin lesions blanch with pressure, residual brown pigment, erythema nodosum on shins without scarring

75-90% spontaneous resolution without rx in 2 yr; more chronic and fatal in blacks

Restrictive lung disease (r/o chronic berylliosis—Ann IM 1988;108:687); pulmonary cavities with aspergillus; pleuritis occasionally with exudative lymphocytic effusions (Ann IM 1974;81:190); hypercalcemia and hypercalciuria with renal stones; meningitis with low sugar; pituitary tumors with thirst and diabetes insipidus; Bell’s palsy; arthritis esp of knees and ankles

r/o primary biliary cirrhosis overlap syndrome; berrylliosis; Wegener’s granulomatosis; tuberculosis; histoplasmosis; and LÖFGREN’S SYNDROME, a sarcoid variant in young person w erythema nodosum, bilateral hilar adenopathy, and often bilateral ankle arthritis, which is self-limited in 6 mo w no residua (Am J Med 1999;107:240)

Lab:

Chem:Elevated angiotensin-converting enzyme, but very nonspecific; elevated Ca⁺⁺

Noninv:PFTs show decreased volumes, decreased diffusion capacity, pO₂ often ok at rest but decreases with exercise

Path:Bx of minor salivary gland, supraclavicular node, or transbronchial (95% positive) shows noncaseating granuloma

Xray: Hilar adenopathy and interstitial pattern (1 or both present in 90%)

Gallium scan positive over lung (macrophages) and nodes, very nonspecific; MRI, PET

Rx:

Often just watchful waiting for worsening or remission

Steroids, eg, prednisone 30-40 mg po qd × 8-12 wk, then taper to 10-20 mg qod over 6-12 mo; possibly antitumor necrosis factor (TNF) meds like infliximab (Ann IM 2001;135:27)

Methotrexate

of elevated calcium and/or renal calcium stones: steroids, decrease vit D intake, chloroquine as above (Nejm 1986;315:727)