The spleen mayappearunaffectedgrossly,butinaboutthree-fourthsofcases,itcontainsgranulomas.Inapproximately10%,itbecomesclinicallyenlarged.The liver demonstratesmicroscopicgranulomatouslesions,usuallyintheportaltriads,aboutasoftenasthespleen,butonlyaboutone-thirdofpatientsdemonstratehepatomegalyorabnormalliverfunction.Sarcoidinvolvementofbone marrow isreportedinasmanyas40%ofpatients,althoughitrarelycausesseveremanifestations.Otherfindingsmayincludehypercalcemiaandhypercalciuria.ThesechangesarenotrelatedtobonedestructionbutratherarecausedbyincreasedcalciumabsorptionsecondarytoproductionofactivevitaminDbythemacrophagesthatformthegranulomas.
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In many affected individuals, the disease is entirely asymptomatic, discovered on routine chest films as bilateral hilar adenopathy or as an incidental finding at autopsy. In others, peripheral lymphadenopathy, cutaneous lesions, eye involvement, splenomegaly, or hepatomegaly may be presenting manifestations. In about two-thirds of symptomatic cases, there is gradual appearance of respiratory symptoms (shortness of breath, dry cough, or vague sub-sternal discomfort) or constitutional signs and symptoms (fever, fatigue, weight loss, anorexia, night sweats). A definitive diagnostic test for sarcoidosis does not exist, and establishing a diagnosis requires the presence of clinical and radiologic findings that are consistent with the disease, the exclusion of other disorders with similar presentations, and the identification of noncaseating granulomas in involved tissues. In particular, tuberculosis must be excluded.
Sarcoidosis follows an unpredictable course characterized by either progressive chronicity or periods of activity interspersed with remissions. The remissions may be spontaneous or initiated by steroid therapy and often are permanent. Overall, 65% to 70% of affected individuals recover with minimal or no residual manifestations. Another 20% develop permanent lung dysfunction or visual impairment. Of the remaining 10% to 15%, most succumb to progressive pulmonary fibrosis and cor pulmonale.
Sarcoidosisisamultisystemdiseaseofunknownetiology;thediagnostichistopathologicfeatureisthepresenceofnoncaseatinggranulomasinvarioustissues.
ImmunologicabnormalitiesincludehighlevelsofCD4+ TH1cellsinthelungthatsecretecytokinessuchasIFN-γ.
Clinicalmanifestationsincludelymphnodeenlargement,eyeinvolvement(siccasyndrome[dryeyes],iritis,oriridocyclitis),skinlesions(erythemanodosum,painlesssubcutaneousnodules),andvisceralinvolvement(liver,skin,bonemarrow).Lunginvolvementoccursin90%ofcases,withformationofgranulomasandinterstitialfibrosis.
Hypersensitivity pneumonitis is an immunologically mediated inflammatory lung disease that primarily affects the alveoli and is therefore often called allergic alveolitis. Most often it is an occupational disease that results from heightened sensitivity to inhaled antigens such as those found in moldy hay (
Table 13.4 ). Unlike bronchial asthma, in which bronchi are the focus of immunologically mediated injury, the damage in hypersensitivity pneumonitis occurs at the level of alveoli. Hence, it manifests predominantly as a restrictive lung disease with the typical decreases in diffusion capacity, lung compliance, and total lung volume. The responsible occupational and household exposures are diverse, but the syndromes share common clinical and pathologic findings and probably have a very similar pathophysiologic basis.
Table 13.4 Sources of Antigens Causing Hypersensitivity Pneumonitis
Source of Antigen Types of Exposures