Skin. Mostpatientshavediffusefibrosisoftheskinandassociatedatrophy,whichusuallybeginsinthefingersanddistalregionsoftheupperextremitiesandextendsproximallytoinvolvetheupperarms,shoulders,neck,andface.EdemaandperivascularinfiltratescontainingCD4+Tcellsareseen,togetherwithswellinganddegenerationofcollagenfibers,whichbecomeeosinophilic.Capillariesandsmallarteries(150–500µmindiameter)mayshowthickeningofthebasallamina,endothelialdamage,andpartialocclusion.Withdiseaseprogression,thereisincreasingfibrosisofthedermis,whichbecomestightlyboundtothesubcutaneousstructures.Fibrosisoftenisaccompaniedbythinningoftheepidermis,lossofretepegs,atrophyofthedermalappendages,andhyalinethickeningofthewallsofdermalarteriolesandcapillaries(
Fig.5.29B ).Subcutaneouscalcificationsmaydevelop,especiallyinpatientswithCRESTsyndrome.Inadvancedstagesthefingerstakeonatapered,clawlikeappearanceandhavelimitedjointmobility,andthefacebecomesadrawnmask.Lossofbloodsupplymayleadtocutaneousulcerationsandatrophicchanges(
Fig.5.29C )orevenautoamputationoftheterminalphalanges.
Alimentary Tract. Thealimentarytractisaffectedinapproximately90%ofpatients.Progressiveatrophyandfibrousreplacementofthemuscularismaydevelopatanylevelofthegutbutaremostsevereintheesophagus.Thelowertwothirdsoftheesophagusoftendevelopsarubber-hose–likeinflexibility.
Theassociateddysfunctionoftheloweresophagealsphinctergivesrisetogastroesophagealrefluxanditscomplications,includingBarrettmetaplasia(Chapter15)andstrictures.Themucosaisthinnedandmayulcerate,andthereisexcessivecollagenizationofthelaminapropriaandsubmucosa.Lossofvilliandmicrovilliinthesmallbowelistheanatomicbasisforamalabsorptionsyndromethatsometimesisencountered.
Musculoskeletal System. Inflammationofthesynovium,associatedwithsynoviocytehypertrophy,iscommonintheearlystages;fibrosislaterensues.Thesechangesarereminiscentofrheumatoidarthritis,butjointdestructionisnotcommoninsystemicsclerosis.Inasmallsubsetofpatients(approximately10%),inflammatorymyositisindistinguishablefrompolymyositismaydevelop.
Kidneys. Renalabnormalitiesoccurintwo-thirdsofpatients.Themostprominentarethevascularlesions.Interlobulararteriesshowintimalthickeningasaresultofdepositionofmucinousmaterialcontainingglycoproteinsandacidmucopolysaccharidesandconcentricproliferationofintimalcells.Thesechangesresemblethoseseeninmalignanthypertension,butinsystemicsclerosisthealterationsarerestrictedtovessels150to500µmindiameterandarenotalwaysassociatedwithhypertension.Hypertension,however,doesoccurin30%ofpatients,andin20%ittakesanominouslyrapid,downhillcourse(malignanthypertension).Inhypertensivepatients,vascularalterationsaremorepronouncedandareoftenassociatedwithfibrinoidnecrosisofarteriolesthatcanleadtothrombosisandinfarction.Suchpatientsoftendieofrenalfailure,whichaccountsforabout50%ofdeaths.Therearenospecificglomerularchanges.