Cause:Genetic? Autoimmune?
Pathophys:Autoantibodies against platelet-derived growth factor and various other cellular antigens (Nejm 2009;360:1989; 2006;354:2667). Fetal Y chromosomes found in some skin lesions suggesting it may be a fetal graft-vs-host disease at least in some women (Nejm 1998;338:1186)
Collagen deposition in skin and muscles, esp smooth muscle, associated with increased mast cells (Ann IM 1985;102:182); debate if fibrosis or vascular disease is primary (J Rheumatol 1999;26:938)
Progressive sclerosis of skin, esophagus and rest of gut, lung, heart. Cardiac sx due to microvascular changes causing fibrosis (Nejm 1986;314:1397), which can be cold-induced (Ann IM 1986;105:661). GI cmplc all due to bacterial overgrowth from diminished large and small bowel motility
Predominant in middle age, peak age 45 yr; 2.7 new patients/million/yr; female/male = 8:1; rising incidence (Arth Rheum 1989;32:998)
Sx:Dx criteria (Bull Rheum Dis 1981;31:1): major = proximal scleroderma (proximal to mcp joints), 91% sens, 99% specif; minor = sclerodactyly*, digital pitting, basilar pulmonary fibrosis (30% false neg, 2% false pos)
Raynaud’s* (86%); esophageal* reflux, dysphagia (75% gi involvement) w eventual nonmotile esophagus, pulmonary sx esp cough (50%), cardiovascular sx (20%), polymyositis, arthritis
Si:Pitting edema early, brawny nonpitting later, then thin mummy-like skin with increased pigmentation; periungual telangiectasias* (r/o constant hot water exposure); subcutaneous calcinosis*
Renal disease, progressive but reversible (60%—Ann IM 2000;133:600), 76% 1-yr survival with ACE inhibitor (Ann IM 1990;113:352); malabsorp/digestion; Sjögren’s (17%—Ann IM 1977;87:535); progressive acute and chronic pulmonary failure and HT (Arth Rheum 1999;42:2638); primary hypothyroidism (Ann IM 1981;95:431); heart block and arrhythmias (Ann IM 1981;94:38); MIs and microcirculatory changes (J Rheumatol 2000;27:155); impotence
r/o sclerodactyly from air hammer use or ergot; porphyria cutanea tarda; EOSINOPHILIC FASCIITIS (Ann IM 1980;92:507) w “peau d’orange” skin and flexion contractures esp of upper extremities and complicated by carpal tunnel syndrome (Arth Rheum 1995;38:1707); and EOSINOPHILIC/MYALGIA SYNDROME caused by contaminated tryptophan, spares hands and feet, no Raynaud’s (Nejm 1990;323:357; Ann IM 1990;113:124); similar syndrome related to increased 5-HT with pyridoxine, tryptophan, and carbidopa
(rx—Nejm 1980;303:782)
Lab:
Path:Skin bx shows increased collagen, epidermal degeneration
Serol:C' normal, SPEP shows increased IgG, rheumatoid titer elevated (25%), cryoglobulins, false-positive serologic tests for syphilis. ANA positive (Ankle and Foot Injuries), esp speckled (centromere-staining antibodies) type, which is present in 90+% of CREST; antinuclear antibodies positive in 54% but 26% of SLE pos and 10% of RA. Scl-70 specific but nonsensitive, positive in only 20%
Xray:Hand films show distal phalanx tuft resorption (cf psoriasis) with periarticular calcification. UGIS shows esophageal dysmotility and reflux. BE shows “wide mouth” diverticula
Rx:(Semin Arth Rheum 1993;23:22; 1989;18:181)
Physical therapy
Steroids; avoid doses >10 mg/d because they may provoke renal crisis
Relaxin, human recombinant type (Ann IM 2000;132:871) 25 µgm/kg sc qd; slows skin thickening and perhaps lung fibrosis
D-Penicillamine 500-1500 mg po qd, helps skin, organs, and survival (Ann IM 1982;97:652), but 1/3 can’t tolerate (Ann IM 1986;104:699) and has fallen out of favor since the 1990s
ACE inhibitors, prevent renal failure even if no HT
Nifedipine for cardiac changes (Nejm 1986;314:1397) and Raynaud’s
Octreotide, a somatostatin analog, po helps gi motility (Nejm 1991;325:1461)
Colchicine may help pruritis but of equivocal overall effectiveness
of GERD: proton pump inhibitors (Peptic Ulcer Disease (Gastric Ulcer [GU], Duodenal Ulcer [DU], Gastritis))
of pulmonary fibrosis: cyclophosphamide (Nejm 2006;354:2655; Ann IM 2000;132:946)