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Systemic Sclerosis & Raynaud Phenomenon

Name: Systemic Sclerosis & Raynaud Phenomenon
Creator: Veli Bakalov, MD

From cold white fingers to renal crisis: know the antibody, screen the organs

Rheumatology·Connective Tissue Disease & Myositis·5 min read·8 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Primary Raynaud is young-onset, symmetric, and benign with normal nailfold capillaries and a negative ANA; ulcers, pitting scars, abnormal capillaries, or a positive ANA indicate secondary Raynaud.
Treat Raynaud with warmth and trigger avoidance, then nifedipine or amlodipine, then a PDE-5 inhibitor or topical nitrate, and IV iloprost for critical digital ischemia; avoid β-blockers, ergots, and stimulants.
Limited cutaneous SSc (CREST) carries anti-centromere antibodies and a risk of late isolated pulmonary arterial hypertension.
Diffuse cutaneous SSc: anti-Scl-70 predicts ILD, and anti-RNA polymerase III predicts renal crisis, rapid skin progression, and cancer.
Screen every SSc patient at diagnosis and yearly with PFTs with DLCO and echocardiography; confirm pulmonary hypertension by right heart catheterization.
ILD is the leading cause of SSc-related death; mycophenolate is first-line, with nintedanib or tocilizumab as options.
Scleroderma renal crisis (abrupt hypertension, AKI, MAHA) is linked to prednisone above 15 mg/day and is treated with an ACE inhibitor that is continued even if creatinine rises.
SSc GI disease: esophageal dysmotility and GERD (high-dose PPI), GAVE with iron-deficiency anemia (argon plasma coagulation), and SIBO (rifaximin).

Raynaud phenomenon

The attack. Cold or emotional stress triggers episodic vasospasm of the digital arteries, producing sharply demarcated color change: white from ischemia, blue from deoxygenated blood, then red from reactive hyperemia on rewarming, with numbness, tingling or throbbing pain. The fingers are typical, but toes, ears and nose can be affected.

Primary versus secondary Raynaud

Feature	Primary	Secondary
Onset	Teens to 20s, mostly women	Later, after about 30–40
Attacks	Symmetric, mild	Severe, often asymmetric
Tissue injury	None	Digital ulcers, pitting scars, gangrene
Nailfold capillaries	Normal	Dilated or giant loops, hemorrhages, dropout
Laboratory	ANA negative, normal ESR	ANA often positive; features of the underlying disease

Secondary causes. Systemic sclerosis is the classic cause: more than 90% of patients have Raynaud, often years before other signs. SLE, mixed connective tissue disease, Sjögren disease, dermatomyositis, cryoglobulinemia and vibrating-tool use are others. β-blockers, ergotamines and stimulants such as amphetamines and cocaine can provoke or worsen attacks. The evaluation includes ANA, CBC, ESR and nailfold capillaroscopy; an SSc pattern on capillaroscopy predicts progression from isolated Raynaud to SSc.

Treating Raynaud

Conservativekeep the whole body warm, gloves and layers, avoid cold, stop smoking and vasoconstrictors
Calcium channel blockerlong-acting nifedipine or amlodipine
Add or switchPDE-5 inhibitor (sildenafil, tadalafil) or topical nitrate
Critical digital ischemiahospitalize for IV prostacyclin such as iloprost
Refractory diseasedigital sympathectomy

Primary disease. Primary Raynaud is benign. Warming, trigger avoidance and reassurance come first, and a calcium channel blocker is added only when attacks remain frequent or disabling.

Nonselective β-blockers leave α-mediated vasoconstriction unopposed; together with ergots, triptans, decongestants and stimulants they worsen vasospasm.

Systemic sclerosis: forms and antibodies

Pathogenesis. Endothelial injury and autoimmunity activate fibroblasts, largely through TGF-β, to deposit collagen in skin and internal organs. Early puffy fingers progress to sclerodactyly, digital pitting scars and a tight face with a small mouth. Skin thickening of the fingers of both hands extending proximal to the MCP joints is sufficient to classify SSc, and ANA is positive in more than 90%.

Limited versus diffuse cutaneous systemic sclerosis

Feature	Limited cutaneous	Diffuse cutaneous
Skin extent	Distal to elbows and knees, ± face	Proximal limbs and trunk
Tempo	Years of Raynaud first; slow course	Raynaud and skin change close together; rapid progression in first 3–5 years
Features	CREST: calcinosis, Raynaud, esophageal dysmotility, sclerodactyly, telangiectasias	Tendon friction rubs, early organ involvement
Antibodies	Anti-centromere	Anti-Scl-70 (topoisomerase I); anti-RNA polymerase III
Main organ threats	Isolated PAH, late	Early ILD (anti-Scl-70); renal crisis and cancer (anti-RNA polymerase III)

Anti-RNA polymerase III warrants age-appropriate cancer screening at diagnosis; breast cancer is the classic association.

Skin, joints and heart. Palpable tendon friction rubs mark diffuse disease and predict renal crisis and cardiac involvement. Calcinosis cutis and digital ulcers cause pain and infection, and flexion contractures limit hand function. Progressive skin thickening, followed with the modified Rodnan skin score, is treated with methotrexate or mycophenolate. Myocardial fibrosis causes arrhythmias, conduction block and heart failure, and pericardial effusions are common.

Lung and pulmonary vascular disease

Screening. At diagnosis, obtain PFTs with DLCO and HRCT for ILD and echocardiography for pulmonary hypertension; PFTs and echocardiography are repeated yearly. An isolated or disproportionate fall in DLCO with preserved FVC suggests PAH.

Interstitial lung disease. ILD, usually an NSIP pattern with basal ground glass and reticulation, is the leading cause of SSc-related death and is most common in diffuse, anti-Scl-70-positive disease. Mycophenolate is first-line, cyclophosphamide is an alternative, nintedanib slows progressive fibrosis and tocilizumab helps early disease. High-dose glucocorticoids are avoided because they provoke renal crisis. Reflux with microaspiration can worsen ILD, so acid suppression also protects the lungs.

Pulmonary arterial hypertension. PAH typically appears late in limited, anti-centromere-positive disease. Echocardiography screens, but right heart catheterization must confirm precapillary pulmonary hypertension before PAH therapy with endothelin receptor antagonists, PDE-5 inhibitors or prostacyclins.

Scleroderma renal crisis

Recognition. Renal crisis occurs mainly in early diffuse disease, particularly with anti-RNA polymerase III antibodies, and glucocorticoids above 15 mg/day of prednisone raise the risk. Renin-driven, it causes abrupt severe hypertension with headache, retinopathy or encephalopathy, rapidly rising creatinine, microangiopathic hemolytic anemia with thrombocytopenia, and a bland urine or mild proteinuria. About 10% of cases are normotensive, and these fare worse.

>15 mg/dayprednisone dose linked to scleroderma renal crisis

~72 hourstarget for normalizing blood pressure with an ACE inhibitor

Treatment. A short-acting ACE inhibitor such as captopril is started immediately and titrated to normalize blood pressure within about 72 hours, with a calcium channel blocker added if needed. The ACE inhibitor is continued even when creatinine rises or dialysis is required, because renal recovery can occur over months. ARBs are not a substitute, plasma exchange (a TTP therapy) is not the answer, and prophylactic ACE inhibitors are not recommended.

Gastrointestinal disease

Esophagus. The esophagus is the most frequently involved internal organ. Smooth-muscle atrophy of the distal two-thirds and a weak lower esophageal sphincter cause dysphagia to solids and liquids, severe GERD, strictures and Barrett esophagus. Manometry shows absent distal peristalsis with low sphincter pressure, and treatment is high-dose PPI with prokinetics.

Stomach. Gastric antral vascular ectasia (watermelon stomach) appears as longitudinal red stripes converging on the pylorus and causes chronic occult bleeding with iron-deficiency anemia. It is treated with endoscopic argon plasma coagulation and, unlike portal hypertensive gastropathy, does not respond to lowering portal pressure.

Small bowel. Hypomotility causes small intestinal bacterial overgrowth with bloating, diarrhea, malabsorption, low vitamin B12 and high folate, treated with rotating antibiotics such as rifaximin; intestinal pseudo-obstruction can develop.