Abbreviations and Acronyms:ACE (angiotensin-converting enzyme inhibitor), ATG (antithymocyte globulin), DU (digital ulcer), FVC (forced vital capacity), HRCT (high-resolution computed tomography), HSCT (hematopoietic stem cell transplantation), ILD (interstitial lung disease), PAH (pulmonary arterial hypertension), PH (pulmonary hypertension), QOL (quality of life), RP (Raynaud phenomenon), SRC (scleroderma renal crisis), WHO (World Health Organization)
- Rannou F.
- Poiraudeau S.
- Berezne A.
- et al.
Making a Diagnosis
- Koenig M.
- Joyal F.
- Fritzler M.J.
- et al.
|Centromere proteins B, C|
|Topoisomerase I (Scl-70)|
|RNA polymerase III|
Define the Clinical Phenotype
1. Define the clinical phenotype: The disease has a highly variable expression.
2. Evaluate for specific organ involvement: The disease is deeper than the skin.
3. Define the clinical stage and activity of the disease: The biology of the disease is dynamic and uniquely complex.
4. Customize and redesign therapy: Specific focused therapy can positively affect longevity and quality of life.
Determine peripheral vascular disease severity: Raynaud phenomenon
- How frequently do attacks occur?
- Does this affect the patient's ADLs and ability to work?
- Are there digital ulcers, pits (signs of prior damage), or signs of active and ongoing ischemia (fixed pallor or violaceous discoloration)?
➢ Therapeutic principle: Dihydropyridine calcium channel blocker therapy is the mainstay first-line treatment for Raynaud phenomenon. For more severe disease (ulcers or active ischemia), PDE5 inhibitors, endothelin receptor antagonists, prostacyclin analogs, and antiplatelet therapy could be added. Sympathectomy or amputation should be a last resort.
|Assess extent of cutaneous/dermal sclerosis and its activity|
Limited: fingers, hands, forearms, lower legs, face
Diffuse: also involving proximal extremities (upper arms, thighs), chest, abdomen
- Is the skin itching?
- Are new body areas involved?
- Is there increasing tightness in already involved body areas?
- What is the pace of change?
- Are there tendon friction rubs on examination?
➢ Therapeutic principle: Traditional cytotoxic Immunosuppressive therapies (eg, methotrexate, mycophenolate, and cyclophosphamide) or novel treatments through participation in clinical trials should be considered in the patient with evidence of active, diffuse cutaneous disease.
|Monitor for cardiopulmonary complications: ILD and PAH|
- Is FVC decreasing on serial PFTs?
- Is the RVSP ≥40 mm Hg OR is the RVSP increasing on serial echocardiograms OR is there an isolated decline in Dlco (without a decrease in FVC)?
- Is there new-onset, unexplained dyspnea?
➢ Evaluation strategies and therapeutic principle: HRCT should be performed in the patient with decreasing FVC to evaluate for ILD. Evidence of ground glass changes with fibrosis may warrant immunosuppressive therapy. In the patient with high or increasing RVSP, or declining Dlco, assessment with exercise testing and right-sided heart catheterization for PAH is necessary.
|Identify dominant gastrointestinal symptoms that are attributable to scleroderma: GERD, dysphagia, abnormal gastric emptying, constipation, diarrhea, and fecal incontinence|
- Are there symptoms of indigestion or heartburn?
- Is xerostomia a contributing factor to dysphagia?
- Is there difficulty with oropharyngeal bolus transfer to suggest pharyngeal weakness?
- Are there episodes of choking to suggest aspiration?
- Is there difficulty swallowing to suggest lower esophageal dysfunction?
- Does the patient have early satiety or regurgitation hours after eating?
- Are there prolonged bouts of constipation, diarrhea, or both?
- Does the patient have episodes of fecal urgency and soilage?
➢ Evaluation strategies and therapeutic principle: For GERD, a trial of proton pump inhibitor therapy should be instituted, dosed 30 minutes before meals. Elevation of the head of the bed and avoiding oral intake for at least 2 hours before bedtime are recommended. Oral dryness should be treated. A cine esophagram should be considered to evaluate for pharyngeal muscle weakness, especially if there is a concomitant myositis. Esophageal manometry, solid- and liquid-phase gastric emptying study, and upper endoscopy is recommended if the patient is not responding to therapy. Titration to twice daily dosing, addition of nighttime histamine2-blocker and/or the addition of a prokinetic drug (metoclopramide or domperidone) may be necessary. Therapy should be directed at the underlying cause. For lower gastrointestinal tract symptoms, a bowel regimen (eg, polyethylene glycol) for constipation and a trial of antibiotics for diarrhea may improve quality of life, and IBS medications may be helpful. Fecal incontinence can be evaluated with anorectal manometry to see if biofeedback therapy is warranted.
Define the Clinical Stage of the Disease
Customize and Redesign Therapy
Interstitial Lung Disease
Pulmonary Vascular Disease
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Grant Support: Dr Wigley's work was supported by the Scleroderma Research Foundation and the Catherine Keilty Memorial Fund for Scleroderma Research. Dr Shah's work was supported by grant K23 AR061439 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health .