Scleroderma Lab Data and Diagnosis Iraj Salehi-Abari MD., Internist Rheumatologist salehiabari@sina.tums.ac.ir

Lab. Data: CBC: Anemia ESR Renal FT, Liver FT FANA: 95%, speckled CXR Salehi I. Lab. Data: CBC: Anemia ESR Renal FT, Liver FT FANA: 95%, speckled Scl-70 ACA CXR Scleroderma

Lab. Data: AOCD; mild, most common IDA: GAVE, chronic esophagitis Salehi I. Lab. Data: AOCD; mild, most common IDA: GAVE, chronic esophagitis Macrocytic anemia: B12, Folate deficiency Drugs: MTX Microangiopathic hemolytic anemia: SRC Scleroderma

Lab. Data: Pancytopenia: Elevated ESR: Drugs SRC Malignancy Myositis Salehi I. Lab. Data: Pancytopenia: Drugs SRC Malignancy Elevated ESR: Myositis Scleroderma

Lab. Data: Antitopoisomerase I (Scl-70) Highly specific for SSc High risk of ILD Associated with dcSSc Anti-centromere antibodies (ACA) Associated with lcSSc Salehi I. Lab. Data: Scleroderma

Lab. Data: AntiU3-RNP (Fibrillarin): SSc + PAH Salehi I. AntiPM-Scl: PM + Scl AntiU3-RNP (Fibrillarin): SSc + PAH Anti RNA polymerase I & III: only in SSc Anti RNA polymerase II: in SLE or SSc RF: 25% Lab. Data: Scleroderma

Attention please: Scl-70 & ACA & Salehi I. Attention please: Scl-70 & ACA & Anti-RNA polymerase III antibody tests are highly specific (> 99.5%) but only moderately sensitive (20-50%) Over 95% of SSc patients have at least one autoantibodies Scleroderma

Lab. Data: GI Endoscopy Doppler Echocardiography HRCT of lung Salehi I. Lab. Data: GI Endoscopy Doppler Echocardiography HRCT of lung Hand X-Ray Manometry, Dlco Spirometry, Pletismography Thyroid FT Skin biopsy Scleroderma

Skin biopsy: Not necessary for diagnosis of SSc Salehi I. Skin biopsy: Not necessary for diagnosis of SSc Only done in doubtful cases For DD with Scleroderma-like disorders May be necessary for localized Scleroderma Should include subcutaneous tissue, fascia, and muscle Scleroderma

Scleroderma-like disorders: Salehi I. Scleroderma-like disorders: Scleredema Scleromyxedema Diabetes Mellitus Hypothyroidism Nephrogenic systemic fibrosis Amyloidosis Eosinophilic fasciitis Chronic GVHD Scleroderma

Limited Cutaneous SSc (lcSSc): Salehi I. Limited Cutaneous SSc (lcSSc): Raynaud’s ph. For years Acro-facial skin sclerosis Dilated nailfold capillary loops( no drop-out ) Accompanied by CREST syndrome Pulmonary Artery Hypertension( PAH ) ILD lately & SRC rarely occurs ACA: 70 - 80% Scleroderma

Diffuse Cutaneous SSc (dcSSc): Salehi I. Diffuse Cutaneous SSc (dcSSc): Raynaud’s ph. Followed, within one year, by puffy skin changes Trunkal & acro-facial skin sclerosis Tendon friction rubs Nailfold capillary dilatation (with drop-out) Early & significant incidence of SRC, ILD, GI & cardiac disease Anti-Scl-70: 30% Scleroderma

Pre-Scleroderma Subclinical Scleroderma Early Scleroderma Salehi I. Pre-Scleroderma Subclinical Scleroderma Early Scleroderma Scleroderma

Pre-Scleroderm Raynaud’s phenomenon plus Salehi I. Pre-Scleroderm Raynaud’s phenomenon plus Nailfold capillary changes &/or Autoantibodies: Scl-70 ACA Anti-RNA polymerase No skin involvement Scleroderma

Diagnosis of SSc: Clinical: Upon No skin biopsy: only for History & Salehi I. Diagnosis of SSc: Clinical: Upon History & Physical examination No skin biopsy: only for Localized Scl. DD with Scl. Like disorders Scleroderma

The ACR/EULAR criteria for the classification of SSc Salehi I. The ACR/EULAR criteria for the classification of SSc 1. Skin thickening of both hands proximal to MCPs 9 p 2. Puffy fingers 2 p 2. Sclerodactyly 4 p 3. Digital tip ulcers 2 p 3. Pitting ulcer 3 p 4. Facial, lip telangiectasia 2 p 5. Abnormal nailfold capillaries 2 p 6. PAH 2 p 6. ILD 2 p 7. Raynaud’s ph. 3 p 8. Autoantibodies: ACA, Scl-70, Anti-RNA polymerase III 3 p Scleroderma

Attention please: The presence of : Calcinosis cutis Salehi I. Attention please: The presence of : Calcinosis cutis Hyperpigmentation &/or Skin telangiectasia and Facial and Fingers features Can differentiate SSc from other DD Scleroderma

Prognosis & Mortality: Salehi I. Prognosis & Mortality: Mortality rate: in dcSSc # 5-8 fold higher than nl population In lcSSc # 2 fold The most common cause of death in dcSSc: Pulmonary fibrosis &/or PAH SRC Cardiac Scleroderma

Management: No cure, No remission Localized or Systemic Scl. Salehi I. Management: No cure, No remission Localized or Systemic Scl. Which type of systemic Scl. Nonpharmacologic therapy Pharmacologic Symptomatic therapy Systemic therapy: Vascular + Immunologic + Fibrotic Minor vs major Scleroderma

Salehi I. Attention please: Elucidation of the precise interplay between the Vascular, Immunologic and Fibrotic components of SSc is likely to be an important first step towards more effective therapy Scleroderma

Disease modifying therapy: Salehi I. Disease modifying therapy: Immunosuppressive therapy: Glucocorticoids (LDS) MTX Mycophenolate mofetil Cyclophosphamide Autologous stem cell transplantation Scleroderma

Disease modifying therapy: Salehi I. Disease modifying therapy: Anti-fibrotic therapy: D-penicillamine: Standard-dose: 750 mg/day Low-dose: 125 mg qod Scleroderma

Disease modifying therapy: Salehi I. Disease modifying therapy: Vascular therapy: Calcium channel blockers: Diltiazem Angiotensin II receptor blockers: Losartan Alpha-1 blocker: prazocin 5-phosphodiesterase inhibitors: Sildenafil SSRI: Fluoxetine Topical nitroglycerine IV prostaglandine: Iloprost Anti-platelet agent: low-dose Aspirin Endothein-1 receptor antagonist: Bosentan Scleroderma

Pulmonary therapy: Severe acute ILD: Cyclophosphamide plus Salehi I. Pulmonary therapy: Severe acute ILD: Cyclophosphamide plus Medium dose Glucocorticoids Symptomatic PAH: Bosentan Sildenafil Scleroderma

Gastrointestinal therapy: Salehi I. Gastrointestinal therapy: GERD: PPI Omeprazole, Pantozol Nexium (esomeprazole) GI bleeding: Watermelon, GAVE Laser photocoagulation Bacterial overgrowth: Metronidazole Erythromycin & Tetracycline Chronic hypomotility: Octreotide Scleroderma

Scleroderma Renal Crisis therapy: Salehi I. Scleroderma Renal Crisis therapy: ACE inhibitors: 90% of cases Hemodialysis: 2/3 of cases In ½ of cases: recovery In ½ of cases who are unable to D/C dialysis after 2 years: Renal transplantation Recurrency of SRC in transplanted kidney is rare Scleroderma

Symptomatic therapy: Pruritus Dry skin Dyspareunia Salehi I. Symptomatic therapy: Pruritus Dry skin Dyspareunia Facial telangiectasis DOE Scleroderma