10 pearls in scleroderma for the family practitioner

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1 10 pearls in scleroderma for the family practitioner Dr Maggie Larche, MRCP(UK), PhD Associate Professor, Division of Rheumatology, McMaster University St Joseph s Hospital Family Medicine Rounds, St Joseph s Hospital, January 2015

2 Objectives To describe clinically pertinent points for family practitioners To outline evidence around each of the pearls To increase knowledge of systemic sclerosis

3 Scleroderma (Systemic Sclerosis) is sclero (Greek meaning hard) + derma (Latin meaning skin) = scleroderma (hard skin) Hippocrates 1945 association with systemic disease

4 Terminology Scleroderma Localised Systemic Morphea Linear (en coup de Sabre) Limited (distal to elbows or knees) Diffuse Images from ACR Image bank

5 Pearls 1. Clinical 2. Red flags in Raynauds 3. Early diagnosis 4. Outcome 5. Risk factors Treatment 6. Raynauds 7. GI 8. Viagra 9. Renal crisis 10. pregnancy

Many aspects of scleroderma Vascular system Raynauds Healed pitting ulcers in fingertips Cutaneous and mucosal telangiectasia

system Arthritis/myositis Flexion contractures Carpal tunnel syndrome Muscle weakness Constitutional: Fatigue/weight loss Skin

Genitourinary system Erectile dysfunction Dyspareunia Ears, nose, and throat Sicca syndrome Poor dentition Hoarseness due to acid

6 Many aspects of scleroderma Vascular system Raynauds Healed pitting ulcers in fingertips Cutaneous and mucosal telangiectasia Gastrointestinal system GERD, GAVE Dysmotility Constipation /diarrhea Respiratory system ILD Pulmonary hypertension Musculoskeletal system Arthritis/myositis Flexion contractures Carpal tunnel syndrome Muscle weakness Constitutional: Fatigue/weight loss Skin Sclerodactyly Edema Digital ulcers Calcinosis Hyper or hypo-pigmentation Cardiovascular system Pulmonary hypertension Arrhythmias Genitourinary system Erectile dysfunction Dyspareunia Ears, nose, and throat Sicca syndrome Poor dentition Hoarseness due to acid reflux with vocal cord inflammation or fibrosis Endocrine system - Hypothyroidism Renal system Hypertension Renal crisis Chronic renal insufficiency

7 Vascular system Raynauds Healed pitting ulcers in fingertips Cutaneous and mucosal telangiectasia Gastrointestinal system GERD, GAVE Dysmotility Constipation /diarrhea Respiratory system ILD Pulmonary hypertension Musculoskeletal system Arthritis/myositis Flexion contractures Carpal tunnel syndrome Muscle weakness Constitutional: Fatigue/weight loss Skin Sclerodactyly Edema Digital ulcers Calcinosis Hyper or hypo-pigmentation Cardiovascular system Pulmonary hypertension Arrhythmias Genitourinary system Erectile dysfunction Dyspareunia Ears, nose, and throat Sicca syndrome Poor dentition Hoarseness due to acid reflux with vocal cord inflammation or fibrosis Pearl 1: clinical aspects Usually presents with Raynauds, and puffy hands Particularly affects lungs, heart, kidneys and skin Can affect almost any organ Endocrine system May overlap with other autoimmune diseases - Hypothyroidism Renal system Hypertension Renal crisis Chronic renal insufficiency

8 Red flag symptoms or signs in Raynauds Sudden and late onset Constitutional features Thickened skin Digital ulcers Rashes Calcium deposits Arthritis Dry eyes/mouth Apthous ulcers Hypertension Dyspnea Muscle weakness Swallowing difficulties GI disturbances

9 Pearl 2: Raynauds Red flags Bottom Lines: Older age Male Digital ulcers Other features of autoimmune diseases

10 New criteria aid early diagnosis Puffy fingers Raynauds phenomenon Dilated nail fold capillaries (ANA) Koenig et al A&R 2008 ACR Image bank

11 2013 ACR/EULAR SSc guidelines Item Sub-item Weight Skin thickening of fingers of both hands extending proximal to MCP joints (sufficient criterion) Skin thickening of fingers (only count higher score) Fingertip lesions (only count higher score) Puffy fingers Sclerodactyly of fingers (distal to MCP joints but proximal to PIP joints Digital tip ulcers Fingertip pitting scars Telangiectasia 2 Van den Hoogen

12 2013 ACR/EULAR SSc guidelines Item Sub-item Weight Abnormal nailfold capillaries 2 Pulmonary arterial hypertension and/or interstitial lung disease (maximum score is 2) Pulmonary arterial hypertension Interstitial Lung Disease Raynaud s phenomenon 3 SSc-related autoantibodies (anticentromere, anti-rna polymerase III, antitopomerase I [anti-scl-70] (Maximum score is 3) Total score = Sum of maximum score in each category Total Score 9 Classified as Definite SSc; Maximum Score is 19 Anti-centromere Anti-topomerase I Anti-RNA polymerase 2 2 3

13 Early diagnosis allows improved monitoring and treatment of complications Diffuse disease more likely to get ILD, PAH, renal disease Intensive monitoring necessary ECHO, PFTs, renal function, BP Improved treatments available

14 Pearl 3: early diagnosis New criteria make it easier to diagnose SSc early Consider in patients with Raynaud s, puffy hands and dilated nailfold capillaries

15 Outcome: Diffuse versus Limited ILD Renal crisis 10 year survival rates: Limited: 90% Diffuse: 60% Up to x8 increased risk of death Raynauds, digital ischemia Esophageal dysmotility Adapted from

Causes of death Pearl 4: Outcome 75% 10 yr survival Pulmonary hypertension (major prognostic factor) 10 year survival rates: Limited: 90% Diffuse: 60% Bottom Lines: Pulmonary fibrosis (age and gender

16 Causes of death Pearl 4: Outcome 75% 10 yr survival Pulmonary hypertension (major prognostic factor) 10 year survival rates: Limited: 90% Diffuse: 60% Bottom Lines: Pulmonary fibrosis (age and gender adjusted Scleroderma Important renal causes crisis of premature mortality death rates 5-8X pulmonary fibrosis, general population) pulmonary hypertension, Huge impact on quality renal failure of life Significant morbidity associated Mayes MD. Scleroderma epidemiology. Rheum Dis Clin North Am. 2003, 29:

17 Mortality: reduced frequency of Scleroderma Renal Crisis - more pulmonary fibrosis Steen and Medsger ARD :940-4

18 Pearl 5: risk factors for poor outcome Diffuse skin involvement Proteinuria PAH Pulmonary fibrosis NYHA class 2 Late onset Raynauds Gurman et al ARD 2010

19 Part 1: Take Home Messages Consider SSc in: new onset Raynauds Raynauds in older patient Puffy fingers Digital ulcers Monitor for: pulm fibrosis with annual PFTs (6 monthly if less than 5 yrs) PAH with annual ECHO refer for RHCath if pressures 40 and dyspnoeic BP and creatinine carefully esp in diffuse disease Beware of steroid dose in SSc 15mg may precipitate Scleroderma Renal Crisis (SRC) Multisystem disease: Talk to colleagues

20 Management of specific aspects of SSc Raynauds Gastro-intestinal Pulmonary fibrosis Pulmonary hypertension Renal crisis

21 Raynauds: Management Conservative measures Smoking cessation and avoiding the cold Emollients Avoid drugs such as Beta blockers Ergotamine Clonidine Cyclosporin Cocaine Heated gloves, socks First line medications Calcium Channel blockers Amlodipine 10-20mg daily Nitrate patches 0.2mcg daily Angiotensin Receptor blockers Losartan mg od 2 nd line treatments Prostacyclins (IVI CCU monitoring) Alprostadil Iloprost PDE5 inhibitors: Sildenafil 100mg od Tadalafil 40mg od SSRIs - Prozac Sympathectomy digital vs axillary

22 Pearl 6: Specific treatments for Raynauds prevent damage Amlodipine 10mg od Losartan 100mg od Prozac +/-Pentoxyfilline Nitrodur patches mcg/day Sildenafil/Tadalafil IV prostacyclins

Treatment of GI manifestations Feature Treatment GERD GAVE (Watermelon stomach) Conservative measures PPI high doses Laser photocoagulation Transfusions Gastroparesis, Dysmotility Pseudoobstruction

23 Treatment of GI manifestations Feature Treatment GERD GAVE (Watermelon stomach) Conservative measures PPI high doses Laser photocoagulation Transfusions Gastroparesis, Dysmotility Pseudoobstruction Bacterial overgrowth Constipation Diarrhoea Incontinence Domperidone 20mg tid Prucalopride 2mg od Octreotide25-50mcg bid 1G liquid Erythromycin q3 days Pyrido- or Neostigmine 1g slow ivi Cyclical antibiotics Rifamixin 200mg tid for 3 days Prucalopride 2mg od Laxatives Codeine or loperamide Low dose loperamide Sacral nerve stimulator

24 Pearl 7: GI treatments High dose PPI for dyspepsia Domperidone 10mg tid for dysphagia Prucalopride 2mg od

PDE5 inhibitors Useful in: Prevention and treatment of Digital ulcers in 15 patients Reduced number of ulcers from 44 to 13 Pulmonary arterial

25 PDE5 inhibitors Useful in: Prevention and treatment of Digital ulcers in 15 patients Reduced number of ulcers from 44 to 13 Pulmonary arterial hypertension Erectile dysfunction Kumar U et al 2013 Rheumatol Int Foocharoen C et al 2012 Arthritis Res Ther Della Rossa et al 2011 Scand J Rheum

26 Pearl 8: 3 reasons to use Viagra in SSc Pulmonary hypertension Digital ulceration (prevention and treatment) Sexual dysfunction

27 Increasing BP Microangiopathic hemolytic anemia Rising Creatinine Renal Crisis ~25%mortality in 1 year 20 to 50% risk of developing end-stage renal disease 2 year mortality 50% (vs 36% in non-scleroderma dialysis) Steen et al 2005 J Rheum

28 Renal Crisis 2012 study: amongst SRC (91patients) 78% Hypertension; 58% encephalopathy; 56% microangiopathy (anemia, reticulocytes, schistocytes, bilirubin, haptoglobolin 70% had received steroids before SRC 54% required dialysis, 41% died Guillevin et al 2012 Rheumatology

29 Renal crisis risk factors Diffuse SSc Male gender Steroids >15mg daily (used for arthritis, myositis, pulmonary fibrosis). 1.5% increased risk for each mg of prednisone/day (Calcium channel blockers protective) DeMarco PJ et al 2002 Arthritis Rheum Steen VD et al 1998 Arthritis Rheum Montanelli et al 2013 Clin Exp Rheum

Pearl 9: Scleroderma Renal Crisis high index of suspicion; treat ~25% mortality in 1 year Monitor BP and creatinine 20 to 50% risk Careful of with dose of oral steroids <15mg daily

30 Pearl 9: Scleroderma Renal Crisis high index of suspicion; treat ~25% mortality in 1 year Monitor BP and creatinine 20 to 50% risk Careful of with dose of oral steroids <15mg daily developing end-stage renal disease ACE-I Captopril 12.5mg tid increasing aggressively 2 year mortality 50% (vs 36% in non-scleroderma dialysis) aggressively Steen et al 2005 J Rheum

31 Pregnancy in SSc High risk pregnancy clinic Increased risk of preterm birth and small for gestational age (placental insuffificnecy) Good maternal and neonatal survival OK to use Hydroxychloroquine and low dose steroids and IVIG Renal Crisis most signficiant complication prompt ACEI Try to avoid pregnancies in dcssc within 5 yrs Taraborelli et al 2012 Arth Rheum Lidar and Langevitz Autoimmunity Review 2012

Biologics/ Stem cell therapy for SSC AntiCD20 Improved skin score (Jordan et al ARD 2014) RECOVER Rituximab study in polyarthritis in SSc (http://www.clinicaltrials.

32 Biologics/ Stem cell therapy for SSC AntiCD20 Improved skin score (Jordan et al ARD 2014) RECOVER Rituximab study in polyarthritis in SSc ( Belimumab + MMF in early Diffuse SSc ( Trials of antiifnr in Ssc Tocilizumab trial underway ( Stem cell treatments for scleroderma: Stem cell therapy of autoimmune disease with focus on scleroderma Dr Alan Tyndall Tuesday, 22 April :00 hrs, New Auditorium, 4 th Floor Juravinski Hospital

33 Pearl 10: Pregnancy Monitor closely Aggressive management of hypertension (with ACE-I) Try to avoid in early diffuse disease

34 Pearls 1. Clinical 2. Red flags in Raynauds 3. Early diagnosis 4. Outcome 5. Risk factors Treatment 6. Raynauds 7. GI 8. Viagra 9. Renal crisis 10. Pregnancy

35 Conclusions Focus on early diagnosis and intensive monitoring Supportive management Specific treatments New hope Pearl 11: ``Team game`` Hamilton Scleroderma Group

36 Thanks St Joseph`s Family Practitioners Multidisciplinary colleagues at Hamilton Scleroderma Group Ellen McDonald the patient s quarterback! Rheumatology Colleagues Scleroderma Society of Ontario Questions: mlarche@mcmaster.ca

38 Treatment of Pulmonary fibrosis Cyclophosphamide oral (2mg kg day) or IV Bottom Lines: (600mgm2) only drug shown to be effective in Several drugs helpful in SSc-ILD RCT Modest improvements Cyclophosphamide in FEV1 and TLC and Tashkin et al 2007 AJRCCM 176:1026 dyspnea scores Mycophenolate Hoyles et al 2006 A&R 54:3962 Improvements Rituximab in skin scores MMF Stem not cell inferior transplantation to Cyclophos showing promise in ILD (Hinchcliff 2013) Rituximab improves GG appearance (Daoussis D et al Clin Exp Rheum 2013) ASTIS trial ARD 2012 Suppl Abs LB0002

39 Treatment of Pulmonary fibrosis Cyclophosphamide oral (2mg kg day) or IV (600mgm2) only drug shown to be effective in RCT Modest improvements in FEV1 and TLC and Tashkin et al 2007 AJRCCM 176:1026 dyspnea scores Hoyles et al 2006 A&R 54:3962 Improvements in skin scores MMF not inferior to Cyclophos in ILD (Hinchcliff 2013) Rituximab improves GG appearance (Daoussis D et al Clin Exp Rheum 2013) ASTIS trial ARD 2012 Suppl Abs LB0002

40 Pulmonary Hypertension Algorithm TT ECHO RVSP 35mmHg RVSP 35-40mmHg RVSP 40mmHg Unlikely PAH No dyspnoea Dyspnoea Suspect PAH Right Heart Catheterisation

41 Pulmonary Hypertension: treatment Improved survival in PAH Supportive therapies: Oxygen (if resting po2 under 60mmHg) Loop diuretics Digoxin (anticoagulation) Calcium channel blockers (after dynamic testing) IV epoprostenol Endothelin receptor antagonists Bosentan, Ambrisentanimproved exercise capacity and functional status PDE5 inhibition- Sildenafil, tadalafil improved exercise capacity

Systemic sclerosis and GI involvement

Systemic sclerosis and GI involvement Dr Maggie Larché, MRCP(UK), PhD Associate Professor, Division of Rheumatology, McMaster University St Joseph s Hospital Scleroderma CME, St Joseph s Hospital, September