SYSTEMIC SCLEROSIS PART 2 by dr seema.pptx

Most useful for dermatologist for seminar presentation

1. Systemic Sclerosis – Part 2 PRESENTER: DR HARSHITA SHRIVASTAVA MODERATOR: DR SURESH JAIN SIR

2. CONTENTS: Juvenille SSc Differential Diagnosis Management Treatment objectives Non pharmacological treatment Treatment of RP/DU Treatment of Skin disease Treatment of Pulmonary involvement Treatment of Cardiac inv. Treatment of GI inv. Treatment of SRC Updates in ACR/EULAR 2023

3. Juvenille SSc ( JSSc ) Chronic, multisystem, CTD characterized by symmetrical fibrous thickening and hardening of the skin combined with fibrous changes in internal organ system in a child <16 year of age. JSSc constitute approx. 3% of all cases of SSc . Onset- insidious. Age of onset- Mean: 8-11 yrs Sex- F>M. Diagnosis is often delayed by 1-2 years Incidence- 0.27 per 1 million children Prevalence- 3 per 1 million children Kids really don’t complain, they just slowly stop doing things like participating in sports, eating food, etc.

4. Presentation: Signs and Symptoms Percentage of patients 1. Skin tightening 84 2. Raynaud’s phenomenon 72 3. Arthralgia 32 4. Muscle weakness and Pain 17 5. Subcutaneous calcification 10 6. Dysphagia 16 7. Dyspnea 14 ( Larregue M, et al. Ann Dermatol Venereol 1983, Martini G, et al. Arthritis Rheum 2003)

5. SPECTRUM

6. JSSc ASSc 1. Mean age 8.8 yr 37 yr 2. Digital Ulceration More common (29-50%) Less (22-40%) 3. Arthritis More common (10-35%) Less (15-17%) 4. Cardiovascular Less common (HTN<other abnormalities) More common (HTN>other abn .) 5. Musculoskeletal Less common (31-42%) More common (50-71%) 6. Respiratory Almost same (36-55%) (44-64%) 7. Prognosis Good prognosis Bad prognosis Stevens A, et. Immunopathogenesis of JSSc . Frontiers in Dermatol. 2019)

7. JSSSS(JS4) - ( Juvenille Systemic Sclerosis Severity Score)

8. TREATMENT ALGORITHM OF JSSc ldCs , low-dose corticosteroids; MMF, mycophenolate mofetil; MTX, methotrexate; CPM, cyclophosphamide; AHSCT, autologous hemopoietic stem cell transplantation; Symptomatic drugs: calcium channel blockers, phosphodiesterase type 5 inhibitor, angiotensin-converting enzyme inhibitors, proton pump inhibitors, prokinetics. Biological agents: rituximab, tocilizumab, abatacept.

9. Differential Diagnosis of SSc Eosinophilic Fasciitis (EF)- RP is not associated and NFC examination is usually normal. ANA and more specific autoantibodies are negative. Skin biopsy- Eosinophilic infiltrate in the deep fascia. Scleromyxedema -RP absent, NFC normal, ANA negative. Skin biopsy- Dermal fibrosis with perivascular inflammation along with deposition of mucin and fibrocytes, which are not usually seen in SSc . Scleredema - Associated with Diabetes mellitus, Monoclonal antibodies, fatigue, infections, and malignancies. RP absent, NFC normal, ANA negative. 

10. Nephrogenic Systemic Fibrosis (NSF)- Asso. with ESRD on exposure to gadolinium contrast. RP absent, NFC normal, ANA negative. Eosinophilia Myalgia Syndrome- Epidemic associated with the use of L-Tryptophan leading to severe myalgias, visceral involvement, and elevated CK. Toxic Oil Syndrome- Epidemic in Spain associated with the intake of adulterated rapeseed oil, leading to livedo reticularis, pulmonary infiltrates, and elevated CK . ( Rotimi Adigun;  Amandeep Goyal ; Anis Hariz .  May 8, 2022)

11. COMPARATIVE FEATURES OF VARIOUS DIFFERNTIALS

12. MANAGEMENT

13. treatment objectives: • To limit or stop the disease’s progression • To reduce sequelae • To improve the patient’s quality of life by managing the disability and loss of function

14. Therapeutic education and lifestyle change It has been defined by the WHO as follows: “TPE enables patients to acquire and maintain the skills they need to better manage their lives with a chronic illness.” Nonpharmacological measures recommended for all patients: • Protection from the cold: Wear gloves, use “thermal” clothes, use heaters, heated gloves. • Protect against microtrauma. • Quit smoking, which multiplies the risk of digital trophic disorders by three. • Avoid vasoconstrictor drugs. “Alternative” therapies such as acupuncture and biofeedback techniques have not been studied rigorously.

15. Disease/Disorder Investigation Management Raynauds phenomenon -Cold challenge/ cold p rovocation test -Nail fold capillaroscopy -Serology 1. Warm clothing, avoid cold, stop smoking and caffeine. 2. Topical GTN microemulsion 3. ARB: Losartan 25–50 mg/day 4. CCB: Nifedipine 10 mg T.D.S. Diltiazem 60 mg B.D., T.D.S. 5. SSRI: Fluoxetine 20 mg/day (has no role in 2023 update) 6. Iloprost (0.5–2 ng/kg/min for 3–5 days) 7. Complimentary therapies- Vitamins C and E, Gingko biloba 9. Sympathectomy 10. Botulinum toxin injection

16. DISORDER DETECTION MANAGEMENT Critical digital ischaemia / Digital ulceration Swab culture X-ray MRI 1. Hydrocolloid occlusion, wound care, pain control, antibiotics 2. PDE5 inhibitor: Sildenafil 25–50 mg T.D.S. (healing) 3. ERB: Bosentan (reduction in new ulcers) 4. Combination of ERB + PDE5 inhibitor + ARB 5. Statin 6. Antithrombotic therapy: Clopidogrel, Aspirin. LMW heparin (not recommended in 2023 update)

17. FLOW CHART FOR MANAGEMENT OF RP/DU

18. Vasoconstrictor drugs contraindicated or used with caution for Raynaud’s phenomenon ( According to frances et al. 2008) Nasal decongestants by local or general administration Pseudoephedrine Phenylephrine Phenylpropanolamine Migraine drugs derived from ergot Dihydroergotamine Ergotamine Beta-blockers Anti-glaucoma beta-blocker eye drops Hyperprolactinemia treatments Bromocriptine Cabergoline Lisuride Antiparkinsonians Pergolide

19. It describes deposition of insoluble calcium salts in the skin and subcutaneous tissue. There are 5 main types of which ‘DYSTROPHIC CALCINOSIS CUTIS ’ is seen in association with Autoimmune CTD (particularly SSc and DM) It results from local tissue injury. TREATMENT PRINCIPLES: Primary goal is to minimize symptoms and alleviate functional limitations. MANAGEMENT OF CALCINOSIS CUTIS

20. Drug therapy- 1) Topical or intralesional Sodium thiosulphate (STS)- MOA: Antioxidant and vasodilatory properties. Compounded 10-25% STS LABD Intralesional STS: 150-250 mg/ml following administration of local anaesthesia . Improvement is seen after 1-4 treatments. 2) Oral Diltiazem: 2-4mg/kg/day. MOA: Inhibits calcium influx in cells. 3) Oral Colchicine: 0.6mg BD. 4) Oral Minocycline: 50-200 mg/day. 5) Others- Bisphosphonates, IVIG, Oral Aluminium hydroxide, ILS, Probenecid, Infliximab, Rituximab.

21. Surgical treatment- Excision Excision with fasciocutaneous flap Debulking with a high speed-burr Incision and drainage CO2 laser vaporization Extracorporeal shock wave lithotripsy. Risks- recurrence, poor wound healing, infection, and sinus formation.

22. INVESTIGATIONS TO DIAGNOSE SYSTEMIC INVOLVEMENT:

23. MANAGEMENT OF SKIN MANIFESTATIONS IN Ssc General Manual lymphatic drainage ( Vodder technique) Physiotherapy Topical therapies Emollient Topical corticosteroids Calcineurin inhibitors (evidence in Morphoea ) Vitamin D analogues (evidence in Morphoea ) Phototherapy PUVA, UVA1 (in SSc ) Diffuse or progressive skin sclerosis MTX 15–25 mg/week MMF 2–3 g/day Diffuse or progressive skin sclerosis with lung involvement IV Cyclophosphamide 600 mg/m2/month for 6 months or 500 mg/ m2 for the first month increasing to 750 mg/m2 Oral Cyclophosphamide up to 2 mg/kg/day for 1 year

24. Diffuse or progressive skin sclerosis without lung involvement if intolerant to MTX/MMF Azathioprine 2–3 mg/kg/day Systemic sclerosis with associated myositis IVIg 2 g/kg over 2–5 days monthly Ciclosporin Pruritus Ketotifen 6 mg/day Naltrexone 2–4.5 mg/day Antihistamines Montelukast Glucocorticoids Calcinosis Surgery, CO2 laser Telangiectasia Pulsed dye laser: better outcomes IPL (intense pulsed light): fewer side effects

25. DISORDER DETECTION MANAGEMENT Cardiorespiratory Pulmonary fibrosis Cough Dyspnoea Palpitations Syncope PFTs (FVC/DLCO) HRCT chest Clinical features ( bibasal coarse crepitations) Immunosuppression Oral MMF 2-3g/day Nintedanib Rituximab Tocilizumab Consider combination therapy- Eg : MMF + Nintedanib MMF + Tocilizumab Nintedanib + Tocilizumab Consider: Cyclophosphamide IV or oral (6-12 months) with MMF (2-3 g/day) or Azathioprine (150mg/day) as maintenance. Prednisolone 10mg OD Rigorous antireflux therapy: PPI, H2-antagonist, prokinetic. Oxygen – int. or long-term low flow

26. DISORDER DETECTION MANAGEMENT PAH Cough Dyspnoea Palpitations Syncope -PFTs -ECG -ACA, Troponin T, Urate -6 min walk test -Doppler Echo -24 h BP -Right heart catheterisation Treatment escalated according to WHO FC stage I-IV. Endothelin receptor blockers: AMBRISENTAN (5-10mg OD), BOSENTAN (62.5mg BD), MACITENTAN. PDE5 inhibitors: SILDENAFIL, TADALAFIL (10-20mg OD) Initial combination therapy recommended. Guanylate cyclase stimulator: RIOCIGUAT (0.5-1mg TDS) Prostacyclin analogues: EPOPROSTENOL (continuous) IV, ILOPROST inhaled or IV, TREPROSTINIL oral/ sc /iv

27. EULAR/ACR (2023 Update) SSc -RP: Dihydropyridine-type calcium antagonists, usually oral nifedipine, should be used as first-line therapy for SSc -RP. PDE5 inhibitors should also be considered for treatment of SSc -RP. Intravenous I loprost should be considered for severe SSc -RP following failure of oral therapy. Digital ulcers: PDE5 inhibitors and/or intravenous I loprost should be considered for the treatment of digital ulcers in patients with SSc . Bosentan should be considered for reduction of number of new digital ulcers in SSc .

28. Drug Mechanism of Action Trial Identifier Phase Romilkimab Bispecific IL4/IL13 antibody NCT02921971 II Sirolimus mTOR inhibitor NCT03365869 II Tofacitinib Janus kinase inhibitor NCT03274076 I/II GSK Oncostatin M inhibitor NCT03041025 II Ziritaxestat Autotaxin inhibitor NCT03798366 II Bortezomib Proteasome inhibitor NCT02370693 II Lenabasum Cannabinoid receptor agonist NCT03398837 III Bermekimab IL-1 alpha inhibitor NCT04045743 II Pirfenidone MMF Antifibrotic NCT03856853 II Brodalumab IL-17 receptor antagonist NCT03957681 III New drugs under trial for treatment of SSc

29. REFERENCES Martin Calderon, L. & Pope, J. E. Scleroderma epidemiology update.  Curr. Opin . Rheumatol .   2021; 33 : 122–7. LeRoy, E. C. et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis.  J. Rheumatol .   1988; 15 : 202–5. De Almeida Chaves, S. et al. Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality.  Arthritis Res. Ther .  2021; 23 : 295. Christopher P Denton, Enrico De Lorenzis , Elen Roblin, Nina Goldman, Begonya Alcacer-Pitarch , Emma Blamont , et al. The 2024 British Society for Rheumatology guideline for management of systemic sclerosis—executive summary,  Rheumatology , 2024 ;63: 2948–55.