Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease

Transcription

1 Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease Patrick Cronin, DO,FACR Clinical Instructor November 15, 2017 Cooper Medical School of Rowan University Cooper University Bone & Joint Institute Division of Rheumatology

2 American College of Rheumatology Systemic Sclerosis (1980): Classification criteria Diagnosis: 1 major (or) 2 minor Major criterion Proximal scleroderma (proximal to the MCP joints) Minor criteria Sclerodactyly Digital pitting or scars or loss substance finger pad Bibasilar pulmonary fibrosis

3 Classification: Scleroderma Systemic Sclerosis Diffuse cutaneous Progressive Systemic Sclerosis Limited cutaneous C.R.E.S.T. (calcinosis, Raynaud s, esophageal dysmotility, sclerodactyly, atelectasis) Syndrome Scleroderma sine scleroderma

4 Scleroderma-Like Syndromes Scleredema Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk, particularly the shoulders and back. The face may also be affected. In severe cases, mobility of the shoulders and chest is markedly impaired. Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients, and internal organ involvement is rare) Scleromyxedema Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head, neck, arms, and upper trunk, commonly occurring over thickened and indurated skin. Middle-aged adults are most commonly affected. The presence of a monoclonal protein, often IgG lambda, detected by immunofixation on samples of serum and/or urine supports the diagnosis of scleromyxedema. Skin biopsy is valuable. Scleromyxedema may be associated with AL amyloidosis and multiple myeloma. Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration. Endocrine disorders may also occur in some patients with monoclonal gammopathies, for example, in the POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes)

5 Scleromyxedema/myxedema

6

7

8 Epidemiology: Scleroderma Female : Male = 3:1 (Greater in African-American women) Age: Peak years Incidence: 19 cases/million/year Prevalence: cases/100,000

9 Scleroderma: Proposed Pathophysiology Cytokines Transforming Growth Factor β (TGF- β) Platelet Derived Growth Factor (PDGF) Endothelial damage releases endothelin increase fibroblast function Collagen I Fibronectin Glycosaminoglycans Endothelial injury Vasoconstriction/Fibroblast Hypoxia -- TGF β Fibroblast

10 Scleroderma

11 Scleroderma: ANA Centromere Homogenous Speckled Nucleolar

12 Scleroderma: Skin

13 Raynaud s Maurice Raynaud in 1862 stated that "local asphyxia of the extremities loss of oxygen to the tissue.

14 Raynaud s

15 Scleroderma: Digital Artery

16 Thermography: Raynaud s Control 1 Raynaud s Scleroderma 15 c 23 c

17 Scleroderma: Raynaud s

18 Raynaud s Episodic Reversible digital color change White to blue to red Well-demarcated Due to vasospasm Usually cold-induced Primary & secondary forms

19 Raynaud s

20 Scleroderma: Raynaud s, Cyanosis

21 Scleroderma: Capillary Microscopy

22

23 Causes of Secondary Raynaud s Connective tissue diseases Scleroderma, systemic lupus erythematosus, MCTD, undifferentiated CTD, Sjogren s syndrome, dermatomyositis, others Occlusive arterial disease Atherosclerosis, anti-phospholipid antibody syndrome, Buerger s disease Vascular injury Frostbite, vibratory trauma Drugs and toxins Beta blockers, vinyl chloride, bleomycin, ergot, amphetamines, cocaine Hyperviscosity/cold-reacting proteins Paraproteinemia, polycythemia, cryoglobulinemia, cryofibrinogenemia, cold agglutinins

24 Raynaud s

25 Scleroderma: Edematous Changes, Hands

26 Scleroderma: Puffy Phase, Hand

27 Scleroderma: Hands

28 Scleroderma: Skin Induration

29 Scleroderma: Acrosclerosis

30 Scleroderma: Acrolysis

31 Scleroderma: Acro-sclerosis & Terminal Digit Resorption

32 Scleroderma: Digital Pitting Scars

33 Limited Systemic Sclerosis: Calcinosis Calcinosis (Hydroxyapatite) Colchicine Calcium Channel Blockers Arthritis Rheum Nov;38(11): Treatment of calcinosis with diltiazem. Palmieri GM, Sebes JI, Aelion JA, Moinuddin M, Ray MW, Wood GC, Leventhal MR. Source University of Tennessee at Memphis 38163, USA.

34 Scleroderma: Calcinosis Cutis

35 Scleroderma: Calcinosis and Acrolysis

36 Limited Systemic Sclerosis: Calcinosis: Arm

37 Scleroderma: Calcinosis

38 Scleroderma: Facial Changes

39 Scleroderma: Facial Changes

40 Scleroderma: Facial Changes

41 Scleroderma: Watermelon Stomach

42 Scleroderma: Dysmotility and Esophagus Upper GI tract GERD Proton Pump Inhibitor Aspiration Pneumonia PPI vs. Carafate Esophagitis/Barrett s

43 Scleroderma: Bowel Dilatation GI Malabsorption Vitamin D Difficult to treat Bacterial Overgrowth Metronidazole Tetracycline Ciprofloxacin Weight Loss/Cachexia TPN Pseudo-obstruction Non-surgical General Measures Octreotide, erythromycin

44 Scleroderma: Wide-Mouth Diverticula Diverticula Wide mouth Rare diverticulitis Pneumatosis Cystoides Intestinalis Non-Surgical

45 Scleroderma: Pulmonary, Cardiac Pulmonary Pulmonary: ILD/HTN - Rule out Embolic disease (APL), CHF, OSA 6 minute walk Echocardiogram yr ly: PAP PFT with DLCO yr ly: compare DLCO Cardiac Contraction band necrosis - arrhythmias Pericardial effusion large, non-tamp. Myocarditis

46 Scleroderma: Pulmonary HTN PHTN Echocardiogram or Right Heart Cath. High mortality 52% at 3 years survival (*) Bosentan (next slide) Sildenafil SUPER-1 trial (1) (*) Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. Lefèvre G, Dauchet L, Hachulla E, Montani D, Sobanski V, Lambert M, Hatron PY, Humbert M, Launay D Arthritis Rheum. 2013;65(9):2412. (1)Sildenafil citrate therapy for pulmonary arterial hypertension. Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. N Engl J Med Nov 17;353(20):

47

48 Scleroderma: Kidney Scleroderma Renal Crisis High Renin State Microangiopathic Hemolytic Anemia HTN and active urine sediment Prednisone may play a role (*), anti-rna polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern Treatment ACE inhibitor Calcium Channel Blocker Minimize steroids (*)Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Steen VD, Medsger TA Jr. Arthritis Rheum Sep;41(9): Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade Jorge A. Lopez-Ovejero, M.D., Stuart D. Saal, M.D., William A. D'Angelo, M.D., Jhoong S. Cheigh, M.D., Kurt H. Stenzel, M.D., and John H. Laragh, M.D. N Engl J Med 1979; 300:

49 Scleroderma: Kidney One year survival, 15% without and 76% with ACE inhibitors (P < 0.001). Courtesy of Carol Black, MD. Graphic Version 6.0 Courtesy of Helmut Rennke, MD. Graphic Version 2.0 Scleroderma Renal Crisis: renal biopsy with fibrinoid deposition, onion-ring muscular hyperplasia Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors. Steen VD, Costantino JP, Shapiro AP, Medsger TA Jr Ann Intern Med. 1990;113(5):352.

50 Raynaud s: Hands Raynaud s Longer term use Aspirin or pentoxifylline Calcium Channel Blockers Bosentan (PAH) Short term use Topical NTG Prostacyclin IV Phosphodiesterase Inhibitor Others SSRI, ARB/ACE, ect. Arthritis Rheum Dec;50(12): Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Korn JH, Mayes M, Matucci Cerinic M, Rainisio M, Pope J, Hachulla E, Rich E, Carpentier P, Molitor J, Seibold JR, Hsu V, Guillevin L, Chatterjee S, Peter HH, Coppock J, Herrick A, Merkel PA, Simms R, Denton CP, Furst D, Nguyen N, Gaitonde M, Black C.

51 Raynaud s: Homeostasis/Prevention Life-Style Changes Dry hands and feet Avoid convection currents Wool socks and mittens Layer chest wall for heat trapping. Quit tobacco; limit caffeine and alcohol

52 Queen Elisa: Raynaud s patient and spokesperson

53 Scleroderma: Treatment Immunosuppression (Diffuse Disease only) Traditional immunotherapy and antifibrotics Methotrexate D-penicillamine Cyclophosphamide Current clinical immunotherapy treatments Mycophenolate mofatil Abatacept* Tocilizumab* Rituximab * Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GH, Tseng CH, Elashoff RM, Sclerodema Lung Study II Investigators Lancet Respir Med. 2016;4(9):708. Epub 2016 Jul 25.

54 Thank You. Questions?