Diseases. Siriporn Juthong, M.D. Division of Rheumatology 23/11/58
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1 Common Connective tissue Diseases Siriporn Juthong, M.D. Division of Rheumatology Songklanagarind Hospital 23/11/58
2 What are the diseases in connective tissue disorder? Sign and symptoms of CTD?
3 Nonspecific organ manifestations of CTD Fatigue/tiredness/malaise Fever Weight loss Enlarged lymph nodes CTD Malignancy (esp.hemato) Chronic infection differential diagnosis to be consider 23/11/58
4 Specific organ/system manifestation of CTD Polyarthritis / Polyarthralgia Raynaud phenomenon Skin/mucosal lesions Serositis/myositis/vasculitis Interstitial lung disease Multi organ systems involvement
5 23/11/58 Typical skin manifestations in CTD
6 SLE 23/11/58
7 23/11/58 Systemic sclerosis
8 23/11/58 Abnormal nail fold capillaroscopy
9 23/11/58 Inflammatory myositis : Dermatomyositis
10 Vasculiticrash 23/11/58
11 23/11/58 Antiphospholipid syndrome
12 23/11/58 Sicca symptom : Sjogren syndrome
13 23/11/58
14 CNTD SLE Rheumatoid arthritis Systemic sclerosis Polymyositis/dermatomyositis common manifestations malar rash, discoid rash, arthritis, oral ulcer Chronic symmetrical polyarthritis of hands joints, erosion +, ±deformities Cutaneous sclerosis, sclerodactyly, digital pitting scar Proximal muscle weakness, CPK, heliotrope, gottron papules SjӦgren syndrome Dry eyes, dry mouth Mix connective tissue diseases Mixed pattern of CNTD manifestations and positive U1RNP
15 RAYNAUD PHENOMENON an exaggerated physiological response of the extremities to exposure to cold or emotional stress classical presentation : fingers turning white (ischaemia) blue (cyanosis) red (reperfusion).
16 Pi Primary or idiopathic (Raynaud s disease) episodic attacks of acral pallor or cyanosis strong and symmetrical peripheral pulses absence of digital pitting, ulceration or gangrene normal nailfold capillaries ANA test : negative normal ESR Patients who do not fulfil these criteria require further evaluation Secondary Raynaud phenomenon Nat. Rev. Rheumatol. 8, (2012)
17 Older age at onset (>35 years) Asymmetrical involvement Digital scar, digital gangrene Abnormal capillary nail fold Clinical features suggestive of a CNT disease Detection of autoantibodies : ANA, anticentromere, anti Scl 70
18 23/11/58
19 A 23 year old woman presents to her general practitioner with a three month history of malaise, fatigue, and arthralgia which she attributes to a viral illness. She had also attended the emergency department with pleuritic chest pain at the start of symptoms. She has had two miscarriages in the past, but has otherwise been healthy. On examination, there are small, non tender lymph nodes in her neck and mildly swollen, tender, proximal interphalangeal jointsinher hands. What are the next investigations? BMJ 2013;347:f5060 doi: /bmj.f5060
20 35 YOF ; joint pain for 3 months PE : all PIP are tender and swelling Chronic symmetrical polyarthritis in young lady CND : rheumatoid arthritis, SLE, systemic vasculitis. Infection : Chikungunya, HIV, HBV Crystal : gout, CPPD Malignancy : paraneoplastic syndrome
21 35 YOF ; joint pain for 3 months PE : all PIP are tender and swelling fever + fatigue, alopecia
22 35YOF ; chronicarthritis arthritis, fever, rash (DLE), palatal ulcer further investigation CBC Hct 28% WBC 3300 (N 92 L 8) Platelet 85,000 PBS normochromic, normocytic ESR 70 mm/hr U/A proteinuria 2+, no WBC, RBC cast + leucopenia, lymphopenia, thrombocytopenia, glomerulonephritis Arthritis, DLE, oral ulcer ANA 1:640 peripheral pattern
23 2012 SLICC : SLE classification criteria SLE occurs if biopsy proven lupus nephritis + ANA or ds DNA or 4 out of 17 criteria At least 1 from clinical criteria and from immunologic criteria Classification criteria for research purposes**
24 SLICC classification system Lancet 2014; 384:
25 Antinuclear antibodies A group of autoab specificities targeting antigens in nucleus, also in cytoplasm. Highly sensitive, but non specific and not diagnostic Serum titer of ANA does not correlate with disease severity and activity
26 Condition Positive ANA associated diseases Pt. with ANA+(%) SLE Systemic sclerosis 97 Polymyositis/dermatomyositis Mixed connective tissue disease 100 Rheumatoid arthritis Sjögren's syndrome Drug induced lupus 100 mmune mic autoi ses Syste disea Autoimmune hepatitis 100 Organspecific Thyroid disease autoimmune Multiple sclerosis 25 diseases Infection/Malignancy Varies widely Chronic disease Relatives of patients with autoimmune diseases 5 25 Normal Normal elderly (> 70 years) 20 Adapted from Kelly Textbook of Rheumatology 8 th edition
27
28 ANA ; Indirect timmunofluorescence Assay (IIF)
29 Healthy persons 1: % 1: % 1:160 5 % 1:320 3% Interpretation Negative result : < 1:80 Positive result : > 1:80 Significant positive titer : > 1:160
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31 ชาย 30 ป บวมขามา 3 เด อน เดอน 3 เด อน บวมท ขาสองข าง ป สสาวะเป นฟอง ปร มาณปกต อาการเป นมาก ข นเร อยๆ น าหน กเพ มข นมา 5 กก. ไม ไข ; BP 160/90 mmhg
32 ชาย 30 ป บวมขามา 3 เด อน CBC : HCT 25 % WBC 2800 ( PMN 75 L 20 Mono 5) Plt 109,000 AIHA : microspherocyte, polychromasia, autoagglutination Thrombocytopenia, leucopenia, lymphopenia
33 ชาย 30 ป บวมขามา 3 เด อน AIHA Thrombocytopenia Leucopenia, lymphopenia UA : protein 3 +, 24 hour urine protein 4 gm/d RBC RBC cast Nephritonephrotic syndrome Lupus nephritis
34 ชาย 30 ป บวมขามา 3 เด อน AIHA Thrombocytopenia Leucopenia, lymphopenia Nephritonephrotic syndrome What are the next investigations? ANA positive 1:1280 peripheral pattern Anti ds DNA positive CH50 25 % C3 low
35 ชาย 30 ป บวมขามา 3 เด อน Diagnosis : Active SLE Hemolytic anemia Thrombocytopenia Leucopenia/ lymphopenia Renal Lupus nephritis ANA positive Anti dsdna positive
36 23/11/58 Pathogenesis of SLE
37 23/11/58
38 23/11/58 Initial assessment of SLE
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40 แม บ านหญ ง 35 ป (Chronic symmetrical polyarthritis) ปวดข อน วม อสองข างมานาน 12 เด อน ฝ ดต งตอนเช านาน 2 ช วโมง, ปวดข อม อ ข อไหล ข อศอก ไม ม ไข อาการปวดเป นตลอด อาการปวดเปนตลอด กนยาแกปวด ก นยาแก ปวด ด ข นเล กน อย ดขนเลกนอย ไม ม ผ นแพ แสง ผมร วง ไม ม น าหน กลด, ไม ม ผ น, ไม ปวดหล ง
41 แม บ านหญ ง 35 ป PE : fusiform soft tissue swelling and tender at all PIP joints, MCP joints. Swelling andtenderboth wrists and elbows. No deformity No rash No nail change No rheumatoid nodule Other WNL Problem list Chronic symmetrical polyarthritis (upper) DDX. Rheumatoid arthritis SLE,other CNTdisease Spondyloarthritis (PsA) OA Crystal induced arthritis (rare) : Gout
42 แม บ านหญ ง 35 ป CBC, ESR, Film both hands ( AP, Oblique), RF Cr, AST, ALT, CXR
43 Summary : แมบานหญง แม บา นหญ ง 35 ปป CBC : WBC 15,120 (PMN 70, L 30), HCT 30% MCV 85, platelet 540,000, ESR 98 mm/hr Rheumatoid factor : negative
44 Rheumatoid arthritis (RA) A progressive immune mediated disease involving the synovium that can culminate in joint destruction, significant functional impairment, and early mortality.
45 Multistep Progression to the Development of Rheumatoid Arthritis. McInnes IB, Schett G. N Engl J Med 2011;365:
46 Signs and symptoms Persistent symmetric polyarthritis (synovitis) of hands and feet (hallmark feature)* Progressive articular dt deterioration ti Extra articular involvement Difficulty performing activities of daily living (ADLs) Constitutional symptoms PE : *** assess the following *** Stiffness Tenderness Pain on motion Swelling Deformity Limitation of motion Extra articular manifestations Rheumatoid nodules # DIP joint are typically spared in RA
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49 Radiographic progression of RA Juxta articular osteopenia Uniform joint space narrowing Marginal M i lerosion
50 Extra articular manifestation
51 Rheumatoid nodule Interstitial lung disease C1 C2 subluxation
52 Extra Articular manifestations of RA Am Fam Physician. 2011;84(11):
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55 Rheumatoid factor (RF) Autoantibodies reactive with epitopes in the Fc portion of IgG 70% of patients with RA have RF positive The titer does NOT correlate with disease activity High titer RF are more likely to have erosive joint disease, more radiographic abnormalities, extra articular manifestations, and greater functional disability Not specific for RA : chronic infections, cirrhosis, malignancy, andotherrheumatic rheumatic disease
56 Female 40 years 8 weeks, joint pain and morning stiffness 60 min. Arthritis of Lt. wrists, allrt. PIPand MCP joints No rheumatoid nodule ESR 60 mm/hr Film hands : periarticular osteopenia, no erosion RF negative
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61 ANTI CYCLIC CITRULLINATED PEPTIDE (Anti CCP) sensitivity 70 80%, specificity 95 98%*** (more than RF) Anti CCP present in early disease highly specific for rheumatoid arthritis predict development of more erosive RA anti CCP could be detected in variety of diseases
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