More rheumatology…. (and a bit of respiratory!)

1. More rheumatology….(and a bit of respiratory!) Sarah Murray

2. Learning Objectives • SLE • Connective tissue disorders • Polymyositis/dermatomyositis • Systemic sclerosis • Vasculitides • Sarcoid

3. SLE – ‘the great pretender’ Multisystem inflammatory autoimmune disease Female 9:1 Male Associated with HLA B8/DR2/DR3

4. SLE • Aetiology: Factors - Genetic, hormonal, environmental Triggers – Drugs (Hydralazine, Phenytoin, Isoniazid), viruses (EBV) ‘Flare’ triggers – sunlight, OCP, infection, stress • Pathology Antibodies to autoantigens, abnormal cell-mediated immunity, B-cell hyperactivity, immune complex formation. Antibodies: • >95% ANA +ve • Anti-ds-DNA • Anti-Ro, Anti-La, Anti-Sm, Anti-RNP • 40% RhF +ve • Anti-histone +ve in 100% drug-induced.

5. SLE – clinical features • 15-40 years • Constitutional symptoms – fatigue, malaise, weight loss, fever, myalgia • Neuro – seizures, neuropathies, chorea • Pulmonary – pleuritis, pleural effusion, pulmonary fibrosis, PHT • Cardiovasular – pericarditis, Libman-Sacks endocarditis, Raynaud’s phenomenon • Renal – glomerulonephritis • MSK – arthralgia(polyarticular, non-erosive) • Haematological – leuco/lympho/thrombocytopenia anaemia Associations: Sjogren’s, autoimmune thyroid disease, Anti-phospholipid syndrome.

6. SLE • Investigations • Bloods – ESR↑, C3/C4↓, anti-dsDNA titres, FBC, U+E, CRP (N/↑) • Urine – blood, protein, casts • Immunology – auto-antibodies • Treatment • General – avoid triggers • Mild – NSAIDs, Hydroxychloroquine • Moderate – corticosteroids, Azathioprine, Methotrexate, Mycophenolate, Rituximab • Severe – admit, urgent IV Cyclophosphamide, high dose Prednisolone

7. Autoimmune Connective Tissue Diseases Polymyositis and dermatomyositis Systemic sclerosis

8. Polymyositis/dermatomyositis • Autoimmune inflammation of muscle±skin • May be paraneoplastic • Features: • Constitutional symptoms • Proximal muscle weakness, arthralgia/myalgia • Myocarditis, respiratory failure, dsphagia/dysphonia • Skin – grotton’s papules, ‘shawl sign’, heliotrope rash • Investigations: • ↑ESR, ↑CK/LDH, Anti-Jo1, Anti-Mi2 • Muscle biopsy definitive diagnosis • Screen for malignancy • Treatment: • High dose steroids, immunosuppressants

9. Fig 1 – Grotton’s papules Fig 2 – Heliotrope rash Fig 3 – Shawl sign Fig 1. http://reidhosp.adam.com/content.aspx?productId=39&pid=1&gid=000839 Fig 2. http://dermatology.cdlib.org/103/NYU/case_presentations/102108n8.html Fig 3. http://www.dermis.net/bilder/CD211/550px/img0082.jpg

10. Systemic sclerosis • Limited • ‘CREST’ (calcinosis, raynaud’s, (o)esophageal dysmotility, sclerodactyly, telangectasia) • Microstomia, furrowing, contractures • Diffuse • CV – Raynaud’s, pericarditis • Resp – fibrosing alveolitis • MSK – arthralgia/joint stiffness Investigations: >95% ANA +ve; limited = anti-centromere, diffuse = anti-topoisomerase

11. Fig 2 - Microstomia Fig 1 - sclerodactyly Fig 1. http://www.sclero.org/medical/symptoms/photos/sclerodactyly/knaggs/1-palms-up-enlarged.html Fig 2. http://dwp.gov.uk/publications/specialist-guides/medical-conditions/a-z-of-medical-conditions/scleroderma/clinical-features/

12. Vasculitides • Inflammation of vessel wall • Consequences – stenosis, thrombosis, dilatation/aneurysms, infarction and haemorrhage. • Features depend on organ affected (skin, kidneys, brain, heart, lungs, eyes) • Large • GCA • Takayasu’s • Medium • Polyarteritis nodosa, Kawasaki’s • Small • ANCA +ve – Wegener’s granulomatosis, Microsopic polyangiitis, Churg-Strauss • ANCA –ve – HSP, Goodpasture’s

13. Vasculitides Giant Cell Arteritis • Presentation: Elderly females, often co-exists with PMR • Affects carotid and branches • Features: • Insidious or abrupt onset • Headache, scalp tenderness, jaw claudication • Thickened tender temporal artery, may be pulseless • Amaurosis fugax • Investigations: • ↑ ESR ↑CRP ↓Hb • Biopsy – inflammatory cells, giant cells, granulomata • Treatment: • High dose Prednisolone

14. Vasculitides

15. Sarcoid Multisystem granulomatous disorder, affecting young adults (age 20-40) Pathology - Epithelioid non-caseating granulomata, in multiple tissues. Presentations • Bilateral hilar lymphadenopathy • Asymptomatic - incidental finding on routine CXR • Acute - lethargy, arthralgia, erythema nodosum • Pulmonary – exertional dyspnoea, dry cough, cor pulmonale. • Extrapulmonary • CV – cardiomyopathy, arrythmias • Abdo – Hepatosplenomegaly, renal stones • Eyes – uveitis, conjunctivitis, keratoconjunctivitis sicca • Skin – erythema nodosum (painful, purple, pretibial) • Face – parotid enlargement, Bell’s palsy • Neuro – CN palsies (esp VII), meningitis, SOL, spinal syndromes

16. Sarcoid Investigations Bloods – FBC (lymphopenia), U+E (↑Ca2+), LFTs (deranged), ↑ESR, ↑Ig Serum ACE - ↑in 75% CXR – BHL, pulmonary infiltrates, fibrosis PFTs – restrictive defect Tissue biopsy – lung (or other) is diagnostic BAL - ↑lymphocytes ↑neutrophils CT/MRI Bone X-rays Treatment BHL – no treatment Acute – rest, NSAIDs, steroids Progressive/extrapulmonary – prednisolone for 6/52 (↓ over 1 year)

17. MEQ - Sarcoidosis A 34-year-old woman has a routine chest x-ray. She is asymptomatic. It shows bilateral hilar lymphadenopathy, and sarcoidosis is suspected. a) List 3 clinical features of sarcoidosis that you would specifically look for on your initial clinical examination. Erythema nodosum Hepatosplenomegaly Parotid enlargement Uveitis/conjunctivitis Bell’s palsy b) List 2 investigations (other than biopsy) that might help confirm the diagnosis. Bloods: Serum ACE, ↑ESR, ↑Ig, U+E (↑Ca2+, deranged LFTS), FBC (↓Hb ↓WCC) Pulmonary function tests (restrictive defect)

18. The above investigations are inconclusive and biopsy of a lymph node is carried out. What is the characteristic microscopic finding in sarcoidosis. • Epithelioid non-caseating granulomas (collections of histiocytes, giant cells and lymphocytes) …3 months later she has a dry non-productive cough and becomes breathless on mild exertion. List 3 cardiovascular/respiratory complications of sarcoidosis that might explain these symptoms. • Pulmonary fibrosis • Cor Pulmonale (RVF secondary to pul disease) • Cardiomyopathy • Arrythmias

19. Questions?

20. EMQ - Complications of sarcoidosis • Anterior uveitis • Cardiomyopathy • Choroidoretinitis • Conduction system disease • Diabetes insipidus • Erythema nodosum • Facial nerve palsy • Lupus pernio • Parotitis • Peripheral neuropathy 1. A 26-year-old woman is referred to ophthalmology outpatients with a 3-day history of ’acute, painful red eyes’. Her symptoms improve with topical corticosteroids but she is referred to the chest clinic where a diagnosis of sarcoid is confirmed. a) Anterior uveitis 2. A 31-year-old man presents to his GP with increasing exertional dyspnoea associated with a macular papular violaceous rash over his nose. His chest X-ray confirms bilateral hilar lymphadenopathy. h) Lupus pernio 3. A 29-year-old woman with known sarcoidosis is admitted for investigation of polyuria and polydipsia. Investigations show hypernatraemia, normal glucose and large urine volumes of low osmolality. She is placed on DDAVP (vasopressin) and her symptoms improve. e) Diabetes insipidus

21. EMQ - Complications of sarcoidosis • Anterior uveitis • Cardiomyopathy • Choroidoretinitis • Conduction system disease • Diabetes insipidus • Erythema nodosum • Facial nerve palsy • Lupus pernio • Parotitis • Peripheral neuropathy 4. A 24-year-old woman presents to her GP with worsening exertional dyspnoea and a large lesion over the anterior surface of her right shin. Chest X-ray confirms bilateral hilar lymphadenopathy. f) Erythema nodosum 5. A 37-year-old woman with known sarcoidosis presents to her GP with increasing exertional dyspnoea and peripheral oedema. O/E she is normotensive, the pulse is 40bpm and regular, and the JVP is raised with cannon waves. Auscultation of he heart is unremarkable. An ECG shows AV dissociation with a narrow complex escape rhythm. d) Conduction system disease

22. EMQ - Vasculitides • Churg-Strauss • Giant cell arteritis • Henoch-Schonleinpurpura • Kawasaki’s disease • Microscopic polyangiitis • Polyarteritisnodosa • Takayasu’s disease • Wegener’s granulomatosis 1. A 42-year-old woman presents to her GP with exertional dyspnoea associated with a dry cough and bloody nasal discharge. She has some swelling of her ankles and fingers. Investigations confirm acute renal failure and high c-ANCA titres. h) Wegener’s granulomatosis 2. A 36-year-old man is admitted to hospital with a BP of 210/130mmHg and frank haematuria. Investigations reveal multiple renal aneurysms on renal angiogram. C-ANCA, p-ANCA and ENA all negative. f) Polyarteritis nodosa 3. A 77-year-old woman presents to her GP with malaise and severe bitemporal headache, associated with scalp tenderness. She denies any visual disturbance or systemic upset. Her ESR is 110mm/h. b) Giant cell arteritis

23. EMQ - Vasculitides • Churg-Strauss • Giant cell arteritis • Henoch-Schonleinpurpura • Kawasaki’s disease • Microscopic polyangiitis • Polyarteritisnodosa • Takayasu’s disease • Wegener’s granulomatosis 4. A 22-year-old man presents to A+E with increasing wheeze and exertional dyspnoea. He has noticed some ankle swelling . Investigations: WCC 13.6 (eosinophils 11.2), K+ 6.3, urea 17.9, creatinine 472; c-ANCA –ve. a) Churg-Strauss 5. A 27-year-old man presents to A+E with a severe rash over his thighs and buttocks, associated with pain and swelling of his knees and ankles. FBC, U+E, antibodies and urinalysis normal, but serum IgA is raised. c) Henoch-Schonlein purpura

24. EMQ - Autoantibodies • Anticardiolipin • Anticentromere • Anti-ds-DNA • Anti-Jo-1 • Anti-La • Anti-RNP • Anti-Ro • Anti-Scl-70 • c-ANCA • p-ANCA 1. 23-year-old woman with increasing malaise, arthralgia, rash over upper cheeks. Investigations: pancytopenia and mild renal impairment. c) Anti-ds-DNA 2. 39-year-old woman with long-standing pain and colour changes in her fingers in cold weather presents with multiple ‘red spots’ over her face and increasing dyspepsia. Recently unable to open mouth fully. b) Anti-centromere 3. 54-year-old man with increasing pain and weakness of upper limbs and rash around eyes. Investigations: CK 22,500 IU/l, CXR shows large lesion right mid-zone. d) Anti-Jo-1

25. EMQ - Autoantibodies • Anti-cardiolipin • Anti-centromere • Anti-ds-DNA • Anti-Jo-1 • Anti-La • Anti-RNP • Anti-Ro • Anti-Scl-70 • c-ANCA • p-ANCA 4. 36-year-old man presents to A+E with increasing exertional SOB and ankle swelling, dry cough and bloody nasal discharge. Investigations: ESR 110mm/h, K+ 7.3, urea 53.6, creatinine 1158. i) c-ANCA 5. 31-year-old woman presents to A+E with acute hemiparesis, facial palsy and expressive dysphasia. Long-standing SLE and several miscarriages in her 20s. a) Anti-cardiolipin