1. NEPHROLOGY PRESENTATION 28/3/2011

2. HISTORY

3.  62 year male from Bethlehem referred with renal failure  1/12 ago: Constitutional complaints No clear focus of infection Raised CRP and lymphopenia Normal renal function  He was treated symptomatically and discharged

4.  On systemic enquiry - fleeting arthralgia of the large joints - myalgia of the arms and thighs with initiation of movement - he denied any ENT symptoms or skin rash - 35 pack year smoking history, diagnosed with emphysema, but never had any episodes of acute bronchospasm HOWEVER, ONE MONTH LATER, HIS SYMPTOMS HAD NOT IMPROVED

5.  Occupation: administrative work, some occasional welding  No previous history of note, i.e. hypertension, DM  No nephrotoxic drugs

6. CLINICAL EXAMINATION

7.  Vitals: BP 105/70, pulse 80/min  Gen: pale with no edema  CVS: loud P2  Resp: hyperinflated with good bilateral air entry  Abdo: normal  CNS: normal  ENT: reddish uvula, no ulcers  Skin: no evidence of vasculitis / connective tissue disease

8. SPECIAL INVESTIGATIONS

9.  Urine dipstix: 3+ hematuria, 2+ proteinuria  Microscopy: active sediment  MCS: no evidence of infection  24 hour collection: dU protein 0.5g URINE

10.  FBC: Hb 8,4 / MCV 88  U+E: urea 11,6 creatinine 299  CRP 69  ESR >90  HIV (-)  Hepatitis B and C (-)  Protein electrophoresis normal  Complement normal  ANA (-)  cANCA (proteinase 3) > 100, pANCA (MPO) - negative  Anti-GBM - pending BLOOD INVESTIGATIONS

11.  Renal ultrasound showed normal sized kidneys  CXR: hyperinflation, but clear  Shoulder x-ray: evidence of OA RADIOLOGY

12.  Segmental necrotizing vaculitis  Few crescents  No granuloma formation  No eosinophillic infiltrates  No immune complexes HISTOLOGY

13. SMALL CELL VASCULITIS AND THE KIDNEY

14.  Vasculitis is a clinicopathological process characterized by inflammation of and damage to the blood vessels  Affected vessels vary in size, type and location  Can occur as result of a primary process or secondary to another underlying disease  Given the numerous and varied types of vessels in the kidneys, renal disease is caused by a variety of systemic vasculitides.

15. Vasculitis Large sized vessels Small sized vessels -Takayasu’s - ANCA (+) -Giant cell arteritis - ANCA (-) Medium-sized vessels - Poly-arteritis nodosa - Kawasaki’s disease

17. ANCA (+)  Wegener’s granulomatosis  Microscopic poliangiitis  Renal limited vasculitis / ANCA GN  Churg Strauss syndrome  Drug induced ANCA (-)  Henloch Shönlein purpura  Cryglobulinemic  Connective tissue disorders  Goodpasture’s disease  Infection induced  Hypersensitivity  Paraneoplastic SMALL VESSEL VASCULITIS

18. ANCA (+)

19.  5-10 / 1 000 000  Granulomatous inflammation and necrotizing vasculitis affecting the nasal passages, airways and kidneys.  Common presentation include upper airway involvement – epistaxis, nasal crusting, hemoptysis, ulceration and deafness secondary to serious otitis media.  Inflammation of the retro-orbital tissue van cause proptosis and optic nerve compression  Untreated nasal discharge leads to bone and cartilage destruction  Migratory pulmonary inflitrates and nodules on CXR  Mostly cANCA(proteinase 3) WEGENER’S GRANULOMATOSIS

22.  8 / 1 000 000  Necrotizing vasculitis affecting the capillaries, venules or arterioles  Typically presentation includes a rapidly progressive GN, often associated with alveolar haemorrhage  Cutaneous and GIT involvement  pANCA (+), but can be cANCA (+)  Considered as part of a clinical spectrum that includes Wegener’s and renal limited vasculitis MICROSCOPIC POLIANGIITIS

23.  Part of the spectrum including Wegener’s and microscopic poly-angiitis  No systemic involvement  Histology: necrotizing GN RENAL LIMITED VASCULITIS

24.  Renal limited vasculitis - vasculitis with necrotizing GN - no systemic symptoms  Microscopic polyangiitis - vasculitis with necrotizing GN - systemic symptoms and involvement  Wegener’s granulomatosis - vasculitis with necrotizing GN - granuloma formation - systemic symptoms and involvement THE SPECTRUM

25.  Also known as allergic granulomatosis and angiitis  1-3 / 1 000 000  Histology similar to WG, but with eosinophillic infiltrates of the vessel walls  Prodromal period for years with allergic rhinitis, nasal polyposis and late-onset asthma  Triad of skin lesions, asymmetric mononeuritis multiplex and eosinophillia on a background of resistant asthma  Necrotizing GN  Mesenteric vascultitis  cANCA or pANCA CHURG STRAUSS SYNDROME

26. ANCA (-)

27.  Characterized by deposition of IgA-containing immune complexes  Children and young adults  Purpura over the buttocks and lower legs, abdominal symptoms, arthritis following an URTI  GN can occur up to 4/52 after initial symptoms  Biopsy shows IgA deposition on IF  Generally good prognosis but adult presentation, hypertension, renal failure, significant proteinuria can progress to ESRF HENLOCH SHÖNLEIN PURPURA

29.  Characterized by the presence of cryoglobulins  Mix of complement and immunoglobulins, that precipitate in the cold  Type 2 (hep C) and 3 ass with vasculitis  Palpable purpura, athralgia, Raynaud’s phenomena, neuropathy  Immune complexes are deposited in the vessel walls ESSENTIAL CRYGLOBULINEMIC VASCULITIS

30.  Some authors use this term to include HSP, mixed cryoglobulinemia, allergic vasculitis and serum sickness  Most properly used to refer to vasculitis occurring as a reaction to a known or suspected substance such as a drug.  Major finding is palpable purpura / petechiae – leucocytoclastic vasculitis on biopsy HYPERSENSITIVITY VASCULITIS

31.  SLE, RA, relapsing polychondritis, Bechet’s disease  Organ involvement is determined by the underlying disease VASCULITIS SECONDARY TO CONNECTIVE TISSUE DISORDER

32.  Hepatitis B, C  HIV, CMV, EBV, Parvo B19  Clinical presentation can be similar to polyarteritis nodosa or microscopic poylangiitis  Even it is immune complex mediated, it must be distinguished form non-viral associated vasculitides, since the treatment is an anti-viral and not an anti-inflammatory regimen VASCULTITIS SECONDARY TO VIRAL INFECTIONS

33.  The presence of a vasculitic disorder should be considered in any patient with an unexplained systemic illness  Patients often present with non-specific symptoms  However, there are a few clinical scenarios where a vascultic disorder should be looked for… - palpable purpura - pulmonary infiltrates and microscopic hematuria - chronic inflammatory sinusitus - mononeuritis multiplex - unexplained ischaemic events - glomerulonephritis

35.  Primary - immunosuppressive therapy: steroids cyclophosphamide - Bactrim - plasma exchange in severe cases  Secondary - treat the underlying cause - antivirals - immunosuppression with connective tissue diseases - stop exposure to possible causative drugs GENERAL MANAGEMENT OF SMALL VESSEL VASCULITIDES

36.  Glomerulonephritis with renal failure  cANCA  Asymptomatic “ emphysema” diagnosis, myalgia and arthalgia  No ENT symptoms  No resistant asthma  No eosinophillia  No skin involvement  No drug exposure  Renal biopsy: necrotizing GN few crescents no granulomata or eosinophillic infiltrates BACK TO OUR PATIENT…

37.  Renal limited vascultitis / ANCA glomerulnephritis  Microscopic polyangiitis DIFFERENTIAL INCLUDES

38.  Started on prednisone 1mg/kg/day cyclophosphamide 2mg/kg/day bactrim ca, titralac, vit D  Follow-up in 10/7 for review MANAGEMENT

39. THANK YOU