a case of anca vasculitis
TRANSCRIPT
Dr TeffyM4 unit
Prof Dr G Elangovan’s unit
Panjatcharam, 51/M, labourer, from Vyasarpadi
Admitted with , Fever - 7 days ,1 wk back Facial puffiness - 7 days Haematuria - 7 days,on& off Epistaxis - 3 days B/L leg swelling - 3 days
H/o fever for 7 days, I wk back - high grade,intermittent,not associated with chills/rigor - cough with minimal mucoid expectoration +; no hemoptysis
H/o facial puffiness - 7days, - periorbital,early morning
H/o haematuria - 7days - painless,early morning
• H/o epistaxis – 3 days - on &off,minimal bleed ,subsides spontaneously
• H/o B/L leg swelling – 3 days - minimal,progressive,
No H/o abdominal distension/breathlessness/decreased urine outputNo H/o loin pain/abdominal pain/dysuria/pyuriaNo H/o chest pain/palpitation/giddiness/syncopeNo H/o jaundice/nausea/vomiting
No h/o head ache/facial pain/rhinitisNo h/o other bleeding tendenciesNo h/o sore throat/skin lesions /jointpains/ rashes/ulcers/drug or native medicine intakeNo h/o trauma
Recently detected to be hypertensive one week backNo h/o DM/CAD/TB/CKD
Personal history: alcoholic & smoker – 30 yrsFamily history : non contributary
• ON EXAMINATION :• conscious , oriented to time,place&person• comfortable at rest• Hydration fair
• Periorbital puffiness +• B/L pitting pedal edema + (minimal)• Grade 1 clubbing +• No pallor/icterus/cyanosis/lymphadenopathy/ skin lesions• Bone & joints – normal; Eyes – normal• No paranasal sinus tenderness
Vital signs : Pulse - 82/min,regular,normal volume;all peripheral
pulses equally feltBP - 150/100 mmHg, Rt arm ,sittingRR -16/min,abdominothoracicTemp – NormalJVP – not elevated
SYSTEMIC EXAMINATION : within normal limit
Possibility of a renal disorder – ? Acute glomerulonephritis
INVESTIGATIONSCOMPLETE BLOOD COUNT
Hb 13
PCV 40
TC 9,800
DC N 60 L38 E2
Platelet count 3,00,000/mm3
ESR 30/64
MCV 86
MCH 29
RFT 16/10 22/10
RBS 104 98
UREA 50 48
CREATININE 1.7 1.6
Na 138 137
K 3.8 3.9
LFT
T Bil 1.0
SGOT 22
SGPT 19
S ALBUMIN 4.4
T CHOLESTEROL 160
URINE ROUTINE & MICROSCOPY
SPECIFIC GRAVITY 1.020
PH 5
GLUCOSE -
BILIRUBIN -
KETONE -
BLOOD 3+
PROTEIN 3+
RBC CASTS +
24 Hr URINE PROTEIN 400 MG/DAY
URINE C/S NO GROWTH
USG ABDOMEN & PELVIS: NORMAL STUDY RK- 10.3;LK – 10.9 Normal PCS,Echoes, CMD+
• ECG : NSR;WNL• ECHO:Normal
• Peripheral smear study : normal
OTHER INVESTIGATIONS :
CRP 25
ASO titre negative
Rheumatoid factor negative
ANA negative
HIV 1&2 Negative
HBs Ag Negative
Anti HCV Negative
S CALCIUM 10.2
S PHOSPOROUS 4.3
S URIC ACID 5.1
NEPHROLOGY OPINION : 16/10 – ? Acute Glomerulonephritis - to do C3,C4,C ANCA,P ANCA - continue antibiotics
C 3 121(90-180)
C4 23.45(10-40)
C ANCA POSITIVE ( IFA)
P ANCA Negative
ANCA vasculitis with epistaxis ? Wegener’s Granulomatosis -PLAN : CT chest CT PNS ENT opinion
CHEST X RAY PA VIEW : WNL
CT CHEST : WNL
CT PNS : B/L PANSINUSITIS –mucosal thickening +;no bony
erosions/expansion/fluid level
Chest X ray
CT Chest
X ray PNS
ENT opinion(23/10) : L/E : Ear,nose,throat -normal DNE with biopsy
NEPHROLOGY REVIEW : 24/10 – C/O ANCA Vasculitis; Epistaxis B/L Pansinusitis - ? Wegener’s Granulomatosis PLAN : Renal biopsy : To start IV methyl prednisolone followed by
oral prednisolone
Renal biopsy
Focal segmental glomerulonephritis ;focal necrosis +No immune deposition
Sinus mucosal biopsy- results pending
FINAL DIAGNOSIS ANCA vasculitis -renal & upper respiratory tract involvement ;
D/D1.Wegeners granulomatosis2.Microscopic polyangiitis3.Idiopathic necrotising glomerulonephritis4.CHURG strauss syndrome
possibly Wegener’s granulomatosis
TREATMENT givenINJ Cefotaxime 1g IV BDINJ Ranitidine 50 mg IV BDINJ Frusemide 20 mg IV BD , 2 daysINJ Methyl prednisolone 1 g in 100 ml NS IV infusion
over 1 hr , 3 days followed byTab Prednisolone 60 mg/day ( 1 mg/kg bw)
ANCA1982 –Davies & colleagues first described ANCA ;
Two types – c ANCA & p ANCA (IFA);
Antigens associated are -- proteinase 3-PR3 – c ANCA --myeloperoxidase –MPO-p ANCA• ANCA positivity by IFA should be confirmed by antigen specific testing for both PR3 & MPO
DISEASE ASSOCIATIONS Vasculitis :- : small vessel vasculitis – WG,MPA,CSS : idiopathic necrotising crescentic glomerulonephritis
Sensitivity of ANCA -50 to 90 % -Negative test does not rule out diagnosis in patients with high pretest probability
Specificity of ANCA ; : If IFA results are combined with antigen specific assays,the
specificity of both PR3-ANCA & MPO-ANCA is exceedingly high. • Influences disease phenotype -- PR3 – WG; MPO - MPA -- PR3 positive patients -> more relapse ->more granuloma -> more extrarenal
others..Rheumatoid arthritis ,SLE, myositis
Cystic fibrosis , endocarditis ,& HIV
Inflammatory bowel disease :UC > crohn’s Sclerosing cholangitis ,autoimmune heaptitis Drugs : Hydralazine ,propylthiouracil high MPO- D penicillamine ,minocycline ANCA
Wegener’s granulomatosis• First described in 1931 by Heinz Klinger ;
• Classic triad-Granulomatous necrotising vasculitis affecting the upper & lower respiratory tract and the kidneys; • Prevalence – 3/1,00,000 persons
• Affects both sexes equally ;
• Affects all ages –( mean age 41 yrs );
• More common in Caucasians
Pathogenesis Exact cause unknown;
HLA-DR1 & HLA-DQw7 association has been reported ;
PR3-ANCA antibodies are highly specific for Wegener’s (90-97%);
ANCA s cause neutrophil degranulation & also cause endothelial damage ;
Evidence of T cell involvement is less direct ;
Clinical featuresPredilection for upper,lower respiratory tract & the
kidneys ;
Mild forms of wegener’s without renal involvement have been described ;
Indolent or rapidly progressive course ;
Unexplained constitutional symptoms like fever and weight loss in one fourth of the patients
Upper airway featuresMost common presenting feature In 70 % of the patients at onset ,ultimately developing in
>90%Sinusitis(MC) initial presentation in 50 -67%;in85 %
during the course of the diseaseSecondary infection-S. aureus is predominant organism;Epistaxis -11-32%Biopsy - granulomatous inflammation with necrosis ;
vasculitis+/- - complete diagnostic triad in 3 – 16%
Renal manifestationsPresence or absence of renal disease defines generalised or
limited wegener’s ;
Early disease mey be clinically silentExtrarenal manifestations may precede renal disease11-18% at presentation & 80% over the course
mild focal & segmental glomerulonephritis with minimal haematuria & little dimunition of GFR tofulminant,diffuse,necrotizing &crescentic glomerulonephritis(RPGN) leading within days to wks to oligoanuria &dialysis
If untreated mean survival is 5 months ;Chronic renal failure in 42% despite treatment ;Urine microscopy most useful tool ;Presence of RBC casts 100% positive predictive value
for glomerulonephritis ;Fulminant WG - can manifest as pulmonary renal
syndrome ( alveolar haemorrhage & RPGN)
Accounts directly or indirectly for most of the mortality in this disease
PATHOLOGY:Focal ,segmental glomerulonephritisFibrinoid necrosis & proliferative changesEpiithelial crescentsSclerotic lesions
Vasculitis – focal in 5-10%
Granulomatous changes –only in 3-20%
Immune complex deposition unusual (pauci immune)
The degree of renal failure & serum creatinine do not always correlate with pathological features
picture
Frequency of Clinical features In 158 pts ; Studied at NIH
MANIFESTATION AT DISEASE ONSET DURING THE COURSE
KIDNEY
Glomerulonephritis 18 77
EAR/NOSE/THROAT 73 92
Sinusitis 51 85
Nasal disease 36 68
Otitis media 25 44
Hearing loss 14 42
Subglottic stenosis 1 16
Ear pain 9 14
Oral lesions 3 10
LUNG 45 85
Pulmonary infiltrates 25 66
Pulmonary nodules 24 58
Hemoptysis 12 30
Pleuritis 10 28
EYES
Conjunctivitis 5 18
Scleritis 6 16
Proptosis 2 15
Visual loss 8
Corneal/retinal lesions,iritis
OTHERS
Arthralgias/arthritis 32 67
fever 23 50
cough 19 46
Skin abnormalities 13 46
Wt loss 15 35
Peripheral neuropathy 1 15
CNS disease 8
Pericarditis 2 6
Venous thromboembolism,Accelarated atherosclerosis
ACR criteria(1990) : WG : atleast 2/4 criteria1. Nasal/oral inflammation2. Abnormal chest radiograph3. Microhaematuria4. Biopsy
Lab diagnosisGeneral :
- leucocytosis ,normochromic normocytic anemia , thrombocytosis
- raised ESR &CRP;
• Pathology : necrosis ; granulomatous changes ; vasculitis
: open lung biopsies – 90 %
ANCA & WG :1985 – Vander woude & colleagues – first to suggest
an association between ANCA & wegener’s
Most likely to be positive in pts with triad disease that is active & untreated
- PR3 ANCA -sensitivity –active disease – 90% remission -40% -specificity - > 95%High titre ANCA + PR3/MPO specific assay with high pretest probability is sufficient to diagnose
even in the absence of tissue confirmation
Regarding monitoring disease activity,
A substantial no of pts with rise in ANCA titre did not flare;hence rise in ANCA titre should not be the sole basis for therapeutic decision making
It was rare to see a flare in the absence of increased ANCA-strong negative predictive value
TREATMENTCYCLOPHOSPHAMIDE + GLUCOCORTICOIDS :
complete remission in 75 % of patientsCyclophosphamide – oral ; 2mg/kg/d - monitor leucocyte count (>3,000)/µl - S/e – haemorrhagic cystitis(30%);bladder
cancer(6%);myelodysplasia(2%); infertility-comtinued for 1 yr after the induction of complete
remission ,taper &discontinue
Glucocorticoids : -Oral;prednisone 1 mg/kg/d initially(1mth);then
alternate day schedule ;taper&discontinue - S/E –
diabetes,cataract,infections,osteoporosis;cushingoid features
- IV pulse methyl prednisolone (1g/d for 3 days ) especially for severe cases
• 50% of remissions are later associated with one or more relapses
Maintenance
Methotrexate – start at 0.3mg/kg single weekly dose - till 2 yrs past remissionAzathioprine- 2mg/kg/dayMycophenolate mofetil – 1000mg twice a day
OTHERS:Methotrexate induction for non severe disease RituximabTMP-SMX(upper airway disease)Organ specific treatment - isolated sinus or joint or skin disease - subglottic stenosis & endobronchial stenosis
Case reports :1. Unusual renal manifestation of Wegener’s -60 yr old female presented
with glomerulonephritis & ,mononeuritis multiplex 2 yrs before development of classic necrotizing granulomatous inflammation of sinuses & nose along with pulmonary nodules
The American Journal of medicine vol64,issue5,may 1978
2. Upper respiratory tract (maxillary & ethmoidal sinusitis) , renal involvement(pauci immune crescentic glomerulonephritis),vasculitis in a 15 yr old girl;c ANCA positive; responded well to steroids & cyclophosphamide
Journal of clinical medicine research vol 2,no 4,august 2010
REFERENCES1. Kellys textbook of Rheumatology2.Oxford textbook of Rheumatology3.Harrison’s Internal Medicine
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