A TRICKY PROBLEM Presenter-Dr Lakshmi PK
Patient particulars 33 years old Male Resident of Andhra Pradesh Occupation-soldier
Chief compliants Headache- 03 days Headache-global,throbbing type Associated with vomitting-non projectile, no blood/bile No other localizing symptomn.
Examination P-90/min reg, all PP palpable BP-180/110 mm of Hg No pallor, icterus, Cyanosis,clubbing,LNnpathy,Pedal oedema Fundoscopy- bilateral flame shaped hemorrhage s/o hypertensive retinopathy S/E-NAD
Investigation-29 SEP 14 Hb TLC PLT 10.1 gm/dl 9700/P65L24 2.33 lakhs Bilirubin 0.6/0.3 OT/PT/SAP 23/20/36 BUN/creatinine 78/12.8 Na/K 131/4.2 Ca/PO4 9.2/4.8 Ur RE/ME ipth Iron/Ferritin/TIBC Blood Sugar 87 25(OH)D3 Prot 4+,6-8 RBCs,8-10 WBCs,8-10 epithelial cells 249.1(14-72pg/dl) 164 mcg/dl, 120ng/ml, 197mcg/dl 17.25(30-100 ng/ml)
ECG
USG KUB RK-8.97 CM LK-8.9CM Increased cortical echogenicity with loss of CMD No HDN/Calculus/Focal lesion
Working diagnosis RPGN CGN-CKD
Management Started on HD + Supportive care Suspicion of RPGN Methyl prednisolone pulse x 3 Oral Prednisolone Kidney biopsy (after stabilization)
ANA canca/panca Anti GBM NEGATIVE NEGATIVE NEGATIVE C3 73.6(84-164 mg/dl) C4 dsdna HBsAg/Anti HCV HIV 24.1(15-48mg/dl) Negative Negative Negative 24 hour urinary protein 2451 mg/gm of creatinine
Kidney biopsy 12 glomeruli,11 obsolescent Marked IF/TA>50% of cortical area IF-2 obselete glomeruli neg for IgG,IgA,IgM,C3,C1q,K/ʎ Imp-chronic glomerulonephritis
Kidney biopsy
Kidney biopsy
Diagnosis Revised diagnosis: Chronic Glomerulonephritis-CKD stage 5D Plan: Tapered steroids Planned for renal transplant.
Course of illness: Asymptomatic for 10 days Dyspnoea & orthopnea Fever -1 day -1 day Examination P-140/min reg BP-160/120 mm of Hg JVP raised SpO2-86% at room air R/R-36/min Chest-bilateral crackles ECG-LVH pattern no new change.
INV Hb TLC Plt BUN Creatinine Na/K PBS 12gm/dl 17100/P64L23 3.71 lakhs 65mg/dl 8mg/dl 133/4.2 meq/l No shift to left No toxic granules
Inv CXR
Possibilities: 1. Pneumonia 2. Fluid overload 3. Combination of both Management: 1. Antibiotics 2. NIV support 3. Intensification of HD Outcome: Dramatic improvement
Repeat CXR CXR-PA: at admission CXR-PA: D-3
Status: Low grade fever persisted Clinically better/ ambulant Recurrence of similar symptoms after 20 days Exam/ Investigations: BP-160/110 mm of Hg Chest-bilateral crepitations CXR-right sided NHO Echo: Global HK, LVEF- 38%
HRCT chest
Therapy and outcome Antibiotics-21 days Intensification of HD Rapid resolution of symptoms Low grade fever persisted 4 th episode on 31 Dec 2015 Associated hemoptysis-30-50 ml 3-4 episodes Nose/ throat/ oral cavity: normal Repeat C3/C4-(normal) ANA-negative ANCA-negative Anti GBM-negative Procalcitonin-86.03 mg/ml(<0.04) On examination T-100 0 F P-138/min reg BP-120/78 mm of Hg SpO2-70% at room air 84% with O2 inhalation Chest-bilateral crackles
Management Working diagnosis: Pneumonia + fluid overload (Kidney + Cardiac) Strong suspicion of vasculitis (Alveolar Hge) Management: NIV support + Antibiotics + HD Immunomodulation:?? (on going infection & raised procalcitonin) IVIg-5 days (cumulative 2 g/kg)
CXR Pre-therapy Post-therapy
Issues Issues: Recurrent episodes of chest infiltrates, improving with antibiotics and intensification of HD. Chronic glomerulonephritis- CKD 5D Alveolar hge Evidence of ongoing infection Negative autoimmune markers Plan: Bronchoscopy + TBLB Repeat kidney biopsy
Bronchoscopy Haemorrhagic BAL fluid
Multiple Thickened Blood Vessels with Interstitial Fibrin deposition
interstitial Fibrin deposition
Capillaritis and Hemosedirin Laden Macrophages
TBLB Organizing pneumonia with pulmonary hemorrhage, interstitial fibrosis and capillaritis Consistent with pulmonary manifestations of collagen vascular disease
Recurrence of symptoms MP x 3 TPE + IVIg x 5 Rituximab 375 mg/m2 weekly x 4 No recurrence of symptoms for the last 1 month
Pulmonary renal syndrome
Diagnosis-Pulmonary renal syndrome Pauci immune vasculitis: IF- neg, normal complements, lung & kidney involvement, Capillaritis, RPGN type picture (now burnt out) Odd point: ANCA negative (Drugs??) Goodpasture's syndrome Anti GBM antibody negative IF of kidney biopsy not supportive
DISCUSSION
Pulmonary Renal syndromes Definition- combination of diffuse alveolar haemorrhage (DAH) and glomerulonephritis Pulmonary small-vessel vasculitis Renal Inflammation of arterioles, venules and alveolar capillaries (necrotic pulmonary capillaritis). Proliferative glomerulonephritis-fibrinoid necrosis/crescent formation Interstitial infiltration, fibrosis and tubular atrophy Necrotizing granuloma Small vessel vasculitis Papiris et al. Critical Care 2007, 11:213
Pulmonary Renal syndromes ANCA asssociated vasculitis-70% 95% ANCA positive Anti GBM antibody associated-20% 92% anti GBM positive 5 10%-without e/o renal activity Zimmerman Cm et al Goodpasture s syndrome with normal renal function. Am J Med 1979;66:163 71. Hiroshi Yamaguchi et al Case Reports in Nephrology Volume 2013,
Diffuse alveolar hemorrhage in PRS 25% -fatal in first episode of DAH 50% require assisted ventilation. Recurrent episodes have sequalae- Obstructive lung disease Pulmonary fibrosis Brown Kevin et al Proc Am Thorac Soc Vol 3. pp 48 57, 2006
Treatment as per disease severity Severe disease defined by - functional impairment of critical organs- renal disease (creatinine- 5.7 mg/dl)/ DAH/ other life-threatening disease Severe disease-plasma exchange followed by maintenance immunosupression Most dialysis dependent Papiris et al. Critical Care 2007, 11:213 Brown Kevin et al Proc Am Thorac Soc Vol 3. pp 48 57, 2006