Bronchiolitis Obliterans Organizing Pneumonia in Rheumatologic Disease Rheumatology Rounds

Bronchiolitis Obliterans Organizing Pneumonia in Rheumatologic Disease Rheumatology Rounds Tuesday September 16, 2003 Tracy S. Roberts CASE • 29F N.A. • Dx with SLE x 8 yrs – Presented with ascending radiculopathy – Transverse myelitis/encephalitis june ’03, Rx with high dose steroids and iv cyclophosphamide with good response CASE • PMH – – – – – seizures osteoporosis osteoarthritis rheumatoid arthritis asthma • MEDS – HCTZ 25mg od – Dilantin 300mg od – Prednisone 40mg am 30 mg pm – Oxazepam 30mg od – Remeron 15mg qhs – Ca/vit D/folic acid – Septra ss tab od HPI • Admitted to medicine August 13th with a 2-3 day hx of progressive SOB, left pleuritic chest pain, weakness and associated neck and back pain • Fever, chills, n/v, diarrhea • No arthralgias/myalgias/rash CLINICAL FINDINGS • Acute distress • T=38 BP=88/50 PR=110 RR=30 Sao2= • • • • 99% on 40% O2 RS : crackles in left base CNS: 3/5 upper limbs, 2/5 lower limbs CVS + ABD: NAD MSK: b/l knee effusions INVESTIGATIONS • Hb 148 wbc 11.5, lymph=.388, plt 156 • Normal lytes, CR, LFT’s incr , ESR=? • CXR-infiltrates in right mid and lower lobe, left • • • • lingula and left lower lobe ECG sinus tachycardia Urinalysis negative ANA(-), anti-dsDNA(-), anti-SmAb(-), HepBsAg NR Effusions : Gram stain(-), no crystals, c+s (-) COURSE IN HOSPITAL • Started on levofloxacin and septra • August 14th worsening SOB, increasing cough and sputum-- ICU • Rx with ceftriaxone/azithromax/septra/ solumedrol 80mg IV q8h • Rpt CXR bilateral airspace disease with multiple foci of consolidation • Intubated on August 15th COURSE IN HOSPITAL • Aug 15th bronchoscopy- BAL marked neutrophilia, PCP (-), scarce AFB, AMTD (-) x2, culture (+) for MAC, CMV (-), fungus(-), (ethambutol/clarithromycin/rifampin) on Aug29th • Quadruple therapy for PTB, then MAC Rx • Tracheostomy Aug 30th • Aug 18th HRCT showed diffuse airspace disease involving all lobes, left> right, small b/l pleural COURSE IN HOSPITAL • No significant response to antibx, continued on high dose steroids • Aug 22nd open lung biopsy of lingula, left lower lobe – Negative for TB/MAC/CMV/HSV vasculitis/malignancy//fungus – c/w BOOP COURSE IN HOSPITAL • Transferred to floor Sept 3rd • MAC Rx d/c’d on Sept 8th • Now on solumedrol 20mg q8h BOOP • First described in 1901 • More cases reported by Epler in 1985 • Age incidence 4th-7th decades • Incidence 6-7/100,000 admissions • Not related to smoking BOOP • aka.. cryptogenic organizing pneumonia • Pathological entity • Excessive proliferation of granulation tissue within small airways and alveolar ducts, associated chronic inflammation of surrounding airways BOOP • Classification – Idiopathic – Post infection- mycoplasma, legionella, CMV, adneovirus, influenza, chlamydia, PCP, crytococcus – Drug induced-amiodarone, bleomycin, gold, dilantin, cocaine, carbamezapine – Rheumatologic-SLE, RA, DMPM, Sjogren’s, AS, Behcet syndrome, PMR – Immunologic disorderscommon variable immunodeficiency, essential mixed cryglobulinemia, GVHD • Classification – – – – Focal nodule Bone marrow transplantation Lung transplantation Miscellaneous- HIV, XRT, myelodysplastic syndrome, lymphoma, chronic thyroiditis, alcoholic cirrhosis, IBD, tryptophan, textile dye printing, seasonal syndrome with cholestasis KEY FEATURES • Intraluminal organizing fibrosis in distal • • • • • • • airspaces Patchy distribution Preserved lung architecture Uniform temporal appearance Mild interstitial chronic inflammation Fibrinous exudates Accumulation of foamy MACS in alveoli Connective tissue polyps KEY NEGATIVE FINDINGS • • • • • • • Lack of interstitial fibrosis Absence of granulomas Lack of neutrophils/abscesses Absence of necrosis Lack of hyaline membranes Lack of prominent eosinophil infiltration Lack of vasculitis BOOP vs Bronchiolitis Obliterans • BOOP – – – – – – – – Alveolar ducts interstitial disorder late crackles patchy infiltrates on CXR Reduced TLC and DLCO Lymphocytes in BAL Good response to RX Good prognosis • BO – – – – – – – – Distal bronchioles Airflow disorder Early crackles Normal CXR Reduced FEV1, FEV1/FVC Neutrophils in BAL Poor response to Rx Poor prognosis PRESENTATION • Flu-like illness :fever, malaise, fatigue • Persistent non-productive cough • Dyspnea on exertion • Wt loss greater than 10 lbs (57%) CLINICAL FINDINGS • Inspiratory crackles • Wheezing (rare) • Clubbing(<5%) • Normal exam (25%) RADIOGRAPHIC FINDINGS • CXR- bilateral, diffuse, patch, peripheral alveolar opacities – Reticular interstitial pattern in minority of cases – Ground glass opacities in > 2/3 of cases – Pleural effusions , cavities, pleural thickening and honeycombing (RARE) – All lung zones may be affected – Severity correlates with the extent of histological involvement of respiratory and alveolar ducts • HRCT- patchy air space consolidation in peripheral and lower lung zones, ground glass opacities, small nodular opacities, bronchial wall thickening and dilatation INVESTIGATIONS • Routine labs non-specific • Leucocytosis-50% • Increased ESR -100mm/hr or > • + CRP • Auto Ab (-) or in very low titre • PFT’s- decreased VC with normal flow rates...mild to moderate restrictive defect, decr. DLCO INVESTIGATIONS • BAL- higher percentage of lymphocytes, neutrophils, eosinophils, low CD4/CD8 • “mixed pattern” of cellularity • Video assisted thorascopic lung biopsy…GOLD STANDARD • Transbronchial biopsy not ideal as may miss representative lesion, and does not adequately allow exclusion of associated lesions DIFFERENTIAL DIAGNOSIS • Bacterial pneumonia • ARDS • Hypersensitivity pneumonitis • Chronic eosinophilic pneumonia • Pulmonary drug reaction • Pulmonary disease associated with CTD TREATMENT • Spontaneous improvement is rare • Prednisone @ 1mg/kg/d for 1-3 mths, then 40mg/d x 3mths, then 10-20mg/d or every other day x 1 year • Methylprednisone 125 to 250mg Q6hx 3-5 days TREATMENT • If deterioration occurs despite steroids or if not tolerated cytotoxic agent…… cyclophosphamide 2mg/kg/d as a single dose (not to exceed 150 mg/d) • Erythromycin, inhaled triamcinolone have been used anecdotally TREATMENT • Relapses may occur when steroids withdrawn • Monitor clinically with CXR, PFTs • Normalization of CXR and clinical improvement in 2/3 of patients over weeks to months • If > 3 recurrences may require continuous prednisone, cyclophosphamide or both OUTCOMES • 1/3 pts have persistent disease • Total recovery 65 to 85% of patients • Mortality 5% PROGNOSTIC FACTORS • Predominantly interstitial pattern on imaging • Lack of lymphocytosis in BAL fluid • Underlying disorder • Scaring and fibrosis on histology BOOP in Rheumatologic Disease • Clinical and radiological findings similar to the idiopathic form • Most commonly seen in SLE,PM-DM, RA, although well documented cases are lacking • Uncommon, but BOOP has been found to be the initial manifestation in SLE and PM • Case reported where BOOP developed during treatment with low dose steroids while the underlying lupus was clinically inactive. • Suggestion that patchy lung involvement has a better prognosis • Responsive to steroid therapy, but less so than idiopathic form TAKE HOME MESSAGE • Consider BOOP early if patient not improving on antibiotic Rx • Establish diagnosis early so that steroids are started before irreversible changes in lung function begin