Pulmonary Fascinomas with a Tuberculosis Attitude. Douglas Hornick, MD Medical Consultant Meeting November 29-30th, 2018.

Transcription

1 Pulmonary Fascinomas with a Tuberculosis Attitude Douglas Hornick, MD Medical Consultant Meeting November 29-30th, 2018 EXCELLENCE EXPERTISE INNOVATION 1 Disclosures Douglas Hornick, MD has the following disclosures to make: No conflicts of interest No relevant financial relationships 2 1

2 Pulmonary Fascinomas with a Tuberculous Attitude Douglas B. Hornick, MD Pulmonologist with an Infectious Attitude University of Iowa Carver College of Medicine Iowa City, Iowa 3 Iowa is no longer left out 4 2

3 Ponder These Cases TB or not TB revisited 5 IA has been good to me 33 yo M from Togo, in IA x 13 yrs (visits Togo annually) B/l uveitis worsening x2 wks (failed local Rx, pred 5 mg) BTW: Cough, b/l pleuritic CP, 20# wt loss x4 weeks PMH: Psoriasis many years; Neg: Smoker, DM Meds: Adalimumab (since 2009); Prednisone 5 mg x 2 wks Exam: Appears chronically ill OU red/injected c/w b/l uveitis; OS granuloma (?) adjacent optic disc Lungs clear Skin w/o obvious psoriasis plaques ID considerations: HIV neg, Denies high risk sexual encounters; No exposure to TB, TST neg q6 mos 6 3

4 Diffuse Bilateral Nodular (miliary) Interstitial Pneumonitis Extensive Mediastinal Adenopathy 7 Additional Data HIV/Lyme/Syphilis/Toxo negative Histo & Blasto Urine antigens negative Q-GIT 0.15 ANA, RF, ANCA negative What Now? Bronchosocopy TBBx, EBUS mediastinal LN and BAL: Granulomas (non-necrotizing), AFB/Fungus stains negative BAL Crypto, Histo/Blasto antigens, galactomannan negative, & TB AFB/PCR negative Treat for TB? 8 4

5 All that glitters is not gold Anti-TNFα Paradoxical Adverse Event Sarcoid??? De novo immune-mediated disease while on biologic agent to treat primary immune-mediated disease Case reports/series: Psoriasis, CD/UC, Uveitis, sarcoidosis, etc Mechanism uncertain/debated: Shift of cytokine profile to unopposed INFγ Sarcoid Rxn more common w/ etanercept & possibly increased INFγ promoting granuloma formation Anticipate with newer biologics (ie, anti-il1, -IL6) Touissirot E. RMD Open More to This Story Adalimumab stopped; No TB Rx 1 Month 2 Months Vision worsened Prednisone 60 mg daily x 2 months Vision, Respiratory symptoms and CXR improved PFTs: Normal Spiro/LV DLCO 70% (56%); TB cultures remained negative 10 5

6 Off Humira Skin Rash Arms/Legs (Patchy/Scaley/Puritic) Skin Biopsy: c/w psoriasis, no granulomas Apremilast added x 9 months Psoriasis resolved; Uveitis & OS optic n granuloma returned Ophtho: Pred 60 x 2 mos, Dex implant OS; CXR pre/post: No respiratory symptoms DLCO 60% Post Prednisone DLCO 55% 11 Progressive Eye/Pulm Disease Progressive adenopathy & interstitial infiltrates R>L (refused PFTs) Persistent/recurrent uveitis Apremilast stopped; Avoiding biologics d/t paradoxic granulomatous rxn Added MTX 20 mg & prednisone 20 mg plus nb UVB for psoariasis Hospital cost affecting his adherence & f/u 12 6

7 Uncertain Dx/Outcome Repeat sputa & IGRAs negative; This was not active TB Biologic Rx (anti-tnfαα; PDE4 inhibitor) related paradoxical adverse event? Sarcoidosis? More biologic use More cases TB/sarcoid mimics w/in patients who also might have TB 13 Ponder These Cases Pleural Paradoxic 14 7

8 My Pleura & My Butt Hurts! 66 yo mildly mentally challenged male who lives alone Presented with rectal pain & biopsy showed inflammation c/w Crohns disease Rectal/GI symptoms worsened despite Prednisone Referred UIHC evaluation starting Inflixamab Chest x-ray abnormalities raised concerns 15 Unable to produce sputum, TST negative Thoracentesis: yellow fluid, exudate, ph 7.25, WBC 14K (12K PMNs, 0.1K L) Gram stain: Many WBCs, no organisms; AFB negative What next? Pleural biopsy: No granulomas Acute Inflammation w/ manyafb Subsequent sputum AFB smear positive Rest of the story: Retrospective AFB stain of rectal biopsy: sheets of AFB (No Granulomas!) W/u for immune deficiency: HIV, INF & other immune deficiency negative Organisms pan susceptible DOT (daily) Treatment: IRZA x 2 months, continued IR x 7 add l months Cured; no relapse or other infections (f/u 2 yrs after finishing Rx) 16 8

9 Gee Whiz Pleural/Pulmonary/Rectal TB Dangerous TB Case: Unsuspected plus steroid Rx AFB positive, no granulomas! (?immunodeficiency) Pleural TB Small number of organisms cause extensive reaction (hypersensitivity) Pleural fluid: lymphocyte predominant, low ph, AFB smear & culture positive ~20%, elevated adenosine deaminase (ADH) Pleural biopsy w/ culture: positive ~75% (x2, to 90%) Next example shows far end of the pleural infection spectrum year-old man w/ no clinically significant medical history, six-month history of an increasing mass on the left side of his back (Panel A) 3 days before seen Serous drainage from L chest CT: Pleural nodules, empyema fluid encasing L lung & leaking out Pleural fluid & bx negative AFB, but granulomas & culture positive Empyema Necessitatis Chaiyasate, K. et al. N Engl J Med 2005;352:e8 18 9

10 MD x 2 = a paradox 48 yo F nurse c/o R back pain (3-7/10) travels around side to front at times & when supine; plus non-prod cough, fatigue, all slowly worsening x4 wks PMH: Migraine & LTBI dx 2.5 yr prior, treated w/ INH x4 months d/t INH hepatitis) SH: Worked MICU, then IR, Travel to Cancun, Nonsmoker, no EtOH, no HIV RF, runs 5 miles/day until last month FH & ROS noncontributory Exam: VS nl, non-dermatomal distribution R lower posterior thorax pain, non-reproduceable w/ pressure, abd/flank normal Blood & urine labs normal Chest x-ray normal 19 One week later (5 weeks since onset) Local ER: T 101.4, pain pleuritic 7-10 radiating to R shoulder What now? Thoracentesis: Exudate, ph 7.42, Lymphocytic, ADA elevated, AFB smear/pcr negative 20 10

11 The story continues Pleural biopsy not done (fluid & sputum AFB cultures ultimately negative) DOT: moxi i/o INH, RZE No medication adverse effects nor intolerance 3 weeks on Rx: DOE, chest pain, low grade fever persists Colleague in IR U/S R thorax more fluid Chest x-ray shows sl increased R pleural shadow What Now? U/S guided thoracentesis attempt: no fluid Pleural Biopsy deferred 21 Stuttering Improvement(?) 2 months No cough, DOE improving, no more fevers Chest x-ray improving Moxi stopped, Daily DOT RZE continued 3 months DOE, Pleuritic chest pain return (3-5/10) Colleague in IR says effusion larger by curbside U/S Looks well, afebrile, no adenopathy, BS R chest Chest x-ray improved cp to last month 22 11

12 Less Pleural Thickening TwoMonths Three Months 23 Stuttering Improvement(?) 2 months No cough, DOE improving, no more fevers Chest x-ray improving Moxi stopped, Daily DOT RZE continued 3 months DOE, Pleuritic chest pain return (3-5/10) Colleague in IR says effusion larger by curbside U/S Looks well, afebrile, no adenopathy, BS R chest Chest x-ray slightly more improved cp to last month No change Rx gradual improvement 6 months Prior 2 weeks: worsening DOE, fatigue, pleuritic CP Colleague in IR curbside U/S Exam unchanged; blood & urine labs unremarkable Chest x-ray 24 12

13 Persistent, more distinct, non-anatomic vertical, linear density R lower lung field Decreased R costophrenic angle thickening compared prior film(s) No cardiomegaly, infiltrates or mediastinal adenopathy What now? 25 Chest CT Pleural based linear ridge of pleural reaction, extending vertically across 4 rib spaces along R lower posterior thorax. Both CT & U/S characteristics: Mostly non-fluid density 26 13

14 What Now? Possible causes progressive changes in TB pt on Rx: Drug resistant organism Poor adherence to Rx Another lung disease HIV patients: Immune Reconstitution Syndrome or Poor drug absorption Paradoxical enlargement on effective TB Rx Best described for tuberculous lymphadenitis (up to 30%), Less often brain tuberculomas & lung infiltrates Pleural space too? Supposedly more common in pediatric TB Pathogenesis uncertain Biopsies: granulomata, rare AFB, usually sterile Speculation: Hypersensitivity response to TB antigens (role of cidal Rx?) Generally resolve spontaneously w/o need for change inrx Exception: Enlarging brain lesions: neurologic sequalae, occurs ~2 months into Rx, steroids helpful Note: Lung Histoplama lesions also enlarge/regress/develop satellite lesions spontaneously Teoh et al: QJMed 1987, Silman et al: AJRCCM 1994, Carter et al: Chest 1994, Palayew & Frank: Radiology TB Pleural Effusion: Paradoxic Reaction on Rx Retrospective Review at King Saud U, Saudi Arabia N = 61 TB effusions Paradoxical fluid increase 10/61 (16%) 6/10 massive w/ significant dyspnea & required therapeutic drainage 5/6 received steroids Recent case report, 26 yo HIV neg M w tuberculous lymphadenitis post 1 month HRZE developed R pleural effusion (exudate, ADA neg, AFB/PCR neg) which resolved gradually w pred x 6 wks & w/o changing Rx Does this match your experience? Al-Majed SA. Resp Med 1996;90:211-14; Bhttacharya A. Clin Med 2017;17(2):

15 Current Status Spontaneously improving w/o changing Rx Suspect Paradoxical Pleural Reaction January 2019 will complete RZE x9 months plus moxi x initial 2 months 29 Be Happy The End! 30 15