RAIN Clinicopathologic ID: 74 year old Chinese woman with past - PowerPoint PPT Presentation

2/16/2018 Case RAIN Clinicopathologic  ID: 74 year old Chinese woman with past medical history of rheumatoid arthritis, who presents with fevers and altered mental status.  HPI. Conference 2018  2 weeks prior to presentation – had L vision loss.  Diagnosed with endophthalmitis, unknown cause, treated with intravitreal vancomycin, ceftazidime, and voriconazole x 2.  CT chest noted incidental LLL cavitary lesion Dr. Chris McGraw, MD, PhD  Started empiric treatment for Toxo (systemic pyrimethamine and sulfadiazine) due to Department of Neurology elevated serum Toxo IgM.  1 week prior to presentation – had AMS with neck tenderness. Dr. Melike Pekmezci, MD Department of Pathology  Diagnosed with multifocal strokes and had full stroke work-up Dr. Felicia Chow, MD  Cardiac monitor with pAFib. Negative TTE. Department of Neurology  Started warfarin for secondary stroke prevention  Started prednisone taper for unclear reasons (?concern for vasculitis) University of California San Francisco  Day of presentation (2 days following discharge from prior admission) – obtunded 2/16/2018  Presented to TB clinic for scheduled outpatient evaluation.  Transferred to ED, promptly intubated, admitted to ICU Case Case Comatose, GCS 6/15  PMH. RA, HTN, R glaucoma, L endophthalmitis, ?strokes. Trip to Guangzhou, China  Medication. Warfarin, Sulfadiazine, Pyrimethamine, leucovorin, Prednisone 20mg. Hydroxychloroquine 200, Metoprolol, Timolol. MRI brain multifocal infarcts  SH. Moved from China 8 years ago. Last visit 4 mos ago. Independent ADLs at baseline. Loss of vision L eye  FH. No history of malignancy, autoimmune or neurologic Lung cavitary lesion disease.  Physical exam. Altered mental status  Gen. Fever 103°F , tachycardic 111, normotensive 120s  Neuro. GCS 6(E1,Vt,M5). L pupil 6mm fixed. Intact cornea, #1 #3 #4 #2 VOR. Weak gag/cough.  Labs. 3 months 0 1 3 23 28 29 32 34  CBC. WBC 11.6 (80% PMNs, 11% Lymphs, 5% monos, 2.2% eos) prior  Unremarkable BMP , LFTs. HIV negative. Days since onset of illness 1

2/16/2018 Initial thoughts? MRI Brain on admission  Dr. Felicia Chow T2 FLAIR 16/28 28/28 27/28 26/28 25/28 24/28 23/28 22/28 21/28 20/28 19/28 18/28 17/28 15/28 1/28 13/28 12/28 11/28 10/28 9/28 8/28 7/28 6/28 5/28 4/28 3/28 2/28 14/28 MRI Brain on admission MRI Brain on admission T2 TRACE T1 PRE + POST 2/69 48/69 53/69 52/69 51/69 3/69 49/69 46/69 47/69 55/69 45/69 44/69 43/69 42/69 41/69 54/69 57/69 56/69 39/69 58/69 59/69 60/69 61/69 62/69 63/69 64/69 65/69 66/69 67/69 68/69 69/69 1/69 40/69 50/69 38/69 11/69 17/69 16/69 15/69 14/69 13/69 12/69 10/69 19/69 9/69 37/69 7/69 6/69 5/69 4/69 18/69 8/69 20/69 30/69 36/69 21/69 35/69 34/69 32/69 31/69 33/69 29/69 23/69 27/69 26/69 22/69 25/69 24/69 28/69 17/25 18/25 19/25 20/25 23/25 21/25 22/25 15/25 24/25 25/25 16/25 11/25 14/25 13/25 12/25 10/25 9/25 8/25 7/25 5/25 4/25 3/25 2/25 1/25 6/25 2

2/16/2018 Routine Labs Microbiology Hospital course – initial treatment Basic metabolic panel Na 146, K 4.8, CL 118, CO2 22, BUN 40, Creat Cerebrospinal fluid (CSF) 0.99, EGFR 55 #1 Appearance, cell Clear, WBC 347H (57% PMN, Complete blood count WBC 17.0 (90% neut, 5% lymph, 2.5% monos, count, diff, glucose, 11%Mono, 31% Lympho, 3% eos),  Initial work-up concerning for toxoplasmosis vs 0.3% eos). Hb 9.2, MCV 89.5, Plts 165. protein RBC 13, glc 30L, protein 71H. 72 H Ammonia nocardia abscesses > TB meningoencephalitis Gram stain. Many PMNs, no organisms. TSH 0.08 (uU/mL) L Bacterial/fungal/AFB Negative Free T4 0.30 (ng/dL) L  Empiric antibiotics covering toxo + nocardia: Cryptococcal Ag Negative (CrAg) Rheumatological Toxo PCR Negative  Ampicillin 2g q6 ANA 1:640 H CSF VDRL Non reactive Rheumatoid Factor 429 H  Cefepime 2g Q12 Negative CSF VZV PCR/IgG/IgM 151.2 H CRP  Metronidazole 500 q8 #2 Appearance, cell Clear, WBC 123H (50% PMN, 17% Microbiology (HD#9) count, diff, glucose, mono, 30% lympho, 3% eos). RBC  Vancomycin Serum Blood cultures (multiple) No growth protein 2. Glc 36L, protein 210H  Sulfadiazine/Pyrimethamine HIV Ab Negative Mixed inflammatory infiltrate, no Cytology malignant cells Toxo PCR/IgM/IgG Negative  Steroids tapered off #3 Appearance, cell Xanthochromic, WBC 123 (50% Negative Coccidioides IgM/IgG (HD#13) count, diff, glucose, PMN, 17% mono, 30% lympho, 3% AFB smear protein eos). RBC 2, glc 36L, prot 210H. Negative x 3 RPR Non reactive Diagnostic imaging Trach No organisms, no Chest CT (OSH) Gram stain/Culture LLL cavitary lesion aspirate growth. Transthoracic No e/o valvular disease MTB PCR Negative Echocardiogram Urine Histoplasma Ag Negative CT Angio No flow limiting stenoses Repeat MRI Brain on Day 10 of hospitalization T2 FLAIR Hospital course – response to treatment  Patient continued to decline rapidly over the 1 st 10 days of hospitalization HD#1  Intermittently febrile despite antibiotics  GCS declining. Initially 6  4 (E1, VT , M3)  2 (E1, VT , M1). Unreactive pupils. Breathing spontaneously.  Brain biopsy #1 was obtained on HD#4 – unimpressive.  Repeat MRI brain on HD#10. HD#10 3

2/16/2018 Additional thoughts? Repeat MRI Brain on Day 10 of hospitalization  Dr. Felicia Chow T1 POST 16/27 27/27 26/27 24/27 23/27 22/27 21/27 20/27 19/27 18/27 17/27 25/27 15/27 6/27 1/27 2/27 3/27 4/27 5/27 14/27 7/27 8/27 9/27 10/27 11/27 12/27 13/27 Hospital course – treatment change Hospital course – response to treatment change  Given clinical and radiographic deterioration,  Worsening hemodynamic stability empiric treatment for toxo was discontinued, and  Worsening mass effect of lesions causing empiric treatment for TB / cocci was started on communicating hydrocephalus HD#10-11.  Extraventricular drain (EVD) is placed for CSF diversion  Rifampin, Isoniazid, Pyrazinamide, Ethambutol HD#13, with elevated ICPs noted  Moxifloxacin  Methylprednisone to reduce swelling  Amphotericin  Worsening exam.  Repeat brain biopsy was obtained on HD#11  No cough/gag.  Patient transitioned to comfort care and expires HD#17. 4

2/16/2018 Additional thoughts? Additional diagnostic studies  Dr. Felicia Chow  Two brain biopsies were obtained  CSF was sent for next generation sequencing Pathology Biopsy #1 (day 4)  Dr. Melike Pekmezci • Clinical • Klebsiella (urine) • Toxoplasmosis IgM+ • Cavitary lung lesion (TB?) • Embolism per initial imaging (? Bacterial source) • Imaging (multiple lesions with reduced diffusion and central enhancement) • Toxoplasmosis • Nocardia • Cryptococcus • PML • Lymphoma/metastasis 5

2/16/2018 Diagnosis: Mild white matter gliosis • No inflammatory component or other features to suggest an infectious process • The findings are mild and nonspecific • Unclear whether the biopsy material is representative of the radiographic abnormality 6

2/16/2018 Biopsy #2 (day 11) • Clinical • Klebsiella (urine) • Toxoplasmosis IgM+ • Cavitary lung lesion (TB?) • Embolism per initial imaging (? Bacterial source) • Imaging (multiple lesions with reduced diffusion and central enhancement) • Toxoplasmosis • Nocardia • Cryptococcus • PML • Lymphoma/metastasis 7

2/16/2018 CD20 CD3 Prebiopsy differential diagnosis • Clinical • Klebsiella (urine) • Toxoplasmosis IgM+ • Cavitary lung lesion (TB?) • Embolism per initial imaging (? Bacterial source) • Imaging (multiple lesions with reduced diffusion and central enhancement) • Toxoplasmosis • Nocardia • Cryptococcus • PML • Lymphoma/metastasis 8

2/16/2018 Vasculitis – Fibrinoid necrosis Vasculitis – Fibrinoid necrosis Lymphocytes, eosinophils, neutrophils Lymphocytes, eosinophils, neutrophils • Primary CNS vasculitis • Primary CNS vasculitis • Primary angiitis of CNS • Systemic diseases • Aβ-related angiitis • PAN, eosinophilic granulomatous polyangiitis • Systemic Lupus Erythematosis • Rheumatoid arthritis Vasculitis – Fibrinoid necrosis Necrotizing vasculitis- SLE Lymphocytes, eosinophils, neutrophils • Primary CNS vasculitis • Systemic diseases • Infectious • Bacterial: Treponema (syphilis), Borrelia (lyme) • Viral: VZV, HCV, HIV • Fungal: Aspergillus, Mucor, Candida, Coccidioides 9

2/16/2018 Vasculitis – Fibrinoid necrosis Aspergillus Lymphocytes, eosinophils, neutrophils • Primary CNS vasculitis • Systemic diseases • Infectious • Bacterial: Treponema (syphilis), Borrelia (lyme) • Viral: VZV, HCV, HIV • Fungal: Aspergillus, Mucor, Candida, Coccidioides • Protozoal: Toxoplasmosis, Trypanosomiasis, Amebiasis Vasculitis – Fibrinoid necrosis Toxoplasmosis Lymphocytes, eosinophils, neutrophils • Primary CNS vasculitis • Systemic diseases • Infectious • Bacterial: Treponema (syphilis), Borrelia (lyme) • Viral: VZV, HCV, HIV • Fungal: Aspergillus, Mucor, Candida, Coccidioides • Protozoal: Toxoplasmosis, Trypanosomiasis, Amebiasis • Nematodes: Toxocariasis • Trematodes: Schistosomiasis • Cestodes: Neurocysticercosis- cerebrovascular form 10