Clinico-Pathological Conference #2 October 6, 2009

The Patient

• 52 yr old female with SLE – scleroderma overlap – Inflammatory polyarthritis– Sclerodermatous skin changes with Raynauds– Extensive GI dysmotility- TPN– Glomerulonephritis– Restrictive lung disease– Hypocomplementemia– Inflammatory myositis / myocarditis

SLE-scleroderma

• 2006- – Polyarthritis– Weakness with myositis

• 2/2008– Esophageal dysmotility • TPN + IV methylprednisolone (30 mg/day)

HPI

• 1 month PTA- volume overload, cardiac dysfunction– R / L cardiac cath: no pulmonary arterial

hypertension or coronary artery disease– Endomyocardial biopsy: inflammatory cells,

scaring: mycophenolate, methylpred (60mg/dy)

Medications

Lasix 20 mg dailyHydrochlorquine 200 mg twice dailyLisinopril 5 mg daily Metoprolol 25 mg twice daily Prednisolone 60 mg intravenously in the morning Reglan 10 mg four times dailyMyfortic 180 mg twice daily Dilaudid 2mg as neededDapsone 100 mg every Monday-Wednesday-Friday Flagyl 500 mg every 8 hours for bacterial overgrowth Protonix 40 mg twice daily Ambien 10 mg as neededErgocalciferol 1000 International Units daily

Course

• 3 weeks later- – OSH: SOB, fever, chills,

rigors, cough– Bilateral infiltrates– Rapid decline with

sepsis, multi-organ failure despite• Vancomycin, pip/tazo,

oral flagyl, caspofungin

• T: 38.5, HR: 108, BP:92/62 on vasopressors, SaO2: 91% on FiO2=0.5General: intubated, sedated, acutely ill, appears somnolent but is arousable. HEENT: clear oropharynx, no thrush, no ulceration. Lungs: coarse breath sounds throughout. CV: rapid and regular heart sounds.Abdomen: Soft, infrequent bowel sounds. Extremities: marked violaceous discoloration of fingers and toes, diffusely and bilaterally; no acute digital infarcts. Skin: Thickening in the trunk and extremities, sclerodactyly. Neuro: moves all four extremities on command, Intact bilateral dorsiflexion and plantar flexion.

• Laboratory Values on Transfer Na 127, K 3.7, Cl 87, bicarbonate 23, BUN 74, creatinine 2.6. Calcium 8.5, protein 5.2, albumin 2.8AST 2859, ALT 1416, alkaline phosphatase 1154, total bilirubin 5.3, ammonia 57,CPK 179.0, troponin 1.96, CK-MB 2%, lactic acid 2.7 LDH 3610WBC 23,110, hemoglobin 7.8, hematocrit 26.2, platelet 221,000, polymorphonuclear cells 91% PT 16.1, INR 1.6, aPTT 31.6Urinalysis: 2 WBC/PHF, 65 RBCs/PHFCultures- Blood cultures negative, Sputum culture positive for yeast, urine culture negative, CSF cultures negativeLegionella DFA-negative, Urine Strep antigen-negative, Serum galactomannan- 0.5

Course

• Bronchosopy:– Ulcerations with vesicular appearance throughout the

main airways– Purulence RLL bronchus

• Dies 7 days later despite “broad spectrum antibiotic” therapy, aggressive supportive care– 13 days after presentation to hospital– 4 weeks after initiation of current symptoms

Summary

Moderately immunocompromised patient with ‘gradual’ respiratory decline, fever (4 week) bilateral pneumonia with acute sepsis – multi-organ dysfunction Ulcerative lesions in airway

Chronic severe paralytic ileus

Important Issues Contributing to Differential

• Degree of immunocompromise– Chronic steroids + pulse, MMF

• Duration of illness– “sub-acute” progression of pneumonia with sepsis

• Appearance of infiltrates– Nodules, ground glass, focal lobar infiltrates

• Time of year: Feb – March• Previous smoker• Chronic GI dysmotility: aspiration• Where is she from? Other risks for infection?

Questions posed

• What are the risk factors for pneumonia in this patient? – Corticosteroid exposure (+MMF?)

• Other prior therapies (TNF-a inhibitors, rituxan?)

– Hypocomplementemia– Underlying airway disease – smoking (ulcerations?)– Underlying structural lung disease – disruption of alveoli

(alveolar hemorrhage / pneumonitis) – GI dysmotility – aspiration– Time of year / antecedent respiratory virus ?

• Myocarditis / myositis 1 month PTA

Differential

• Osler (1904) suggested that pulmonary involvement as part of SLE

Non-infectious– Alveolar hemorrhage /

damage– Lupus pneumonitis /

progressive interstitial lung disease

– Progressive pulmonary hypertension

– Pulmonary embolism– Malignancy

DifferentialInfectious (syndrome)• Community-acquired pneumonia• Progressive hospital-acquired pneumonia• Aspiration pneumonia • Multiple / sequential infections

– Respiratory virus followed by bacterial pneumonia• Influenza – S. pneumonia / S. aureus• Respiratory virus – fungal pneumonia

• Disseminated viral infection – Influenza– Herpes virus (HSV, VZV)– Adenovirus

Infectious Differential• Bacterial

– S. pneumoniae– H. influenzae– S. aureus– Group A / B Streptococcus– Mixed anaerobes (aspiration)– Enterobacteriaceae

• E. coli (ESBL?)• K. pneumonia (ESBL?)

– P. aeruginosa (MDR)– Legionella spp.– Multiple other atypicals:

M. pneumoniae, Chlamydia – Nocardia spp. – Mycobacteria

• Viral – Disseminated Herpes virus – “Respiratory virus” (RSV, influenza,

para-influenza, adenovirus, HMPV, coxsackievirus)

• Fungal – Aspergillosis (airway to invasive)– Cryptococcosis– Misc. filamentous fungus

(e.g. Zygomycetes)– Endemic fungus (Histoplasma,

Coccidiomycosis, Blastomyces)– Pneumocystis

• Parasitic– Toxoplasma gondii– Strongyloides stercoralis

common

common

commonRapidly progressive, necrotizing

Increased colonizationPrior hospitalization

Underlying disease

Tm / slf - dapsone?Tm / slf - dapsone?

Tm / slf - dapsone?

Other organ involvement? Liver / myocarditis?

Airway lesions + GMSuboptimal therapyEndemicity (?)

Deductive reasoning

• Moderately immunosuppressed, sub-acute pneumonia + gram stain / AFB stain negative, with ulcerative airway lesions, + galactomannan– Assumptions:

• Other organ dysfunction (liver, heart) really as described • Omission of sputum / BAL Afb and gram stain not purposeful

(high burden of disease for stain-negative bacterial process)• “Yeast” in sputum = Candida, not from endemic region

Tracheobronchial + invasive aspergillosisRapidity of death / sepsis: likely a secondary bacterial pneumonia