Dyspnea evaluation in immunotherapy patients- Cardiac/Pulm/Myasthenia

 Triage: Dypsnea

• Grade 4- dyspnea at rest or acute dyspnea, cannot speak , fever, acute chest pain, cannot lie flat, any mental status changes--> ER
• Grade 3- self care ADL affected: cannot shower, take meds, use the toilet without help: urgent medical evaluation: same day clinic evaluation in clinic if none of the grade 4 features or ER
• Grade 2- instrumental ADL affected ( shopping, preparing meals), dyspnea with some exertion: also evaluate in the clinic within 24 hr

HPI:

The patient complains of weakness that started *** days ago. He/she received the first dose of pembro/nivo/ipi/atezo on ***. The most recent dose of immunotherapy was on *** which was the 4th(?) cycle.

Specifically, he/she is unable to walk *** feet, climb stairs and is/is not dyspneic at rest. He/she was / was not on home oxygen at baseline.

History reviewed for the following symptoms: chest pain, hemoptysis, leg edema, orthopnea, paroxysmal noctural dyspnea, palpitations, fever, productive cough, syncope or presyncopal symptoms

• ROS positive for: 
• ROS negative for muscle pain, muscle weakness ie lifting arms overhead, or inability to stand up from sitting position worse at the end of the day ( immune mediated myasthenia /myositis)

Past history was reviewed for the following: CAD, cardiac stents, CABG, Afib, heart failure, COPD, prior malignant pleural effusion requiring drainage, pulmonary embolism or lung radiation.  -

• Past hx is positive for: 

Prior hx of autoimmune disorder or immunomodulatory therapy

Clinical exam findings:

O2 sat, vitals, desaturating with ambulation, higher than usual O2 requirement( if on home O2)

Face: plethora, edema, look for ptosis

Neck: JVD+

Lungs: bilateral crackles up to 1/2 of chest, diffuse etc OR reduced breath sounds, suggestive of effusion

CVS: regular, irregular, tachy

Proximal muscle weakness on exam: unable to raise arms overhead bilaterally ( excluding shoulder issues) and or unable to stand up from sitting position without assistance that is new.

Paradoxical respiration: Chest and abdomen contract ( go in) during inspiration and expand during expiration ( ideally pt should be lying down)

Investigations:

1. CT chest /CTA chest:?  e/o progression, PE, pneumonitis

2. Blood cultures/ sputum test/ nasal swab

3. EKG, echo as indicated

4. Creatinine kinase, troponin, NT- pro BNP

Discussion:

1.  IO pneumonitis: immune-mediated pneumonitis is more likely to be bilateral, involve multiple lobes, and have less defined borders than radiation-induced pneumonitis. Differential diagnosis: gemcitabine, pemetrexed and radiation can also cause pneumonitis.

2 Always look for evidence of myasthenia gravis : ptosis, proximal muscle weakness or paradoxical respiration in a patient presenting with dyspnea could indicate a medical emergency. Admit to ICU or close monitoring. Check for myasthenia, myositis and myocarditis ( 3 M)

Treatment:

1. Antibiotics, bronchodilators, diuretics as indicated

2. High dose steroids: 1-2 gm/kg bwt until symptoms grade 2 or less, then taper 10 mg every week.

3. Infliximab- 5 mg/mg bwt single dose. Contraindicated if cardiac dysfunction and hepatitis. Quantiferon Gold TB test.  Hx of TB exposure and risk factors was evaluated prior to administration of infliximab. Quantiferon gold test sent. Patient was counseled of the risk of disseminated TB and extra pulmonary TB in those previously exposed to tuberculosis after infliximab treatment.

4. Consultations:

-pulmonary/ICU: ICU transfer, bronchoscopy is usually not necessary except if pt does not improve after 48-72 on steroids and if alternative diagnosis is under consideration ( atypical pneumonia, progression of cancer). Pulm consultation is appropriate for grade 2 or higher.

-cardiology

5. Steroid refractory: ICU, bronchoscopy, if no alternative etiology for dyspnea, then start immunosuppressive agent, IVIG

Management of myocarditis

G1: Abnormal cardiac biomarker testing without symptoms and with no ECG abnormalities.

---

G2: Abnormal cardiac biomarker testing with mild symptoms or new ECG abnormalities without conduction delay.

---

G3: Abnormal cardiac biomarker testing with either moderate symptoms or new conduction delay.

---

G4: Moderate to severe decompensation, IV medication or intervention required, life-threatening conditions.

• 1% incidence, 40% mortality. Most often with combination ICP. Can be seen even after one dose.
• Permanently discontinue immunotherapy*
• ICU-level monitoring
• Temporary or permanent pacing as required
• Testing: troponin T serially, BNP, Echo, Telemetry, Cardiac MRI
• Management is tailored to response and acuity of presentation. All grades require cardiology input.
• High-dose steroids such as methylprednisolone pulse dosing 1 g/day IV for 3-5 days; switch to oral prednisone, then taper slowly over 4-6 weeks based on clinical response and improvement of biomarkers
• If no improvement within 24 hours on steroids, consider adding other potent immunosuppressive agents: abatacept, mycophenolate, intravenous immunoglobulin (IVIG), alemtuzumab, infliximab (use with extreme caution in patients with reduced left ventricle ejection fraction), antithymocyte globulin (ATG) Mycophenolate mofetil treatment (0.5-1.0 g every 12 hours).