Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

An Unusual Combination of Pulmonary Embolism and Aseptic Meningitis in the Same Patient, Receiving IVIG Treatment for Common Variable Immunodeficiency Syndrome Daniel Butz, B.S, MEng HSE, Arun Adlakha, M.D., FCCP VCOM-Carolinas, Spartanburg, SC & Carolina Lung Clinic, Rockhill, SC.

Abstract

Case Description

Conclusions

A 59-year-old Caucasian female patient was evaluated in 2017 with a 3 year history of recurrent respiratory, urinary, skin and subcutaneous infections. After ruling out other causes, her quantitative immunoglobulin studies and lack of vaccine response indicated a diagnosis of Common Variable Immunodeficiency Disease (CVID). Fall of 2017, she was initiated on a once every three week regiment of IVIG infusion. End of March 2021, she was diagnosed with an acute pulmonary embolism in the right lower lobe, approximately 10 days after receiving her last IVIG infusion. End of May 2021, she was diagnosed with aseptic meningitis within 48 hours of last IVIG infusion. Mid-June 2021 she was readmitted to the hospital and diagnosed with recurrent aseptic meningitis, occurring again within 48 hours of her IVIG infusion. Patient was seen by neurology, who subsequently changed the IVIG medication to a different compound, and slowed the rate of infusion. Additionally, the patient receives pre and post infusion heparin injections, which is also continued for 7 days post the infusion. She has not required hospitalization since this adjustment in her infusion regimen. This case is an excellent demonstration of ensuring timely diagnosis of patients with CVID and being aware of adverse events patients receiving IVIG treatment.

Current IVIG regiment 1. Switched to 3 weekly IV 10% Gammunex, at a dose of 350 mg/Kg 2. Administered over a slower rate of 5 hour 3. Premedicated with twice the dose of IV Solumedrol, Benadryl was changed to IV, IV Promethazine was added, and IV fluids remain the same. 4. Added Furosemide once during the week of IVIG infusion 5. subcutaneous Enoxaparin twice a day, the day of IVIG infusion and continued for a total of 7 days after IVIG infusion. Key Points • Early diagnosis of this condition as the number of infections and hospitalizations drastically decreases. • IVIG associated risks for adverse reactions of aseptic meningitis and PE • Subcutaneous heparin during the week of IVIG infusion could be a useful substitute for patients in DVT prevention, if a patient receiving IVIG infusions would prefer an alternative to daily Apixaban use. • A Review of English Literature did not reveal significant association of PE and aseptic meningitis with SubQ administration of immunoglobulins. • Our patient insisted on continuing IVIG infusion, at this time. With IVIG infusion one is creating the balancing of adequately high immunoglobulin levels to prevent infection, but not too high as to increase the patient’s risk for the PE and aseptic meningitis.

March 2021 • admitted with acute onset of right-side pleuritic chest pain, right upper back pain and worsening dyspnea with no prior history of venous thromboembolism • D-Dimer elevated • CT Angiogram of the chest: acute pulmonary embolism of the right Interlobar and lower lobe segmental and sub segmental vessels • treated with IV Heparin and discharged on oral Xarelto. • discontinued Xarelto after 1 year of uninterrupted use due to patient preference Fall of 2017: Common Variable Immunodeficiency Syndrome diagnosis • Other causes ruled out. • Her Quantitative levels of the serum Immunoglobulins revealed low total IgG, IgG subclass 2 & 3, and IgM. • Qualitative response of the antibodies to 23 Valent Pneumococcal vaccine was flat. IVIG Therapy • Once every 3 week IV 10% Privigen, at 400 mg/Kg dose, over 3.5 hours. • Premedication with Benadryl, Solumedrol and 500cc bolus. • Post infusion 500cc bolus. • The frequency and severity of her infections reduced, as did the septic episodes and need for hospitalization.

Introduction

Common Variable Immunodeficiency (CVID) is a collection of primary immunodeficiency disorders, characterized by impaired B cell differentiation with defective immunoglobulin production. It is the most common form of primary immunodeficiency in adults, with an • Prevalence: 1 in 10,000 to 1 in 100,000 • Common presentations: recurrent respiratory tract infections • Autoimmune diseases: diagnosed in approximately 25 - 30% of CVID patients • Median diagnostic delay: between 4 and 5 years

B

C

A

Table 2 . Acute pulmonary embolism of right interlobar & lower lobe segmental & subsegmental vessels (Arrow) [A] Sagittal View [B] Axial View [C] Coronal View May 2021 • Hospitalized with headache, neck stiffness, nausea, photophobia & low-grade fever. • Started within 48 hours of IV Privigen infusion therapy. • CT/MRI Head were both negative. • Lumbar puncture results:

References

Cell Count Ͷͻ͹ ‡ŽŽ•Ȁ‹ ”‘

Protein Ͷͻ ‰Ȁ†

Glucose

Table 3. May 2021 CSF Analysis

The diagnosis of CVID is made based on clinical presentation, laboratory findings, and negative workup for other causes of immunodeficiency. Diagnostic criteria for CVID are as mentioned in table 1:

https://docs.google.com/document/d/1Hl1gnhT77xlZXIddvCz2Yuq5aYgn5pLLPBiqcbTpsE8/edit?us p=sharing

Diagnosis of Aseptic meningitis, likely related to IVIG Infusion therapy.

June 2021 • readmitted to the hospital with recurrent headache, nuchal stiffness, nausea, photophobia, • Occurring within 48 hours of her IVIG infusion. • CT Head was negative. • Lumbar puncture results: Cell Count Protein Glucose ͵ʹʹ ‡ŽŽ•Ȁ‹ ”‘ Ͷʹ ‰Ȁ†

Table 1 CVID diagnostic criteria Immunoglobulin therapy is the mainstay of treatment for CVID and helps to prevent infections by providing the patients with antibodies that are unable to produce themselves Adverse effects from IVIG

Table 4. June 2021 CSF Analysis

Discharged with a diagnosis of Recurrent Aseptic Meningitis due to IVIG Infusion

Dr. Adlakha

• Thrombotic events: incidence between 1 -16.9% • Aseptic meningitis: incidence between 0.6 – 1%

57

2024 Research Recognition Day