ZSFG Pearls: IVIG, DAH, and a touch of bacterial endocarditis therapy

At the General, we like to keep it spicy, and Sarah Leyde did just that by presenting the case of an older woman w/ fever, HA, and AMS who was found to have IVIG-associated aseptic meningitis from ITP therapy. Now, a word or two about IVIG…

IVIG made simple!

What is it? Intravenous immune globulin, derived from donor plasma. Multiple products exist, and they vary in concentration of immunoglobulin G (IgG), IgA, and additives/stabilizers. Hyperimmune globulins are available as well and refer to products made from plasma with a high titer of the desired antibody

When do we see it used?

  • Immunodeficiency states (congenital), infections (i.e. toxic shock syndrome, chronic parvo infxn c/b anemia)
  • Autoimmune conditions (i.e. ITP, AIHA, GBS, specific chronic neuropathies, MG)
  • Alloimmune process (i.e. post-transfusion purpura, antibody mediated organ transplant rejection)

How does it work?

  1. If one doesn’t have IgG’s, you get an adequate concentration of them to fight a broad range of pathogens w/ passive immunity
  2. If one needs anti-inflammatory effects, IVIG is thought to…
      1. Block Fc receptors on phagocytic cells in the spleen and liver such as splenic macrophages. In ITP, this prevents reticulo-endothelial uptake of autoantibody-coated platelets
      2. Reduce pro-inflammatory subsets of peripheral blood monocytes
      3. Suppress/neutralize cytokines (of course it does! 🙂
      4. Block leukocyte adhesion molecule binding to the vascular endothelium (helps in Kawasaki dz)
      5. Block Fas ligand-mediated apoptosis by anti-Fas antibodies in the IVIG (studied in patients with SJS/TEN)
      6. Work through the complement system: Solubilization and clearance of immune complex deposits and/or inhibition of the binding of active complement components such as C4b and membrane attack complex to target tissues
      7. Clearance of pathogenic IgG (whaaaaaa?! That’s awesome)
      8. If this tickles your immunology side and you want to read more about all the mechanisms, check out the reference article and the aggressive figure below:
        cropped-ivig

 

What to watch out for?

  • Adverse reactions (most are immediate, mild, transient, reversible events such as headache, chills, or flushing) affect 20-50% of folks getting IVIG. Risk factors include dose, infusion rate, underlying hyperviscosity state, and organ dysfunction. Rxn’s most likely to occur during the first infusion
    • Anaphylaxis is EXTREMELY rare. Those with selective IgA deficiency are particularly at risk
  • Delayed reactions include thromboembolic events (arterial or venous, PE/ACS/CVA), central nervous system effects (HA, aseptic meningitis more common in people w/ h/o migraines), renal failure (AKI, hyponatremia), hematologic complications (hemolysis, neutropenia), and dermatologic manifestations (eczematous dermatitis)

 

 

After the fascinating M&M last week on MV Endocarditis 2/2 Enterococcus, we were all wondering, “wouldn’t it be nice to have a quick reference on what antibiotics to start for IE????”

Well, Chip “MRSA-warrior” Chambers brings you the answer that lifelong question in jpeg form:

endo-cropped

From the UCSF archives, comes an Approach to DAH: Consider 5 main categories

  1. VasculitisDdx includes MPA, less likely GPA and Churg-Strauss
  2. Pulmonary-Renal Syndrome: Goodpasture’s, connective tissue dz, IgA nephropathy
  3. Autoimmune diseasesSLE & APLS
  4. MedicationsComplications of anticoagulation, drug-induced thrombocytopenia
  5. Idiopathic pulmonary hemosiderosis (or in women, consider pulmonary endometriosis)

A few more hemorrhagic pearls…

  • The classic DAH presentation is acute onset cough, hemoptysis fever and dyspnea, but up to 33% of patients may not have hemoptysis, even when hemorrhage is severe
  • CXR for DAH classic shows patchy or diffuse infiltrates, and serial lavages on BAL will become progressively more hemorrhagic
    • How do you get the sample? The fiberoptic bronchoscope is wedged into a subsegmental bronchus correlating with radiographic opacities. Sequential BAL is performed by instilling and retrieving three aliquots of 50 to 60 mL sterile saline from bronchus. DAH is confirmed when lavage aliquots are progressively more hemorrhagic (no one specified exactly how many RBC’s 😦
    • Another way to confirm DAH: Hemosiderin-laden macrophages, which may be demonstrated by Prussian blue staining, are also characteristically found in BAL fluid from patients with DAH. If 20% of 200 macrophages stain positive for hemosiderin, a diagnosis of DAH is usually made

cropped-dah

References:

Collard HR, King TE Jr, Schwarz MI. Diffuse alveolar hemorrhage and rare infiltrative disorders of the lung. In: Murray & Nadel’s Textbook of Respiratory Medicine, 6th, Broaddus VC, Mason RJ, Ernst JD, et al. (Eds), Elsevier, New York 2016. p.1207

Ioachimescu, OCTAVIAN C., and JAMES K. Stoller. “Diffuse alveolar hemorrhage: diagnosing it and finding the cause.” Cleveland Clinic journal of medicine 75.4 (2008): 258. https://www.researchgate.net/profile/Octavian_Ioachimescu/publication/5359874_Diffuse_alveolar_hemorrhage_Diagnosing_it_and_finding_the_cause/links/571591e708ae8ab56695b0e9.pdf

https://www.uptodate.com/contents/overview-of-intravenous-immune-globulin-ivig-therapy?source=search_result&search=ivig%20side%20effects&selectedTitle=6~150

Peter, J G, Heckmann, J M, & Novitzky, N. (2014). Recommendations for the use of immunoglobulin therapy for immunomodulation and antibody replacement. SAMJ: South African Medical Journal, 104(11), 796. https://dx.doi.org/10.7196/SAMJ.8965

Evernote: https://www.evernote.com/shard/s354/sh/4d4f5132-8741-4b2d-a363-bcc3d532fcb3/6c7fda0f89ea76666ea19bc2ecbe5d2b

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