Category: Immunology

Angioedma

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General Approach to Treatment

Icatibant for Angioedema

The Inside Scoop on Icatibant

Anand Swaminathan MD and Gentry Wilkerson MD   

 

Take Home Points

  • A previous phase II trial found the time to resolution of ACE-inhibitor induced angioedema was shorter after icatibant.
  • Another recent  randomized, controlled trial of icatibant compared to epinephrine, glucocorticoids and antihistamines found no benefit.
  • Our current understanding of the pathophysiology of ACE-inhibitor induced angioedema may be incorrect.

 

  • Wilkerson is a researcher in angioedema and icatibant. He has received research funding from Dyax, the makers of ecallantide and Shire, the makers of icatibant. This funding did not include salary support or speaking honoraria.

 

  • Bas, M et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015 Jan 29;372(5):418-25. OPEN ACCESS LINK
    • This study found the time to resolution of ACE-inhibitor associated angioedema was significantly shorter with the use of icatibant compared to the combination therapy of glucocorticoid and antihistamine.

 

  • Glucocorticoid and antihistamines are not thought effective in ACE-inhibitor angioedema. Why not compare to fresh frozen plasma?
    • The authors state that using glucocorticoids and antihistamines are standard care in the sense that they are usual care. They do not imply that these are effective. They discuss the ineffectiveness of these medications in the introduction to the paper.
    • It would not be appropriate to study one unproven medication versus another unproven medication to see which is better. There are 13 case reports of FFP working in the treatment of ACE-inhibitor induced angioedema. These aren’t studies of effectiveness.

 

  • The natural course of angioedema is to get better; our role is to protect the patient until it does. While FFP contains the ACE enzyme which can break down accumulated bradykinin, it also contains high molecular weight kininogen which is a precursor to bradykinin. Theoretically, this could lead to increased bradykinin production.

 

  • We don’t have any proven treatment and we don’t know enough about the disease to design treatment. We think that the disease is due to bradykinin accumulation but we do not have proof.

Pathophysiology

 

https://www.evernote.com/Home.action#n=6662f9ec-af12-48a3-9bbd-79c4c32f96cd&b=3aceb0f0-4320-4120-b610-e4ea19ab60d2&ses=4&sh=1&sds=5&

 

Angioedema Following TPA administration for stroke

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tPA & Acute Angioedema

Orolingual angioedema is an underestimated and potentially life-threatening complication of tPA treatment for acute ischemic stroke that typically occurs within 120 minutes of administration. The risk of angioedema is estimated to be 2-5%, but a considerably higher relative risk of 13.6 is described for patients taking ACE inhibitors (1,2).

The etiology is felt to be a simultaneous activation of complement system and kinin cascades by plasmin, produced by tPA-induced cleavage of plasminogen. The angioedema usually occurs contralateral to the ischemic lesion, likely because of acute changes in the vasomotor tone of the hemiparetic side caused by central dysfunction of the autonomic nervous system.

Most patients in case reports had acute ischemic strokes involving the mid-posterior insular region of the brain. Insular infarction may be an important factor for developing angioedema and may be related to a catecholamine surge or other autonomic mechanism associated with insular strokes.

The angioedema is usually mild and reversible within 24 hours (1), but in severe cases it might extend bilaterally to the oropharynx. The potential for rapid progression of edema should prompt careful observation for the need for prophylactic intubation in selected cases in order to avoid the need for cricothyroidotomy following tPA administration. Stroke patients receiving ACE inhibitors and with insular stroke should be monitored especially closely.

It has been noted that a CT of the tongue can distinguish hematoma as a complication of thrombolysis from angioedema in this setting (3).

References:
(1) Cerebrovasc Dis 2009;27:307-308.
(2) Neurology 2003; 60: 1525-1527.
(3) J Neurol 2005; 252:1167.
(4) Neurology 2003;60:1525-1527.
(5) Neurology 2012;78:S03.007.

Necrotizing skin lesions secondary to vasculitis: 2 cases mimicking as Skin Inection

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Vasculitis presenting as hemorrhagic bullae
Propylthiouracil-related ANCA-positive vasculitis. The patient was admitted to the hospital for further management of her vasculitis and treated with amoxicillin/clavulanate for her associated cellulitis. She had an excellent clinical response 9 days after she discontinued receiving propylthiouracil and was administered methylprednisolone. Skin biopsy showed leukocytoclastic vasculitis, and a serum perinuclear antineutrophil cytoplasmic antibody (ANCA) result was elevated. She underwent subtotal thyroidectomy for controlling Graves’ disease 2 weeks after the cessation of propylthiouracil.
The diagnosis of drug-induced ANCA-associated vasculitis is based on the temporal relationship between clinically evident vasculitis and administration of the offending drugs, and excluding medical conditions that mimic vasculitis and other definable types of vasculitis.1 ANCA positivity may range from 4.1% to 64% in patients receiving propylthiouracil, with very few developing associated vasculitis.2 Prognosis is favorable with timely discontinuation of propylthiouracil and consideration of an alternate hyperthyroidism therapy such as radioiodine therapy or thyroidectomy.

http://www.annemergmed.com/article/PIIS0196064412000443/fulltext

http://www.nejm.org/doi/full/10.1056/NEJMcpc1208146

Sweet’s syndrome (acute febrile neutrophilic dermatosis) is characterized by the presence of two major findings: the abrupt onset of erythematous-to-violaceous, edematous cutaneous lesions and the histopathological finding of superficial dermal edema and a dense dermal neutrophilic infiltrate. Two of four minor criteria must also be present for the diagnosis: high fever, leukocytosis, a rapid response to glucocorticoids, and an associated underlying condition or exposure.