History and Physical

Journal Article Summary

Type of article: Systematic Review

Title of article: Efficacy of Treatment of Non-hereditary Angioedema

Published in Clinical Reviews in Allergy & Immunology on 9/27/16

Although this is a foreign-based article from the Netherlands, I chose this article because it’s a great systemic review that used multiple databases National Guideline Clearinghouse, CBO guidelines, Trip Database, the Cochrane Library, PubMed, EMBASE, and Scopus.

61 articles were included in the study. In addition, only articles describing the pharmacological treatment of AE were included. This included both observational studies (case reports and case series) and intervention trials (cohort studies or randomized controlled trials, RCTs). And only articles written in English, Dutch, or German were included so the authors who performed the selection of studies had full understanding of scientific content.

Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be divided as bradykinin or mast cell mediated, or from an unknown cause. The focus of the systematic review was to provide an overview of the efficacy of different treatment options for refractory non-hereditary AE with or without wheals and with normal C1INH. Therapies were also described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Patients with ACEi-AE who present to the ED can be treated with FDA label medications or off-label medications. Treatment options include ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab.

Key points:

• Hereditary AE caused by C1 esterase inhibitor (C1INH) deficiency, results in the release of the key mediator bradykinin. An increase in bradykinin can also be from ACEi.
• Patients with ACEi-AE generally do not respond to conventional therapy. Pathophysiology suggests that drugs registered for hereditary angioedema (HAE) due to C1INH deficiency could also be effective in ACEi-AE.
• Several drugs are currently available, including:

(1) antifibrinolytic agents such as tranexamic acid (TA)

(2) attenuated androgens such as danazol

(3) replacement of deficient proteins using fresh frozen plasma (FFP)

(4) C1INH concentrates, which inhibit the formation of bradykinin

(5) the selective plasma kallikrein inhibitor ecallantide

(6) the selective bradykinin B2 receptor antagonist icatibant

• In this systematic review, several treatment options for patients with refractory AE were found.
• For acute attacks of AE, several articles described treatment with icatibant, C1INH, TA, FFP, and ecallantide.
• For prophylactic treatment of AE, omalizumab, TA, and C1INH were shown effective, and, with fewer included articles, also progestin and MTX.
• In patients suffering ACEi-AE or an acute attack of idiopathic AE, ecallantide seems to have an effect in a limited number of patients, if any, whereas icatibant, C1INH, TA, and FFP often lead to symptom relief within 2 h, in addition to a good safety profile.

Overall, this systematic review provided an overview of therapeutic options (acute attacks vs prophylactic treatment) in patients with Angioedema with normal C1INH. However, an important limitation to keep in mind is that although patients responded quickly after treatment with icatibant, C1INH, and TA, most of the included studies were not controlled and therefore of lower quality in terms of scientific reliability. There is a need for additional studies with a high level of evidence. The main conclusion of the study, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.

Citation:

van den Elzen, M., Go, M. F. C. L., Knulst, A. C., Blankestijn, M. A., van Os-Medendorp, H., & Otten, H. G. (2018). Efficacy of Treatment of Non-hereditary Angioedema. Clinical reviews in allergy & immunology, 54(3), 412–431. https://doi.org/10.1007/s12016-016-8585-0

Site Evaluation Presentation Summary

My site evaluator for my second rotation was Professor Sajid Mohamed. During my site evaluation, I presented 3 H&Ps that I had written on my patients from my time in Emergency Medicine at New York Presbyterian Queens Hospital. The 1st H&P I presented was a case of a 27-year-old who presented with a complaint of belly pain. The patient already had a history of appendicitis that was treated with antibiotics 6 months ago (not with surgery). His physical exam was notable for RLQ tenderness to palpation, guarding, rebound tenderness, psoas sign was present, and obturator sign was present. My differentials included recurrent acute appendicitis. The plan was to admit the patient for surgery and start him on Ceftriaxone, Metronidazole, and Ketorolac. We had a conversation about how some patients are being treated with antibiotics only for acute appendicitis instead of surgery, but often patients will later have a return episode of appendicitis. 

On my second site visit, I presented a case of a 39-year-old male who had no past medical history and presented with RLQ abdominal pain radiating to RUQ, NBNB vomit, and subjective cells. On exam, the patient had a lot of specific abdominal findings, which made his differentials broad. When I performed the physical exam, the patient was in mild discomfort with hypoactive bowel sounds, diffuse mild pain to palpation, guarding was present, murphy sign was present, psoas sign was present, and obturator was present. Because the patient had all these prominent physical exam findings, his differential included cholecystitis, appendicitis, and cecal volvulus. However, once his labs came back the U/A was notable for cloudy urine with large amounts of RBC and protein with the rest of his labs being unremarkable. A CT of Abd and Pelvis was done, which reported mild Right Hydroureteronephrosis, R Perinephric Edema, and a 3mm R UVJ Calculus. Turns out the patient had a kidney stone. The plan was to start Morphine IV and Zofran. Also to discharge the patient with Tamsulosin and for urology follow-up. This was a great case to discuss because his of wide differentials. A recommendation I got from Professor Mohamed, was that IV Toradol can also be given for kidney stone pain in the ED and additionally upon discharge. In addition, the patient can be discharged with Zofran, since he would also experience nausea/vomiting during the passing of the stone. 

Typhon Posting

Rotation Self Reflection

1. What was a memorable patient or experience that I’ll carry with me?

Without a doubt, the ED will always leave a mark on anyone who rotates there. During my first week at the ED, I experienced the pleasure of having bile thrown at me by an altered patient that was not under my care. I learned to pack an extra pair of scrubs since then. The ED is also known for its high-acuity patients. There were a lot of situations that were hard for me to watch; like my 1st code during my shift on the Red Team for a patient that had a lower GI bleed and was on an anticoagulant. It was also hard to see a 1-year-old get stitches on his lip for a laceration repair. As hard as it was to see, it was also amazing to watch the ED providers handle these cases with dexterity. 

2. Skills or situations that are difficult for you (e.g. presentations, focused H&Ps, performing specific types of procedures or specialized interview/pt. education situations) and how you can get better at them.

It was a challenge for me to figure out which lab orders are relevant according to the ED. Initially, I thought the ED would order extra labs, however, because of cost issues and time constraints sometimes they wouldn’t check Hepatitis B panel for patients with Cirrhosis. I also had a hard time thinking of differentials, however, I found that using the VINDICATE mnemonic worked. I also learned from another provider about the SPIT mnemonic, which helps identify the most Serious, Probable, and Interesting differentials. And the T stands for treatment. 

3. Types of patients you found challenging in this rotation and what you learned about dealing with them.

For this rotation I actually found the most challenging patient to not be the patient, instead, it’s their family member. I had a situation where I needed collateral information from the daughter because her mother was Alerted and Oriented x 2 (to person and place). However, I found that the daughter was very a poor historian and when I tried to ask the patient if she felt any pain, her daughter would interrupt and mention her mother wouldn’t understand anything. After I reported my findings to my preceptor, who also went to check on the patient, he noted the daughter was very paternal and domineering. However, he still asked the patient if she felt any pain and told the daughter that even if she had dementia she should still be able to report where it hurts. 

4. What do you want to improve on for the following rotations? What is your action plan to accomplish that?

For my following rotations, I want to get better at the physical exams. Although physical exams are considered objective, I have a hard time telling if a patient has “true” pain when I palpate their abdomen. I also have to consider, that perhaps their pain is muted because they were already given pain medications. My plan to get better at physical exams is a lot more practice, exposure, and compare my findings to the preceptor. 

I also want to get better at the plan portion for H&P. I’ve gained a lot more experience in taking down a good history. However, I want to get better at knowing the 2nd line pharmacological interventions, knowing the exact dosage of medications, and knowing the absolute contraindications of medications.