Case Study: 43-year-old Asian Female with Postural Dizziness and Hypertension after Diclofenac Sodium SR

Case Summary

Our patient is a 43-year-old Asian female presenting with generalized itching, hives and postural dizziness after taking diclofenac sodium slow release (SR) for migraine an hour prior. She only has a past medical history of migraine, without any known food or drug allergy. She previously developed itching in her palms after taking diclofenac sodium SR, which resolved on its own.

Vitals on presentation: 

• Heart rate 110 bpm 
• Supine blood pressure 200/100 mmHg 
• Respiratory rate 16
• SpO2 99%

Physical Examination:

• Skin erythema 
• Cutaneous oedema 
• Mild urticaria 
• Scattered rhonchi in both lungs

The patient was given intravenous (IV) Hydrocortisone 200mg and IV Chlorpheniramine 10mg. Intramuscular (IM) Adrenaline was withheld due to high blood pressure; nebulized adrenaline or salbutamol was withheld due to tachycardia. The patient’s cutaneous and respiratory symptoms improved with treatment. 

However, 40 minutes after receiving treatment, the patient was advised to sit up on the bed without standing as she insisted on using the washroom. Her dizziness and lightheadedness recurred, and her blood pressure measured was 80/60 mmHg. She was immediately put back in a supine position and was given IM adrenaline 0.5mg and IV fluid bolus. As blood pressure remained low, she was given another 2 doses of IM adrenaline spaced 5 minutes apart until systolic blood pressure was more than 100 mmHg. Her postural symptoms resolved after, though her blood pressure readings fluctuated over 24 h with frequent high readings (though not as high as her blood pressure at presentation) and the patient was tachycardic. All vitals and laboratory tests were normal and she was discharged 2 days later with a blood pressure of 165/95 mmHg. 

What is the probable diagnosis?

Upon discharge, the diagnosis was anaphylaxis to diclofenac sodium with probable essential hypertension. She has been prescribed an adrenaline autoinjector for emergency use. She came back for a follow-up 2 weeks later and was diagnosed with hypertension, for which she has been prescribed Telmisartan 40mg ON and Amlodipine 2.5mg ON. 

Learning points

Prompt recognition and early treatment with adrenaline are important in the treatment of suspected anaphylaxis. If immediate confirmatory tests cannot be done, the diagnosis of anaphylaxis is based on pattern recognition. Common organs involved in anaphylaxis include the skin (90% of episodes), followed by the respiratory system (70%), and cardiovascular system involvement is recognized among only 10–45% of patients. When anaphylaxis is triggered by a specific antigen, the mast cells and basophils are activated, where they both play a key role in initiating and amplifying the allergic reaction by releasing inflammatory mediators. The pro-inflammatory properties of these mediators lead to increased vascular permeability, vasodilatation, increased glandular secretions, and smooth muscle spasms. This results in hypotension and postural symptoms. 

This patient presented with skin and respiratory symptoms following exposure to a known allergen, making anaphylaxis the most likely diagnosis. She was previously healthy and had no postural symptoms in the past, therefore, anaphylaxis with cardiovascular involvement is the most probable explanation for her postural dizziness.

The patient’s high BP on admission points toward a possibility of anaphylaxis-induced hypertension, as although pre-existing hypertension or anxiety leading to sympathetic activation is possible, anaphylaxis with cardiovascular involvement should result in low or reduced blood pressure from baseline. 

Hypertensive anaphylaxis has been reported previously by Solmazgul et al.4. During the development of anaphylaxis, internal compensatory vasopressor mechanisms are activated, which releases vasoactive substances to compensate for vasodilation and fluid extravasation induced by inflammatory mediators2,3,. Solmazgul et al. hypothesized that these initial compensatory mechanisms could be dominant in some patients, resulting in hypertension. However, these compensatory mechanisms may not be adequate to maintain the blood pressure when posture changes from supine to upright, which could explain the postural dizziness experienced by the patient. 

Adrenaline is the drug of choice in the management of anaphylaxis3, however, the safety of adrenaline administration when the patient has elevated blood pressure is a key concern. While a delay in administering adrenaline may complicate subsequent management of anaphylaxis, administration of adrenaline can further elevate the already high blood pressure, increasing the risk of intracranial haemorrhages and fatal arrhythmias. In the study by Solmazgul et al., two of the eight patients who had hypertensive anaphylaxis were treated with IM adrenaline. Their pretreatment systolic BP was 150 mmHg, and both the anaphylaxis and hypertension recovered completely without adverse reactions after the administration of IM adrenaline. Others recovered without IM adrenaline4.

Conclusion 

The medical team initially delayed the administration of  IM adrenaline due to the patient’s high blood pressure, and this is likely the reason for her near-fatal collapse after 2 hours from the onset of her symptoms. Delayed use of adrenaline is associated with increased severity and fatalities in anaphylaxis. While glucagon can be an alternative therapy in patients experiencing anaphylaxis with high blood pressure, a less common side effect is severe hypertension as well. Thus, since studies on the use of glucagon in hypertensive anaphylaxis are limited, adrenaline should still be considered for patients with hypertensive anaphylaxis and it should be done with extreme caution and close monitoring. Postural symptoms despite high blood pressure should signal cardiovascular involvement and close monitoring in a supine position is recommended.

References: 

1. Govindapala D, Senarath US, Wijewardena D, Nakkawita D, Undugodage C. An unusual presentation of anaphylaxis with severe hypertension: A case report. Journal of Medical Case Reports. 2022;16(1). 
2. Simons FE. Anaphylaxis. Journal of Allergy and Clinical Immunology. 2010;125(2). 
3. Reber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. Journal of Allergy and Clinical Immunology. 2017;140(2):335–48. 
4. Kemp SF, Lockey RF, Simons FE. Epinephrine: The drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy. 2008;63(8):1061–70. 
5. Solmazgul E, Kutlu A, Dogru S, Ozalper V, Cetindagli I, Sezer O, et al. Anaphylactic reactions presenting with hypertension. SpringerPlus. 2016;5(1). 
6. Pumphrey RSH. Fatal posture in anaphylactic shock. Journal of Allergy and Clinical Immunology. 2003;112(2):451–2. 
7. Ko BS, Kim JY, Seo D-W, Kim WY, Lee JH, Sheikh A, et al. Should adrenaline be used in patients with hemodynamically stable anaphylaxis? incident case control study nested within a retrospective cohort study. Scientific Reports. 2016;6(1). 
8. Pumphrey. Lessons for management of anaphylaxis from a study of fatal reactions. Clinical & Experimental Allergy. 2000;30(8):1144–50. 
9. Muraro A, Roberts G, Worm M, Bilò MB, Brockow K, Fernández Rivas M, et al. Anaphylaxis: Guidelines from the European Academy of Allergy and Clinical Immunology. Allergy. 2014;69(8):1026–45.