From the Prince of Monaco's yacht to component diagnostics
The history of research on anaphylaxis (Greek: ana – against, Greek: phylaxis – protection) began in the early years of the 20th century. During a voyage on the yacht of the Prince of Monaco, Paul Portier and Charles Richet desensitized their dog Neptune to a venomous jellyfish and caused the death of the animal due to shock symptoms. This gave rise to an interest in the pathophysiology of anaphylaxis and even the development of worldwide allergology.
We know that the clinical symptoms of anaphylaxis classically begin with generalized skin lesions, followed by shortness of breath, drop in blood pressure, loss of consciousness. But this is not always the case. The phenotype of anaphylaxis sometimes demonstrates only faint skin lesions. There may be spasmodic abdominal pain and a feeling of terror preceding the onset of shock.
Anaphylaxis can be caused by three groups of allergens: foods, drugs, insect venom. According to available data, idiopathic anaphylaxis (without an identifiable cause) occurs in about 20% of cases, although this percentage is currently lower thanks to the possibility of component diagnosis.
| Anaphylaxis | |
| Causes | · foods – 33.2%, · insect venom – 18.5%, · drugs – 13.7%, · cause unknown – about 20%. |
| Symptoms | · skin (burning, itching, hives), · gastrointestinal tract (spasmodic abdominal pain, vomiting, diarrhea), · respiratory system (shortness of breath), · cardiovascular system (tachycardia, arrhythmia), · disturbance of consciousness, · shock, · “coming doom” (coming terror). |
| Anaphylactic shock | |
| Risk factors | · hypersensitivity to: drugs, foods, insect venom, latex, radiological contrast agents, biological agents, · previous history of anaphylactic reaction |
| Complications | · damage to internal organs (kidneys, heart), · intravascular coagulation syndrome, · stress ulcer, · capillary transudate – up to 72 hours, · phase II shock – after 6-8 hours. |
| Remember! | · The threat of shock exists even when the early symptoms are mild in nature. · Shock can occur without preceding symptoms. |
The threat of shock is a challenge for all physicians. One must take this pathology into account even when early symptoms are poorly expressed. Anaphylaxis can develop rapidly, without preceding skin lesions. Loss of consciousness and hypotonia (hypotension) are dangerous for the functioning of the central nervous system. They pose a risk of intravascular coagulation.
Moreover, about 30% of patients develop a second phase of anaphylaxis, regardless of the patient’s successful recovery from the first phase. This obliges doctors to observe the patient for 24 hours, and certainly to secure adrenaline for personal administration.
Adrenaline - to live or to die. We are no longer condemned to injections
Adrenaline (epinephrine) is invariably the drug of first choice in the treatment of anaphylaxis, saving patients’ lives. No other drug can replace it. For the patient, it is to be or not to be.
Adrenaline, in the case of contraction of our vessels, initiates the fight against hypotension. It also causes relaxation of the smooth muscle of the bronchial tree and prevents further development of immunoallergic organ inflammation. The most common cause of possible failures in the treatment of anaphylaxis is the late and inappropriate administration of adrenaline. It is worth realizing that there is no contraindication to the use of adrenaline in a situation of developing shock. Note that such an obstacle is not tachycardia. Tachycardia is a symptom of developing shock.
So, failure or too late administration of epinephrine due to one or another anxiety (e.g., fear of injection, psychological blockade) can be life-threatening. And hence the idea was born to propose other routes of administration of this drug: intranasal, sublingual and inhalation.
Intranasal adrenaline
There is research evidence that intranasal adrenaline has the same pharmacodynamic and pharmacokinetic characteristics as injectable adrenaline (taking into account the dose difference). Injectable adrenaline is administered at a dose of 0.3 mg, while intranasal adrenaline is administered at a dose of 2 mg. Studies have shown that both routes of adrenaline administration are equally effective. Intranasal adrenaline has Food & Drug Administration (FDA) and European Medicines Agency registration. We are waiting for it to be available in Poland as well, which could be in a few weeks.
Sublingual adrenaline
Another proposed form of epinephrine is sublingual tablets. How do they work? Adrenaline is absorbed at the level of the oral mucosa, rather than in the gastrointestinal tract, which ensures adequate bioavailability. The effectiveness of this form of drug administration is comparable to adrenaline administered by injection. With that said, the dose must, of course, be higher (2 mg). It is an attractive alternative and has FDA and European Medicines Agency registration. On the other hand, we have strong reasons to believe that intranasal adrenaline will appear in Poland sooner, followed by the sublingual tablet.
Inhaled adrenaline
The introduction of inhaled adrenaline has also been proposed, but there is critical research evidence that the bioavailability of this adrenaline is low, which translates into its systemic effect. This form of administration does not protect circulatory stabilization. In addition, the dose of inhaled adrenaline must be many times higher than the injectable dose – up to 8 mg is said to be required. The research is ongoing, and it is worth following, but this form of administration has not yet met with acceptance and does not have FDA registration.
New areas of anaphylaxis research
As we know, science is a never-ending story. Every advance is like a light in the tunnel – it stimulates to initiate further research, because we always want more and better. Studies are beginning to be conducted to determine the genetic predisposition to the development of anaphylaxis in conjunction with a defect in the immune system. Proving IgE-dependent sensitization is not enough. The question remains why it does not always cause such a dangerous clinical manifestation as anaphylaxis.
Prof. dr hab. n. med. Barbara Rogala
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translation: Julia Majsiak
