Penicillin Allergic Reaction: Symptoms, Diagnosis & Treatment

Table of Contents

Penicillin Allergic Reaction

Penicillin is a B-lactam antibiotic discovered by Scottish scientist Alexander Flemming in 1928 A.D. It was only on the 1940s that penicillin was used for clinical trials. Penicillin includes Penicillin G, Penicillin V, Procaine penicillin and benzathine penicillin. It is one of the first antibiotics to be effective against the streptococcal and staphylococcal infection. Despite the emerging cases of the penicillin-resistant, It is still widely used all over the world. Penicillin allergies are reporting about 10% of cases and the remaining 90% are non-allergic. Serious complications of the penicillin allergy occur in about 0.03% of cases. It is the most common cause of drug allergy.

Symptoms of Penicillin allergic reaction

Mild forms of penicillin allergy are very common and are present in about 10% of total people consuming it. These mild symptoms are:-

  1. Hives
  2. Angioedema
  3. Skin Rashes
  4. Fever
  5. Swelling
  6. Shortness of breath and wheezing
  7. Running nose
  8. Itchy, watery eyes

Anaphylaxis occurring in about 0.03% of cases is less common and is a life-threatening condition requiring a quick medical condition. This occurs in patients highly sensitive to penicillin.

Anaphylaxis present with the systemic symptoms in addition to the skin symptoms which are mentioned below:-

  1. Skin symptoms such as hives, itchiness, and flushing.
  2. Running nose.
  3. Swelling of the lips, tongue and/or throat.
  4. Central nervous system symptoms such as lightheadedness, Loss of consciousness, headache, anxiety.
  5. Respiratory symptoms such as shortness of breath (Dyspnea) wheezes or strider, hoarseness, pain with swelling, cough.
  6. A cardiovascular symptom such as bradycardia (Slow heart rate) or Tachycardia (Increased heart rate), hypotension (low blood pressure), syncope.
  7. Gastrointestinal symptoms such as cramping abdominal pain, diarrhea, vomiting.
  8. Pelvic pain and loss of bladder control.

Risk factor for penicillin allergy reaction

Before prescribing penicillin your doctor would want to know about the risk factors. The presence of any of the risk factors given below may increase the risk of penicillin allergy. Risk factors include:-

  1. History of any other allergies such as food allergy or hay fever.
  2. History of allergic reaction to any other drugs.
  3. Family history of drug allergy.
  4. Increased exposure to penicillin, which may be due to high doses, repetitive use or prolonged use.
  5. Certain diseases associated with drug reactions such as HIV or Ebstein Barr virus infection.
  6. People of age between 20 years and 40 years are believed to be at the risk of penicillin-allergic reaction. This theory is still conversing and the reasons for a penicillin-allergic reaction of this age group is unknown.
  7. It is more common as parenteral route than the oral form of penicillin.
  8. Atopic disease like Bronchial asthma is not a risk factor for penicillin, but if penicillin allergic occurs in people with an atopic disease. It usually takes a severe clinical course.

Immunological response to penicillin/cause of allergic penicillin reaction

Allergic reaction to the penicillin is caused due to the defect in our own immune system, It occurs on the second time you take penicillin. On the first dose of penicillin, the body may be preparing antibiotics for the drug which was recognized as foreign by the immune system. The penicillin allergic reaction may be an immediate hypersensitivity reaction or delayed hypersensitivity reaction.

Immediate hypersensitivity reaction occurs within 20 minutes of penicillin use. It is mediated by IGT antibiotics in response to penicillin, which was recognized as foreign by the immune system. It coats mast cells and the basophilia when penicillin recognized as foreign bridges the gap between mast cell and the basophil, these cells undergo degranulation and the releases histamines which are responsible for an allergic reaction to penicillin.

The severity of immediate hypersensitivity reaction ranges from mild symptoms such as skin rash, running nose, itching of skin to anaphylaxis causing Bronchospasm, larynx edema, hypotension and even death.

Delayed allergic reactions occur after 48-72 hours of penicillin use. It is mediated by T cells and macrophages. The antigen is presented to the antigen-specific (in this case penicillin) T cells by antigen presenting cells. Antigen-specific memory T cells becomes activated and produces chemicals that causes the inflammatory cells to move into the area causing tissue antigen delayed hypersensitivity reactions causes serum sickness-like symptoms, Hypersensitive myocarditis, Jarish-Hevxheimer reaction characterized by Increase temperature, sweating myalgia headache, tachycardia, hyperventilation, flushing and mild hypertension has been reported in treatment of spirochetes with penicillin.

Some symptoms of penicillin-allergic reactions may be presented after days or weeks after the penicillin use and may persist for a long time even after stopping the use of penicillin. For example:-

  1. Serum sickness: – Symptoms like fever, joint pain, skin rash, swelling, and nausea.
  2. Anaemia Drug-induced:- It presents with fatigue, shortness of breath on exertion. Pale skin, cramping of legs, dizziness etc.
  3. Dress short forms of drug reaction with casinophilia and systemic symptoms present with fever, lymphadenopathy, blood abnormalities like easinophilia, thrombocytopenia, and atypical lymphocytosis. It may also the recurrence of dormant hepatitis infection.
  4. Nephritis(Inflammation of the kidneys) will give rise symptoms such as fever, Haematuria(blood in urine), Generalized swelling of the body, confusion etc.


Accurate diagnosis of penicillin-allergic reaction is very essential. The wrong diagnosis of penicillin-allergic reaction leads to prescribing least appropriate antibiotics or more expensive alternative antibiotics.

Once you visit your doctor, he will take a history of onset of symptoms, time of penicillin use and improvement or worsening of symptoms with time, allergic history in the family, any other allergic history such as food allergy, medical history such as HIV and Epstein Barr virus infection. These questions along with physical examination lead to a diagnosis of penicillin-allergic reaction. Lab tests are needed to confirm the diagnosis most important test is a skin test.

Skin test

This involves the introduction of the penicillin into the skin and waiting for the response such as redness or wheal on the skin. A skin test is called positive if the wheel and redness on the skin occur within 15 minutes and the diameter of the wheel is more than 5 mm.

Graded drug challenge

If skin tests are not confirmatory then graded drug challenge may be used. This test starts with a small dose of penicillin and the dose is increased slowly. If an allergic reaction doesn’t occur up to the therapeutic dose, you are diagnosed as non-allergic to penicillin. This test requires strict supervision from your doctor to manage complications that may occur in the use of penicillin.


Treatment of penicillin-allergic reaction can be divided into two strategies:-

  1. Treatment of the allergic symptoms
  2. Desensitization to penicillin

1. Treatment of the allergic symptoms includes:-

Withdrawal of drug

If you experience any symptoms causing discomfort to you after the use of penicillin, stop the use of the drug immediately and contact your doctor.


Available over the counter antihistamines can be used to reduce the allergic symptoms. This blocks the chemical mediators of the immune systems, histamine. Do not forget to contact your doctor even if you are free of allergic symptoms.


Serious penicillin allergic reaction warrants for the use of corticosteroids (oral or intravenous).

Treatment of Anaphylaxis

Anaphylaxis is a serious medical condition and needs urgent medical attention without which people may die. Treatment of anaphylaxis includes maintenance of airway, breathing, and circulation.

  1. Prompt maintenance of the airway and breathing is needed. The patient may need endotracheal intubation.
  2. Circulation is maintained by gaining intravenous access and infusion of large amounts of fluid. Intravenous epinephrine and intravenous corticosteroids should be given immediately after intravenous access.

2. Drug sensitization

It is used only in cases where the alternatives to the penicillin are not present to treat a certain infection. It includes the use of small doses of penicillin and increasing it progressively every 15 to 30 minutes over the course of several hours of the days. If you reach the therapeutic dose without any reactions then you can continue the treatment. It requires strict supervision of a consultant and is rarely done if you have a history of life-threatening anaphylactic reaction at any point in your lifetime.

Prevention of penicillin-allergic reaction

As penicillin allergic doesn’t occur with the first dose, it cannot be prevented completely, but still, some measures can be taken to reduce the incidence:-

  1. Before prescribing penicillin a doctor must ask your history of allergic reaction, allergic reactions running in family, past medical diseases etc.
  2. Patients with known cases of penicillin-allergic reaction should always mention it to the doctor.
  3. All medical documents should mention the history of penicillin allergy.

The best way to prevent a penicillin-allergic reaction is to stop the use of penicillin.

Waiting a bracelet providing information about the penicillin allergy may be helpful in an emergency to ensure a proper treatment.

In some developed countries, Epinephrine auto-injector is prescribed to the patients who are suffering from anaphylaxis. This helps in preventing the severe form of penicillin drug reaction.


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