Hypersensitivity skin reactions: Clinical practice
AssessmentsHypersensitivity skin reactions: Clinical practice
USMLE® Step 2 style questions USMLE
A 57-year-old man comes to the emergency department for evaluation of a painful skin rash. The patient had a mole removed from the tip of his nose last week. He broke out in a painful facial rash over the weekend and has subsequently been experiencing fevers and chills. Past medical history is notable for poorly controlled type II diabetes mellitus, hypertension, lymphedema, and a left kidney transplant for which he is on tacrolimus. The patient develops hives when he takes penicillin. At arrival, temperature is 38.0°C (100.4°F), pulse is 104/min, respirations are 16/min, and blood pressure is 161/82 mmHg. Physical examination is notable for the following finding:
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Which of the following is the most appropriate treatment for this patient’s clinical condition?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Salma Ladhani, MD, Evan Debevec-McKenney, Antonella Melani, MD
Hypersensitivity skin reactions are due to an exaggerated immune system reaction towards an antigen, and some reactions can be life-threatening.
Hypersensitivity skin reactions include urticaria, erythema multiforme, Staphylococcal scalded skin syndrome, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Urticaria, also called hives, are slightly raised, well-defined wheals that are 1 millimeter to 10 centimeters in diameter. They’re usually red, blanch with pressure, are extremely itchy, and can pop up anywhere in the body.
The key feature is that these lesions come and go very rapidly - meaning one might appear on the leg as another disappears from the arm.
The reaction involves the epidermis and dermis layers of the skin, and the whole thing typically resolves within 24 hours.
Typically no treatment is needed, but if the itching is really bad, topical cooling moisturizers or oral second-generation histamine H1 blockers can be used like loratadine, desloratadine, fexofenadine, cetirizine, or levocetirizine. If these don’t work, immunomodulatory agents, like cyclosporine or methotrexate can also be used.
Now, if there’s recurrent urticaria, it’s good to try to identify a trigger, so that it can be avoided.
One way is with in vivo skin prick tests, which is where small drops of up to 40 allergens, like pollens, fungi, animal dander, house dust mites, and various foods, are pricked into the skin on the forearm or upper back.
After that, if there are signs of urticaria within about 20 minutes, that implies that the substance is a trigger.
Unfortunately, it’s a bit uncomfortable and requires that the individual doesn’t take any antihistamines and doesn’t have any other skin diseases.
Another way is with in vitro blood tests that look for IgE antibodies against specific allergens, such as foods, insect venoms, pollen, mold, latex, or antibiotics. This takes longer, is more expensive, but is more convenient, and isn’t affected by medications or skin diseases.
Unfortunately, both of these tests can have lots of false positives, meaning that the test might suggest a problem allergen, even though a person might really have no symptoms from that allergen, and the tests can have lots of false negatives, meaning that the test might suggest that an allergen causes no reaction, even though a person might really have symptoms from that allergen in their daily life.
Occasionally, in addition to urticaria an individual might also develop angioedema, which can happen almost anywhere on the skin, like on the hands, feet, trunk and urogenital area, but it’s most common, on the face, like around the eyes or nose.
It involves even deeper skin layers, like the subdermis and mucosal layers, like the subdermal tissue.
When it involves the skin, angioedema doesn’t cause intense itching, but can cause tenderness and burning.
Angioedema can also happen internally - involving the gastrointestinal mucosa, and causing nausea, vomiting, or diarrhea, or the mucosa of the mouth, lips or tongue, which can progress down to the larynx, closing off the airway.
Now in rare situations, urticaria or angioedema can worsen and cause anaphylaxis.
To diagnose anaphylaxis, at least one of three criteria has to be met.
One criteria is a rapid onset of symptoms that involve skin or mucosa -like urticaria or angioedema, plus at least one other organ system, like the respiratory system, causing dyspnea, the cardiovascular system causing hypotension, or the nervous system, causing syncope.
The second criteria is exposure to a likely allergen, followed by symptoms in any two organ systems.
The third criteria is exposure to a known allergen, for example something that they have been previously tested positive for, followed by hypotension.
Both acute angioedema and anaphylaxis are medical emergencies, so they have to be treated right away - that means an intramuscular shot of 1:1000 epinephrine with an EpiPen shot in the thigh. This contains 1 mg/mL of epinephrine and the dose is 0.01 mg/kg with a maximum of 0.5 mg.
Oral, second- generation antihistamines, such as cetirizine, can also be used to relieve some of the symptoms.
Close monitoring for at least a day after symptoms resolve is important, in case there’s a biphasic reaction and another wave of symptoms.
Before they leave, it’s important that these individuals should be given epinephrine autoinjectors that they can use right away if there’s a future attack.
For children weighing less than 30 kg, an EpiPen Junior Autoinjector is used which delivers 0.15 mg of epinephrine, and for those over 30 kg, an adult EpiPen with 0.3 mg of epinephrine is used.
Moving on, there’s erythema multiforme which affects the skin, usually the extremities, and mucous membranes, and it’s usually triggered by an infection like Herpes simplex virus or medications including penicillins, sulfonamides, ciprofloxacin, and anticonvulsants such as phenytoin and carbamazepine.
As the name suggests, erythema multiforme can appear in a variety of shapes and sizes. There can be macules, which are flat red, or pink patches. There can be vesicles which are small, raised, fluid-filled lesions or bullae which are large, raised, fluid-filled lesions. There can also be papules which are solid elevations containing no fluid.
However, the most characteristic of all erythema multiforme lesions are targetoid lesions which are between 2 millimeters and 2 centimeters, and have central necrosis of the epidermis, surrounded by concentric rings of erythema, making them look like a bull’s eye or target.
The diagnosis of erythema multiforme is based on the classic skin rash along with the hemorrhagic crusting of the lips.
The involvement of the oral mucosa makes it hard for a person to eat and drink - leading to dehydration. So, part of treatment is maintaining good hydration which may include IV rehydration as well as pain control.
Now erythema multiforme is frequently self-limiting and requires no further treatment. If there is an underlying cause it should be dealt with - for example, an infection should be treated and an offending medication should be stopped.
Systemic corticosteroids can be used to help reduce inflammation.
In cases of recurrent bouts of erythema multiforme due to herpes simplex virus, continuous oral acyclovir or valacyclovir can be used for prevention.
Next up there’s Staphylococcal scalded skin syndrome.
Staphylococcus aureus produces exfoliative toxins that cleave adhesions between the epidermis and dermis, leading to the formation of bullae in a disease called bullous impetigo.