How Common is Hypersensitivity Cross-Reactivity with NSAIDs?

Patient Presentation
A 5-year-old female came to clinic with a history of acute pharyngitis that was positive for Group A, β-hemolytic Streptococcus. When reviewing her medications and allergies, the resident noted that she was allergic to ibuprofen and her mother said that she had problems breathing and an urticarial rash twice after receiving ibuprofen that required her to go to the emergency room. The mother said that she used acetaminophen for pain and fever relief without any problems. The pertinent physical exam showed a mildly ill child with normal vital signs and growth parameters. She had exudative pharyngitis and anterior cervical nodes bilaterally that were 0.5-1.0 cm in size. She had no rash. The diagnosis of acute streptococcal pharyngitis was made. When discussing the patient with her attending physician, the resident noted that she had not encountered an allergy to ibuprofen before and asked how often there was cross-reactivity with other non-steroidal anti-inflammatory drugs. The attending physician said that she also didn’t seem to see much of this hypersensitivity but knew that it was relatively common. She also didn’t know how often there was cross-reactivity. They decided to look up the question when they had time later in the day.

Discussion
NSAIDs (non-steroidal anti-inflammatory drugs) are commonly used for pain and fever relief. They work by inhibiting the cyclooxygenase enzymes COX-1 and COX-2. Most are non-selective such as aspirin, ibuprofen, and acetaminophen. Currently Celecoxib is the only COX-2 selective inhibitor available in the United States.

Hypersensitivity to NSAIDs is caused by immunological and non-immunological mechanisms. Immune-mediated reactions are rare and drug-specific. Symptoms include conjunctivitis, rhinitis, bronchospasm, angioedema, hypersensitivity pneumonitis, meningitis, urticaria and anaphylaxis. Non-immune reactions may be caused by imbalance in the arachidonic acid pathway. These reactions are not drug-specific and symptoms include rhinitis, bronchospasm, urticaria and angioedema. Hypersensitivity can be difficult to determine as there are not reliable in vitro tests and provocative challenge testing may not be ethical in individual patients because of the risk of anaphylaxis.

Learning Point
Hypersensitivity to NSAIDs is the most frequently reported reaction to drugs. Hypersensitivity reactions to NSAIDs in the general adult population is 0.3% in adults and is similar in children.
One study that evaluated hypersensitivity reactions to NSAIDs in children classified them as cross-reactive (58%) with other NSAIDs or selective to the offending drug only (42%).
Ibuprofen is the most common NSAIDs to show cross-reactivity. In this study, acetaminophen did not show cross-reactivity which is different than other studies that have shown ~25% cross-reactivity. The authors note that they did challenge testing which is different than many studies that use clinical history as the defining element of cross-reactivity.

Questions for Further Discussion
1. What is the definition of angioedema?
2. What evaluation should be considered for a patient with potential NSAID hypersensitivity reaction?
3. What treatment options are available for pain and fever relief for patients with an NSAID hypersensitivity reaction?

Related Cases

    Symptom/Presentation: Pain

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Drug Reaction.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Liew WK, Chiang WC, Goh AE, Lim HH, Chay OM, Chang S, Tan JH, Shih E, Kidon M. Paediatric anaphylaxis in a Singaporean children cohort: changing food allergy triggers over time. Asia Pac Allergy. 2013 Jan;3(1):29-34.

Zambonino MA, Torres MJ, Muñoz C, Requena G, Mayorga C, Posadas T, Urda A, Blanca M, Corzo JL. Drug provocation tests in the diagnosis of hypersensitivity reactions to non-steroidal anti-inflammatory drugs in children. Pediatr Allergy Immunol. 2013 Mar;24(2):151-9.

Kay E, Ben-Shoshan M. Anaphylaxis to ibuprofen in a 12-year-old boy. BMJ Case Rep. 2013 Jan 14;2013.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    16. Learning of students and other health care professionals is facilitated.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

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    How Do You Treat Minor Pressure Ulcers?

    Patient Presentation
    A 13-year-old female came to clinic with a complaint of recurrent wounds on her buttocks. These occurred over the past 3 months and had been getting worse during the summer. She and a friend had been training for a 7-day bike trip and had been increasing their mileage considerably over the past 2-3 weeks. She said that there had been several sore spots that changed in location over time but she now had two that were particularly painful and were not healing. She complained of general itching of the buttocks. She was also spending a great deal of time at the local pool sitting in wet bathing suits. She had put some lotion onto the area a few times without help. The past medical history showed a healthy female with no history of athletic injuries, but with mild atopic dermatitis.

    The pertinent physical exam revealed a healthy female with normal growth and vital signs. Skin examination showed a tanned individual with keratosis pilaris of the upper outer arms and thighs. She had skin irritation under her breasts and in the axillary area. Her bilateral buttocks had multiple areas of discrete 1-2 mm erythematous macules or papules consistent with folliculitis particularly in the area where the buttocks meet the top of the thighs. There were two erythematous 13-15 mm round lesions without skin breakdown but the left buttock also had a 5-mm shallow crater to the dermis in the center that was dry. The lesions overlied the ischial tuberosities bilaterally. The buttocks appeared overall dry and irritated without discrete scratch marks. The genital area was normal.

    The diagnosis of small pressure ulcers or saddle sores was made along with folliculitis of the buttocks and atopic dermatitis. The physician recommended several things to heal the current ulcers and prevent additional ones. First he discussed that the skin problems were due to a combination of pressure, friction and shearing forces along with moisture. He recommended using clean clothes for each practice that had no seams or few seams in the offending areas. Additionally he recommended that she use lubricants in the areas during practice and that specifically for biking many people used a chamois cloth to decrease friction. He also recommended that she go to the local bicycle shop and make sure that the bike and particularly the seat was fitted to her properly. To help heal the lesions he recommended regular bathing, especially after practice, with the use of iodine or alcohol to decrease bacteria in the area. He said that this could also cause drying so that an emollient should also be used afterwards and regularly to decrease irritation. Sitting in a wet bathing suit and sitting on hard surfaces was also not helping the situation and he recommended avoiding these activities, and moving as frequently as possible. At a health maintenance visit in the early fall, the patient reported that she still had some “small bumps” in the lower buttocks from time to time that coincided to when she wasn’t doing her skin care. The pressure ulcers had resolved on physical examination and she still had minor folliculitis.

    Discussion
    A pressure ulcer is defined as “a localized area of tissue damage developed when soft tissue (fat, muscle, arterial, and venous vasculature, etc.) is compressed between a bony prominence and any external surface for a prolonged period.” The ulcer forms when the compression cuts off the blood supply to an area resulting in tissue hypoxia, cellular death, and injury to the surrounding area. Some important risk factors include immobility or decreased mobility, poor nutrition, presence of infection, decreased oxygenation/perfusion, and underlying medical problems including sensory perception. Acutely ill patients such as trauma patients in an ICU setting are often thought of as being at risk, but patients with chronic problems such as neurological or orthopaedic problems also are at risk. The areas most affected in infants and small children are the head, sacral area, ear lobes and heels. Other areas include scapula and ankles. For hospitalized children, the Braden and Braden Q scoring systems aid in predicting pressure ulcer risk and help in planning preventive measures.

    Learning Point
    Skin care treatment revolves around treatment of moisture, pressure, friction and shearing forces. For patients with underlying medical problems, adequate nutrition is also a key determinant.

    To decrease moisture, clothing that wicks moisture away is best. Close fitting (but not too tight) clothing can absorb the moisture and allow it to not gather or drain. Not tucking the ends of a shirt into the pants helps to decrease pooling of moisture in the pelvic area. For women use of feminine hygiene pads may help with leukorrhea, but they need to be regularly changed so they do not add to the moisture problem. Similarly, use of tampons instead of pads during menses can decrease moisture too. Changing clothing regularly (even during a practice) is important and clean, dry clothing should be used. People should shower or bathe regularly with good attention to drying.

    Protection from repeated pressure or methods to spread out the pressure over a body part are an important part of a sport. Well-fitting equipment that is used properly is key. In bicycling, different seat types may fit different individuals better, but seat height, handle bar height and a bike that fits well overall are probably equally or even more important.

    Friction and shearing forces may be obvious in the particular sport, such as bicycle seat friction. Padding and use of a lubricant are the usual treatment. For bicycling, using a soft chamois in the bicycling short along with a lubricant helps to prevent saddle sores. Sometimes the friction and shearing forces may not be so obvious such as seamlines in clothing, or breast tissue that is repeatedly moving. Well-fitting clothing and use of lubricants usually will improve the problem. Additionally, modification of the equipment or way the activity is performed may be necessary to accommodate the particular individual.

    Once skin breakdown and/or ulcers begin they need to be treated promptly. Cleansing of the skin is needed to decrease bacterial counts but aggressive cleaning or rubbing can cause drying, friction and increased breakdown so a balance is needed. Topical or oral antibiotics may be needed. Moisture control measures should be instituted particularly with frequent dressing changes if dressings are used. Tapes and dressings themselves may cause friction so if they are used, care needs to be taken with them. Some dressings do not need tape and can be held in place by clothing or a loose gauze dressing. Decreasing friction can be aided by other dressings such as Tegaderm® to cover an area where friction frequently occurs. Pressure also needs to be relieved. This is best done by increasing mobility and frequent position changes.

    Questions for Further Discussion
    1. What types of positioning methods can be implemented for immobile children to decrease pressure ulcers?


    2. What types of bedding can be used for immobile children to decrease pressure ulcers?


    3. What types of dermatological problems can be anticipated for people involved in different sports such as weight lifting, running, rowing, swimming, hockey, etc.?

    4. What are the grades of pressure ulcers?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Pressure Sores.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Butler CT. Pediatric skin care: guidelines for assessment, prevention, and treatment. Dermatol Nurs. 2007 Oct;19(5):471-2, 477-82, 485.

    McCaskey MS, Kirk L, Gerdes C. Preventing skin breakdown in the immobile child in the home care setting. Home Healthc Nurse. 2011 Apr;29(4):248-55; quiz 256-7.

    Bernabe KQ, Pressure ulcers in the pediatric patient. Current Opinion in Pediatrics. 2012;24(3):352-356.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital