Fluorodeoxyglucose-induced allergic reaction: A case report

Introduction

Fluoride, the ionic form of fluorine, represents the 13th most abundant element in the crust of the earth. Fluorine’s highest electronegativity makes it one of the most chemically reactive elements, giving unique properties to many of its compounds. Organic fluorine compounds are widely used in medicine. Despite the remarkable impact of fluorinated molecules in clinical medicine, they are not completely devoid of risk. Contact dermatitis and acne-like eruptions have been associated with fluorinated toothpaste.^1,2 Occupational contact dermatitis and allergies to fluorinated anesthetics have been described in anesthesiology staff.^3,4 Occasional reports of hypersensitivity reactions have been reported with many other fluorinated agents such as quinolones,^5,6 antifungals,^7–10 selective serotonin reuptake inhibitors, ¹¹ and even fluorinated corticosteroids.^12–14 We report an allergic reaction to fluorine-18-labeled fluorodeoxyglucose (F18-FDG), the most common radiopharmaceutical used in positron emission tomography. To the best of our knowledge, there are no previous reports of allergic reactions to F18-FDG in the world literature.

Case report

We describe a 59-year-old male with history of squamous cell carcinoma of the right pyriform sinus (T1N2aM0), status post-transoral robotic surgery, supracricoid right hemipharyngolaryngectomy and neck dissection, followed by chemoradiotherapy. The patient reported having recurring body rash and itching after two of his restaging positron emission tomography/computed tomography (PET/CT) scans done 3.5 months apart. Each PET/CT scan was performed 60 min after injection of circa 15.0 mCi of F18-FDG. No oral contrast or other medications were administered during the scan visits. The prominence of the body rash and itching for over 24 h prompted a visit to a dermatologist who prescribed fexofenadine, with some symptom relief.

The patient had known allergies to bupropion (hives), penicillins (rash, fever), trimethoprim–sulfamethoxazole (diarrhea, dry heaves, stomach cramps) and clindamycin (rash). Notwithstanding, none of these medications were taken in that period. Past medical history was significant for hypertension, hyperlipidemia, and hypothyroidism. At baseline, he complained of chronic dry mouth, mild taste disturbance, and difficulty swallowing, which developed as a result of chemoradiation and remained stable over time. The medications he was taking included aspirin 81 mg orally daily and l-thyroxine 175 mcg orally daily.

Skin examination revealed the presence of pruritic, red papules on the face, trunk, and extremities. A few scratch marks were present in his back. Physical examination was otherwise unremarkable.

Laboratory studies performed several days after the scan showed the following: hemoglobin 14.8 g/dL, hematocrit 42%, white blood cell count 3.9 × 10³µL⁻¹, neutrophils 72%, lymphocytes 11%, monocytes 10%, eosinophils 6%, basophils 1%, and platelets 259 × 10³µL⁻¹. His baseline eosinophils during previous year varied between 0% and 3%.

The PET/CT scans showed post-surgical changes in the larynx and right neck, with no abnormal foci of increased radiotracer uptake to suggest residual or metastatic disease.

As a premedication before future PET/CT scans, the patient was prescribed prednisone 50 mg (one tablet 12 h prior to scan and one tablet 2 h prior to scan) and 25 mg diphenhydramine (one tablet 10 h prior to scan). This proved to be effective and no allergic symptoms were reported during a subsequent PET/CT scan.

Discussion

F-18 FDG PET scan is a relatively new, but expanding imaging modality. With increasing number of individuals exposed to F18-FDG, the number of allergic reactions is expected to increase. To date, there are no published reports of allergic reactions to F18-FDG and, to our knowledge, this represents the first such case.

Chemically, F18-FDG represents a glucose molecule with an attached positron emitting radioactive isotope fluorine-18 in the 2′ position. Given a variety of allergic reactions reported to fluorinated molecules, we hypothesize that allergic reactions to F18-FDG can also be expected. Adverse effects to possible chemical impurities are at least a theoretical consideration. ¹⁵ The probability of an allergic reaction in our patient was estimated by an overall score of 9 on Naranjo nomogram for adverse drug reaction assessment. A score in this range defines an allergic reaction as ‘definite’. However, the exact mechanism is not known and represents a matter of debate. T-cell-mediated hypersensitivity to various drugs, including fluorinated quinolones, has been described in the literature.^6,16 Non-immune, idiopathic urticariform reactions, mediated by complement system and other plasmatic systems are also possible. Apart from the borderline elevated eosinophils compared to baseline values, no other distinct laboratory abnormalities suggestive of an allergic reaction were found in our patients.

In conclusion, along with the expanding of the FDG-PET/CT imaging, allergic reactions to F18-FDG may occur. Although rare, they must be made widely known to insure early diagnosis and potentially fatal outcomes. Although there are no established treatment recommendations for the FDG-induced allergies, it would not be unreasonable to follow standard protocols for the management of allergic reactions. We advocate secondary prophylactic measures, such as premedication with steroids and H₁-receptor blockers, for patients with known allergies to the F18-FDG before exposing them again to these agents.