Iodine-Induced Sialadenitis Requiring Intubation After Intracranial Venous Sinus Stenting: A Case Report

Introduction

Iodine-induced sialadenitis (iodine-induced mumps) is a rare, noninfectious inflammatory condition characterized by acute swelling of the salivary glands after exposure to iodine-containing contrast agents. First described in 1956 as sialadenitis resembling viral mumps after the administration of inorganic iodine compounds, this entity remains underrecognized despite the widespread use of iodinated contrast in modern medicine [1]. Since the 1950s, more than 75 million doses of iodinated contrast agents have been administered globally, but only 77 confirmed case reports had been documented as of 2020 [2,3]. This discrepancy highlights the rarity of the condition but also indicates potential for underreporting or misdiagnosis, particularly in emergency and inpatient settings where acute neck swelling has a broad differential diagnosis.

Demographically, iodine-induced mumps shows no clear predilection for a specific population. Patients in reported cases exhibit a wide age range – from 8 to 80 years – with a median age of 63 years and a slight male predominance (approximately 61%) [2]. Cases have been documented across diverse ethnic backgrounds and geographical locations, suggesting no regional or genetic predisposition. The condition has also been linked to several exposure routes, including intravenous injection (most common), intra-arterial contrast delivery during angiography, and oral administration of iodine-containing compounds [2,4,5]. This variability in patient demographics and exposure routes adds complexity to clinical recognition. Because iodine-induced sialadenitis can occur without classic risk factors for contrast-related complications – such as advanced age, renal impairment, or prior allergic reactions – it is often not considered during initial evaluation.

The broad variability in patient demographics and routes of contrast exposure contributes to the difficulty of recognizing iodine-induced mumps. Its presentation often resembles more common conditions such as viral parotitis, bacterial sialadenitis, angioedema, or deep neck space infections, which can lead to misdiagnosis and unnecessary treatment. The absence of classic risk factors further complicates timely identification. Without clear diagnostic criteria or standardized management guidelines, clinical responses considerably vary, especially in acute care settings.

The present case illustrates the potential severity of iodine-induced mumps, demonstrating that airway compromise can occur even in low-risk patients. The use of allergy testing provided a path to safer future imaging, reflecting a proactive approach to long-term management. By contributing to the limited literature, this report emphasizes the need for greater clinical awareness, a structured imaging approach beginning with ultrasound (US), and early airway monitoring. Broader recognition and further research are essential to improving diagnosis, guiding treatment, and preventing recurrence.

Case Report

A 37-year-old Caucasian woman presented for evaluation of idiopathic intracranial hypertension. Papilledema was noted during funduscopic examination by an ophthalmologist, and lumbar puncture revealed an elevated opening pressure. A catheter-based diagnostic cervical–cerebral angiogram with cerebral venography and manometry was performed. During the procedure, 174 mL of iopamidol (Isovue 300) were administered.

The patient was deemed a candidate for venous sinus stenting. One week later, she underwent endovascular intracranial venous sinus stenting for cerebral venous outflow obstruction. An additional 171-mL volume of iopamidol was administered during the procedure, and she was admitted to the neuro–critical care unit for monitoring. The procedure targeted the left transverse sinus and was performed via the left internal artery and common carotid artery. Three hours post-procedure, the patient developed painful, right-sided parotid and submandibular gland swelling. She exhibited increased work of breathing, odynophagia, and tenderness in the parotid region. Stridor was absent, and airflow initially was adequate. However, she displayed progressive respiratory effort with increasing use of accessory muscles.

The differential diagnosis included acute sialadenitis, sialolithiasis, angioedema, anaphylaxis, and deep neck infection. Infectious and obstructive causes were less likely due to the lack of fever, purulence, or prior history. The absence of hypotension, rash, and urticaria made classic anaphylaxis unlikely. Deep neck infection was considered but lacked supporting clinical or imaging findings. Given the rapid onset after contrast exposure and unilateral gland involvement, iodine-induced mumps was suspected. Because of concern about an evolving hypersensitivity reaction or anaphylaxis, the patient was administered methylprednisolone (Solumedrol), diphenhydramine, and epinephrine. She was subsequently intubated for airway protection, and laryngoscopy revealed normal-appearing vocal cords without edema. She displayed tachycardia but remained normotensive and did not develop a rash.

Soft-tissue neck computed tomography (CT) revealed clinically significant swelling in the right parotid and submandibular spaces, which remained unchanged 1 day later (Figure 1). Carotid artery Doppler US demonstrated pronounced neck edema and a 1.7×3.2 cm mass on the right side of the neck. Given the clinical presentation, iodine-induced mumps was suspected, and the patient was treated with dexamethasone 4 mg every 6 h, with a 2-week taper scheduled at discharge. She was extubated 3 days later – with substantial resolution of right-sided glandular swelling – and then discharged.

Laboratory findings during hospitalization included a venous blood gas pH of 7.25, which prompted intubation due to pronounced acidosis, and a baseline creatinine of 0.8 mg/dL, which remained stable throughout the admission period. C1 esterase inhibitor and C3/C4 complement levels were within normal limits. Subsequent outpatient allergy testing revealed a strongly positive diluted skin prick test result for iopamidol. Both diluted and full-strength skin prick test results for iohexol (Omnipaque) were negative. Further intradermal testing with iohexol also demonstrated no evidence of hypersensitivity.

Discussion

Imaging plays a crucial role in diagnosing and managing salivary gland swelling. US is widely recognized as the first-line imaging modality due to its ease of use, low cost, and rapid results. In more than 97% of cases, US imaging has provided sufficient information about salivary masses and swelling [6–8]. US can differentiate among benign and malignant lesions, congenital abnormalities, and other disorders that cause glandular swelling [9]. However, US results can be limited by operator experience, edema-related regional heterogeneity, and the superficial nature of the images. CT imaging of the soft tissues of the neck should be considered when a lesion is suspected to be deep or when there is concern regarding airway compromise [8]. Magnetic resonance imaging is typically reserved for lesions with features suggestive of malignancy [7]. In the present case, increased work of breathing and US limitations arising from pronounced edema made CT imaging particularly useful.

Notably, in this case, contrast was administered only via the left internal artery and common carotid artery, but swelling was isolated to the right submandibular and parotid glands. These findings suggest that iodine-induced mumps represents a systemic reaction, rather than a local response to contrast exposure. Additionally, although approximately 85% of reported cases involve bilateral swelling, our patient demonstrated only right-sided involvement, highlighting variability in presentation [2,5].

Iodinated contrast agents differ in osmolarity, radiopacity, and levels of organically bound iodine. Isovue 300 (ie, iopamidol) contains a higher concentration of bound iodine and is favored for accurate CT measurements, whereas Omnipaque 300 (ie, iohexol) is associated with a better safety profile, particularly among patients with renal or cardiac dysfunction [10]. In the present case, the patient had an immunological reaction to iopamidol but tolerated iohexol, as demonstrated through allergy testing. For patients with prior contrast reactions, immunological evaluation of alternative iodinated agents may enable future imaging without recurrence.

The mechanism underlying iodine-induced mumps remains poorly understood, but the prevailing theory involves iodine accumulation within the salivary glands. The minimum recommended daily dietary intake of iodine in the United States is 150 μg [11]. Standard chest CT, using 100 mL of contrast, can deliver up to 30 g of organically bound iodine. Manufacturer specifications require that the concentration of free (unbound) iodine be much lower, with an upper limit of 50 000 μg/L [12]. In the present case, 171 mL of contrast were administered, containing approximately 8550 μg of free iodine – more than 50 times the minimum daily intake. Iodine is primarily excreted renally (approximately 98%), and the remainder is taken up by exocrine glands [2,12]. Salivary glands have the capacity to concentrate iodine to levels 20 to 100 times higher than those in serum [13–15]. The parotid gland is the most active component of the iodine concentration process, which may explain why it is often affected by adverse iodine reactions. Animal models have shown that excessive iodine can trigger mononuclear cell infiltration and inflammation in the salivary glands [16]. Further research is needed to characterize the downstream effects of this inflammatory response in humans.

Early case reports of iodine-induced mumps involved hemodialysis patients or patients with known renal impairment [1,17]. Because most iodine is renally excreted, renal impairment was initially considered a primary contributing factor in excess serum iodine and subsequent salivary gland swelling. However, a meta-analysis showed that recent case reports did not support this assumption. Only 39% of patients with iodine induced sialadenitis had creatinine levels above 1.1 mg/dL, and the median creatinine level of those with renal impairment was 2.0 (range: 1.2–31.5, N=9) [2]. In the present case, the creatinine level was 0.8 mg/dL, and the patient had no history of renal disease, emphasizing that normal renal function does not eliminate risk.

Various treatments have been proposed to manage post-contrast salivary gland swelling. Most reported cases have been self-limited and required only supportive treatment [5]. To decrease the relative concentration of iodine in the salivary glands, sour candy, hydration, and saline gargles have been suggested, although none have demonstrated a clear benefit in reducing symptom duration [2]. Anecdotally, steroids and antihistamines have provided symptomatic relief, but robust efficacy data are unavailable [5,18]. Further studies are needed to determine optimal management strategies.

Although often described as a self-limiting condition, iodine-induced mumps can – in rare instances – require intensive interventions [2,19,20]. Other reports have documented respiratory distress requiring airway management [21–23]. Clinicians should remain vigilant and monitor patients closely, particularly in inpatient settings where respiratory symptoms may evolve rapidly.

Finally, iodine-induced mumps is likely underreported. In an observational study, otolaryngology providers trained to identify the condition detected 4 cases in 2 months, whereas emergency physicians without specialized training identified 0 cases in the same population. Retrospective chart review revealed several additional patients who met clinical and radiographic criteria for iodine-induced mumps [24]. Greater provider awareness is essential to ensure accurate diagnosis, avoid unnecessary diagnostic workups, and implement timely treatment for this rare but potentially serious complication.

Conclusions

Iodine-induced mumps is an uncommon but clinically important complication of iodinated contrast exposure, characterized by acute salivary gland swelling that can – in rare cases – progress to airway compromise. Our report contributes to the growing recognition that such reactions can occur even in younger patients with normal renal function and no prior contrast sensitivity.

The present case highlights several practice-changing insights. First, it reinforces the value of a stepwise imaging approach. US should be the initial modality of choice to evaluate salivary gland swelling because of its accessibility, rapid turnaround, and diagnostic utility in differentiating benign lesions from more concerning lesions. However, when sonographic interpretation is limited – such as in cases with pronounced edema or deep-space involvement – CT imaging should be pursued promptly to assess the extent of swelling and identify potential airway compromise. Adoption of this imaging algorithm can help clinicians more efficiently arrive at the correct diagnosis while avoiding unnecessary or invasive procedures.

Early recognition of iodine-induced mumps also has the potential to substantially reduce the scope of diagnostic workup. Awareness of this condition allows providers to avoid extensive evaluations for infectious, autoimmune, or neoplastic causes, thereby limiting patient exposure to unnecessary tests, consultations, and empiric treatments. In the present case, familiarity with the condition helped avoid delay in securing the airway, illustrating how early suspicion can guide timely and potentially life-saving interventions.

Finally, allergy evaluation plays an important role in long-term management. As demonstrated here, targeted skin testing can help identify specific contrast agents that triggered the reaction and thus guide the selection of safer alternatives for future imaging. This identification is particularly important for patients with chronic conditions that may require repeated exposure to contrast media. The ability to distinguish hypersensitivity to 1 agent from intolerance of an entire class can preserve diagnostic options while minimizing future risk.

In conclusion, this case illustrates that iodine-induced mumps, although rare and often self-limiting, can present with serious complications and should be considered in any patient who develops salivary gland swelling shortly after contrast administration. Increased provider awareness, a thoughtful diagnostic strategy, and early airway assessment can improve patient safety. The integration of allergy testing into post-reaction evaluation may also facilitate safer imaging pathways in the future.