Contrast media delayed

Plain computed tomography (CT) after the administration of contrast medium (delayed CT) shows wedge-shaped contrast enhancement in the bilateral kidneys, which persists for 1-3 days. 

Numerous positive delayed skin tests in patients with contrast medium-induced non-immediate skin reactions have been reported when the patients were tested with the culprit contrast medium [summarized in 1]. In a large European multicenter study, 37% of patients with non-immediate reactions were positive in delayed IDEs and/or patch tests [13]. The majority of the patients also reacted to the culprit contrast medium and also to other, structurally similar RCM. Notably, in more than 30% of those skin test-positive patients a RCM had been administered for the first time. Thus, there is a lack of a sensitization phase. Again it may be hypothesized that these previously non-exposed patients may have already been sensitized. Different patterns of RCM cross-reactivity indicate that several chemical entities could be involved. No positive skin tests have been obtained with other contrast medium excipients, such as ethylenediaminetetraacetic acid (EDTA), and only rarely patients have been found to react to inorganic iodide. 

Courvoisier S. Bircher AJ Delayed-type hypersensitivity to a nonionic, radiopaque contrast medium. Allergy 1998 53 1221-1224. 

Fig. 6. Delayed CT 48 h after the administration of contrast medium. The serum creatinine level was high (5.5mg/dl), and the contrast-enhanced areas were more extensive than those in Fig. 2 (serum creatinine 1.6mg/dl). Patchy contrast enhancement changed to diffuse contrast enhancement...

Fig. 7. Delayed CT 24h after the administration of contrast medium (the upper and lower rows show different slices)...

Visualization of Residual Contrast Medium on Delayed CT in Relation to the Interval from the Administration of Contrast Medium (Assessment of Regional Kidney Function)... 

Fig. 19. Delayed CT 17h after the administration of contrast medium to the patient in Fig. 18. Wedge-shaped contrast enhancement was observed in the bilateral kidneys (From [22], with permission)...

Wedge-shaped contrast enhancement on plain CT from a few hours to 72 h after the administration of a contrast medium (however, delayed CT after administration of the contrast medium is not essential to making a diagnosis). 

Delayed CT 72 h after administration of contrast medium 47 s after administration of contrast medium 1 min 15 s after... 

Fig. 25. Left. Delayed CT 24 h after the administration of contrast medium. The area of contrast enhancement was more extensive than that seen at a serum creatinine level of 1.6mg/dl (Fig. 2) (From [41], with permission). Right. Dynamic CT in the presence of wedge-shaped lesions (72 h after the administration of contrast medium). In a portion of the left kidney (arrows), the medulla was contrast-enhanced 2-3 min later, suggesting that kidney function in this area was normal...

Fig. 28. Delayed CT 12, 18, 41, and 96h after the administration of contrast medium. Patchy contrast enhancement persisted for 41 h...

This patient, who had autosomal dominant polycystic kidney disease (ADPKD), almost drowned and then developed ALPE. On July 20, 1990, he nearly drowned in the sea at 1500 hours, and was brought to our hospital by ambulance for dyspnea and severe loin pain at 1620 hours. On admission, metabolic acidosis was observed. His CRP, serum creatinine, CPK, amylase, and urinary protein levels were 1+, 1.5mg/dl, 116 U/l, 592IU/1 (derived from the salivary gland), and 2+, respectively. His body temperature was 37.7°C, and his blood pressure was 110/60 mmHg. His pulse and respiratory rate were 120/min and 22/min, respectively. Delayed CT 6h after the administration of contrast medium showed wedge-shaped contrast enhancement in the noncystic renal parenchyma (Fig. 34). On July 24, a bone scan with MDP revealed patchy lesions (Fig. 35). His serum creatinine level was 1.3 mg/dl, which had decreased to 1.0 mg/dl on July 27. The patient was then discharged. 

Fig. 34. Delayed CT 6h after the administration of contrast medium to an autosomal dominant polycystic kidney disease (ADPKD) patient with ALPE. Top. Wedge-shaped contrast enhancement can be seen in the noncystic renal parenchyma region at onset. Bottom. CT under the same conditions in the recovery phase did not show wedge-shaped contrast enhancement...

Fig. 36. Top. Plain CT showing a renal swelling (serum creatinine 3.7mg/dl). Bottom. Delayed CT 18h after the administration of contrast medium showed a diffuse uptake, although the patient s serum creatinine level had decreased to 1.8mg/dl...

This patient, who had ADPKD, developed ALPE after a sprint. On October 1,1995, he participated in two 100-m races at an athletics meeting in the morning. After a few hours, severe loin pain occurred, and he attended our department the following morning. There were no other abnormal findings, and his blood pressure, pulse, and serum creatinine values were 120/66 mmHg, 64/min, and 1.6mg/dl (serum creatinine level before onset 0.9mg/dl), respectively. On October 2, delayed CT 4 and 24 h after the administration of contrast medium showed patchy lesions (Fig. 37). On October 14, his serum creatinine level returned to 1.1 mg/dl, and CT 4h after the administration of contrast medium showed no contrast enhancement. 

Fig. 43. Delayed CT 24 and 48 h after the administration of contrast medium. Contrast enhancement can be detected 48 h after administration, although it is less marked...

We performed delayed CT after the administration of contrast medium in 11 patients with both ALPE and renal hypouricemia. In 10 of the 11 patients, patchy renal ischemia was noted [4], suggesting that renal ischemic conditions after anaerobic exercise were similar regardless of the presence or absence of renal hypouricemia. 

On June 6, this patient developed severe loin pain after he participated in two 150-m sprints at a town athletics meeting. After 5 days, he was referred to the outpatient clinic of our department. His serum creatinine and uric acid levels and FEUA, were 2.9mg/dl, 2.1 mg/dl, and 49.7%, respectively. His creatine phosphokinase (CPK) level was normal. When his serum creatinine level decreased to 1.58 mg/dl, a contrast medium was administered. A delayed computed tomography (CT) scan after 24 and 48 h confirmed patchy wedge-shaped contrast enhancement (Fig. 58). Under a diagnosis of ALPE, his body water balance (hydration) was controlled. In this patient, recovery was achieved 4 weeks after onset, and his serum creatinine and uric acid levels were then 1.0 mg/dl and 0.6 mg/dl, respectively. Furthermore, load tests with a uric acid reabsorption inhibitor (benzbromarone) and a uric acid excretion inhibitor (pyrazinamide) suggested presecretory reabsorption defect-related renal hypouricemia. A kidney biopsy 16 days after onset confirmed the recovery from acute tubular necrosis. 

Fig. 74. Delayed CT in apatient with ALPE and a patient with myoglobinuric acute renal failure with a serum creatinine level of 1.5mg/dl. In the patient with ALPE, wedge-shaped contrast enhancement was observed 24 h after the administration of a contrast medium. However, wedge-shaped contrast enhancement could not be confirmed in the cortical phase 20-40 s after the administration, or in the excretory phase 3 min after the administration (see Fig. 17). The patient with myoglobinuric acute renal failure showed diffuse contrast enhancement...

In the patients with ALPE, plain CT of the kidney (delayed CT) a few hours, 24 h, and 48 h after the administration of 40 ml contrast medium showed wedge-shaped contrast enhancement. When physicians hesitate to administer a contrast medium, patchy accumulation can be sometimes detected by magnetic resonance imaging (MRI) with gadolinium-diethylenetriaminopentoacetic acid (Gd-DTPA), bone scan with MDP, or ultrasonography with Levovist. 

The following issues, including the etiology, remain to be clarified (a) the pathogenesis of ALPE, (b) the prevention of relapse, and future exercise guidance, (c) why delayed CT shows patchy contrast enhancement even in the recovery phase, (d) whether or not patchy renal vasoconstriction persists for 1-2 weeks, (e) why a contrast medium is present in the kidney for 72 h maximum, (f) the association between ALPE and disorders of type II muscle fibers, (g) the reasons for the less marked increases in serum myoglobin and creatine phosphokinase (CPK), and (h) why ALPE frequently develops in patients with renal hypouricemia. 

Delayed reactions are generally benign, but not always. In a Japanese study, the incidence of delayed reactions was investigated in 6764 patients who received the low-osmolar non-ionic contrast medium iohexol intravenously (33). Delayed reactions (rash, pruritus, nausea, vomiting, fever, headache, and others) occurred in 192 patients (2.8%). There were no severe delayed reactions. A history of allergy and hay fever were risk factors for delayed adverse reactions. 

The authors attributed these events to a severe delayed reaction to the contrast medium, manifesting as prolonged hypotension. 

Hearing disturbances attributable to contrast agents are extremely rare. The hearing loss in this patient developed more than 1 hour after the injection of iohexol, without any evidence of other causes. The authors suggested that the hearing disturbance might have been attributable to cochlear impairment caused by a delayed allergic reaction or chemical toxicity of the contrast medium. 

The authors suggested that the skin manifestations had been due to graft-versus-host disease triggered by the contrast medium and not a type-IV immunological reaction. Skin biopsy in one of the patients showed typical features of graft-versus-host disease. In addition, the reactions in these patients lasted for longer than one would expect in simple delayed reactions with skin manifestations, which usually resolve within 7-10 days. 

Munechika H, Hiramatsu Y, Kudo S, Sugimura K, Hamada C, Yamaguchi K, Katayama H. Delayed adverse reactions to nonionic contrast medium (iohexol) in IV use multicentric study. Acad Radiol 2002 9(Suppl 1) S69-71. 

Erdmann S, Roos T, Merk HF, Grussendorf-Conen Eli, Rubben A, Dahl T. Delayed hypersensitivity reaction to the non-ionic contrast medium ioversol. H G Z Hautkr 2000 75 169-71. 

---