Anterior view Posterior view

Figure 1. Gallium-67 citrate whole-body scintigraphy performedprior to treatment. After intravenous injection of 74 MBq of gallium-67 citrate, the 48-hour delayed image shows increasedtracer accumulation in bilateral external ears (more markedly onthe left side), neck, mediastinum and bilateral pulmonary hili(arrows).

Kaohsiung J Med Sci June 2008 • Vol 24 • No 6328© 2008 Elsevier. All rights reserved.

Relapsing polychondritis is a rare multisystem autoim-mune disorder of unknown origin. The cartilaginoustissues are the primary targets of destruction, mostcommonly the ears, nose, joints and respiratory sys-tem. Gallium-67 citrate scintigraphy (gallium scan) isa sensitive tool for evaluating inflammatory activity.We present a case of polychondritis and assess thevalue of gallium scanning in detecting inflammationand monitoring a patient’s response to treatment.

CASE PRESENTATION

A 57-year-old man complained of a 10-day history oflow-grade fever and progressive pain, swelling anderythema of both external ears. Laboratory data

Received: Aug 20, 2007 Accepted: Oct 23, 2007Address correspondence and reprint requests to:Dr Wan-Yu Lin, Department of Nuclear Medicine,Taichung Veterans General Hospital, 160,Taichung Harbor Road, Section 3, Taichung 407,Taiwan.E-mail: wylin@vghtc.vghtc.gov.tw

VALUE OF GALLIUM-67 SCANNING IN MONITORING

THERAPEUTIC EFFECTIVENESS IN A

PATIENT WITH RELAPSING POLYCHONDRITIS

Ming-Che Chang, Shih-Chuan Tsai, and Wan-Yu LinDepartment of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

We present a 57-year-old man who had low-grade fever and painful, swollen and erythematousears. Gallium-67 citrate scintigraphy (gallium scan) performed prior to the commencement of treat-ment showed increased gallium uptake in bilateral external ears, neck, mediastinum and bilateralpulmonary hili. The results of ultrasonography of both ears were compatible with the diagnosis ofchondritis. The patient’s clinical condition and laboratory data improved after a course of non-steroidal anti-inflammatory drugs and steroids. Gallium scan performed after treatment showeda diminished uptake in the external ears, neck, and mediastinum. Gallium scintigraphy is a valuabletool for evaluating inflammatory activity and monitoring therapeutic response in patients withrelapsing polychondritis.

Key Words: gallium-67 citrate, polychondritis, therapeutic response (Kaohsiung J Med Sci 2008;24:328–33)

Gallium scan in relapsing polychondritis

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showed leukocytosis (white blood cells, 21,550/mm3;neutrophils/lymphocytes, 89.1%/6.5%), thrombo-cytosis (platelet count, 707×103/mm3), elevated C-reac-tive protein (CRP) level of 24.7mg/dL (normal range,<0.8mg/dL), and erythrocyte sedimentation rate (ESR)>140mm/hour (normal range in males, 0–15mm/hr).

A whole-body scan was performed 48 hours afterintravenous injection of 74 MBq (2 mCi) gallium-67citrate and demonstrated increased gallium-67 citrateuptake in both ears (especially on the left side), neck,mediastinum and bilateral pulmonary hili (Figure 1).An inflammatory process involving the external ears,trachea and central bronchi was highly suspected. No

histologic study of the external ears or the respiratorytract was performed because of the patient’s refusal.Chest radiography showed normal appearance of themediastinum and bilateral pulmonary hili. Dopplerultrasonography of both ears revealed swelling of thecartilage of the external ears, pericartilage edematouschange and significant hypervascularity, which wascompatible with chondritis (Figure 2).

The patient recovered rapidly following a 1-weekcourse of a nonsteroidal anti-inflammatory drug(cataflam) and steroids (methasone and prednisolone).Laboratory investigations revealed a CRP level of0.27 mg/dL, a platelet count of 292 × 103/mm3 and

Upper portionRight ear lobe

Middle portionRight ear lobe

Lower portionRight ear lobe

Upper portionLeft ear lobe

Middle portionLeft ear lobe

Lower portionLeft ear lobe

B

A

Figure 2. Ultrasonography of both external ears performed prior to therapy shows cartilage swelling of both ears. (A) Power Dopplerultrasonography shows hypervascularity over the anterior-upper, upper and middle portions of the left ear. The cartilage-free lower lobewas spared. (B) Power Doppler ultrasonography of the right external ear shows a similar sonographic pattern to that of the left externalear. The sonographic findings in bilateral ears were compatible with the pathophysiology of chondritis.

normalizing leukocytosis (white blood cells, 16,700/mm3; neutrophils/lymphocytes, 74.5%/18.1%). Agallium-67 citrate whole-body scan performed 1 monthlater showed diminished gallium uptake in bilateralexternal ears, the nasal region, neck, mediastinum, and

bilateral pulmonary hili (Figure 3), compatible withclinical remission. Doppler ultrasonography of bothears also revealed normalized vascularity (Figure 4).The patient remained afebrile and pain-free over the17-month follow-up period.

DISCUSSION

Relapsing polychondritis is a rare multisystem auto-immune disorder of unknown origin. The cartilagi-nous tissues are the primary targets of destruction,but the immune damage can spread to involve non-cartilaginous tissues like the kidney and blood ves-sels [1]. Relapsing polychondritis can be diagnosedwhen one or more signs of McAdam [2] are presentalong with histologic confirmation, or when chondri-tis is present in two or more separate anatomic lesionsand is responsive to steroids [3]. Since two or moresites of chondritis and a response to steroids are nec-essary to make a diagnosis, a convenient examinationwith abilities to evaluate whole-body inflammatoryactivity and to monitor the effect of treatment is pre-ferred. Pre- and posttreatment gallium-67 whole bodyscintigraphy is a suitable examination to aid diagnosis.

In patients with relapsing polychondritis, the auri-cles, larynx and upper trachea are the most frequent-ly affected sites [2,4,5]. Gallium scanning, a sensitive

Anterior view Posterior view

Figure 3. Gallium-67 citrate whole-body scintigraphy performed1 month after treatment with a nonsteroidal anti-inflammatorydrug and steroids. Scintigraphy was performed 48 hours afterintravenous injection of 74 MBq of gallium-67 citrate. Diminishedtracer uptake in bilateral external ears, neck, mediastinum andbilateral pulmonary hili was noted when compared with the pre-vious imaging study shown in Figure 1.

Upper portionRight ear lobe

Upper portionLeft ear lobe

Middle portionRight ear lobe

Lower portionRight ear lobe

Middle portionLeft ear lobe

Lower portionLeft ear lobe

Figure 4. Ultrasonography of both external ears performed after therapy shows normalized vascularity as compared with Figure 2.

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M.C. Chang, S.C. Tsai, and W.Y. Lin

indicator of active inflammation, could reflect inflam-matory activity prior to any morphologic change. Inaddition, the ability to perform whole-body imagingwithin an acceptable period of about half an hourmakes gallium scanning a convenient examination tosimultaneously evaluate inflammation in differentsystems and at different sites, which is not uncommonin relapsing polychondritis. Auricular chondritis inpolychondritis patients may be unilateral or bilateral,and the onset of auricular disease can be acute or sub-acute. The inflammatory status may be different in theears due to the heterogeneous nature of the diseasepresentation. Gallium-67 avidity has been reportedto be correlated with inflammatory activity [6,7]. In ourcase, the gallium-67 avidity in the right ear was lowerthan that in the left ear, which may reflect more activeinflammation in the left ear than in the right ear. Ultra-sonography of the ears showed hypervascularity inboth external ears, but no difference in inflammatoryactivity between the ears. In contrast, gallium-67 scan-ning clearly demonstrated the different amount oftracer uptake between the ears. Moreover, single pho-ton emission computed tomography can offer addi-tional localization information as well as good spatialresolution to identify inflammatory sites [8].

In areas like the larynx and upper trachea, com-puted tomography (CT) may provide excellent anato-mic information, including circumferential thickeningor deformity of cricoid or tracheal cartilage and edema,fibrosis, or ossification of soft tissues [9,10]. However,the inflammatory process may fluctuate and precedemorphologic changes and development of symptoms,and this can result in an unremarkable CT scan despiteactive inflammation [11,12]. Real-time power Dopplerultrasonography can readily detect active inflamma-tion, seen as increased blood flow [13]. However,deep cartilage structures in the lower trachea andbronchi cannot be easily detected by conventionalultrasonography.

A patient’s clinical condition and inflammatorymarkers are usually used to monitor their treatmentresponse. Gallium scanning is another reliable andobjective method to evaluate the effect of treatmentin inflammatory diseases. Gallium scans show goodcorrelation with treatment response in inflammatorydisease, which may be associated with lactoferrin [14].The changes in gallium uptake seen in this case wereconsistent with clinical improvement and normalizinglaboratory data, indicating that gallium scans may be

used to evaluate treatment responses. Okuyama et al[15] reported similar findings in a patient with relaps-ing polychondritis, in whom the abnormal increasedgallium uptake in the neck disappeared after steroidtherapy. Gallium-67 scanning has also been reportedto play a role in monitoring therapeutic effects in in-flammatory pulmonary disease [16,17], retroperitonealfibrosis [18], lupus nephritis [19], Wegener’s granulo-matosis [20], and chronic sarcoid myopathy [21].

CT can be used to assess anatomic changes, but hasnot been reported to be useful for evaluating treatmentresponses in relapsing polychondritis patients. One ofthe possible reasons for this is that the resolution ofmorphologic changes on CT scans lags behind treat-ment response and clinical improvement [22]. This isdue to the fact that, once fibrosis or cartilage ring de-struction occurs, it may never or take a long time toreturn to normal, despite the absence of inflammatoryactivity [23]. Power Doppler ultrasonography mayreveal normalized blood flow in inflamed sites aftereffective treatment, as seen in our case. Again, conven-tional ultrasonography has a limitation in assessingdeep cartilage structures.

In our case, histopathologic evidence of chondritisin the mediastinum was not obtained. Although theincreased gallium uptake in the neck and mediastinumcould be due to chondritis in the trachea and centralbronchi, mediastinal tumors (for example, those inpatients with mediastinal Hodgkin’s disease, non-Hodgkin’s lymphoma, or metastasis), infection (forexample tuberculosis), and sarcoidosis, as well as radi-ation mediastinitis, may also cause intense galliumuptake in the mediastinum and should be taken intoconsideration. There was no history of malignancy orradiation to the thorax in this case. During the 17-monthfollow-up period, the patient showed no symptomsor signs related to mediastinal malignancy, sarcoido-sis or mycobacterial infection. Furthermore, this pa-tient had a normal chest radiograph, which makesthe diagnosis of sarcoidosis or mycobacterial infec-tion less likely. Although there was no pathohistologicevidence, given the patient’s recovery was correlatedwith gallium-67 scintigraphic changes, a subclinicalinflammatory process involving the trachea and centralbronchi is the most likely explanation for the gallium-avid regions in the neck and mediastinum.

Although gallium-67 citrate is readily available inpractice, its shortfalls include a less well-known up-take mechanism in inflammation, suboptimal physical

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characteristics for imaging, and delayed imaging up to 48 hours after injection due to the slow clearance ofbackground radioactivity. Other radiopharmaceuticalsused to evaluate inflammation, such as 111In-oxine/99mTc-hexamethylpropylenamine oxime-labeled leuko-cytes or 99mTc-labeled granulocytes, may either increasethe specificity or shorten the examination time [24].However, scintigraphy using these radiopharmaceuti-cals in patients with relapsing polychondritis has neverbeen reported, and further investigation is needed.Bone scintigraphy using 99mTc-methylene diphospho-nate has been reported to demonstrate inflammatorycartilage and joints [25–27].

In conclusion, gallium scanning may be a valuabletool for evaluating inflammatory activity and moni-toring treatment responses in patients with relapsingpolychondritis.

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