Clinical value of Tc-99m MDP SPECT/CT bone imaging for early diagnosis of Relapsing Polychondritis: a report of 5 cases

Abstract

Background

Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient’s prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases.

Case presentation

These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time.

Conclusions

The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition.

Background

Relapsing Polychondritis (RP) is a rare inflammatory and destructive disease [1], exhibiting an incidence of merely 3 cases per million individuals, with no marked disparity in occurrence between genders, and a mean age of onset of 47 years [2], which mainly involves the auricle and nasal cartilage, but also other locations such as the trachea, the bronchial tree, and the heart valves.

Respiratory tract involvement is the leading cause of poor prognosis in RP [3]. Lin et al. reported that the percentage of respiratory system involvement and the percentage of death from respiratory failure were higher in Chinese RP patients than in other countries, (43%: 14–38%), (67%: 10–28%) [4]. The diagnosis of respiratory involvement in the context of known RP patients is not difficult. However, the diagnosis of RP with respiratory involvement as the first symptom is difficult and tends to have a delayed diagnosis. A previous study reported cases of respiratory involvement only, and these patients had no typical manifestations except for respiratory symptoms [3]. Thus, the potential for early visualization offered by Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) bone imaging holds promises for significantly improving early diagnosis in these patients.

Case presentation

Case 1

A 55-year-old man was hospitalized with a two-month history of productive cough and one-week of fatigue. The patient was admitted to the hospital three months post-initial exposure to the Corona Virus Disease 2019 (COVID-2019), subsequently presenting with a persistent cough. Approximately one month later, the cough intensified in frequency, yielding a modest amount of sputum, which was readily expectorated. At a local hospital, the patient received intravenous antibiotics (specific drug and dosage undisclosed). Unfortunately, his symptoms remained unrelieved. One month later, the cough escalated and evolved into a nocturnal variant, occasionally accompanied by chest pain that exacerbated post-coughing. Subsequently, the patient was admitted to our institution and prescribed Cefdinir along with Eucalyptus and Pine Enteric Soft Capsules. Regrettably, these treatments did not ameliorate the aforementioned symptoms.

Physical assessment revealed marginal deviation in nasal cartilage rigidity from the norm. Ear cartilage displayed no observable abnormalities. Moreover, no noteworthy tenderness was identified in the costal cartilages or large joints. Additionally, the patient experienced low back pain, myalgia, and fatigue.

The patient’s relevant laboratory tests are listed in Table 1. In addition, the patient also tested Creatine Kinase (CK) and Creatine Kinase Iso MB (CK-MB) to rule out the possibility of rhabdomyolysis muscle pain. Chest CT scans revealed tracheal, main bronchi, and distal bronchial wall thickening. Subsequently, the patient underwent fiberoptic bronchoscopy (FOB), revealing widespread tracheal mucosa edema across all levels. The biopsy results of the bronchial mucosa are shown in Table 1. During the hospitalization, the patient developed bilateral knee discomfort, with the right side experiencing more pronounced symptoms. Subsequent to FOB, the patient exhibited an irritating cough. Consequently, methylprednisolone was administered to alleviate inflammation and asthma symptoms. Following glucocorticoid administration, the patient’s cough symptoms, as well as low back and knee discomfort, significantly improved. Subsequently, the patient developed a fever alongside bilateral knee discomfort. Nonsteroidal anti-inflammatory drugs proved ineffective in managing these symptoms, necessitating the reinstatement of methylprednisolone at a dosage of 40 mg, which elicited a favorable response from the patient.

Table 1 Clinical data of 5 patients

The patient’s condition was considered more likely to be RP. Therefore, the patient underwent ^99mTc-MDP SPECT/CT bone imaging. The inspection revealed areas of tracer accumulation and relative concentration within the annular cartilage, alongside the identification of multiple bilateral regions displaying abnormal costal cartilage (Fig. 1). These findings supported the diagnosis of RP. Given that prior attempts at anti-infective treatment proved ineffectual, the patient was then initiated on a daily regimen of 40 mg of methylprednisolone. The patient’s fever and knee discomfort resolved. The patient was then discharged and received regular glucocorticoid therapy outside the hospital. When the patient came back to do a follow-up check 3 weeks later, the subjective symptoms improved significantly, the anemia was relieved, the platelet count was back to normal, and the C-reactive Protein (CRP) was back to normal (Table 2). This evidence suggests that patients respond well to glucocorticoids.

Fig. 1

Whole Body Bone Scan of patient 1. Image a is the whole body bone imaging of patient 1, showing abnormal concentration of tracers in the neck, costal cartilage, and sternocostal joints. Image b, c, and d are cross-sectional images of the patient, with CT images in the first row, radionuclide tomograms in the second row, and fusion images in the third row. Image b shows increased uptake of tracers in the cricoid and thyroid cartilage, and ossification of the thyroid cartilage plate. Image c shows an increase in tracer uptake at the first sternocostal joint. Image d shows increased uptake of tracer in the costal cartilage

Table 2 Follow-up laboratory data for five patients

Case 2

A 46-year-old woman was admitted to the hospital due to a prolonged ailment characterized by persistent hoarseness, dyspnea exceeding three months, and a fever lasting more than a month. Approximately three months prior to her hospitalization, the patient initially reported hoarseness as her primary symptom. She underwent laryngoscopy at an external medical facility, revealing no discernible abnormalities. Subsequently, she experienced dyspnea, particularly during the inspiratory phase, coupled with discomfort when lying down, which was alleviated in the seated position. She later sought care at multiple external hospitals for her respiratory distress and received anti-infective therapy, which proved ineffective in delivering substantial relief. Her medical history includes a recent COVID-19 infection, though specific treatment details remain unknown. Subsequently, she exhibited an elevated body temperature with a characteristic diurnal rhythm, featuring normal values in the morning, followed by fluctuations between 38.5 and 38.8 °C in the afternoon, which could be alleviated through physical cooling. Testing for Mycobacterium tuberculosis-specific antigen returned a negative result.

Chest CT findings indicated tracheal thickening and partial tracheal wall involvement, suggestive of recurrent polychondritis, amyloidosis not excluded. Subsequently, the patient underwent a ^99mTc-MDP bone imaging, revealing abnormal tracer concentrations in the thyroid cartilage and cricoid cartilage (Fig. 2). This confirmed the diagnosis of RP. The patient exhibited symptom improvement following glucocorticoid treatment. The patient was treated with oral glucocorticoids and cyclophosphamide regularly outside the hospital. When the patient came back to do a follow-up check 3 months later, the patient underwent a ^99mTc MDP bone scan again It can be seen that the abnormal concentration of tracers in the neck, the joints between the ribs and the costalis and the sternocostal joints were significantly reduced (Fig. 3). Laboratory tests also indicated that the patient’s anemia was in remission and the platelet count was back in the normal range (Table 2). This suggests that the ^99mTc MDP bone scan may have great potential in the follow-up of RP.

Fig. 2

Whole Body Bone Scan of patient 2 at initial visit. Image a is the whole body bone imaging of patient 2 at initial visit, showing abnormal concentration of tracers in the neck, where the ribs join the costal cartilage, and sternocostal joints. Image b, c, and d are cross-sectional images of the patient, with CT images in the first row, radionuclide tomograms in the second row, and fusion images in the third row. Increased tracer uptake was observed in the cricoid and thyroid cartilage (image b), at the first sternocostal joint (image c), and at the costo-costal junction (image d)

Fig. 3

Whole Body Bone Scan of patient 2 after treatment. Image a is the whole body bone imaging of patient 2 after treatment. It can be seen that the abnormal concentration of tracers in the neck, the joints between the ribs and the costalis and the sternocostal joints were significantly reduced. Image b, c, and d are cross-sectional images of the patient, with CT images in the first row, radionuclide tomograms in the second row, and fusion images in the third row. The cricoid and thyroid cartilage (image b), and the tracer uptake at the 1st sternocostal joint (image c) and the 1st sternocostal joint (image d) were significantly less than before

Case 3

A 50-year-old woman was admitted to the hospital due to a persistent two-month cough and wheezing for over a month. Her symptoms began with a fever, reaching up to 39℃, triggered by a recent cold, accompanied by chills, generalized muscle aches, and pains. Her fever was not associated with coughing or sputum production, but rather with wheezing. She was seen at a local clinic for 3 days for fluids (exact medication not known) and her temperature dropped to normal. Approximately 40 days before her hospital admission, the patient developed a cough that was exacerbated by physical exertion. This cough was characterized by pronounced nocturnal symptoms and significant wheezing, though no laryngeal rales were observed. She sought treatment at another hospital, where she received Budesonide Fumotro Powder Inhalation and intravenous fluids (specific details unknown) to alleviate her symptoms. Although her cough improved slightly, she still could not comfortably recline at night. She returned to the hospital, where her symptoms significantly improved after receiving glucocorticoid treatment. Outside the hospital, she received regular Cymbicort inhalation but continued to experience a significant nocturnal cough with wheezing, disrupting her sleep quality. Hence, the patient sought care at our outpatient clinic, where pulmonary function tests revealed moderate obstructive ventilatory dysfunction with a fractional exhaled nitric oxide (FENO) level of 9 ppb.

The results of the patient’s physical examination and laboratory data are listed in Table 1. In terms of family history, the patient reported a family history of systemic lupus erythematosus.

The chest CT revealed generalized thickening of the tracheal wall, extending from the large airway to both the right and left main trachea, with some areas measuring more than 4 mm in thickness. There was no indication of tracheal wall involvement in the posterior region. Later, the patient underwent FOB, which revealed congestion and edema of the mucosa in the main bronchus. The surface appeared irregular, marked by small diffuse elevations, particularly noticeable from the subglottic valve to the upper-middle part of the trachea. The membranous section of the trachea remained unaffected. A biopsy was conducted on the upper part of the trachea. The biopsy results are also listed in Table 1.

The ^99mTc MDP bone imaging revealed regions with a relative concentration of circumferential cartilage tracer (Fig. 4). In conjunction with clinical and associated assessments, a diagnosis of RP was established. Therefore, the patient was administered a daily dose of 40 mg methylprednisolone, and a positive response to glucocorticoid therapy was observed. When the patient come back to do a follow-up check four and a half months later, the subjective symptoms improved significantly, the anemia was relieved, the platelet count was back to normal, and the CRP was back to normal (Table 2).

Fig. 4

Whole Body Bone Scan of patient 3. Image a is the whole body bone imaging of patient 3, showing abnormal concentration of tracers in the neck, where the ribs join the costal cartilage, and Sternoclavicular joint area. Image b, c, and d are cross-sectional images of the patient, with CT images in the first row, radionuclide tomograms in the second row, and fusion images in the third row. Increased tracer uptake was observed in the cricoid (image b), sternoclavicular joint (image c), and costo-costocartilage junction (image d)

Case 4

A 56-year-old woman was admitted to the hospital due to recurrent episodes of wheezing over the past 8 years, with worsening in the last 3 months. Eight years ago, the patient’s initial hospitalization was prompted by episodes of wheezing that typically followed upper respiratory tract infections. These episodes were accompanied by sensations of chest tightness and breath-holding, and were exacerbated by physical activity. She denied any history of wheezing triggered by exposure to fumes, gases, or other irritants. During her previous treatment at a local hospital, the patient received anti-inflammatory and hormonal therapy for asthma, leading to symptom improvement. Subsequently, she underwent irregular, short-term inhalation therapy with “Symbicort” and for over 7 years, she experienced no acute exacerbations. Moreover, vigorous coughing episodes often elicited vague anterior chest and rib pain, with a notable correlation between pain and deep breathing movements. At a different hospital, the patient received a diagnosis of ‘bronchial asthma’ and experienced symptom relief after an unspecified course of symptomatic treatment. Unfortunately, upon discharge from the hospital, her symptoms regressed and worsened compared to her previous state.

The results of the patient’s physical examination, laboratory data and pulmonary function tests are listed in Table 1. Subsequently, FOB was performed, revealing normal vocal cord mobility, diffuse mucosal congestion and edema, poorly defined tracheal rings, bulging, and slight lumen collapse with respiration. The left main bronchus, upper lobe and lower lobe bronchioles, right main bronchus, upper lobe dorsal segment bronchioles, middle lobe, and lower lobe bronchioles were all open and clear. However, diffuse congestive edema of the mucosa resulted in lumen narrowing, which collapsed after coughing.

Suspecting RP based on these findings, the patient underwent a bone scan, which revealed areas of abnormal tracer concentration/relative concentration in the thyroid cartilage and multiple areas of rib cartilage bilaterally (Fig. 5). So we made the diagnosis of RP for the patient. The patient was then regularly treated with glucocorticoid and cyclophosphamide. When the patient come back to do a follow-up check two and a half months later, the subjective symptoms improved, the anemia was relieved, and the CRP was back to normal (Table 2).

Fig. 5

Whole Body Bone Scan of patient 4. Image a is the whole body bone imaging of patient 4, showing abnormal concentration of tracers in the neck, costicartilage and Sternocostoclavicular area. Image b, c, and d are cross-sectional images of the patient, with CT images in the first row, radionuclide tomograms in the second row, and fusion images in the third row. Increased uptake of tracer in thyroid cartilage (image b), increased uptake of cricoid cartilage and slightly higher density of thyroid cartilage (image c), and increased uptake of tracer s in 1st sternocostal joint (image d)

Case 5

A 53-year-old man sought care at the Rheumatology and Immunology Clinic of our hospital due to a persistent cough of over 3 months and a week-long fever. The patient’s cough symptoms began more than three months prior to his visit, accompanied by a fever reaching a maximum temperature of 39 °C. Despite receiving symptomatic treatment for cough and phlegm, his fever persisted. Subsequently, the patient visited a local hospital, where a chest CT scan revealed thickening of the tracheal wall. Antibiotic treatment was administered, but the symptoms did not improve, leading the local physician to recommend a visit to our hospital for bone imaging.

The patient reported rib and anterior chest wall pain, without pain in other major peripheral joints. The nasal cartilage demonstrated slight reduction in hardness compared to a normal individual. The patient’s clinical data are listed in Table 1.

Subsequently, the patient underwent bone imaging, revealing multiple regions with abnormal tracer concentration in cartilage and joint areas throughout the body (Fig. 6). The primary clinical diagnosis was RP. Based on the clinical assessment, a diagnosis of RP was established, and glucocorticoid treatment was initiated, resulting in a positive response from the patient. Subsequently, the patient underwent regular glucocorticoid therapy, and the patient’s perceived discomfort symptoms improved significantly. Unfortunately, the patient did not return to our hospital for follow-up.

Fig. 6

Whole Body Bone Scan of patient 5. Image a is the whole body bone imaging of patient 5, showing abnormal concentration of tracers in the neck, costicartilage and Sternocostoclavicular area. Image b, c, and d are cross-sectional images of the patient, with CT images in the first row, radionuclide tomograms in the second row, and fusion images in the third row. The tracer uptake of thyroid cartilage was increased and the density of thyroid cartilage was slightly higher (image b), tracer uptake of cricoid cartilage was increased (image c), and tracer uptake of first sternocostal joint imaging agent was increased (image d)

Discussion

RP is a rare disease of the immune system with clinical symptoms mostly characterized by functional impairment and dysfunction of cartilage-associated tissues, which was first described by Jaksch-Wartenhorst in 1923, and a similar case was reported by PERSON in 1960, who named it RP. The etiology of RP remains partially obscured. Presently, the primary diagnostic criteria employed include McAdam’s, Damiani’s, and Michet’s criteria. These criteria are rooted in clinical presentation and biopsy analysis [5].

Respiratory failure presently constitutes the foremost cause of mortality in RP cases, followed by cardiovascular events [6]. Airway involvement is significantly higher in Chinese populations than in European and American populations [4]. Therefore, for the Chinese population, early diagnosis and treatment become more important to improve the prognosis of RP. Regrettably, the misdiagnosis rate for RP persists at an elevated level today. RP is an uncommon ailment that is often unrecognised by clinicians [7]. At present, the diagnosis of RP predominantly hinges on clinical manifestations and biopsy procedures. Novel diagnostic techniques, including laboratory tests and imaging studies, have yet to be integrated into the diagnostic criteria to enhance diagnostic sensitivity [8].

The clinical presentation of these five patients was atypical, and would not meet the accepted diagnostic criteria [5]. Cartilage biopsy stands as the definitive method for RP diagnosis, but the overall positivity rate from tracheoscopic biopsy samples is often meager [9], and this approach carries certain limitations. These limitations may be linked to the challenges in accessing cartilaginous tissue through bronchoscopy. Furthermore, the safety of this procedure cannot be consistently guaranteed [10, 11].

CT findings of RP can be challenging to distinguish from Wegener’s granulomas and airway amyloidosis, necessitating the need for biopsy to substantiate the diagnosis. In contrast, ^99mTc MDP bone imaging unveils more specific findings, characterized by bead-like areas of concentrated contrast in rib cartilage, thyroid, and annular cartilage, as well as the ossification of cartilage in these focal areas (Figs. 1, 2, 3, 4, 5 and 6).

Supported by previous literature, the initial stages of the disease typically reveal almost normal cartilage histology with infiltration of polymorphic inflammatory cells into the cartilage membrane. Subsequently, chondrocyte apoptosis and focal calcification or fibrosis become the primary histological hallmarks [12]. These bone imaging findings harmonize with these pathological changes. This undoubtedly buys time for early diagnosis of recurrent polychondritis and earlier pharmacological intervention, and can also be used for differential diagnosis of Wegener’s granulomatosis and tracheal amyloidosis, offering the possibility of diagnosing the disease without resorting to biopsy.

Bone imaging findings in RP have been reported previously [13, 14]. Leveraging technological advancements, the amalgamation of SPECT with CT fusion technology, and the adoption of novel materials like Cadmium Zinc Telluride, the anatomical localization of SPECT imaging is now feasible. This breakthrough paves the way for quantitative and semi-quantitative analyses, enabling the potential monitoring of treatment effectiveness.

It had been previously documented that ¹⁸F FDG PET/CT neither demonstrated sensitivity nor specificity in evaluating therapeutic efficacy [11]. A past study also highlighted ⁶⁷Ga visualization as a characteristic feature of RP, capable of guiding biopsy site selection [15]. Regrettably, ⁶⁷Ga imaging remains underutilized in China, thereby limiting its application. Additionally, the high cost associated with PET/CT restricts its usage [16].In terms of differential diagnosis, amyloidosis and bronchial tuberculosis also show diffusely increased tracheal uptake on ¹⁸F FDG PET/CT [17]. The disadvantage of bone scanning compared to ¹⁸F FDG PET/CT is that it does not show airway involvement.

In addition, these cases were patients in whom airway involvement was the first presentation. In one of the largest clinical studies in China, the RP population was divided into two groups (respiratory involvement and cardiovascular involvement). This study showed that costochondral joint involvement is a risk factor for respiratory system involvement and limb joint involvement is a risk factor for cardiovascular system involvement [18]. Previous studies have reported that the clinical presentations of the two groups of patients are to some extent mutually exclusive [19].Whether the bone scan characteristics of the other group of patients were distinguishable from the group with respiratory involvement needs to be further summarized.

Conclusion

In case a patient with suspicion for RP but not fulfilling current diagnostic criteria, a SPECT/CT bone may be helpful in confirming the diagnosis and allowing early intervention, especially if the patient presents with respiratory symptoms. If conditions permit, it is also helpful to add CT fusion images to obtain more accurate anatomical location and information.