Case Report: Dynamic Contrast‐Enhanced Magnetic Resonance Imaging Depicting Intramuscular Small Vessel Vasculitis in a Patient With Anti‐Neutrophil Cytoplasmic Antibody‐Associated Vasculitis

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic vasculitis predominantly affecting small vessels with potential multi-organ damage, including the lungs, kidneys, skin, and muscles [1]. Previous reports have highlighted the usefulness of MRI sequences, such as short tau inversion recovery (STIR) and contrast-enhanced T1-weighted imaging (T1WI), in evaluating muscular lesions in small to medium-sized vasculitis [2, 3]. Muscular lesions in patients with AAV and polyarteritis nodosa are identified on STIR as abnormal perivascular signals, and MRI of the skeletal muscle is crucial in estimating the size of the affected vessels [2]. Moreover, contrast-enhanced T1WI depicts areas of inflammation more accurately than STIR [3]. Furthermore, to date, only our previous case report has utilized dynamic contrast-enhanced (DCE) MRI to evaluate muscular lesions in AAV [4]. However, it did not address the pathological findings or the association between disease activity and DCE MRI. Here, we describe a patient who underwent a muscle biopsy of the lower leg following DCE MRI findings of abnormal contrast enhancement, which revealed vasculitis with fibrinoid necrosis, leading to a diagnosis of microscopic polyangiitis (MPA). A 62-year-old man was admitted to our hospital with intermittent fever, pain, and paresthesia in the lower extremities. Five months prior to admission, the patient experienced pain in the posterior lower legs, followed by the onset of paresthesia in the same region 2 months before admission. Eleven days prior to admission, the patient sought care at another hospital due to fever. Blood tests revealed increased C-reactive protein (CRP) levels and computed tomography (CT) of the chest showed ground-glass opacities in the right inferior lung lobe. Past medical history included tonsillitis, appendicitis, and overactive bladder. On admission, the patient's body temperature was 37.1°C, with normal blood pressure, heart rate, and oxygen saturation levels. Physical examination identified myalgia in the thighs and posterior lower legs and paresthesia in the distal lower legs. Chest auscultation revealed fine crackles on the right posterior lung, with no cardiac murmurs. Laboratory investigations demonstrated an increased white blood cell count (9300/μL), with elevated fractions of neutrophils (75.1%) and eosinophils (8.9%). Hemoglobin levels were mildly decreased at 11.5 g/L. Elevated levels of creatinine (1.16 mg/dL), CRP (6.3 mg/dL), and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA, 105 U/mL) were noted, whereas creatine phosphokinase (CPK, 89 U/L) and Krebs von den Lungen-6 (187 U/mL) levels remained within the normal range. The results for antinuclear and proteinase-3 anti-neutrophil cytoplasmic antibodies were negative. Urinalysis revealed no hematuria or casts, and a 24-h urine collection showed no significant proteinuria (0.15 g/day). Nerve conduction studies demonstrated decreased sensory nerve action potentials in the bilateral sural nerves, suggesting sensory axonopathy, consistent with a diagnosis of mononeuritis multiplex. A nerve biopsy was not performed because of the patient's concerns regarding potential complications. Whole-body CT revealed ground-glass opacities in the bilateral inferior lung lobes without other pulmonary lesions, such as nodules, cavities, or consolidations. Bronchoscopy was not conducted, as the patient did not develop respiratory failure or worsening anemia during the clinical course, and alveolar hemorrhage was considered unlikely. No evidence of rhinosinusitis or mastoiditis was found. DCE MRI of the lower legs revealed multiple blurred dot- and nodule-like contrast enhancements within the muscles, predominantly in the posterior lower legs (Figure 1A,B, Video S1). A subsequent muscle biopsy of the left gastrocnemius muscle revealed the following histological findings: inflammatory cell infiltration was noted in the perivascular areas of the fascia and perimysium. Additionally, one arteriole in the fascia exhibited multinucleated leukocyte infiltration, nuclear debris, and fibrinoid necrosis with destruction of the arteriole wall (Figure 2), though no granuloma was identified. In contrast, no evidence of idiopathic inflammatory myopathies, such as perifascicular atrophy, lymphocytic infiltration of myofibers, or necrosis or regeneration of myofibers, was found. The patient had not used any drugs known to cause secondary AAV, such as propylthiouracil, penicillamine, hydralazine, or allopurinol. Based on the findings of MPO-ANCA positivity, mononeuritis multiplex, interstitial pneumonia, and necrotizing vasculitis, the patient was classified as MPA according to the European Medicines Agency algorithm [5] and 2022 American College of Rheumatology/European League Against Rheumatism classification criteria [6]. The patient was treated with 1 mg/kg (50 mg/day) of oral prednisolone (PSL) and 375 mg/m2 of intravenous rituximab (RTX) weekly for 4 weeks. Clinical symptoms improved, and CRP levels normalized by day 25 of admission. The ground-glass opacities partially resolved on chest CT performed on day 36 after admission. On day 37 after admission, follow-up DCE MRI showed complete resolution of the abnormal contrast enhancement in the lower legs (Figure 1C,D, Video S2). PSL was tapered, and the patient was discharged 41 days after admission. CPK levels remained normal, and MPO-ANCA levels normalized 65 days post-discharge, with no recurrence. We encountered a patient whose muscle biopsy of the lower leg, following the detection of abnormal contrast enhancement on DCE MRI, revealed vasculitis with fibrinoid necrosis, leading to a diagnosis of MPA. This case underscores that the abnormal contrast enhancements observed on DCE MRI were attributable to small vessel vasculitis, and further highlights that DCE MRI may be superior to conventional sequencing in precisely identifying the location of muscular vasculitis in AAV. Our case emphasizes two key points. Firstly, the muscle biopsy targeting areas of abnormal blurred dot- and nodule-like contrast enhancement on DCE MRI revealed pathological vasculitis with fibrinoid necrosis. Secondly, these abnormal contrast enhancements on DCE MRI resolved following treatment of AAV. These observations suggest that the abnormal contrast enhancements on DCE MRI were indicative of intramuscular small vessel vasculitis of AAV in our case. Several studies have demonstrated the use of DCE MRI to evaluate diseases affecting small vessels, similar to AAV. For example, DCE MRI has been applied in cases of atherosclerosis to assess tissue blood flow. Specifically, it has been reported that DCE MRI can evaluate reduced tissue blood flow by analyzing signal changes over time within the region of interest, as seen in arteriosclerosis obliterans [7]. However, to the best of our knowledge, no studies have used DCE MRI to perform morphological evaluations of arteriosclerosis in a manner similar to the approach presented in this case. The possible mechanisms underlying the abnormal DCE MRI findings in AAV are as follows. A review of DCE MRI applications in the musculoskeletal system indicates that malignant tumors can be distinguished from normal tissues by increased vascular permeability, with malignant tumors exhibiting early arteriole contrast enhancement compared to normal tissues [8]. DCE MRI is also useful for evaluating small vessels, including feeding and draining vessels, in vascular malformations [8]. Increased vascular permeability is involved in the pathogenesis of AAV, primarily causing inflammation in small vessels [1]. Therefore, DCE MRI may be useful in detecting AAV lesions. To the best of our knowledge, only one previous case report of muscular lesions in AAV evaluated by DCE MRI has been published [4]. Abnormal dot- and nodule-like contrast enhancements were observed on DCE MRI at the site of the painful lesions, as in the present case. However, the previous report did not include pathological findings and assessment of MRI after treatment. Therefore, this is the first case report to demonstrate that the abnormal contrast enhancement on DCE MRI findings is consistent with pathological vasculitis and to compare these DCE MRI findings before and after treatment. Our findings strongly suggest that the abnormal contrast enhancements on DCE MRI were due to vasculitis. Furthermore, DCE MRI may be useful for evaluating disease activity in vasculitis. DCE MRI is more effective than conventional sequencing in revealing the location of muscular vasculitis in AAV. Unlike STIR and contrast-enhanced T1WI, which capture lesions at a single time phase, DCE MRI enables continuous evaluation of lesions over time. STIR often highlights high-intensity areas in both normal and inflamed tissues, whereas contrast-enhanced T1WI exhibits high intensity in both inflamed tissues and normal blood vessels. Therefore, distinguishing truly abnormal areas based on conventional sequences is challenging. In DCE MRI, continuous temporal sequencing improves the ability to differentiate between normal blood vessels and abnormalities caused by inflammation. Consequently, DCE MRI facilitates better identification of lesion locations than conventional MRI sequences. Moreover, DCE MRI provides broader spatial coverage and allows for the visual identification of areas with high lesion density. Biopsies from areas with high lesion densities are more likely to yield vasculitis findings. Muscle involvement, which may be the initial manifestation of AAV, occurs in 48.6% of patients [9]. In AAV with muscular lesions, a muscle biopsy at the site of abnormal contrast enhancement observed on DCE MRI can facilitate early definitive diagnosis. In the present case, a muscle biopsy performed at the site exhibiting abnormal contrast enhancement on DCE MRI revealed the presence of necrotizing vasculitis. Post-treatment, the abnormal contrast enhancement demonstrated resolution, strongly indicating intramuscular vasculitis of AAV. These results also suggest that DCE MRI may be superior to conventional MRI sequences for detecting the location of intramuscular vasculitis. However, as this is a single case report, further studies are needed to investigate the association between DCE MRI and pathological findings in a larger cohort of patients with AAV and other inflammatory diseases involving the skeletal muscles of the lower extremities. All authors contributed to the conception and article design, manuscript drafting, and critical revision of the intellectual content. All authors approved the final version for publication and agreed to be accountable for all aspects of the work. The authors thank Editage (www.editage.jp) for the English language editing. Written informed consent for publication was obtained from the patient. The authors declare no conflicts of interest. The data underlying this article will be shared on reasonable request to the corresponding author. Video S1 Coronal (A) and sagittal (B) dynamic contrast-enhanced magnetic resonance imaging of the lower legs before treatment. Contrast enhancement of normal vessels observed from 44.9 to 49.7 s. Multiple blurred dot- and nodule-like enhancements, mainly in the posterior lower legs, appearing from 54.4 to 68.7 s. Video S2 Coronal (A) and sagittal (B) dynamic contrast-enhanced magnetic resonance images of the lower legs after treatment. Contrast enhancement of normal vessels obtained from 47.7 to 56.9 s. No blurred dot- or nodule-like enhancements are noted at the end of the sequence. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.