Concurrent seronegative spondyloarthropathy and Takayasu's arteritis: a case report and literature review.

The patient had a one-year history of generalized fatigue, bilateral shoulder and neck pain, bilateral thigh myalgia, and intermittent low back pain with left-sided predominance, accompanied by morning stiffness that improved with activity, worsened with rest, and was partially relieved by non-steroidal anti-inflammatory drugs (NSAIDs). She denied fever, chills, rash, or other systemic symptoms and did not seek medical evaluation. These symptoms were alleviated by physical activity and were not accompanied by fever, chills, rash, or other systemic manifestations. One day prior to admission, the patient experienced sudden-onset dizziness, nausea, vomiting, and vertigo. There were no preceding triggers or associated neurological symptoms. The patient was admitted to the emergency department due to acute dizziness. On admission, vital signs were unremarkable: respiratory rate, heart rate, blood pressure, and pulse were all within normal limits. Blood pressure was equal in both upper and lower limbs, with no significant inter-limb difference (<10 mmHg). Cardiovascular, pulmonary, abdominal, and neurological examinations revealed no abnormalities. All peripheral arteries were palpable. Musculoskeletal examination showed mild tenderness in both shoulders. Both Patrick’s (FABER) tests were negative; finger-to-floor distance was 5 cm and occiput-to-wall distance was 0 cm. Laboratory evaluations produced the following findings: (1) Complete blood count: White blood cells count was 4.77 × 10 9 /L (within normal limits), hemoglobin was 79 g/L (consistent with mild anemia), and platelet count was 275 × 10 9 /L (within normal limits). Coagulation function was normal. (2) Biochemical panel: serum iron was 3.80μmol/L (7.8–32.8.3umol/L), and other biochemical parameters were within reference ranges. (3) Anemia panel: Vitamin B12 levels were 1262 pg/ml (197-771pg/ml), ferritin was 204 ng/ml (13-150ng/ml), and total iron-binding capacity was 28.90 μmol/L(45–86μmol/L).A head CT scan revealed sphenoid sinusitis. The complete laboratory inspection results are shown in Table  1 . Table 1 Patient’s laboratory test indicators Category Test Item Result Reference Range (Example) Notes Complete Blood Count (CBC) White Blood Cell Count (WBC) 4.41 × 10⁹/L (4.0–10.0) Normal Hemoglobin (Hb) 73 g/L (115–150) Significantly decreased Mean Corpuscular Volume (MCV) 78.1 fL (82–100) Decreased Mean Corpuscular Hemoglobin (MCH) 23.8 pg (27–34) Decreased Mean Corpuscular Hemoglobin Concentration (MCHC) 305 g/L (316–354) Normal–low Platelet Count (PLT) 275 × 10⁹/L (100–300) Normal Thyroid Function — No abnormalities detected — — Coagulation Function Fibrinogen (FIB) 5.17 g/L (2.0–4.0) Elevated Urinalysis Leukocyte Esterase (LEU) 1+ Negative Positive Stool Test — No abnormalities detected — — Tumor Markers Carbohydrate Antigen 153 (CA153) 34.90 U/mL (<31.3) Mildly elevated Biochemistry Total Protein (TP) 58.7 g/L (65–85) Decreased Albumin (ALB) 31.2 g/L (35–55) Decreased High-sensitivity C-reactive Protein (hs-CRP) 43.61 mg/L (<3.0) Significantly elevated Rheumatology/Immunology C-reactive Protein (CRP) 41.6 mg/L (<8.0) Significantly elevated Erythrocyte Sedimentation Rate (ESR) 100 mm/h (<20) Markedly increased Ferritin 143 ng/mL (15–150) Normal Antinuclear Antibody (ANA) Positive, speckled pattern 1:100 Negative Positive Autoimmune Liver Disease Antibodies Negative Negative — Patient’s laboratory test indicators The anemia observed in this patient likely resulted from a combination of chronic inflammation associated with sinusitis and low iron levels. Further investigation may be needed to determine the exact cause of the anemia and guide optimal treatment strategies. The patient, who has a family history of ankylosing spondylitis (a feature included in the 2010 ASAS SPA classification criteria), presented with fatigue. Laboratory investigations demonstrated anemia and elevated inflammatory markers. These findings suggest a potential autoimmune disorder such as undifferentiated spondyloarthropathy or rheumatoid arthritis. A comprehensive evaluation provided the following findings: Hematologic panel: white blood cells: 4.41 × 10 9 /L; hemoglobin: 73 g/L; mean corpuscular volume: 78.1 fL; mean corpuscular hemoglobin: 23.8 pg; mean corpuscular hemoglobin concentration: 305 g/L; platelets: 275 × 10 9 /L. Thyroid function: normal. Coagulation function: fibrinogen: 5.17 g/L. Urine routine: Positive for leukocyte esterase (1+). Stool analysis: normal. Tumor markers: CA153: 34.90 U/mL. Biochemical panel: liver function, creatine kinase, electrolytes, and blood sugar were within normal limits. Total protein: 58.7 g/L; Albumin: 31.2 g/L; High-sensitivity CRP: 43.61 mg/L. Rheumatology and immune panel: CRP: 41.6 mg/L; ESR: 100 mm/h; Ferritin: 143 ng/mL; Positive antinuclear antibody (nucleolar pattern, 1:100); Autoimmune liver disease markers: negative. Imaging Studies: Echocardiography: mild regurgitation of the mitral and tricuspid valves; Chest CT: small nodule in the lower lobe of the right lung (follow-up recommended), and aortic sclerosis. Upper abdominal and pelvic CT: multiple liver cysts, splenomegaly, small amount of pelvic effusion, and abdominal aorta sclerosis. Bone marrow examination: Bone marrow aspiration and biopsy: markedly active bone marrow hyperplasia, bone marrow granulocyte and megakaryocyte hyperplasia, increased erythroid series (clinical correlation recommended). Flow cytometry: Normal T lymphocyte phenotype, no monoclonal B lymphocytes, plasma cells, or abnormalities in granulocytes, monocytes, no obvious abnormalities in the phenotype of primitive cells. Iliac bone marrow biopsy: patchy active proliferation of hematopoietic tissue with normal granulocyte-to-erythrocyte ratio, granulocyte differentiation was primarily in myelocytes and metamyeloctes stages. Scattered immature and mature megakaryocytes were observed, as well as a few plasma cells. Immunohistochemical staining: MPO (scattered +), CD42b (scattered +), CD3 and CD20 both (scattered +), CD38 and CD138 both (scattered +), reticular fiber (-). A consultation with rheumatology and immunology specialists was undertaken to evaluate the possibility of polymyalgia rheumatica. A PET-CT scan was recommended to exclude neoplastic processes and a regimen of prednisone acetate 15 mg QD was initiated. Following this intervention, the patient experienced slight improvement in fatigue and myalgia symptoms. Mild thickening of the thoracic aorta, left common carotid artery, proximal left subclavian artery, and abdominal aorta wall, accompanied by increased metabolic activity. Evidence of arthritis and enthesitis was observed including bilateral involvement of the sternoclavicular joints, shoulder joints, hip joints, sacroiliac joints as well as surrounding enthesitis. Additional areas of abnormal metabolic activity were noted at the bilateral ischial regions, femoral regions, and greater trochanter regions, along with multiple vertebral facet joints and posterior spinous process. These findings demonstrated mild and uneven metabolic increases consistent with inflammatory arthropathy and enthesitis. ① Bilateral tonsils appeared enlarged with symmetrical metabolic activity; ② Mild thickening with increased metabolism was observed in the bilateral and top walls of the nasopharynx; ③ Bilateral submandibular and parotid glands demonstrated increased density symmetrical uptake. These findings are suggestive of inflammatory changes or physiological metabolic variations. Multiple small lymph nodes (largest 6 mm, SUVmax 2.4) were identified in the left supraclavicular fossa, bilateral axillae, pulmonary hila, mediastinum, bilateral iliac chains and inguinal regions; surgical review considered the supraclavicular node too small for safe biopsy, and PET-CT showed no evidence of lymphoproliferative or malignant disease. These nodes exhibited mild metabolic activity consistent with inflammatory etiology. Bone marrow aspiration ruled out hematological disorders. Findings from PET-CT were suggestive of rheumatic immune system diseases, prompting the patient referral to our department for further diagnostic evaluation. Laboratory testing and imaging findings were as follows: HLA-B27: positive; anti-neutrophil cytoplasmic antibody: negative. Inflammatory mediators: interleukin-6 (IL-6): 11.3 pg/mL, interleukin-8 (IL-8):151 pg/mL, TNF-α: 109 pg/mL; interferon gamma release assay (T-spot): negative. Microbiological testing: influenza A and B virus nucleic acid testing: negative; novel coronavirus nucleic acid testing: negative; sputum bacterial culture: negative. Thoracic aorta and abdominal aorta CTA: A small inflammatory focus in the upper lobe of the right lung, a small subpleural nodule in the lower lobe of the left lung. Aortic sclerosis: Mild thickening of the abdominal aortic wall at the L3-4 level; sclerosis of the abdominal aorta, bilateral common iliac arteries, and their branches. Sacroiliac joint CT: Increased bone density at the iliac surface of the bilateral sacroiliac joints, degenerative changes of the bilateral sacroiliac joints, gas accumulation beneath the joint surface of the bilateral iliac bones. Pelvic magnetic resonance imaging: Adenomyosis, multiple small cervical cysts, a small amount of pelvic effusion. A diagnosis of SpA combined with TA was established based on clinical presentation, medical history and family history, and findings from post-admission examinations rand laboratory results. Consistent with the 2018 EULAR recommendations for active Takayasu arteritis (initial prednisone 40–60 mg/day), and because the patient had ongoing nausea and vomiting, we administered i.v. methylprednisolone 40 mg daily, combined with oral mycophenolate mofetil at 750 mg twice daily, targeting the primary disease. Adjunctive therapies for gastric protection, osteoporosis prevention, and anemia management were also administered. This regimen led to significant improvement in the patient’s fatigue, myalgia, and lumbar pain. Follow-up laboratory tests showed normalization of ESR and CRP levels. The corticosteroids dose was gradually tapered, and the patient was maintained on oral methylprednisolone at 8 mg daily. However, the patient later experienced intermittent lumbar pain and morning stiffness. Re-evaluation revealed elevated CRP and ESR levels compared to prior measurements. Mycophenolate mofetil was discontinued and the treatment plan was adjusted to include methylprednisolone 8 mg orally once daily and etanercept 50 mg subcutaneously once weekly. This modification resulted in CRP and ESR levels decreasing to the normal range, with continued improvement in the condition of the patient (see Figs.  1 , 2 , 3 and 4 ). Fig. 1 Sagittal STIR MRI of the lumbar spine in a 54-year-old woman showing hyperintense corners of vertebral bodies, consistent with active inflammatory Romanus lesions (vertebral corner inflammation) in axial spondyloarthritis Sagittal STIR MRI of the lumbar spine in a 54-year-old woman showing hyperintense corners of vertebral bodies, consistent with active inflammatory Romanus lesions (vertebral corner inflammation) in axial spondyloarthritis Fig. 2 Sacroiliac joint MRI Sacroiliac joint MRI Fig. 3 Sacroiliac joint CT Sacroiliac joint CT Fig. 4 Chest and abdominal CTA Chest and abdominal CTA

In summary, the coexistence of SpA and TA is a rare clinical occurrence. Its insidious onset and atypical clinical presentation pose a significant risk for misdiagnosis or delayed diagnosis, potentially leading to adverse outcomes. In patients with SpA presenting with persistent inflammatory responses, intermittent low-grade fever, fatigue, and inadequate response to standard therapies, the possibility of concurrent TA should be thoroughly evaluated. Early consideration of this association is crucial to reducing diagnostic oversight and improving patient prognosis.

SpA is a heterogeneous group of rheumatic immune system disorders strongly associated with HLA-B27. SpA primarily affects the spine, causing inflammatory lower back pain, and may also involve peripheral joints with synovitis. The 2009 classification criteria established by the Assessment of SpondyloArthritis International Society are widely applied in for the diagnosis and classification of SpA in clinical practice and research [ 6 ]. In contrast, TA is a rare chronic large-vessel vasculitis of unknown etiology. TA predominantly involves the aorta, its major branches, and the pulmonary arteries. The disease typically follows a progressive clinical course, beginning with non-specific systemic symptoms such as fatigue, low-grade fever, and unintentional weight loss. As the condition advances, inflammatory processes affect various segments of the involved blood vessels, resulting in a diverse range of ischemic manifestations. The 2022 classification criteria for TA, jointly established by the American College of Rheumatology and the European Alliance of Associations for Rheumatology, have become standard tools for diagnosis and treatment [ 7 ]. SpA and TA are both chronic inflammatory diseases and certain studies suggest a potential link between their pathogenesis with evidence that these conditions may coexist in some patients. Between the 1960 s and 1980 s, researchers including Paloheimo [ 1 ], Ghozlan [ 2 ], and Hull et al., [ 3 ] identified seven cases of SpA combined with TA, with a significantly higher prevalence in females (six females and one male). In 1988, Magaro et al., published the first case report in the Annals of the Rheumatic Diseases describing a patient with HLA-B27- positive AS coexisting with TA [ 8 ]. This case involved a female patient initially presenting with inflammatory lower back pain who over a period of five years developed intermittent fever, frequent headaches, and disappearance of bilateral radial artery pulses. Subsequent investigations including aortic CTA confirmed the diagnosis of TA. A formal comparison with previously reported cases of overlapping SpA and TA was precluded by the heterogeneity and incomplete documentation of the available case reports. Evidence suggests that in certain patients with long-standing SpA there may be a potential association with secondary TA. This relationship might not be coincidental. A study by Gudbrandsson et al. reported 22 cases of TA per million individuals in Northern Europe [ 9 ]. Among patients with TA, the incidence of SpA was found to be 7%, while Crohn’s disease was observed in 8% of cases. In comparison, the prevalence of SpA in the general French population is estimated at approximately 0.3%. Similarly, a study by Gan et al. in the Chinese population demonstrated that the prevalence of SpA in patients with TA, and vice versa, exceeded the prevalence in the general population [ 10 ]. These findings suggest that the coexistence of SpA and TA is not entirely coincidental, but rather indicative of shared pathological mechanisms. From a pathological perspective, cardiac complications associated with spondyloarthropathy (SpA) originate from a distinct form of aortitis. The core pathological feature is acute and chronic inflammation of the aortic root, a process described by Bulkley and Roberts as a “mixture of fibrous proliferation and inflammation” [ 11 ], which ultimately leads to thickening and dilation of the aortic wall and root, culminating in a functional consequence—aortic regurgitation (AR) without stenosis [ 12 ]. Microscopically, the lesions are characterized by inflammatory cell infiltration, predominantly CD4+ T lymphocytes, involving the intima and entire vascular wall, accompanied by significant fibrous tissue proliferation leading to diffuse intimal thickening. Notably, this inflammatory pattern demonstrates significant overlap with other large-vessel vasculitides, particularly Takayasu arteritis (TA) and giant cell arteritis (GCA) [ 13 ]. Although some have contended that aortic pathology in SpA can be distinguished from other conditions such as AS [ 11 ], its microscopic pattern is not pathognomonic when compared to TA and GCA. Indeed, all forms of large-vessel vasculitis may share key pathological manifestations, including lymphocytic infiltration, intimal thickening, vascular endothelial inflammation, and even granuloma formation and presence of giant cells [ 14 ]. This high degree of histological similarity has been confirmed in SpA cases with aortitis not diagnosed as TA [ 15 – 18 ], rendering it difficult for pathologists to definitively differentiate SpA-associated aortitis from idiopathic large-vessel vasculitis (e.g., TA) based solely on aortic biopsy specimens. Consequently, pathological diagnosis must be closely integrated with clinical context (e.g., HLA-B27 status, articular, intestinal, or ocular manifestations) [ 12 ] to accurately determine the etiology of the aortitis. The aortitis in SpA can be regarded as a pathological expression of a systemic disease within the vascular wall, with inflammation potentially spreading from the root to the distal aorta and its branches, which partially explains the complex comorbidity observed between SpA, inflammatory bowel disease (IBD), and Takayasu-like arteritis [ 19 – 22 ]. One hypothesis for this association involves antigenic similarities between the aortic root and tendon entheses, contributing to the concurrent development of both diseases. Experimental evidence by Sherlock et al. supports this, demonstrating that interleukin-23 (IL-23) can activate CD3 + CD4 - CD8 - lymphocytes at tendon insertions, thereby driving localized inflammatory responses [ 23 ]. Moreover, IL-23R + CD4 - CD8 - T cells were identified in the aortic root. In recent years researchers have proposed that SpA with TA may represent a distinct subtype within the spondyloarthritis spectrum [ 24 ]. Another hypothesis suggests that SpA with aortic vasculitis may represent stages of a single disease process, with aortitis and TA reflecting progressive manifestations. Clinically, patients with SpA combined with TA tend to exhibit a more insidious onset and heightened inflammatory response compared to those with isolated SpA. A retrospective study by Rivière et al., involving 14 patients with concurrent SpA and TA, highlighted several distinguishing characteristics [ 23 ]: (1) A predominance of female patients with a male-to-female ratio of 1:2.5; (2) A higher median age at SpA diagnosis (43.5 years); (3) A greater frequency of HLA-B27 negativity; (4) Significantly elevated acute phase reactants such as CRP and ESR. In patients with SpA presenting with unexplained elevations of acute phase reactants not attributable to other factors such as infection, the possibility of TA should be considered. Physicians are advised to perform a thorough clinical assessment including peripheral pulse palpation and vascular auscultation. For patients with clinical features suggestive of SpA combined with TA, vascular imaging studies are strongly recommended. CTA and MRA are widely regarded as first-line diagnostic tools due to their high diagnostic accuracy. For cases with insidious onset or where differentiation from other conditions proves challenging, PET-CT can facilitate early detection of enthesitis and aortitis, offering substantial diagnostic value. The coexistence of large vessel vasculitis and a heightened inflammatory response in patients with SpA combined with TA often necessitates a therapeutic approach involving corticosteroids in combination with immunosuppressive agents such as methotrexate, leflunomide, or sulfasalazine. This combination has demonstrated high efficacy in managing both conditions. Elevated levels of TNF-α are frequently observed in patients with TA, and numerous case reports and clinical trials have confirmed the safety and sustained efficacy of TNF-i in severe and refractory cases of TA. However, caution is warranted, as rare cases of TA have been reported following the use of TNF-i for the treatment of SpA [ 5 ].

Seronegative spondyloarthropathy (SpA) and Takayasu’s arteritis (TA) are distinct autoimmune disorders characterized by chronic inflammation. These conditions typically present as isolated entities and their coexistence is rare [ 1 – 3 ]. Patients with concurrent SpA and TA often present with a more insidious onset and pronounced systemic inflammatory response compared to those with SpA alone. A retrospective study by Rivière et al. involving 14 patients with concomitant SpA and TA identified several key characteristics [ 4 ]: (1) female predominance, with male-to-female ratio of approximately 1:2.5; (2) delayed diagnosis of SpA, with a median age of 43.5 years; (3) reduced prevalence of human leukocyte antigen B27 (HLA-B27) allele; (4) elevated levels of acute-phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). In cases where patients with SpA exhibit unexplained elevations in acute-phase reactants and infection has been ruled out, underlying TA should be considered as a differential diagnosis. For patients with an insidious disease onset or diagnostic uncertainty, positron emission tomography-computed tomography (PET-CT) can aid in the early detection of enthesitis and aortitis thereby improving diagnostic accuracy. The standard treatment regimen for SpA and TA typically involves corticosteroids and immunosuppressants. In recent years, tumor necrosis factor inhibitors (TNF-i) have emerged as an additional therapeutic option for patients with both conditions. Combining TNF-i with corticosteroids or methotrexate can be particularly effective in managing both SpA and TA. However, it is crucial to exercise caution as there have been isolated case reports of TA developing post initiation of tumor necrosis factor-alpha (TNF-α) receptor inhibitor therapy for SpA [ 5 ]. In the case presented, the patient initially presented with myalgia and intermittent back pain followed by insidious onset of dizziness. Laboratory tests indicated elevated acute inflammatory markers including CRP and ESR. PET-CT and aortic CT angiography (CTA) subsequently confirmed the diagnosis of SpA concurrent with TA. The addition of immunosuppressants and biologics to the treatment regimen led to significant improvement in the patient’s condition, highlighting the importance of early diagnosis and appropriate therapeutic intervention in this rare clinical scenario.