Back pain (BP), associated with the degenerative disc disease (DDD), poses a heavy social and economic burden due to early disability and indications to surgery, emerging in young adults. Pathophysiological basis of premature intervertebral disc (IVD) degeneration is being actively studied. The study was aimed to define the profiles of inflammatory cytokines in DDD, as well as their relationship to the structural spine diseases. The molecular genetic analysis of the mRNA gene abundance in patients with BP and herniated IVD after discectomy and healthy individuals was performed by the quantitative polymerase chain reaction method. High expression of TNFα, IL17 was revealed in the IVD tissues of the affected patients (p < 0.01); the levels of TNFα and IL1β correlated with the DDD severity (r = 0.301 and 0.37; p < 0.05). Elevated expression of IL1β, IL6 was found in peripheral white blood cells (p < 0.01); the levels of IL6 negatively correlated with Modic type 1 and 2 changes (r = –0.31; p < 0.05), and the levels of IL17 positively correlated with the IVD herniation in combination with erosions of the adjacent vertebral body endplates and Modic changes (r = 0.401; p < 0.05). The expression of VEGF-А in the IVD tissues and white blood cells negatively correlated with the DDD grades (r = –0.85; p < 0.001), indicating reduced vascularization in the terminal phase of the disease. The findings on DDD demonstrate the contribution of the local low-immune inflammation, coupled with the intense disc vascularization at the earlier stages, and associated with the reactive inflammation in vertebral bodies. The results are prerequisites for developing the anti-inflammatory and reparative therapy based on the DDD grade and the presence of Modic changes in young adults with BP.
Back pain (BP) due to degenerative disc disease (DDD) is a severe, often disabling condition. The aim of this study was to determine the association between the expression level of proinflammatory cytokines (IL-1β, IL-6, and IL-17), angiogenesis markers (VEGF-A and CD31) in intervertebral disc (IVD) tissue and IVD degeneration in young people with discogenic BP. In patients who underwent discectomy for a disc herniation, a clinical examination, magnetic resonance imaging of the lumbar spine, histological and immunohistochemical analyses of these factors in IVD were performed in comparison with the parameters of healthy group samples (controls). Histology image analysis of IVD fragments of the DDD group detected zones of inflammatory infiltration, combined with vascularization, the presence of granulation tissue and clusters of chondrocytes in the tissue of nucleus pulposus (NP). Statistically significant increased expression of IL-1β, IL-6, IL-17, VEGF-A and CD31 was evident in the samples of the DDD group compared with the controls, that showed a strong correlation with the histological disc degeneration stage. Our results denote an immunoinflammatory potential of chondrocytes and demonstrates their altered morphogenetic properties, also NP cells may trigger the angiogenesis.
Aim. To present a clinical case of late diagnosis of granulomatosis with polyangiitis (GPA), which for a long time was interpreted as a pulmonary form of tuberculosis with the passage of anti-tuberculosis therapy without effect, which led to severe structural changes and resection of the lungs and deformation of the bones of the facial skeleton.Materials and methods. Patient S., 31 y. o., was hospitalized in the rheumatology department with complaints of bloody discharge from the nose with the formation of crusts, hearing loss on both sides, weakness, nose deformity. From the anamnesis: in 2012, a cough with mucous sputum appeared. During examination at the Center for Combating Tuberculosis, on the basis of multiple rounded foci of both lungs, despite a negative diaskin test and the absence of mycobacterium tuberculosis in the sputum analysis, infiltrative tuberculosis was diagnosed. For two years, combined therapy with anti-tuberculosis drugs was carried out. In 2013, a staged combined resection of the left lung was performed; in 2014, a resection of the lower lobe of the right lung was performed. In 2015, nasal discharge increased, large crusts began to stand out, followed by bleeding, and a change in the shape of the nose was observed. In 2016, due to hearing loss in the left ear, he turned to an otorhinolaryngologist, diagnosed with ulcerative necrotic rhinitis, perforation of the nasal septum. Antibiotic therapy - no effect. Blood tests revealed positive antibodies to proteinase-3. In March 2017, he was hospitalized in the rheumatology department.Results. There were CT signs of fibrotic changes in the lungs with calcifications, areas of compaction of the “frosted glass” type in the upper lobes of the lungs. Laboratory examination revealed positive antibodies to proteinase-3, decreased glomerular filtration and tubular reabsorption. Analysis of the biopsy material from the lung and nasal mucosa revealed morphological signs of granulomatosis with polyangiitis. For the first time in 5 years, granulomatosis with polyangiitis was diagnosed, generalized form, chronic course, moderate activity, with damage to the upper respiratory tract (pansinusitis, rhinitis, chronic bilateral adhesive otitis media), lungs (nonspecific interstitial pneumonia), kidneys (microhematuria, proteinuria), joints (arthralgia). The activity index according to the Birmingham BVAS scale is 16 points, the VDI organ damage index is 6 points. In a retrospective analysis, tuberculosis was not confirmed. Therapy with prednisolone, cyclophosphamide (endoxan), biseptol was carried out, against which the patient's condition improved significantly.Conclusion. The presented clinical case demonstrates the difficulties of differential diagnosis of GPA with other granulomatous processes. Late diagnosis led to damage to vital organs: lungs, kidneys, deformity of the back of the nose, which, most likely, could have been avoided in case of timely diagnosis and early initiation of adequate therapy. As a result of an erroneous diagnosis at the onset of the disease, the patient underwent unjustified resection of both lungs twice. Timely diagnosis of the granulomatous process with the involvement of several pathologists as experts, including those with a torpid course of pulmonary tuberculosis, significantly improves the prognosis of patients and avoids fatal complications.
Introduction. One of the distinguishing features of systemic vasculitis is their manifestation under the guise of a lesion of one or another organ system, which is often multi-organ in nature with signs of systemic inflammation. The latter is interpreted primarily as part of an infectious or paraneoplastic process, which causes a delay in the diagnosis.The aim of the study was to present the diversity of the clinical picture in vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), the speed and large volume of diagnostic measures with the effective cooperation of therapeutic and surgical specialists, radiologists on the way to verifying granulomatosis with polyangiitis in a young woman.Materials and methods. Patient K., 46 y. o., was hospitalized in the Otolaryngology Department of the N.I. Pirogov City Clinical Hospital No. 1 of the Moscow Health Department with complaints of hearing loss, pain and stuffiness in the left ear, unproductive cough, hoarseness and fever up to 38.5 °C. According to the radiography (RG) of the chest organs, right-sided pneumonia was detected. Conducted antibiotic therapy without effect. As part of the differential diagnostic search, the following nosologies were excluded: infective endocarditis, sepsis, tuberculosis, primary multiple or central lung cancer complicated by paracancer pneumonia, metastatic lesion, infectious, brucellosis spondylodiscitis.Results. In the blood test, attention was drawn to a decrease in the level of hemoglobin to 111 g / l, an increase in the rate of erythrocyte sedimentation to 45 mm / h and the level of C-reactive protein to 142 mg / l, microhematuria according to the general urine analysis. Instrumental research methods – RG of 16.02.22, MSCT of the chest organs on 17.02.22, 27.02.22, 10.03.22 showed progressive bilateral focal pneumonia with a focus of consolidation in the middle lobe, EchoCG, ultrasound of the abdominal cavity and small pelvis, RG of the temporal bone, bronchoscopy with bronchoalveolar lavage and microscopic analysis, for atypia and bacteriological culture. A gynecological examination and a smear from the cervical canal for microscopic analysis were performed, atypical cells, consulted by a phthisiatrician (no data for tuberculosis), consulted three times by a thoracic surgeon (exclusion of volumetric formation of the middle lobe of the right lung). Given the history and clinical presentation (female gender, young age, bilateral otitis media, hoarseness, and destructive nature of pneumonia), granulomatosis with polyangiitis was suspected, and tests for ANCA were prescribed. A transthoracic biopsy of the right lung was performed. A rheumatologist prescribed induction pulse therapy with corticosteroids, and after serological and histological confirmation (antibodies to Proteinase-3 Anti-PR3 > 200 IU / ml, productive pneumonitis, granulomas without signs of tuberculosis), immunosuppressive therapy with cyclophosphamide. Against the background of pathogenetic treatment, a pronounced clinical and laboratory effect was noted.Conclusion. In this clinical situation, the simultaneous involvement of specialists of various profiles, the performance of a large number of laboratory and instrumental studies in dynamics, the absence of delay in histological verification made it possible to quickly exclude common diseases in the population and suspect systemic vasculitis, establishing a correct diagnosis within 5 weeks of the hospitalization period.
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