Significance of early diagnosis and surgical management in treating Mycobacterium immunogenum-related pyogenic extensor tenosynovitis: a case report.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental organisms that are increasingly contributing to human infections. Mycobacterium immunogenum, a variant of NTM discovered in 2001, is a rapidly growing mycobacterium that exhibits multidrug resistance. Reports of infections caused by this organism, particularly tenosynovitis in the musculoskeletal system, are limited. CASE PRESENTATION: A 71-year-old female with vesicular pemphigus, undergoing immunosuppressive therapy, presented with a progressively enlarging tumour on the dorsum of her right hand, along with erythematous papules that extended across her right forearm. The specimens of skin tissues and blood cultures revealed the presence of M. immunogenum. Magnetic resonance imaging evaluation led to the diagnosis of pyogenic extensor tenosynovitis. A multidrug regimen, comprising amikacin and clarithromycin, was initiated, followed by synovectomy. The patient underwent a course of 180 days of antimicrobial therapy and demonstrated no signs of disease recurrence one year after treatment completion. CONCLUSION: Early diagnosis and surgical intervention are crucial to prevent the adverse prognostic implications of pyogenic extensor tenosynovitis caused by M. immunogenum. Effective management requires precise microbial identification and susceptibility testing, necessitating collaborative engagement with microbiological laboratories.

Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state.

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

Risk factor analysis of perioperative complications in patients with rheumatoid arthritis undergoing primary cervical spine surgery.

BACKGROUND: Rheumatoid arthritis (RA) often causes cervical spine lesions as the disease condition progresses, which induce occipital neuralgia or cervical myelopathy requiring surgical interventions. Meanwhile, patients with RA are susceptible to infection or other complications in the perioperative period because they frequently have comorbidities and use immunosuppressive medications. However, the risk factors or characteristics of patients with RA who experience perioperative complications after cervical spine surgery remain unknown. A risk factor analysis of perioperative complications in patients with RA who underwent primary cervical spine surgery was conducted in the present study. METHODS: A total of 139 patients with RA who underwent primary cervical spine surgery from January 2001 to March 2020 were retrospectively investigated. Age and height, weight, serum albumin, serum C-reactive protein, American Society of Anesthesiologists Physical Status (ASA-PS), Charlson comorbidity index, medications used, cervical spine lesion, surgery time, bleeding volume, and procedures were collected from medical records to compare the patients with complications to those without complications after surgery. The risk factors for perioperative complications were assessed by univariate and multivariate logistic regression analysis. RESULTS: Twenty-eight patients (20.1%) had perioperative complications. Perioperative complications were significantly associated with the following factors [data presented as odds ratio]: lower height [0.928, p=0.007], higher ASA-PS [2.296, p=0.048], longer operation time [1.013, p=0.003], more bleeding volume [1.004, p=0.04], higher rates of vertical subluxation [2.914, p=0.015] and subaxial subluxation (SAS) [2.507, p=0.036], occipito-cervical (OC) fusion [3.438, p=0.023], and occipito-cervical/thoracic (long) fusion [8.021, p=0.002] in univariate analyses. In multivariate analyses, lower height [0.915, p=0.005], higher ASA-PS [2.622, p=0.045] and long fusion [7.289, p=0.008] remained risk factors. High-dose prednisolone use [1.247, p=0.028], SAS [6.413, p=0.018], OC fusion [17.93, p=0.034], and long fusion [108.1, p<0.001] were associated with severe complications. CONCLUSIONS: ASA-PS and long fusion could be indicators predicting perioperative complications in patients with RA after cervical spine surgery. In addition, cervical spine lesions requiring OC fusion or long fusion and high-dose prednisolone use were suggested to be risk factors for increasing severe complications.

Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: results from the multicenter observational cohort study, FRANK Registry.

BACKGROUND: To further improve rheumatoid arthritis (RA) treatment, it is necessary to understand each RA patient's satisfaction and to identify the factors affecting their satisfaction. Despite the rise in medical costs for RA, little is known about the factors that influence patient satisfaction with the cost of treatment in RA patients. METHODS: This is a multicenter observational study of Japanese RA patients from the FRANK Registry with data analyzed from March 2017 to August 2020. We collected data on demographic characteristics, clinical data, quality of life which was evaluated using the EuroQol 5-dimensional questionnaire (EQ5D), and patient satisfaction. The four categories of patient satisfaction were evaluated individually (i.e., cost, treatment efficacy, activities of daily living [ADL], and global treatment satisfaction). We analyzed the factors that affected each patient's satisfaction, such as age, sex, EQ5D, disease duration, disease activity, and treatment. RESULTS: This study included 2235 RA outpatients (406 males, 1829 females). In RA patients, "very satisfied" and "satisfied" were given for nearly half of each satisfaction aspect (cost 49%; efficacy 72%; ADL 58%; global treatment 66%) at the time of the initial registration. To investigate the factors influencing each satisfaction, multivariate analysis has revealed that the use of b/tsDMARDs increased satisfaction of treatment effect (odds ratio [OR] 0.66) and ADL (OR 0.78) but decreased cost satisfaction (OR 2.21). Age (50-64 years; OR 0.91; 65-74 years, 0.55: ≥ 75 years, 0.35), female (OR 0.81), and history of musculoskeletal surgery (OR 0.60) all increased cost satisfaction. Patients with lower disease activity and higher EQ5D scores had higher levels of satisfaction in all areas. CONCLUSIONS: In this study, patient satisfaction in terms of cost, treatment effect, ADL, and overall treatment was generally higher, but some patients were dissatisfied. The cost of satisfaction increased with age and a history of musculoskeletal surgery, while it decreased with a lower EQ5D score and the use of b/tsDMARDs.

Have the radiographic characteristics of total knee arthroplasty recipients in rheumatoid arthritis changed after the induction of biologic disease modifying antirheumatic drugs?

OBJECTIVES: Whether the characteristics of patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA) have changed in the era of biologic disease-modifying antirheumatic drugs (bDMARDs) is unclear. We compared the radiographic findings of the knees in TKA recipients with RA before and after the introduction of bDMARDs. METHODS: Consecutive patients who underwent primary TKA between 1999 and 2002 (115 knees; 79 patients, group A) and between 2013 and 2017 (117 knees; 95 patients, group B) were retrospectively evaluated. Clinical data, including disease duration, medication, C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor, were collected. The Larsen classification, joint space narrowing (JSN), bone erosion, and geode and osteophyte formation were evaluated on preoperative radiographs. RESULTS: Osteophyte formation was significantly increased, and bone erosion and geode formation were significantly decreased in group B. In addition, medial-dominant JSN was significantly increased, and bicompartmental JSN was significantly decreased in group B. Medial-dominant JSN was positively and bone erosion was negatively associated with osteophyte formation. CONCLUSIONS: Following the introduction of bDMARDs, typical radiographic findings of rheumatoid knees have decreased, and secondary osteoarthritis-like changes, characterized by osteophyte formation and medial-dominant JSN, have increased in the knees of TKA recipients.

Bone fragility via degradation of bone quality featured by collagen/apatite micro-arrangement in human rheumatic arthritis.

Although increased bone fragility is a well-recognized consequence in patients with rheumatoid arthritis (RA), the essential cause of degenerate bone strength remains unknown. This study aimed to determine factors contributing to bone dysfunction in RA by focusing on the bone matrix micro-arrangement, based on the preferential orientation of collagen and the related apatite c-axis as a bone quality index. The classical understanding of RA is limited to its severe pathological conditions associated with inflammation-induced bone loss. This study examined periarticular proximal tibiae from RA patients as compared with osteoarthritis (OA) patients as controls. Bone tissue material strength was disrupted in the RA group compared with the control. Collagen/apatite micro-arrangement and vBMD were significantly lower in the RA group, and the rate of decrease in apatite c-axis orientation (-45%) was larger than that in vBMD (-22%). Multiple regression analysis showed that the degree of apatite c-axis orientation (ß = 0.52, p = 1.9 × 10-2) significantly contributed to RA-induced bone material impairment as well as vBMD (ß = 0.46, p = 3.8 × 10-2). To the best of our knowledge, this is the first report to demonstrate that RA reduces bone material strength by deteriorating the micro-arrangement of collagen/apatite bone matrix, leading to decreased fracture resistance. Our findings represent the significance of bone quality-based analysis for precise evaluation and subsequent therapy of the integrity and soundness of the bone in patients with RA.

Mid-term clinical outcome of constrained condylar knee prosthesis for patients with rheumatoid arthritis.

Objectives: This study retrospectively investigated the mid-term outcome of Legacy constrained condylar knee (LCCK) prosthesis in patients with rheumatoid arthritis (RA) having severe varus/valgus deformity, instability, and/or bone loss. Methods: Between January 2000 and December 2015, LCCK prostheses had been performed in 32 knees of 25 patients with RA, and 23 knees of 17 patients of the postoperative follow-up minimum 2 years were analyzed in this study (Primary: 14 knees, Revision: 9 knees). The average of follow-up duration was 6.9 ± 2.7 years, all were female, and the average of age and RA duration at the surgery was 59.0 ± 9.5 years and 26.6 ± 13.5 years, respectively. Clinical result was analyzed by Knee Society Score (KSS) knee and function at preoperative time and final visit. Imaging outcome was investigated by femoral tibial angle (FTA), four component alignment angles, and radiolucent line at pre-/postoperative time. Results: KSS knee/function scores and radiographic FTAs were improved after operation. Radiolucent lines around components were seen in 17 knees (73.9%), of which only one knee (4.3%) has shown aseptic loosening. The seven-year Kaplan-Meier survivorship analysis resulted in 91.7%. Conclusion: LCCK prosthesis in RA patients was achieved to the excellent mid-term clinical and radiographic result.

Reconstruction of Acute Patellar Tendon Rupture after Patellectomy.

Acute rupture of the knee extensor mechanism after patellectomy is extremely rare. We present the case of a patient with acute patellar tendon rupture who had undergone patellectomy 53 years before. Twelve days after the injury, the ruptured patellar tendon was repaired with end-to-end suture. Postoperatively, we splinted the knee for 6 weeks but permitted the patient to walk without limiting weight bearing at 1 week postoperatively. At one-year follow-up, the patient is able to move his knee almost full range of motion and the Lysholm knee score is 81. The patient is satisfied with the outcome. This is the first report to treat acute rupture of the patellar tendon in a patient who had undergone patellectomy. Although careful rehabilitation is required, end-to-end suture might be an adequate surgical procedure for acute rupture of the knee extensor mechanism after patellectomy.

Minimum 10-year results of cementless total hip arthroplasty in patients with rheumatoid arthritis.

OBJECTIVES: To retrospectively evaluate the long-term results of cementless total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) and postoperative patient mortality after THA. METHODS: This study included 191 hips in 149 RA patients who underwent cementless THA between 1998 and 2005. Mean age at surgery was 54.2 years, and mean follow-up was 12.6 years. Implant and patient survivorships were determined using the Kaplan-Meier method, and the associated influencing factors were determined. RESULTS: Implant survivals at 17 years were 99.5% for stems, 93.9% for cups, and 90.8% for liners. Among the liners used, THAs with highly cross-linked polyethylene showed better survivals compared with those with conventional polyethylene and alumina-bearing surface (93.4%, 90.9%, and 52.2%, respectively). A total of 64 deaths occurred; 45 patients died within 10 years and 19 patients died between 10 and 17 years. Malignancy (25.0%) was the leading cause of death, followed by pneumonia (20.8%) and sepsis (20.8%). The patient survival rate was 36.9% at 17 years after THA. Multivariate analysis exhibited that older age at operation and greater dose of concomitant corticosteroid resulted in shorter patient survivals. CONCLUSIONS: Cementless THA worked well in patients with RA. Mortality remained high among RA patients who needed THA.

Interleukin-21 signaling in B cells, but not in T cells, is indispensable for the development of collagen-induced arthritis in mice.

BACKGROUND: Interleukin-21 (IL-21) is a T-cell-derived cytokine whose receptor is expressed on a variety of cells and therefore might have pleiotropic roles in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated the involvement of IL-21 signaling in the development of collagen-induced arthritis (CIA), an animal model of RA, using IL-21 receptor knockout (Il21r KO) mice. METHODS: Il21r KO mice or wild-type (WT) C57BL/6 mice were immunized with chicken type II collagen (CII) emulsified in complete Freund adjuvant on day 0 and were given a boost injection on day 21. The production of anti-CII antibody, development of T-cell and B-cell subsets, and T-cell responses to CII were analyzed. CIA was induced in Rag2 KO mice to which combinations of WT or Il21r KO CD4 T cells and WT or Il21r KO B cells had been transferred, in order to examine the role of IL-21 signaling in each cell subset. RESULTS: Il21r KO mice were resistant to the development of CIA. CII-specific IgG but not IgM production was impaired in Il21r KO mice. This is consistent with a reduction of germinal center B cells in the draining lymph nodes. In contrast, CII-specific Th1 and Th17 responses were unaffected in Il21r KO mice. There was also no difference in the number of CII-specific follicular helper T cells between WT and Il21r KO mice. By analyzing the development of CIA in T-cell and B-cell mixed transfer experiments, we confirmed that IL-21 receptor expression on B cells, but not on T cells, was essential for the development of CIA. CONCLUSION: IL-21 signaling in B cells, but not in T cells, plays essential roles in the production of pathogenic autoantibodies that induce CIA development.

Brief report: successful in vitro culture of rheumatoid arthritis synovial tissue explants at the air-liquid interface.

OBJECTIVE: To establish a method to culture synovial tissue explants from patients with rheumatoid arthritis (RA). METHODS: Synovial tissue explants obtained from 10 patients with RA were cultured at the air-liquid interface or were submerged in culture medium. As a control, synovial explants were engrafted subcutaneously into SCID mice. The synovial explants were harvested at different time points, and histologic or flow cytometric analysis was performed. Cytokine levels in the culture supernatants were measured by enzyme-linked immunosorbent assay. Infliximab was added to the air-liquid interface culture to evaluate the effect of tumor necrosis factor α blockade on inflammatory cytokine production. RESULTS: The histologic features of RA synovitis, including a hyperplastic lining layer and the presence of cellular infiltrate in the sublining layer, were maintained in synovial tissue explants in air-liquid interface culture. In synovial grafts harvested from SCID-HuRAg mice, the cellular infiltrate was well maintained in the sublining, but the lining layer was lost. Viable CD4+ T cells and macrophages were abundant after air-liquid interface culture but were virtually absent after submerged culture. Furthermore, synovial tissue explants in air-liquid interface culture produced interleukin-6 (IL-6) and IL-8 for a prolonged period of time. The addition of infliximab effectively reduced cytokine production. CONCLUSION: RA synovial explants can be maintained for weeks using an air-liquid interface culture. This simple culture system might be useful for analyzing the pathogenesis of RA synovitis and for developing antirheumatic drugs.

Positive selection of self-antigen-specific CD8+ T cells by hematopoietic cells.

In contrast to thymic epithelial cells, which induce the positive selection of conventional CD8(+) T cells, hematopoietic cells (HCs) select innate CD8(+) T cells whose Ag specificity is not fully understood. Here we show that CD8(+) T cells expressing an H-Y Ag-specific Tg TCR were able to develop in mice in which only HCs expressed MHC class I, when HCs also expressed the H-Y Ag. These HC-selected self-specific CD8(+) T cells resemble innate CD8(+) T cells in WT mice in terms of the expression of memory markers and effector functions, but are phenotypically distinct from the thymus-independent CD8(+) T-cell population. The peripheral maintenance of H-Y-specific CD8(+) T cells required presentation of the self-Ag and IL-15 on HCs. HC-selected CD8(+) T cells in mice lacking the Tg TCR also showed these features. Furthermore, by using MHC class I tetramers with a male Ag peptide, we found that self-Ag-specific CD8(+) T cells in TCR non-Tg mice could develop via HC-induced positive selection, supporting results obtained from H-Y TCR Tg mice. These findings indicate the presence of self-specific CD8(+) T cells that are positively selected by HCs in the peripheral T-cell repertoire.

CD4 T cell-intrinsic IL-2 signaling differentially affects Th1 and Th17 development.

IL-2 signaling is involved in clonal expansion of antigen-specific CD4 T cells. IL-2 is also reported to promote Th1 but inhibit Th17 differentiation, although in vivo relevance remains unclear. In addition, IL-2-dependent Foxp3+ CD4 Tregs suppress T cell proliferation, complicating the in vivo role of IL-2 in the development of Th cell responses. To elucidate the roles of cell-intrinsic IL-2 signaling in CD4 T cells, we cotransferred TCR-Tg CD4 T cells from IL-2Rα (CD25)-deficient and WT mice and analyzed development of antigen-specific Th1 and Th17 responses. It was revealed that Th17 development of antigen-specific CD4 T cells was largely unaffected, whereas Th1 development was impaired by the lack of IL-2 signaling. Similar data were obtained from mixed BM chimera experiments using BM cells from CD25-deficient and WT mice. In addition, although in vitro blockade of IL-2 during Th17 development greatly increased the percentages of Th17 cells, it did not affect their numbers, indicating that in vitro Th17 development is also IL-2-independent. Th1 development was dependent on IL-2 in vitro as well. Thus, our data suggest that cell-intrinsic IL-2 signaling is critical for Th1 development but plays a limited role in Th17 development in vitro as well as in vivo.

The central role of CD30L/CD30 interactions in allergic rhinitis pathogenesis in mice.

CD30 ligand (CD30L) plays an important role in the amplification and/or activation of effector CD4(+) T cells, irrespective of Th cell subset. To examine the role of CD30L in allergic rhinitis, we evaluated an OVA model of allergic rhinitis in CD30L knock out (KO) mice on a BALB/c background sensitized with OVA. Symptoms of allergic rhinitis such as eosinophil infiltration into the nasal mucosa were drastically diminished in OVA-sensitized CD30L KO mice following intranasal challenge with OVA. The levels of OVA-specific IgE in the sera and the Th2 response in nasopharynx-associated lymphoid tissues and cervical LNs of CD30L KO mice were significantly lower than those of WT mice following intranasal challenge with OVA. Intranasal administration of CD30-Ig during the effector phase with OVA significantly prevented the development of allergic rhinitis in WT mice. These results suggest that CD30L plays an important role in allergic rhinitis and that the inhibition of CD30L/CD30 signaling might be useful as a novel biological therapy for allergic rhinitis.

Preferential accumulation of activated Th1 cells not only in rheumatoid arthritis but also in osteoarthritis joints.

OBJECTIVE: It was previously found that Th1 but not Th17 cells were predominant in the joints of rheumatoid arthritis (RA). To verify whether this is a unique feature of CD4 T cells in RA joints, we performed comparative flow cytometric analysis of CD4 T cells in RA and osteoarthritis (OA) joints. METHODS: Mononuclear cells were isolated from peripheral blood (PB), synovial membrane (SM), and synovial fluid (SF) from a total of 18 RA and 12 OA patients. The expression of surface molecules and cytokine production of CD4 T cells was examined by a flow cytometer. RESULTS: Most CD4 T cells in RA joints expressed memory/activation markers, such as CD45RO, HLA-DR, and CD69. CCR5 was highly expressed on CD4 T cells in SF but not in PB or SM. With regard to Th17-related molecules, CD4 T cells expressing CCR6 were not enriched in either SF or SM. In contrast, CD161-positive cells were abundant in the joint, many of which, however, produced interferon-γ but not interleukin 17A. Virtually all T cells in OA joints, although much less numerous than in RA joints, expressed activation markers. Th1 cells were predominant in both OA and RA joints, while there were a few Th17 cells. The frequency of Th17 cells in the joint tended to be lower in OA than RA. CONCLUSION: There was a quantitative but not qualitative difference in CD4 T cells, including the expression of activation markers and cytokine profiles, between RA and OA joints.