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ID PMID Title PublicationDate abstract
21527186 Primary Sjögren's syndrome with minimal change disease--a case report. 2011 May Glomerular involvement in patients with primary Sjögren's syndrome (pSS) has rarely been reported. Among them, membranoproliferative glomerulonephritis and membranous nephropathy are the more common types. We report a middle-aged female presenting concurrently with nephrotic syndrome and microscopic hematuria, and her pSS was diagnosed by positive anti-Ro (SSA)/anti-La (SSB) autoantibodies, dry mouth, severely diffuse impaired function of both bilateral parotid and submandibular glands, and a positive Schirmer test. Renal pathology revealed minimal change disease and thin basement membrane nephropathy. The patient's nephrotic syndrome resolved after treatment with corticosteroids. To our knowledge, this is the first report of minimal change disease in a patient with pSS.
21487733 Sicca complex among Egyptian patients with chronic hepatitis C virus infection. 2011 Oct The objective of this study was to assess the prevalence of sicca complex (SC) in patients with chronic hepatitis C virus (HCV) infection and its association with clinical and laboratory features of liver disease. Subjective and objective criteria of xerophthalmia and xerostomia were investigated in 120 HCV Egyptian patients. The lacrimal gland function was assessed by: tear film break-up time and lid parallel conjunctival folds test (LIPCOF), dacroscintigraphy (DSG) for lacrimal drainage and that of salivary glands by sialoscintigraphy. Sixty six of 120 patients (55%) had SC; all (100%) were proved to have xerostomia by sialoscintigraphy and xerophthalmia detected by ophthalmologic tests. Using dacroscintigraphy all SC patients (100%) were positive for lacrimal drainage abnormalities. Only 10.1% were symptomatic for SC. None of our patients had anti-Ro or anti-La antibodies. The presence of SC was associated with older age (r = 0.28, p = 0.00), female gender (p = 0.001), cirrhosis (r = 0.34, p = 0.00), thrombocytopenia (r = -0.72, p = 0.00), and rheumatologic manifestation (p = 0.000), but not with viral load (r = 0.19, p = 0.06). DSG showed significant statistical correlation with ophthalmologic tests (r = 0.87, p = 0.00). High prevalence of SC in HCV Egyptian patients was detected. LIPCOF and DSG are objective and noninvasive methods for early diagnosis of xerophthalmia and assessment of the nasolacrimal drainage, respectively. Hindrance of lacrimal drainage proved by DSG was frequently encountered in HCV patients with SC (100%) and strongly correlated with xerophthalmia.
21327453 Onset of adult-onset Still's disease following influenza vaccination. 2011 Aug We describe that case of a 61-year-old woman who developed high spiking fever, sore throat, polyarthralgia, and salmon pink evanescent rash following influenza vaccination. A diagnosis of adult-onset Still's disease (AOSD) was made based on clinical and laboratory findings. Methylprednisolone pulse therapy followed by oral prednisolone resulted in a favorable outcome. This is the second published case in which a causal relationship between vaccination and onset of AOSD is suggested. Bystander activation would appear to play an important role in inducing the immune reaction.
21507567 The association of sporadic inclusion body myositis and Sjögren's syndrome in carriers of 2011 Sep Sporadic inclusion body myositis (sIBM) usually occurs as an isolated condition, but it may occur in association with another autoimmune disorder such as Sjögren's syndrome. We reviewed sIBM cases with Sjögren's syndrome (sIBM/SS) from the Perth Inflammatory Myopathies Database to determine whether they are distinguishable from other sIBM cases. Six such cases were identified, representing 12% of all sIBM cases. Muscle biopsies confirmed the presence of an inflammatory myopathy with rimmed vacuoles and the characteristic muscle fibre inclusions of sIBM. Five of the six were females, contrasting with a 2:1 male preponderance in the rest of the sIBM cohort. The mean age-at-onset and the pattern of muscle weakness were similar in the two groups. Four out of five sIBM/SS patients treated with immune therapies had improvement in muscle strength lasting for 6-24 months, whereas only 27% of other sIBM patients improved. All 6 patients with sIBM/SS carried the HLA-DRB1*0301 allele, or its equivalent HLA-DR3 serological specificity, compared with 83% of other sIBM cases and all carried some or all of the major markers of the 8.1 MHC ancestral haplotype which is also associated with Sjögren's syndrome. Patients with sIBM/SS represent a subgroup of sIBM cases who are more likely to be female and carriers of HLA-DR3 and the 8.1 MHC ancestral haplotype, and are more likely to respond to treatment. The association of sIBM and Sjögren's syndrome is likely to be due to a common genetic predisposition linked to the MHC and supports the notion that sIBM has an autoimmune basis.
22770665 Critical involvement of macrophage infiltration in the development of Sjögren's syndrome- 2012 Sep Lymphocytic infiltration of the lacrimal gland and ocular surface in autoimmune diseases such as Sjögren's syndrome (SS) causes an aqueous-deficient dry eye that is associated with significant morbidity. Previous studies from our laboratory and others have established autoimmune regulator (Aire)-deficient mice as a useful model to examine exocrinopathy and ocular surface disease associated with SS. Consistent with human SS, autoreactive CD4(+) T cells play an indispensible role in the development of exocrine and ocular surface disease in Aire knockout mice. We report that in addition to CD4(+) T cells, a large number of macrophages infiltrate the corneal stroma, limbus, and lacrimal glands of diseased mice. Adoptive transfer of autoreactive CD4(+) T cells from Aire knockout mice led to local infiltration of macrophages and ocular surface damage in immunodeficient recipients. Depletion of local macrophages, through subconjunctival injection of clodronate liposome, attenuated lissamine green staining and improved ocular phenotype. Alternatively, systemic depletion of macrophages had no effect on ocular phenotype but led to significant improvements in lacrimal gland exocrinopathy and tear secretion. Our results suggested that autoreactive CD4(+) T cells provoked macrophage infiltration to the eye and lacrimal gland, where they played a functional role in directing the development of autoimmune dry eye.
21921989 Na(+)/K(+)-ATPase in the lacrimal glands of rabbits and its changes during induced autoimm 2011 PURPOSE: To test the hypothesis that expression of Na(+)/K(+)-ATPase subunits in the lacrimal glands (LGs) of rabbits with induced autoimmune dacryoadenitis (IAD) changes. METHODS: LGs were obtained from adult female rabbits with IAD and age-matched female control rabbits. The LGs were processed for laser capture microdissection (LCM), real time RT-PCR, western blot, and immunofluorescence for the detection of mRNA and proteins of the α1, α2, β1, β2, and β3 subunits of Na(+)/K(+)-ATPase. RESULTS: In the rabbits with IAD, mRNA levels of α1, β1, and β3 from whole LGs were significantly lower. In samples of acini and epithelial cells from various duct segments, collected by LCM, mRNA levels of α1, β1, β2, and β3 were significantly lower in the rabbits with IAD, although mRNA for α2 could not be detected. However, western blots demonstrated that all five subunits were significantly higher in the rabbits with IAD, although their distribution patterns were similar to those of the control rabbits, as demonstrated by immunofluorescence. CONCLUSIONS: The data presented herein demonstrated significant changes in mRNA and protein expressions of Na(+)/K(+)-ATPase subunits in rabbits with IAD, suggesting that these changes may play a role in the pathogenesis of Sjögren's syndrome and altered LG secretion, as observed in these animals.
20012054 A case of juvenile idiopathic polyarticular arthritis complicated by IgA deficiency in 22q 2011 Aug Chronic arthritis may occur in association with antibody deficiency and chromosomal aberrations. This report presents the case of a 6-year-old girl with chromosome 22q11 deletion syndrome and chronic arthritis. The onset of arthritis occurred at 4 years of age. The chronic arthritis course has been the polyarticular type. Neither antinuclear antibody nor rheumatoid factor was detected. Serum IgA was extremely low. She was diagnosed with juvenile idiopathic polyarticular arthritis (JIA) complicated by IgA deficiency in the 22q11 deletion syndrome. There is an increased prevalence of chronic arthritis in association with 22q11 deletion syndrome with IgA deficiency, but the reasons for this association are unknown. This study evaluated the possible correlation between cytokines and the susceptibility to chronic arthritis in the 22q11 deletion syndrome with IgA deficiency. The expression of pro-inflammatory cytokines such as IL-8, IL-6, MIP-1β, and MCP-1 suggests that T and B cells, macrophages and neutrophils modulate joint inflammation by an immune response. And the presence of IL-10 and IL-5 might suggest that the synovitis is associated with JIA and IgA deficiency.
22324470 IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. 2012 Jun IL-17 (interleukin-17), a hallmark cytokine of Th17 (T-helper 17) cells, plays critical roles in host defence against bacterial and fungal infections, as well as in the pathogenesis of autoimmune diseases. The present review focuses on current knowledge of the regulation, functional mechanisms and targeting strategies of IL-17 in the context of inflammatory autoimmune diseases. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumour necrosis factor) α. Although IL-17 was originally thought to be produced mainly by Th17 cells, a newly defined T-cell subset with a specific differentiation programme and tight regulation, several other cell types (especially innate immune cells) are also found as important sources for IL-17 production. Although IL-17 activates common downstream signalling, including NF-κB (nuclear factor κB), MAPKs (mitogen-activated protein kinases), C/EBPs (CCAAT/enhancer-binding proteins) and mRNA stability, the immediate receptor signalling has been shown to be quite unique and tightly regulated. Mouse genetic studies have demonstrated a critical role for IL-17 in the pathogenesis of variety of inflammatory autoimmune diseases, such as RA (rheumatoid arthritis) and MS (multiple sclerosis). Importantly, promising results have been shown in initial clinical trials of monoclonal antibodies against IL-17 or its receptor (IL-17R) to block IL-17-mediated function in treating autoimmune patients with psoriasis, RA and MS. Therefore targeting IL-17/IL-17R, IL-17-producing pathways or IL-17-mediated signalling pathways can be considered for future therapy in autoimmune diseases.
21339747 Adenosine abolishes MTX-induced suppression of osteoclastogenesis and inflammatory bone de 2011 May Methotrexate (MTX) is widely utilized for the treatment of patients with rheumatoid arthritis (RA); however, recent observation of the MTX-resistant patients proposed some difficulty in MTX-dependent therapeutic approach for RA. To access cellular events related to MTX resistance in RA in respect to inflammatory bone destruction, we investigated on an involvement of the potent inflammatory mediator adenosine in the regulation of osteoclastogenesis and inflammatory bone destruction. In rats with adjuvant-induced arthritis (AA rats), MTX efficiently suppressed bone destruction when it was administrated within 3 days after adjuvant injection, while it could not suppress inflammatory bone destruction if MTX was injected at the time of onset of inflammation (at day 10 after adjuvant injection). Time-course change in the level of plasma adenosine of AA rats was estimated by use of high-performance liquid chromatography and elucidated that adenosine level was markedly elevated till 10 days after adjuvant injection. In vitro bone marrow culture system for evaluating osteoclastogenesis, MTX markedly suppressed osteoclastogenesis in a stromal cell-dependent manner. This MTX-induced suppression of osteoclastogenesis was abrogated by the addition of adenosine. MTX suppressed the expression of mRNA for the receptor activator NF-κB ligand (RANKL), but it did not suppress the expression of osteoprotegerin (OPG). The addition of MTX and adenosine together markedly suppressed the level of OPG expression. Abolishment of MTX action by adenosine was significantly blocked by MRS1754, a highly selective antagonist for the A(2b) adenosine receptor (A(2b)AR), but not by caffeine, an antagonist for A₁, A(2a), A₃ AR (A₁AR, A(2a)AR, and A₃AR), which suggests that adenosine acts through A(2b)AR. Immunohistochemical studies showed abundant expression of A(2b)AR in cells localized in the bone-bone marrow boundary of the distal tibia in AA rats but not in control rats. When adenosine was injected in the ankle joints of MTX-treated AA rats, the suppressive effects of MTX on bone destruction was abolished. The current data therefore suggest that upregulation of adenosine production abolished the suppressive effect of MTX on osteoclastic bone destruction. Involvement of the adenosine-A(2b)AR system may explain MTX resistance in RA.
23762768 Mindfulness-based interventions for physical conditions: a narrative review evaluating lev 2012 Research on mindfulness-based interventions (MBIs) for treating symptoms of a wide range of medical conditions has proliferated in recent decades. Mindfulness is the cultivation of nonjudgmental awareness in the present moment. It is both a practice and a way of being in the world. Mindfulness is purposefully cultivated in a range of structured interventions, the most popular of which is mindfulness-based stress reduction (MBSR), followed by mindfulness-based cognitive therapy (MBCT). This paper begins with a discussion of the phenomenological experience of coping with a chronic and potentially life-threatening illness, followed by a theoretical discussion of the application of mindfulness in these situations. The literature evaluating MBIs within medical conditions is then comprehensively reviewed, applying a levels of evidence rating framework within each major condition. The bulk of the research looked at diagnoses of cancer, pain conditions (chronic pain, low back pain, fibromyalgia, and rheumatoid arthritis), cardiovascular disease, diabetes, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), and irritable bowel syndrome. Most outcomes assessed are psychological in nature and show substantial benefit, although some physical and disease-related parameters have also been evaluated. The field would benefit from more adequately powered randomized controlled trials utilizing active comparison groups and assessing the moderating role of patient characteristics and program "dose" in determining outcomes.
22876881 Discovery and in vivo evaluation of dual PI3Kβ/δ inhibitors. 2012 Sep 13 Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kβ/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kβ and δ isoforms in the treatment of a number of inflammatory diseases.
21865697 Tonsil-related skin diseases and possible involvement of T cell co-stimulation in chronic 2011 Some inflammatory skin diseases are known to be related to tonsil focal infection at their onset. Administration of antibiotics is adequate treatment in most acute or subacute cases. However, chronic focal infections in the tonsils could cause chronic skin diseases like pustulosis palmaris et plantaris (PPP), and it is our frequent experience that tonsillectomy leads to a dramatic and persistent improvement of PPP skin lesions. The expression of inducible co-stimulator (ICOS), a co-stimulatory receptor on activated T cells, was significantly higher in tonsil tissues from PPP patients than in tonsil tissues from non-PPP patients. Moreover, ICOS expression in tonsil tissues from 3 patients with psoriasis vulgaris that was strongly suspected to be related to tonsil focal infection was also high, suggesting that the activation of T cells via ICOS costimulation in focal infections likely triggers inflammation associated with tonsil-related skin diseases. PPP is notable today for paradoxically induced skin lesions in patients treated with TNF-α antagonists for rheumatoid arthritis, Crohn's disease, psoriasis and psoriatic arthritis. It is important to clarify the immunological milieu in PPP not only for the treatment approach but also for understanding these unexpected reactions.
21991368 Enhanced Th17-cell responses render CCR2-deficient mice more susceptible for autoimmune ar 2011 CCR2 is considered a proinflammatory mediator in many inflammatory diseases such as rheumatoid arthritis. However, mice lacking CCR2 develop exacerbated collagen-induced arthritis. To explore the underlying mechanism, we investigated whether autoimmune-associated Th17 cells were involved in the pathogenesis of the severe phenotype of autoimmune arthritis. We found that Th17 cells were expanded approximately 3-fold in the draining lymph nodes of immunized CCR2(-/-) mice compared to WT controls (p = 0.017), whereas the number of Th1 cells and regulatory T cells are similar between these two groups of mice. Consistently, levels of the Th17 cell cytokine IL-17A and Th17 cell-associated cytokines, IL-6 and IL-1β were approximately 2-6-fold elevated in the serum and 22-28-fold increased in the arthritic joints in CCR2(-/-) mice compared to WT mice (p = 0.04, 0.0004, and 0.01 for IL-17, IL-6, and IL-1β, respectively, in the serum and p = 0.009, 0.02, and 0.02 in the joints). Furthermore, type II collagen-specific antibodies were significantly increased, which was accompanied by B cell and neutrophil expansion in CCR2(-/-) mice. Finally, treatment with an anti-IL-17A antibody modestly reduced the disease severity in CCR2(-/-) mice. Therefore, we conclude that while we detect markedly enhanced Th17-cell responses in collagen-induced arthritis in CCR2-deficient mice and IL-17A blockade does have an ameliorating effect, factors additional to Th17 cells and IL-17A also contribute to the severe autoimmune arthritis seen in CCR2 deficiency. CCR2 may have a protective role in the pathogenesis of autoimmune arthritis. Our data that monocytes were missing from the spleen while remained abundant in the bone marrow and joints of immunized CCR2(-/-) mice suggest that there is a potential link between CCR2-expressing monocytes and Th17 cells during autoimmunity.
21130134 The CCN family: a new class of inflammation modulators? 2011 Mar Uncontrolled or sustained inflammation is the underlying cause of or actively contributes to the progression of many chronic pathologies such as atherosclerosis, arthritis, or neuroinflammatory diseases. Matricellular proteins of the CCN family (CYR61/CTGF/NOV) have emerged as localized multitasking signal integrators. These structurally conserved secreted proteins specifically interact with and signal through various extracellular partners, in particular integrins, which enable them to play crucial roles in various processes including development, angiogenesis, wound healing and diseases such as fibrosis, vascular disease and cancer. In this review, we discuss the possibility that the CCN family members could represent a putative new class of modulators of inflammation. In this context, we focused on their relationship with cytokines and chemokines. In vitro, CCN expression is finely regulated by diverse inflammatory mediators including cytokines (TNFα, IL1β, TGF-β), small factors such as prostaglandins, nitric oxide, histamine and serotonin, and extracellular matrix enzymes. In addition, CCN proteins acting alone or in concert with their specific partners appear to be potent regulators of the production of cytokines and chemokines in a context-dependent manner. Finally, emerging studies suggest a potential role for CCN proteins in chronic inflammatory diseases such as atherosclerosis, rheumatoid arthritis, inflammatory kidney diseases and neuroinflammatory pathologies such as Alzheimer's disease. CCN members could therefore represent new potential therapeutic targets for drug development against such diseases.
22688423 Sustained Rap1 activation in autoantigen-specific T lymphocytes attenuates experimental au 2012 Sep 15 Altered Ras superfamily guanine nucleotide triphosphatase signaling may contribute to the activation of autoreactive T cells in diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here, we show that transgenic expression of activated Rap1, a Ras-related protein which is protective in murine arthritis, in both wildtype (WT) and 2D2 mice, enhances autoreactive T cell activation by myelin oligodendrocyte glycoprotein peptide in vitro and in vivo. However, RapV12 reduces the number of autoreactive T cells in both WT and 2D2 mice, and increases murine survival in experimental autoimmune encephalitis, suggesting Rap1 activation restricts autoimmune T cell-mediated pathology through enhancing tolerance.
21953000 Therapeutic effects of exercise training in patients with pediatric rheumatic diseases. 2011 Sep Over the past decades, the role of exercise training in rheumatic diseases has been largely explored. Currently, physical activity is well known to benefit patients with osteoporosis, osteoarthritis, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathy, fibromyalgia and rheumatoid arthritis. Therefore, exercise training has been considered a valuable tool for treating rheumatic patients. The therapeutic effects of exercise training have also been investigated in pediatric rheumatic diseases. Collectively, studies have revealed the therapeutic potential of exercise in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis, juvenile fibromyalgia and other causes of chronic pain. The aim of this review is to familiarize the pediatric rheumatologist with the exercise science field; discuss the potential benefits of exercise training in pediatric rheumatic diseases, emphasize both research and clinical perspectives of this promising field; and propose practical models of pre-participation examinations and contraindications to exercise.
22371543 The role of arthroscopic synovectomy in patients with undifferentiated chronic monoarthrit 2012 Mar We investigated the clinical response to arthroscopic synovectomy in patients with undifferentiated chronic monoarthritis (UCMA) of the wrist. Arthroscopic synovectomy was performed on 20 wrists in 20 patients with UCMA of the wrist who had not responded to non-steroidal anti-inflammatory drugs. The mean duration of symptoms at the time of surgery was 4.3 months (3 to 7) and the mean follow-up was 51.8 months (24 to 94). Inflamed synovium was completely removed from the radiocarpal, midcarpal and distal radioulnar joints using more portals than normal. After surgery, nine patients had early remission of synovitis and 11 with uncontrolled synovitis received antirheumatic medication. Overall, there was significant improvement in terms of pain relief, range of movement and Mayo score. Radiological deterioration was seen in five patients who were diagnosed as having rheumatoid arthritis during the follow-up period. Lymphoid follicles and severe lymphocyte infiltration were seen more often in synovial biopsies from patients with uncontrolled synovitis. These results suggest that arthroscopic synovectomy provides pain relief and functional improvement, and allows rapid resolution of synovitis in about half of patients with UCMA of the wrist.
21801113 Leflunomide: dermatologic perspective. 2013 Apr Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug. It has successfully been used for the treatment of rheumatoid arthritis as a feasible alternative to methotrexate. Recently, leflunomide has been used in certain dermatologic conditions. Medline/PubMed search revealed only 201 articles of its application in dermatologic conditions, of which 21 were relevant for inclusion. Prime mode of action of leflunomide is through the inhibition of dihydroorotate dehydrogenase, a key enzyme in the de novo pyrimidine synthesis pathway used by lymphocytes for clonal expansion. The current level of evidence and strength of recommendation suggest its use in psoriasis and psoriatic arthritis. However, the use of leflunomide in severe atopic dermatitis, systemic lupus erythematosus, Wegener's granulomatosis, primary Sjögren's syndrome, bullous pemphigoid, dermatomyositis, sarcoidosis and systemic sclerosis still requires further evaluation.
21723254 Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide producti 2011 Jul 22 Molecular hydrogen has been reported to be effective for a variety of disorders and its effects have been ascribed to the reduction of oxidative stress. However, we have recently demonstrated that hydrogen inhibits type I allergy through modulating intracellular signal transduction. In the present study, we examined the hydrogen effects on lipopolysaccharide/interferon γ LPS/IFNγ-induced nitric oxide (NO) production in murine macrophage RAW264 cells. Treatment with hydrogen reduced LPS/IFNγ-induced NO release, which was associated with a diminished induction of inducible isoform of nitric oxide synthase (iNOS). Hydrogen treatment inhibited LPS/IFNγ-induced phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream signaling molecules, p38 MAP kinase and JNK, as well as IκBα, but did not affect activation of NADPH oxidase and production of reactive oxygen species (ROS). As ROS is an upstream activator of ASK1, inhibition of ASK1 by hydrogen without suppressing ROS implies that a potential target molecule of hydrogen should be located at the receptor or immediately downstream of it. These results suggested a role for molecular hydrogen as a signal modulator. Finally, oral intake of hydrogen-rich water alleviated anti-type II collagen antibody-induced arthritis in mice, a model for human rheumatoid arthritis. Taken together, our studies indicate that hydrogen inhibits LPS/IFNγ-induced NO production through modulation of signal transduction in macrophages and ameliorates inflammatory arthritis in mice, providing the molecular basis for hydrogen effects on inflammation and a functional interaction between two gaseous signaling molecules, NO and molecular hydrogen.
21150623 Arthritis, foot pain and shoe wear: current musculoskeletal research on feet. 2011 Mar PURPOSE OF REVIEW: Both arthritis and foot pain are major public health problems. Approximately 24% of adults have foot ailments, and the prevalence increases with age. Foot pain, particularly related to shoes, footwear and rheumatic disorders, may be an important modifiable factor. Surprisingly, this topic has received little attention in the rheumatology community. RECENT FINDINGS: Despite the major focus of structure and alignment in arthritis, remarkably little work has focused on the foot and nonsurgical foot interventions that might affect lower extremity joint alignment, structure and pain in rheumatic diseases. Emerging research suggests that there may be a significant role for foot orthotics and footwear in the treatment of rheumatoid arthritis and osteoarthritis of the hip, knee and foot. This review highlights the current understanding on the topic of foot orthotics and footwear in adults with rheumatic diseases. SUMMARY: Biomechanical evidence indicates that foot orthotics and specialized footwear may change muscle activation and gait patterns to reduce joint loading. Emerging evidence suggests that orthotics, specific shoe types and footwear interventions may provide an effective nonsurgical intervention in rheumatic diseases. Yet good data are sparse, and it is premature to recommend guidelines. As there are a limited number of studies that underpin the foot's role in arthritis cause and progression, clinical trials and prospective studies are of utmost importance to unravel the links between foot pain, foot conditions and interventions that lessen the impact of rheumatic diseases.