Seronegative spondyloarthropathy-associated inflammatory bowel disease

Seronegative spondyloarthropathy(SpA)usually starts in the third decade of life with negative rheumatoid factor,human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis,dactylitis,enthesitis and extra-articular manifestations(EAMs).Cases can be classified as ankylosing spondylitis,psoriatic arthritis,reactive arthritis,enteropathic arthritis,or juvenileonset spondyloarthritis.Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease(IBD),with shared genetic and immunopathogenic mechanisms.IBD is a common EAM in SpA patients,while extraintestinal manifestations in IBD patients mostly affect the joints.Although individual protocols are available for the management of each disease,the standard therapeutic guidelines of SpA-associated IBD patients remain to be established.Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA,whereas their use is controversial in IBD due to associated disease flares.Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy.Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD,and a drug of choice for treating SpA-associated IBD.Janus kinase inhibitors,approved for treating SpA and ulcerative colitis,are promising therapeutics in SpA coexistent with ulcerative colitis.A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.

Enteropathic spondyloarthropathy:A common genetic background with inflammatory bowel disease?

The association between spondyloarthropathy and in flammatory bowel disease(IBD) is largely established, although prevalence is variable because of different population selection and diagnostic methodologies.Most studies indicate that as many as 10%15% of cases of IBD are complicated by ankylosing spondylitis(AS) or other forms of spondylarthritis(SpA).Of note, ileal inflammation resembling IBD has been reported in up to two thirds of cases of SpA, and it has been suggested that the presence of ileitis is associated with the chronic ity of articular complications.Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of patients with SpA by ileocolonos copy is not indicated in the absence of gut symptoms, as only a small proportion of patients with subclinical gut inflammation will develop overt IBD over time.The existence of familial clustering of both IBD and AS, the coexistence of both conditions in a patient, the evidence of an increased risk ratio among f irstand seconddegree relatives of affected AS or IBD patients and f inally, the increased crossrisk ratios between AS and IBD, strongly suggest a shared genetic background.So far, however, IL23R is the only identified susceptibility gene shared by both IBD and AS.Although functional studies are still needed to better understand its pathogenic role, great ef fort is being spent therapeutically targeting this pathway that may prove effective for both disorders.

NSAID-induced deleterious effects on the proximal and mid small bowel in seronegative spondyloarthropathy patients

AIM:To investigate the small bowel of seronegative spondyloarthropathy(SpA) patients in order to ascertain the presence of mucosal lesions.METHODS:Between January 2008 and June 2010,54 consecutive patients were enrolled and submitted to avideo capsule endoscopy(VCE) examination.Historyand demographic data were taken,as well as the history of non-steroidal anti-inflammatory drug(NSAID) consumption.After reading each VCE recording,a capsule endoscopy scoring index for small bowel mucosal inflammatory change(Lewis score) was calculated.Statistical analysis of the data was performed.RESULTS:The Lewis score for the whole cohort was 397.73.It was higher in the NSAID consumption subgroup(P = 0.036).The difference in Lewis score between NSAID users and non-users was reproduced for the first and second proximal tertiles of the small bowel,but not for its distal third(P values of 0.036,0.001 and 0.18,respectively).There was no statistical significant difference between the groups with regard to age or sex of the patients.CONCLUSION:The intestinal inflammatory involvement of SpA patients is more prominent in NSAID users for the proximal/mid small bowel,but not for its distal part.

Rare extraintestinal manifestations of ulcerative colitis treated with dual biologic therapy:A case report

BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying frequency depending on the affected organ.The most common ones are musculoskeletal EIMs,affecting up to 33%-40%of IBD patients.These include,among others,inflammatory back pain,tendinitis,plantar fasciitis and arthritis.Only a few case reports in literature discuss Achilles tendinitis.CASE SUMMARY This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine,mesalazine,glucocorticosteroids,infliximab and tofacitinib,a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy(DBT)-ustekinumab and adalimumab(ADA).CONCLUSION This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.

Current issues in pediatric inflammatory bowel diseaseassociated arthropathies

Joint involvement is the most common extraintestinal manifestation in children with inflammatory bowel disease (IBD) and may involve 16%-33% of patients at diagnosis or during follow-up. It is possible to distinguish asymmetrical, transitory and migrating arthritis (pauciarticular and polyarticular) and spondyloarthropathy (SpA). Clinical manifestations can be variable, and peripheral arthritis often occurs before gastrointestinal symptoms develop. The inflammatory intestinal pattern is variable, ranging from sub-clinical inflammation conditions, classified as indeterminate colitis and nodular lymphoid hyperplasia of the ileum, to Crohn’s disease or ulcerative colitis. Unlike the axial form, there is an association between gut inflammation and evolution of recurrent peripheral articular disease that coincides with a flare-up of intestinal disease. This finding seems to confirm a key role of intestinal inflammation in the pathogenesis of SpA. An association between genetic background and human leukocyte antigen-B27 status is less common in pediatric than n adult populations. Seronegative sacroiliitis and SpA are the most frequent forms of arthropathy in children with IBD. In pediatric patients, a correct therapeutic approach relies on the use of nonsteroidal antiinflammatory drugs, local steroid injections, physiotherapy and anti-tumor necrosis factor therapy (infliximab). Early diagnosis of these manifestations reduces the risk of progression and complications, and as well as increasing the efficacy of the therapy.

Persistence of high CD40 and CD40L expression after restorative proctocolectomy for ulcerative colitis

AIM： To focus on the role of CD40 and CD40L in their pathogenesis. METHODS： We analyzed by immunohistochemistry the CD40 and CD40L expression in the pouch mucosa of 28 patients who had undergone RPC for UC, in the terminal ileum of 6 patients with UC and 11 healthy subjects. We also examined by flow cytometry the expression of CEH0 by B lymphoo/tes and monocytes in the peripheral blood of 20 pouch patients, 15 UC patients and 11 healthy controls. RESULTS： Ileal pouch mucosa leukocytes presented a significantly higher expression of CD40 and CD40L as compared to controls. This alteration correlated with pouchitis, but was also present in the healthy pouch and in the terminal ileum of UC patients. CD40 expression of peripheral B lymphocytes was significantly higher in patients with UC and pouch, respect to controls. Increased CD40 levels in blood B cells of pouch patients correlated with the presence of spondyloarthropathy, but not with pouchitis, or inflammatory indices. CONCLUSION： High CD40 expression in the ileal pouch mucosa could be implied in the pathogenesis of pouchitis following proctocolectomy for UC, whereas its increased levels on peripheral blood B lymphocytes are associated with the presence of extraintestinal manifestations.

Occurrence of human leukocyte antigen B51-related ankylosing spondylitis in a family:Two case reports

BACKGROUND Ankylosing spondylitis(AS)is strongly associated with the human leukocyte antigen(HLA)B27 haplotype.In regions where conventional polymerase chain reaction for HLA typing is available for antigens such as HLA B27 or HLA B51,it is common to perform the HLA B27 test for evaluation of AS.While HLA B27-associated clustered occurrences of AS have been reported in families,we report the first case series of HLA B51-related occurrences of AS in a family.CASE SUMMARY A father and his daughters were diagnosed with AS and did not have the HLA B27 haplotype.Although they were positive for HLA B51,they exhibited no signs of Behçet’s disease(BD).Of the five daughters,one had AS,and three,including the daughter with AS,were positive for HLA B51.The two daughters with the HLA B51 haplotype(excluding the daughter with AS)exhibited bilateral grade 1 sacroiliitis,whereas the daughters without the HLA B51 haplotype did not have sacroiliitis.Thus,this Korean family exhibited a strong association with the HLA B51 haplotype and clinical sacroiliitis,irrespective of the symptoms of BD.CONCLUSION It is advisable to check for HLA B51 positivity in patients with AS/spondyloarthropathy who test negative for HLA B27.

Distinguishing erosive osteoarthritis and calcium pyrophosphate deposition disease

Erosive osteoarthritis is a term utilized to describe a specific inflammatory condition of the interphalangeal and first carpal metacarpal joints of the hands. The term has become a part of medical philosophical semantics and paradigms, but the issue is actually more complicated. Even the term osteoarthritis(nonerosive) has been controversial, with some suggesting osteoarthrosis to be more appropriate in view of the perspective that it is a non-inflammatory process undeserving of the "itis" suffix. The term "erosion" has also been a source of confusion in osteoarthritis, as it has been used to describe cartilage, not bone lesions. Inflammation in individuals with osteoarthritis actually appears to be related to complicating phenomena, such as calcium pyrophosphate and hydroxyapatite crystal deposition producing arthritis. Erosive osteoarthritis is the contentious term. It is used to describe a specific form of joint damage to specific joints. The damage has been termed erosions and the distribution of the damage is to the interphalangeal joints of the hand and first carpal metacarpal joint. Inflammation is recognized by joint redness and warmth, while X-rays reveal alteration of the articular surfaces, producing a smudged appearance. This ill-defined, joint damage has a crumbling appearance and is quite distinct from the sharply defined erosions of rheumatoid arthritis and spondyloarthropathy. The appearance is identical to those found with calcium pyrophosphate deposition disease, both in character and their unique responsiveness to hydroxychloroquine treatment. Low doses of the latter often resolve symptoms within weeks, in contrast to higher doses and the months required for response in other forms of inflammatory arthritis. Reconsidering erosive osteoarthritis as a form of calcium pyrophosphate deposition disease guides physicians to more effective therapeutic intervention.

Full Length Spine CT and MRI

Spine is a complex and long structure in the human body. Visualization of the spine is essential to treat and manage spine disease and commonly requires further imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). In most clinical fields, spine CT and MRI examinations are focused on the region of interest. However, spine is composed of cervical, thoracic, lumbar, sacrum and coccyx and sometimes demands examination of entire structure as well as regional spine depending on disease, patient’s state and physician’s decision. This review considers the available literature to describe when and how full length spine evaluation by CT and MRI is applied according to each spinal disease such as spinal trauma, deformity, infection, axial spondyloarthropathy and metastatic tumor.

What qualifies as rheumatoid arthritis?

Expansion of diagnostic criteria for rheumatoid arthritis and deletion of exceptions increases sensitivity, but at the expense of specificity.Two decades later, modification of criteria included the caveat: "absence of an alternative diagnosis that better explains the synovitis."That puts great faith in the diagnostic skills of the evaluating individual and their perspectives of disease.The major confounding factor appears to be spondyloarthropathy, which shares some characteristics with rheumatoid arthritis.Recognition of the latter on the basis of marginally distributed and symmetrical polyarticular erosions, in absence of axial(odontoid disease excepted) involvement requires modification to avoid failure to recognize a different disease, spondyloarthropathy.Skeletal distribution, pure expression of disease in natural animal models and biomechanical studies clearly rule out peripheral joint fusion(at least in the absence of corticosteroid therapy) as a manifestation of rheumatoid arthritis.Further, such studies identity predominant wrist and ankle involvement as characteristic of a different disease, spondyloarthropathy.It is important to separate the two diagnostic groups for epidemiologic study and for clinical diagnosis.They certainly differ in their pathophysiology.

Inflammatory bowel diseases and spondyloarthropathies: From pathogenesis to treatment

Spondyloarthropathies(SpA) include many different forms of inflammatory arthritis and can affect the spine(axial SpA) and/or peripheral joints(peripheral SpA) with Ankylosing spondylitis(AS) being the prototype of the former. Extraarticular manifestations, like uveitis, psoriasis and inflammatory bowel disease(IBD) are frequently observed in the setting of SpA and are, in fact, part of the SpA classification criteria. Bowel involvement seems to be the most common of these manifestations. Clinically evident IBD is observed in 6%-14% of AS patients, which is significantly more frequent compared to the general population. Besides, it seems that silent microscopic gut inflammation, is evident in around 60% in AS patients. Interestingly, occurrence of IBD has been associated with AS disease activity. For peripheral SpA, two different forms have been proposed with diverse characteristics. Of note, SpA(axial or peripheral) is more commonly observed in Crohn's disease than in ulcerative colitis. The common pathogenetic mechanisms that explain the link between IBD and SpA are still ill-defined. The role of dysregulated microbiome along with migration of T lymphocytes and other cells from gut to the joint("gut-joint" axis) has been recognized, in the context of a genetic background including associations with alleles inside or outside the human leukocyte antigen system. Various therapeutic modalities are available with monoclonal antibodies against tumour necrosis factor, interleukin-23 and interleukin-17, being the most effective. Both gastroenterologists and rheumatologists should be alert to identify the coexistence of these conditions and ideally follow-up these patients in combined clinics.

Potential of (18)~F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies

AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. METHODS: This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. RESULTS: The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and nonsymmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. CONCLUSION: 18F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.

Non-invasive investigation in patients with inflammatory joint disease

Gut inflammation can occur in 30%-60% of patients with spondyloarthropathies.However, the presence of such gut inflammation is underestimated, only 27% of patients with histological evidence of gut inflammation have intestinal symptoms, but subclinical gut inflammation is documented in two-thirds of patients with inflammatory joint disease.There are common genetic and immunological mechanisms behind concomitant inflammation in the joints and intestinal tract.A number of blood tests, e.g.erythrocyte sedimentation rate, orosomucoid, C-reactive protein, and white cell and platelet counts, are probably the most commonly used laboratory markers of inflammatory disease, however, these tests are difficult to interpret in arthropathies associated with gut inflammation, since any increases in their blood levels might be attributable to either the joint disease or to gut inflammation.Consequently, it would be useful to have a marker capable of separately identifying gut inflammation.Fecal proteins, which are indirect markers of neutrophil migration in the gut wall, and intestinal permeability, seem to be ideal for monitoring intestinal inflammation:they are easy to measure non-invasively and are specific for intestinal disease in the absence of gastrointestinal infections.Alongside the traditional markers for characterizing intestinal inflammation, there are also antibodies, in all probability generated by the immune response to microbial antigens and auto-antigens, which have proved useful in establishing the diagnosis and assessing the severity of the condition, as well as the prognosis and the risk of complications.In short, noninvasive investigations on the gut in patients with rheumatic disease may be useful in clinical practice for a preliminary assessment of patients with suspected intestinal disease.

Chronic Inflammatory Rheumatic Diseases in Rheumatological Practice in Lomé(Togo)

Chronic inflammatory rheumatism is a pathology of variable frequency and severity with a significant impact on the socio-economic, personal and family level. Study Aim: To describe the epidemiological, clinical, laboratory, radiological, therapeutic and evolutive features of chronic inflammatory rheumatic diseases in rheumatological practice in Togo. Patients and Methods: This was a multicenter cross-sectional study conducted from January 2011 to December 2019 on patients examined in the three rheumatology departments in Lomé (Togo). Patients 18 years old and above who have presented joint pain with or without synovitis, and/or rachialgia (back pain) for at least three months were included. The diagnosis of chronic inflammatory rheumatic diseases was made according to international consensus criteria. Results: Out of the 20333 patients whose files were collected during our study period, 290 (1.43%) suffered from chronic inflammatory rheumatic diseases. There were 226 (77.93%) females and 64 (22.07%) males. The mean age of the patients was 42.79 ± 15.18 years. The mean duration of symptoms was 40.80 ± 54.09 months. Arthritis (67.24%) was the main reason for consultation, followed by joint pain (31.38%). rheumatoid arthritis (41.03%), unclassified chronic inflammatory rheumatic diseases (38.62%), spondyloarthropathies (15.17%) and systemic lupus erythematosus (2.41%) were the major clinical forms. The immunological tests performed in 13.79% of cases were positive in 52.94% of cases. Carpitis (57.55%) and diffuse osteoporosis (45.28%) were the commonest radiographic features of the hands. 289 patients (99.66%) received symptomatic treatments such as NSAIDs (73.36%) and corticosteroids (51.90%) and 90 patients (31.03%) were treated with synthetic DMARDs such as methotrexate (88.89%). The outcome was favorable in 27.93% of cases. Conclusion: Chronic inflammatory rheumatic diseases are common diseases in rheumatological practice in Togo that deserve special attention. The establishment of a specialized immunology laboratory could be very useful for the diagnosis and early management of these diseases.