Grainne Murphy

Fractalkine in rheumatoid arthritis: a review to date

Rheumatoid arthritis (RA) is characterized by the expansion of the synovium, with infiltration of pro-inflammatory cells, neovascularization and an abundance of pro-inflammatory cytokines resulting in tissue destruction and bone erosion. Fractalkine (FKN), a recently described chemokine, possesses chemotactic, angiogenic and adhesive functions that associates it with all of these destructive processes. In this review, we describe the research to date, which implicates FKN and its receptor in the pathogenesis of RA and propose that this molecule may represent a future therapeutic target for RA.

Cogan’s syndrome: present and future directions

Cogan’s syndrome, typified by the combination of interstitial keratitis and immune-mediated sensorineural hearing loss, is a rare condition, and commonly associated with a diagnostic delay. Using a standard search protocol, we review the literature to date, focusing on a number of key areas pertaining to diagnosis, presentation and treatment. Using a case illustration of atypical disease which led to fulminant aortic regurgitation, we highlight the need for continued and collaborative research in order to identify negative prognostic factors and thus tailor therapeutic regimens. Atypical Cogan’s syndrome is more commonly associated with systemic manifestations than typical disease, and may be refractory to immunosuppressive treatment. We discuss the application of laboratory (e.g antibodies targeting inner ear antigens) and radiological (PET-CT) aids to disease confirmation and detection of sub-clinical vascular inflammation. As illustrated by the included case description, some patients remain refractory to intense immunosuppression and delineation of adverse prognostic factors which may direct treatment, perhaps including the use of PET-CT, will contribute in the future to improving patient outcomes

Systemic listeriosis with adalimumab therapy.

Systemic listeriosis is caused by infection with the gram-positive, facultative intracellular rod Listeria Monocytogenes. Although infection is rare, it is a well-known cause for concern in particular subgroups, such as pregnant females and the immunocompromised patient population. In the latter, infection may manifest as meningoencephalitis or sepsis, in contrast with the more nonspecific symptoms of malaise, gastrointestinal disturbance, and lymphadenopathy, which are more typical of the immunocompetent host. Tumor necrosis factor alpha (TNF ) plays a pivotal role in both the pathogenesis of rheumatoid arthritis, and in host defense. The use of the TNF inhibitors, infliximab, etanercept, and adalimumab have indeed, lead to significant improvements in disease control in both early and refractory rheumatoid arthritis. There remains debate, however, surrounding the accompanying potential increase in severe infections. Biologically, TNF plays an important role in innate immunity and is essential for granuloma formation and maintenance. This is of particular importance in the case of infection with intracellular pathogens, such as Mycobacterium Tuberculosis, histoplasmosis, and L. Monocytogenes. Although the increased incidence of reactivation of latent tuberculosis is now well reported with all 3 anti-TNF agents, in particular, infliximab, there also appears to be a small but increased risk of listeriosis in this patient cohort. Here, we describe the case of a 58-year-old lady who developed systemic listeriosis within the first 6 months of adalimumab commencement. A 58-year-old woman was diagnosed with seropositive rheumatoid arthritis in 2000, presenting at that time with a 10-month history of pain and swelling in the small joints of her extremities. Her history of subsequent disease modifying therapy includes an initial trial of hydroxychloroquine owing to patient choice and a lack of erosive disease. With ongoing evidence of disease activity, methotrexate was introduced in conjunction with intermittent lowdose corticosteroids. Despite an initial response to both diseasemodifying antirheumatic drugs, she had recurrent flares of arthritis, leading to the initiation of adalimumab in February of 2006. Although, this led to a significant improvement in both clinical and laboratory markers of disease, she presented to the emergency department 5 months after anti-TNF commencement, with a 3-day history of severe diarrhea and vomiting in conjunction with a pyrexia of 38°C. At this time her immunosuppressive medications included adalimumab 40 mg fortnightly, methotrexate 10 mg weekly, and Deltacortril 12.5 mg once daily. On admission, she was hypovolemic, hypotensive, and tachycardic with ongoing gastrointestinal symptoms. She had no signs or symptoms of meningism throughout the duration of her illness. Although stool cultures did not show growth of significant pathogens, cultures of blood samples taken on admission showed growth of L. Monocytogenes on day 3. She was treated with a combination of high-dose ampicillin (2 g, 3 times a day) and gentamicin which was continued for a duration of 2 weeks. This treatment regimen led to a rapid resolution of both gastrointestinal and systemic symptoms with discharge shortly upon completion of antibiotic therapy. She remains well and her arthritis is currently controlled with a combination of methotrexate and minimal maintenance dose of corticosteroid. This represents the second reported case of listeria infection in a patient receiving adalimumab for the treatment of rheumatoid arthritis. On review of the literature, only one previous case with this, the most recent of the anti-TNF medications to come to the market, was found. That patient was identified through the British Society for Rheumatology Biologics Register and presented with septic arthritis. There have, however, been a number of case series reporting an increased incidence of infection with both etanercept and infliximab. Using data from postmarketing surveillance, through the US Food and Drug Administration, both Slifman et al and Wallis et al have published case series reporting the incidence of listerial infections in patients receiving TNF inhibitors. The former reported on 15 cases, and the latter 38 cases, during a 4-year period. Both series found that the incidence of infection was increased in patients where the treatment indication was rheumatoid arthritis, and when infliximab was the anti-TNF of choice. The reason for the discrepancy with, for example inflammatory bowel disease, is unclear but may reflect differences in concurrent immunosuppression or infection risk relating to the underlying disease. When compared with annual incidence rates of listeria infection in the general population the rates were as follows: 0.5 per 100,000 in the general population; 15.5 per 100,000 in those receiving infliximab, and 1.8 in those receiving etanercept. Although the most common presentation in these patient series was either sepsis or meningitis, there have been a number of cases of listerial infection manifesting as septic arthritis. This is an important point as the standard treatment regimen for septic arthritis is inadequate for listerial joint infection. Hence, this should be borne in mind, in particular, in patients on biologic therapy, who are not responding to standard antimicrobials or who have additional risk factors. The incidence of infection was not characterized in adalimumab under the encompass of these studies as it did not receive licensing until after the study completion dates in 2002. Although, the incidence of listeriosis appears to be lower on this TNF inhibitor, it should be noted that this is the most recently licensed and further study is required to ascertain the comparative risk of nontuberculous granulomatous infections with this agent. This case highlights the need for increased vigilance for intracellular organisms as a cause of infection in all patients receiving anti-TNF therapy. It also raises the question of whether we should advise our patients who are receiving such treatment to avoid foods that are potential sources of this organism such as soft cheeses, unpasteurized milk, etc. Nonetheless, early recognition and consideration of this organism as a cause of infection is necessary to direct treatment and to reduce the morbidity and mortality associated with this disease. Finally, it should be noted that although most cases of listeriosis in patients receiving biologic therapy occur in those receiving infliximab therapy, vigilance is warranted in all patients receiving TNF-targeting therapies. From the *Department of Rheumatology, Cork University Hospital, Wilton, Cork, Ireland; and †St. Vincent’s University Hospital, Dublin, Ireland. Correspondence: Grainne Murphy, MB, MRCPI, Department of Rheumatology, Cork University Hospital, Wilton, Cork, Ireland. E-mail grainne.murphy@ucc.ie. Copyright

An unexpected cause of sacroiliitis in a patient with gout and chronic psoriasis with inflammatory arthritis: a case report

BackgroundInflammatory back pain is a condition characterized by inflammation of the sacroiliac joints and lower spine. It is frequently seen in patients with spondyloarthropathies like ankylosing spondylitis, psoriatic arthritis, enteropathic arthritis and reactive arthritis. Inflammatory back pain can be caused by many other conditions like infection and crystal deposition such as gout. In this case, it is difficult to specifically identify gout as a cause by ordinary imaging like magnetic resonance imaging (MRI) or ultrasound.Case presentationThis case report describes a young man with severe psoriasis, presumptive psoriatic spondyloarthropathy and chronic extensive tophaceous gout which was difficult to treat because of non-compliance with medications and lifestyle. He presented with inflammatory type low back and buttocks pain with raised inflammatory markers. MRI of the lower back and sacroiliac joints showed features of active sacroiliitis. He was subsequently treated with a Tumor Necrosis Factor (TNF) alpha inhibitor for presumed axial psoriatic arthritis and had no significant benefit. Two attempts DECT of the lumbar spine was not executed correctly. CT lumbar spine and SIJs showed L2/3 endplate and left SIJ erosions mostly related to gout. Rasburicase was introduced. The tophi decreased in size peripherally with marginal improvement in back pain. From this study, we want to bring to the attention of physicians that gout can lead to back pain with inflammatory changes on MRI. We also want to address the importance of other imaging modalities if the cause of the back pain is not clear.ConclusionThis case is meant to highlight an important but overlooked cause of active sacroililitis and inflammatory type back pain in patients who have gout, and to bring to the attention that plain X-ray, MRI and ultrasound cannot differentiate between inflammatory sacroiliitis caused by seronegative arthritis versus gouty arthritis. CT scan can add more information but DECT is the preferred method for differentiation and identification of axial tophaceous gout.

Investigating idiopathic inflammatory myopathy; initial cross speciality experience with use of the extended myositis antibody panel

The discovery of unique autoantibodies has informed and altered our approach to the diagnosis and management of the inflammatory myopathies. This study reports the initial clinical experience of use of the Extended Myositis Antibody (EMA) panel in the largest university teaching hospital in Ireland. We conducted a retrospective review of all patients who had serum samples tested for myositis specific antibodies and myositis associated antibodies from April 2014 to March 2015. A positive EMA panel was of significant clinical utility in facilitating decisions on appropriate investigations, and need for onward referral to other physicians. Furthermore, this paper highlights the diversity of possible presentations of idiopathic inflammatory myopathy with subsequent need for multi-speciality involvement, and serves to heighten awareness among clinicians of the diagnostic use of extended myositis antibody testing in these cases.

Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex multisystem autoimmune disorder with a heterogeneous presentation and clinical course. The pathogenesis is multifactorial with evidence of genetic susceptibility, environmental triggers, and aberrancy in both the innate and adaptive immune systems. Although significant therapeutic advances have been made in recent decades, there remains a significant increase in mortality, highlighting the need for further understanding of the underlying immune mechanisms.