Graydon Howe

New onset sarcoid-like granulomatosis developing during anti-TNF therapy: an under-recognised complication

Tumour necrosis factor‐alpha (TNF‐α) antagonists have advanced the treatment of inflammatory arthropathies, and are even considered for use in refractory sarcoidosis with some success. Paradoxically, cases of new onset sarcoidosis‐like diseases are increasingly reported in patients receiving TNF‐α antagonists. Here, we report three cases of sarcoid‐like granulomatosis that developed during treatment with TNF‐α antagonists. Review of the Biologics clinic data base at Westmead, Sydney, Australia identified three patients whom, during anti‐TNF therapy, developed non‐caseating granulomas consistent with sarcoidosis. These three cases are described with review of the literature from 2000 to 2009 using PubMed. One hundred and sixty‐nine patients within our data base were reviewed for the period 2003–2009. Sarcoidosis‐like granulomas developed in three patients within a period of 3 to 36 months of treatment with etanercept and/or adalimumab. All cases demonstrated non‐infective, non‐caseating granulomas on renal or lymph node biopsy. Improvement was seen in two cases upon cessation of TNF‐α antagonist and steroid therapy. Interestingly, clinical deterioration was noted upon re‐challenge with the same TNF‐α antagonist in one patient. To date, a total of 37 cases of sarcoid‐like granuloma development after anti‐TNF therapy have been reported in the literature. Development of sarcoidosis‐like granulomatosis in patients treated with TNF‐α antagonists is a phenomenon previously under‐recognised. All three anti‐TNF agents have been observed to cause this phenomenon, suggesting a ‘class effect’ rather than being drug specific.

Secondary screening for osteoporosis in patients admitted with minimal-trauma fracture to a major teaching hospital

Abstract

Methotrexate: long-term safety and efficacy in an Australian consultant rheumatology practice

Background: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment.

Clinical images: Calcifying pseudoneoplasm of the neuraxis

Hantzschel H. B lymphocytopenia in rheumatoid arthritis is associated with the DRB1 shared epitope and increased acute phase response. Arthritis Res 2002;4:R1. 46. Bos WH, Wolbink GJ, Boers M, Tijhuis GJ, de Vries N, Bruinsma IE, et al. Arthritis development in prospectively followed arthralgia patients is dependent on anti–citrullinated protein antibody status [abstract]. Arthritis Rheum 2008;58 Suppl:S290.

Magnetic resonance imaging in Löfgren’s syndrome: demonstration of periarthritis

In Löfgren’s syndrome, pain and swelling commonly involves the ankle joints. In this prospective case series, the magnetic resonance imaging findings of ankle joint involvement are described. Extensive subcutaneous and soft tissue oedema was commonly seen around the ankles. Bone, cartilage, ligaments and tendons were typically uninvolved. Small amounts of joint and tenosynovial fluid were present without evidence of synovial thickening or synovitis. The fluid is probably reactive to adjacent inflammation in the para-articular soft tissues and probably not representing a primary site of involvement. These findings demonstrate that the arthritis in Löfgren’s syndrome stems primarily from periarthritis. This is consistent with prior descriptions using ultrasonography.

Failure of anti-TNF therapy to reactivate previously septic prosthetic joints.

A patient with long-standing rheumatoid arthritis was admitted with Streptococcus pneumoniae septicaemia and bilateral septic knee joints. He was treated conservatively with intravenous antibiotics and arthroscopic washouts and discharged home on oral antibiotics. Six months posthospital discharge, following re-exacerbation of arthritis, an informed consent was given by the patient to continue antitumour necrosis factor therapy. After 5 years of observation, there has been no recurrence of sepsis and the rheumatoid arthritis remains in remission.

Circulating fibroblast activation protein and dipeptidyl peptidase 4 in rheumatoid arthritis and systemic sclerosis

To quantify circulating fibroblast activation protein (cFAP) and dipeptidyl peptidase 4 (cDPP4) protease activities in patients with rheumatoid arthritis (RA), systemic sclerosis (SSc), and a control group with mechanical back pain and to correlate plasma levels with disease characteristics.

The role of 99mTc-labelled glucosamine (99mTc-ECDG) in the evaluation of rheumatic joint disease: a screening experience.

ObjectivesWe investigated the localization pattern of a novel imaging agent, 99mTc-labelled glucosamine (ECDG), in a variety of rheumatic conditions. Materials and methodsSixteen patients were recruited into the study, with either active rheumatoid arthritis or osteoarthritis. 99mTc-ECDG was prepared in-house and patients received 400 MBq intravenously; thereafter, static images were acquired 15 min, 2 h and 4 h later, using a dual-head Siemens e-cam. Images were interpreted by an experienced physician for (a) accumulation of tracer at sites of known disease; (b) relative activity over time; (c) detection of subclinical disease; (d) detection of unrelated disease; and (e) distribution of tracer at involved joints. ResultsOptimal images were obtained by 2 h after injection in all patients. 99mTc-ECDG accumulated at all clinically known sites of disease. Uptake was most pronounced in the patients with active but untreated disease. Relative tracer activity at involved joints increased with time when compared with activity in the adjoining soft tissue, liver and cardiac blood pool. Focal uptake was seen with local pathology such as supraspinatus tendinitis. Tracer uptake correlated well with disease severity, and insignificant tracer accumulation was evident at sites with no documented disease. Tracer distribution in joints appeared to conform predominantly to the synovium in patients with rheumatoid arthritis, whereas it was articular in patients with degenerative joint disease. Conclusion99mTc-ECDG accumulates at sites of active rheumatic disease and is able to differentiate between synovial and bone uptake. This agent may have a role in the assessment and monitoring of rheumatic conditions.

A preliminary investigation of cognitive function in rheumatoid arthritis patients on long-term methotrexate treatment

Some studies suggest that cognitive function is impaired in rheumatoid arthritis patients. One possible influence may be commonly used rheumatoid arthritis treatment, methotrexate. This study examined cognitive function in long-term methotrexate users with rheumatoid arthritis and, using a 24-hour pre- and post-methotrexate dose administration, investigated whether there may be transient cognitive function changes. Rheumatoid arthritis patients (n = 35) were assessed immediately before taking methotrexate and 24 hours later. Low and high methotrexate dose groups were then compared. Cognitive performance was unchanged across two assessment points and was within the normal range, although lower in high methotrexate dose group.

Cauda equina syndrome in ankylosing spondylitis.

A 56-year-old woman with a long-standing history of ankylosing spondylitis (AS) presented with a 2-year history of bladder and bowel symptoms. She complained of constipation and tenesmus requiring occasional manual evacuation. She had to strain to pass urine and occasionally applied manual pressure in the suprapubic region to initiate and maintain urine flow. There was no current back pain. She had a background of recurrent uveitis and peripheral large joint arthritis. Past therapy included intermittent nonsteroidal anti-inflammatory drugs for