SUMMARYAdhesion mechanisms play a major role in the recruitment of peripheral blood lymphocytes (PBL) which characteristically infiltrate rheumatoid arthritis (RA) synovium and other chronically inflamed tissues. Through a sequential series of complex integrated adhesion and signalling events,`multistep model of migration', specific subsets of PBL are recruited into inflamed tissues. In this process both leucocyte receptors and microvascular endothelial (MVE) counter-receptors play a critical role. The MVE in particular, during an inflammatory state, is the target of various inflammatory mediators that cause the up-regulation of several cell adhesion molecules (CAM). One of the most important factors known to be a powerful inducer of MVE CAM is TNF-a . Conversely, blocking TNF-a causes a downmodulation of CAM expression. To test directly the capacity of TNF-a to induce cell migration into RA synovium we adapted a model in which synovial grafts were implanted into SCID mice subcutaneously.Using this model we demonstrate that: (i) transplants remain viable and become vascularized and fed by mouse subdermal vessels; (ii) the mouse vasculature connects to the transplant vasculature which maintains the ability to express human CAM; (iii) intragraft injections of TNF-a up-regulate the expression of human CAM, following the down-regulation which occurred 4 weeks post-transplantation; and (iv) the up-regulation of graft CAM is associated with increased human PBL migration into the transplants. This study provides direct evidence in vivo of the capacity of TNF-a to induce cell migration. In addition, it provides the experimental background for the optimal use of this model.

Thirty-six patients with non-Hodgkin's lymphoma (NHL) (comprising patients with refractory or relapsed disease and eight elderly, unfit patients with de novo disease) were treated with mitozantrone, chlorambucil and prednisolone on an out-patient basis. Fifteen patients had low grade (LG) disease, five patients intermediate grade (IG) disease and 16 patients high grade (HG) disease and 31/36 had stage IV disease. All elderly patients had IG or HG disease. The regimen was well-tolerated. After six courses of chemotherapy, there was a 69 per cent response rate with 33 per cent in complete remission. The median duration of remission was 15 months. The overall 3-year projected survival was 38 per cent; 27 per cent for LG disease and 47 per cent for HG and IG disease. Responses did not appear durable for either HG or LG disease unless CR was achieved early on. Three of the eight patients treated de novo (mean age 71 years) have survived disease-free, between 28 and 38 months from entry. This study indicates that mitozantrone-based regimens have promising activity in NHL and require further evaluation. The low toxicity combined with worthwhile remissions make this an attractive first-line option for elderly patients.

Mycobacteriumchelonae is one of the rapidly growing non-tuberculous mycobacteria that can be isolated from water, soils and aerosols. Localised infections have been reported associated with tattoo parlours, pedicures and cosmetic procedures. But disseminated infection is usually associated with individuals who are immunocompromised, predominantly affecting limbs but sparing abdomen and back. We herein present a case where patient was on immunosuppressive therapy and developed locally severe infection around right ankle. A 69-year-old woman known to rheumatology presents in outpatients with severe pain in right ankle, unable to bear weight, oedematous right foot and lower leg. There was extensive erythematous cellulitic skin rash around right ankle and lower leg. She had background history of systemic lupus erythematosus with previous history of cardiac myositis and left foot drop. She had six cycles of cyclophosphamide for flare of lupus and after last cycle developed this presentation. Skin biopsy was arranged with dermatologist, cultures from which grew M.chelonae. She was admitted and started on triple regimen for M.chelonae as per Microbiology guidelines with intention to complete 6–12 months treatment. Patient responded very well to treatment but unfortunately, she died after 5 months on treatment due to other comorbidities and likely cause of death was cardiac arrhythmia.

Background Mycobacterium chelonae is a rapidly growing non-tuberculous mycobacteria that can be isolated from water, soils and aerosols. Localised infection has been reported associated with surgical and cosmetic procedures. Disseminated infection is rare and usually occurs in individuals who are immunocompromised. We present a patient with severe SLE on immunosuppressive therapy who developed localised severe cutaneous infection of the foot. Methods A 69-year-old lady with complex SLE - RNP+, Raynaud's, arthritis, stable for several years had deteriorated within the last year with cardiac myositis and, peripheral neuropathy. Three months pulsed intravenous cyclophosphamide (EUROLUPUS regime) was completed in November 2018. Five weeks later she developed severe pain, inability to weight-bear and extensive erythema and swelling of the right ankle and lower leg. An MRI showed extensive skin thickening especially dorsally in the R foot and anteriorly in distal leg. There was also increased signal in the distal achilles tendon. Orthopedic review confirmed no evidence of septic arthritis or osteomyelitis. A skin biopsy was performed, cultures from which grew Mycobacterium chelonae. She was admitted and started on tobramycin, on which she developed long QTc, linezolid which caused thrombocytopenia and clarithromycin. In March 2019 she was re-admitted with confusion, weakness and AKI, secondary to clarithromycin. She was, then switched to clofazimine and low dose clarithromycin, on which she was stabilized. MRI brain scan was normal, lumbar puncture was negative for M chelonae PCR and MRI spine confirmed cervical cord compression and cervical and lumbar canal stenosis due to osteophytes and disc disease. Results The infection improved considerably after 5 months of successful mycobacterial treatment. It was then possible to treat with rituximab for a deteriorating peripheral neuropathy confirmed on EMG and cardiac myositis. Sadly, whilst awaiting rehabilitation, the patient died unexpectedly in April 2019 from an arrhythmia. Conclusion Mycobacterium chelonae is an uncommon cause of soft tissue infection, which is resistant to all anti-tuberculous drugs. It is susceptible to a wider range of antimicrobial agents including tobramycin, imipenem, clarithromycin, linezolid, co-trimoxazole. A high index of suspicion is necessary for diagnosis, particularly in immunocompromised patients. The incidence may be increasing, possibly due to enhanced detection. Infection can mimic MSK presentations including capsulitis, tendonitis and tenosynovitis. Close monitoring is required as anti-microbial therapy complications are common including prolongation of QTc on tobramycin. Vigilance for disseminated multiorgan involvement is essential due to high mortality, particularly with CNS and lung involvement. Atypical infections should always be considered in the immunocompromised, particularly mycobacteria, nocardia & fungi. Disclosures S. Rasool None. A. Afifi None. D. De Lord None.

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