Janice Harper

The development of sarcoidosis with the use of alemtuzumab – clues to T-cell immune reconstitution

Alemtuzumab is a monoclonal antibody active against CD52, which has been increasingly used in the treatment of rare T-cell lymphoproliferative disorders, such as mycosis fungoides (MF)/Sezary syndrome (SS). The development of sarcoidosis, a multisystemic disease with a predominance of activated T-helper cells, has not previously been reported as a consequence of treatment with alemtuzumab. We hypothesise that, after stopping the drug, the immune reconstitution may have involved mainly the T-helper cell type, which led to the development of the autoimmune disorder.

UK Renal Registry 11th Annual Report (December 2008): Chapter 11 Blood pressure profile of prevalent patients receiving dialysis in the UK in 2007: national and centre-specific analyses

Introduction: Blood pressure (BP) control is assessed annually from patients on Renal Replacement Therapy at renal centres in England, Wales and Northern Ireland by the UK Renal Registry. Methods: Patients alive and receiving RRT on 31st December 2007 with a BP reading in either the fourth or third quarter of 2007 were included. Summary statistics were calculated for each renal centre, nation and renal disease category. Linear regression analyses were performed for prevalent patients between 2000 and 2007. Results: Significantly more haemodialysis patients achieved the BP standard (44.6% pre-HD and 48.8% post-HD) than peritoneal dialysis (32.8%) or renal transplant patients (26.7%). Median BP fell significantly between 2000 and 2007 for each treatment modality. There was significant variability in BP control between renal centres (p < 0.0001) for haemodialysis and transplant patients. Hypertension was significantly more common in haemodialysis patients with vascular disorders such as diabetes and renovascular disease (56.8%) than in glomerulonephritis (51.0%) or tubular disorders (45.1%). The effect was less prominent in peritoneal dialysis and not evident in transplant patients where few achieved the BP standard. Conclusion: A minority of patients on RRT achieved BP standards in 2007. There remained a significant variation in achievement of standards between renal centres.

Chapter 11: Blood Pressure Profile of Prevalent Patients Receiving Dialysis in the UK in 2008: national and centre-specific analyses

Introduction: The UK Renal Registry (UKRR) assesses blood pressure (BP) control annually for patients receiving renal replacement therapy (RRT) at renal centres in England, Wales and Northern Ireland. Methods: Patients alive and receiving RRT on 31st December 2008 with a BP reading in either the fourth or third quarter of 2008 were included. Summary statistics were calculated for each renal centre, nation and primary renal disease (PRD) category. Longitudinal analyses were performed to assess the long-term impact of treatment modality and PRD on BP control for incident and prevalent patients. Results: In 2008, only 26.3% of peritoneal dialysis (PD) and 27.4% of transplant (Tx) patients achieved the Renal Association (RA) guidelines standard of BP <130/80 mmHg. Since the cessation of BP targets for haemodialysis (HD) patients, there has been a reduction (compared to 2007) in the number of HD patients achieving BP <130/80 mmHg. In 2008, 43.1% of patients achieved BP <140/90 mmHg pre-HD and 46.8% BP <130/ 80 mmHg post-HD. BP control varied significantly between renal centres for each treatment modality (p < 0.001). Adjusted mean systolic BP fell significantly during the first year on dialysis (6 mmHg for PD and 8 mmHg for HD). Hypertension was more common in HD patients with vascular disorders such as diabetes and renovascular disease (59.0%) than in patients with glomerulonephritis (51.9%) or tubular disorders (46.7%). Conclusions: In 2008, a minority of patients on RRT achieved the recommended BP standards. There remained a significant variation in achievement of standards between UK renal centres. Since the removal of specific BP targets for HD patients, there has been an increase in systolic BP pre-and post-HD. BP falls significantly during the first year after starting dialysis and patients with vascular disorders have significantly worse BP control.

Combined Use of Rituximab and Intravenous Immunoglobulin for Severe Autoimmune Cicatricial Conjunctivitis—An Interventional Case Series

Purpose: Despite the availability of systemic immunosuppressants, cicatricial conjunctivitis (CC) remains a potentially blinding ocular surface disease. We aim to describe the combined use of rituximab (RTX) and intravenous immunoglobulin (IVIg) for severe recalcitrant autoimmune CC. Methods: In this single-center retrospective interventional case series with follow-up between 32 and 65 months, 3 cases with mucous membrane pemphigoid (patients 1–3) and 1 case with linear IgA disease (patient 4) were included. Initial conventional immunosuppressive therapy regimens included systemic steroids, dapsone, and mycophenolate. At the time of initiation of RTX and IVIg, all patients had only one eye with good visual acuity or good visual potential. Treatment included 1 to 2 cycles of RTX (1000 mg twice at an interval of 2 weeks apart), and 2 to 9 monthly courses of IVIg (2 g/kg over 3 days). Outcome measures were blindness, as defined by best spectacle-corrected visual acuity <0.05 on a decimal scale, and clinical staging of cicatricial disease (Rowsey and Foster staging). Results: In 4 presented cases, progression of cicatricial disease was stopped as assessed by the Foster grading scale and visual acuity was stabilized in all patients. Conjunctival scarring was stabilized in 2 cases and continued to progress in 2 cases. One patient developed septicemia 6 weeks after RTX infusion, which was successfully treated. Conclusions: Combination therapy of RTX and IVIg is a potent treatment regimen for recalcitrant autoimmune CC. Further prospective controlled studies on efficacy and safety are warranted before widespread clinical application.

Appendix D: Methodology used for Analyses of PCT/ Local Authority Incidence and Prevalence Rates and of Standardised Ratios

The areas used were the 148 English primary care trusts (PCTs), the 4 English care trusts, the 22 Welsh local authorities, the 32 Scottish council areas and the 26 Northern Ireland district council areas – these different types of area are collectively called PCT/LAs here. In Northern Ireland, Scotland and Wales, the health authority boundaries align with the LAs and these areas have been included along with the English PCTs in the tables.

Appendix E: Additional Data Tables for 2008 new and existing patients

Abrdn 85 15 L Rfree 84 11 4 Airdrie 92 8 L St.G 62 18 20 Antrim 90 10 LWest 86 4 9 B Heart 84 14 2 Leeds 69 20 11 B QEH 73 23 4 Leic 79 10 12 Bangor 86 14 Liv Ain 98 2 Basldn 83 18 Liv RI 66 27 7 Belfast 84 12 4 M Hope 46 46 7 Bradfd 85 15 M RI 71 16 13 Brightn 66 33 1 Middlbr 80 13 8 Bristol 75 19 6 Newc 72 22 6 Camb 87 10 3 Newry 85 15 Cardff 78 15 7 Norwch 79 15 5 Carlis 74 23 3 Nottm 73 22 5 Carsh 85 14 1 Oxford 62 27 12 Chelms 73 27 Plymth 56 26 19 Clwyd 92 8 Ports 68 24 8 Colchr 100 Prestn 74 20 6 Covnt 74 19 6 Redng 70 25 5 Table E.1.2. Number of patients per treatment modality at 90 days

UK Renal Registry 11th Annual Report (December 2008): Appendix D Methodology used for analyses of PCT incidence and prevalence rates and of standardised ratios

The areas used were the 152 (English) Primary Care Trusts (PCTs), the 22 Welsh local health boards, the 32 Scottish council areas and the 26 Northern Ireland district council areas – these different types of area are collectively called PCTs here. Prior to 2007, only some of the boundaries of PCTs and Local Authorities (LAs) in England were similar. There were roughly twice as many PCTs as LAs and the registry reports published analyses by LA in the main report and prevalence rates by PCT as an appendix. In October 2006, the Office for National Statistics reduced the number of PCTs and re-aligned many of the PCT boundaries in England with those of Local Authorities. As a result, in the 2008 Report these analyses will be presented by PCT (not LA). For data for years before the boundaries changed, patients are allocated to the new PCTs as they are now. In Northern Ireland, Scotland and Wales, the Health Authority boundaries align with the LAs and these areas have been included along with the English PCTs in the tables.