Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a series of 52 patients from a single centre.

OBJECTIVES: Some studies have shown efficacy of intravenous immunoglobulin (IVIG) in the treatment of systemic lupus erythematosus (SLE) but its use still lacks of confirmation in large cohorts. METHODS: This observational, retrospective, single-centre clinical study included 52 SLE patients who received at least one cycle of IVIG (400 mg/kg/day for 5 days) from January 2001 to February 2011. Twenty-seven SLE patients were treated with IVIG for active disease and concomitant infection, while 26 received the IVIG as resistant to standard therapy. The indications for IVIG in the SLE patients were mainly cutaneous, haematological, neuropsychiatric and heart involvements. RESULTS: In patients with active disease and concomitant infections, the response to IVIG treatment was a complete remission (n=9), partial remission (n=8), and no response (n=8). We recorded any response (total or partial) in 17 out of 27 patients (62.96%). In patients with active disease refractory to standard therapy, the response to IVIG treatment was a complete remission (n=6), partial remission (n=12), and no response (n=8). We recorded any response (total or partial) in 18 out of 26 patients (69.23%). Seven of these patients relapsed after a mean time of 8.9 months (3-23 months). CONCLUSIONS: In a long-term study in the largest published cohort of SLE patients, IVIG was found to be effective in selected manifestations such as haematological and cardiac involvement or when other therapeutic approaches are not available, such as in patients with active disease and concomitant infection.

Mannose-binding lectin deficiency and predisposition to recurrent infection in adults.

AIMS: The effects of mannose-binding lectin (MBL) deficiency are well known in children and in those with a compromised immune system. However, its effects in adults are debateable, with little research having been carried out in the UK regarding infection risk in otherwise healthy adults with an MBL deficiency. METHODS: Using an ELISA, we investigated the prevalence of MBL deficiency in both healthy adults and those with recurrent infection. The aim was to determine first if there was a disparity in MBL levels between the two groups and second to investigate the effect of severe deficiency. RESULTS: Overall, the difference between the two groups for MBL level was found not to be statistically significant (p=0.203); however, there was a higher prevalence of severe deficiency (MBL<75 ng/mL) in the patients with recurrent infection (p=0.03). CONCLUSIONS: It was concluded that there is justified reason for continuing to perform the MBL test in adult patients suffering recurrent infection.

Thalidomide for the treatment of resistant cutaneous lupus: efficacy and safety of different therapeutic regimens.

PURPOSE: Thalidomide is effective for the treatment of severe cutaneous lupus. Our aim was to study the safety and efficacy of different doses of thalidomide in this condition. METHODS: We studied patients with severe cutaneous lupus that was unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n = 17), or 50 mg on alternate days (n = 15) were compared. The response to thalidomide was categorized as complete remission, partial remission, or no visible improvement. All patients received a baseline electromyogram (EMG) followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms developed. RESULTS: Forty-eight patients (46 female; mean [+/- SD] age, 44 +/- 12 years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24) were included. The response rate was 81%, including 29 patients (60%) in complete remission and 10 (21%) in partial remission. Nine patients (19%) failed to respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG-proven in 11, including 4 patients in the 50-mg alternate-day group. Other side effects included drowsiness, constipation or abdominal pain, and amenorrhea. The relapse rate after stopping thalidomide was 67% (26/39). There was no association between a positive response to the drug and either starting doses or cumulative dose. Similarly, no association was found between peripheral neuropathy and the starting or cumulative dose. CONCLUSION: Thalidomide is effective for the treatment of severe cutaneous lupus. There were no clear dose-dependent effects. However, the high incidence of neurotoxicity, even at low doses, suggests that it may be most useful as a remission-inducing drug.

The relationship between pro-resorptive inflammatory cytokines and the effect of high dose vitamin D supplementation on their circulating concentrations.

Inflammatory/pro-resorptive cytokines and chemokines form part of a complex inter-dependent network and may be influenced by vitamin D. We investigated their inter-relationship and the effect of a loading dose of vitamin D. We measured plasma concentrations of an array of cytokines including tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-6, IL-17, IL-8, granulocyte macrophage colony stimulating factor (GM-CSF), and the chemokine monocyte chemoattractant protein-1 (MCP-1). Cytokines, 25 (OH) vitamin D, 1,25 (OH)2 vitamin D, the Wnt inhibitor, DKK1 concentrations and bone turnover markers were measured at baseline and 3 months following a bolus dose (300,000 IU) of vitamin D2 in 39 subjects with vitamin D insufficiency. We observed strong correlations between TNF-α with GM-CSF (r=0.628, p<0.001), IL-17 (r=0.7, p<0.001) and MCP-1 (r=0.5, p=0.001), between IL-1ß with IL-17 (r=0.45, p=0.004) and between the 2 chemokines, IL-8 and MCP-1 (r=0.45, p=0.004). A positive correlation was seen between DKK1 and IL-1ß (r=0.35, p=-0.029). Following vitamin D loading at 3 months, the relationships between some of the cytokines changed (TNF-α and MCP-1: r=0.38, p=0.017, IL-1ß and IL-17: r=0.3, p=0.06). 1,25 (OH)2 vitamin D increased markedly following supplementation. Significant correlations were seen between 25 (OH) vitamin D (r=0.4 p=0.016) and 1,25 (OH)2 vitamin D (r=0.39 p=0.02) with plasma CTX (marker of bone resorption) at 3 months. TNF-α and IL-1ß increased significantly at 3 months (p<0.05). The close association between several cytokines is influenced by vitamin D status. Acute increases in 1,25 (OH)2 vitamin D, achieved with loading doses of vitamin D, lead to increases in pro-resorptive cytokines.

The role of immune complexes in atherogenesis.

Atherosclerosis is now recognized as a chronic inflammatory disease and is characterized by features of inflammation at all stages of its development. It also appears to display elements of autoimmunity, and several autoantibodies including those directed against oxidized low-density lipoprotein (ox-LDL) and heat shock proteins (Hsps) have been identified in atherosclerosis. Immune complexes (ICs) may form between these antigens and autoantibodies and via Fc receptor signaling and complement activation may modulate the inflammation in atherosclerosis. Antibody isotype may direct the role that ICs play in atherogenesis, immunoglobulin G (IgG) being potentially pro-atherogenic and immunoglobulin M (IgM) playing a protective role. Therapeutic options targeting complement activation and those which are potentially Fc-receptor mediated have been investigated in animal models, though targeting Fc receptor signaling is an area that needs further investigation.

Mycophenolate mofetil in systemic lupus erythematosus: efficacy and tolerability in 86 patients.

OBJECTIVE: To assess the indications, efficacy, and tolerability of mycophenolate mofetil (MMF) in patients with systemic lupus erythematosus (SLE) resistant to other immunosuppressive therapy. METHODS: Records of 93 patients with SLE were retrospectively reviewed. Seven patients were excluded. The remaining 86 patients received other immunosuppressive drugs before MMF. Efficacy was measured by changes in daily oral prednisolone dose, European Consensus Lupus Activity Measurement Index (ECLAM), erythrocyte sedimentation rate (ESR), C-reactive protein, and dsDNA antibody titer. In renal patients, changes in serum creatinine, creatinine clearance, chromium-51 EDTA glomerular filtration rate (EDTA-GFR), and 24 hour urine protein excretion were also evaluated. RESULTS: Indications for MMF were mainly renal involvement (59% of patients), uncontrolled disease activity (14%), and other SLE related manifestations (13%). Overall, we found a significant reduction in the steroid dosage, ECLAM, ESR, and anti-dsDNA antibody titer. Renal patients (n = 35) showed a significant reduction in urinary 24 hour protein excretion. Levels of serum creatinine, creatinine clearance, and EDTA-GFR showed no significant change during treatment. Thirty-seven patients (42.8%) developed adverse events. Gastrointestinal intolerance in 25 (29%) and infections in 20 (23.2%) were the most frequent. The drug was discontinued in 14 (16.3%) patients due to side effects and 6 patients discontinued MMF because they achieved disease remission and were trying to conceive. MMF was stopped due to lack of efficacy in 12 patients. CONCLUSION: Our data suggest that MMF is a good therapeutic alternative for patients with SLE and renal involvement or refractory disease activity.