M Y Karim

Mycophenolate mofetil as a treatment for autoimmune haemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome

Unresponsive autoimmune haemolytic anaemia (AIHA) may require therapy with second-line drugs. There is no consensusthat any one of these agents is more effectivethan another. Mycophenolatemofetil (MMF) is an immunosuppressivedrug proven to be effectivein reducing renal allograftrejectionas well as being used in autoimmune diseases including systemic lupus erythematosus (SLE). We describe its use in two patients who were treated with MMF for AIHA in the context of underlying SLE and antiphospholipid syndrome (APS). The patients showed a good response to treatment with MMF, suggesting a possible role in the treatment of AIHA.

Update on immunotherapy for systemic lupus erythematosus—what's hot and what's not!

There have been significant advances in the treatment of SLE, which have produced major impacts on morbidity and in some cases mortality. The major drugs of the last three decades in treatment of SLE have been corticosteroids, AZA, MTX and cyclophosphamide. However, these drugs have considerable toxicities, and with the increasing knowledge of the immune system, and further understanding of SLE immunopathogenesis, many groups are seeking to identify and trial novel immunotherapeutic strategies. These have included therapies aimed at influencing particular immune cells (e.g. B cells) and molecules (e.g. costimulatory molecules, cytokines) which are thought to be important in disease pathogenesis. The advantage of such therapies is that efficacy may be achieved with lower toxicity, and without wide-ranging suppression of the immune system. Success has not always been achieved by specific design of immunotherapies for SLE, and the best recent example has been the use of B-cell depletion therapy, a concept derived from its successful use in RA. In this article, we discuss those immunotherapeutic strategies that have arrived as far as clinical trials in human subjects. In addition to these relatively specific immunotherapies, we also highlight the use of mycophenolate mofetil, an anti-proliferative immunosuppressant which has had good success over the last 10 yrs, with similar early efficacy to cyclophosphamide when used as induction therapy for lupus nephritis. Data are presented on more generalized immune strategies, such as the use of stem cell transplantation and intravenous immunoglobulin.

Update on therapy - thalidomide in the treatment of lupus

Thalidomide has been shown to be an effective treatment for cutaneous forms of lupus erythematous refractory to other therapies. Thalidomide has very serious side effects, including teratogenicity and neuropathy, which limit its clinical use in lupus to such severe refractory cases. Efficacy has been confirmed in several studies, although recurrence after discontinuation of treatment is frequent. More recent experience suggests that lower doses than originally used may be effective, which may result in a reduction in side effects. Much effort has been expended in studying the mechanisms of action of thalidomide, although as yet it is unclear which of the mechanisms identified to date contribute to its efficacy in treating cutaneous forms of lupus erythematosus. Identification of patients suitable for thalidomide therapy requires a rigorous selection process. Potential side effects should be clearly explained, particularly teratogenicity as many patients are young women. Written consent and a negative pregnancy test must be obtained prior to commencement of therapy. Reliable contraceptive measures should be strictly observed by patients taking thalidomide. Close clinical and neurophysiological supervision using nerve conduction studies should be undertaken.

Management of infection in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by abnormal autoantibody production and clearance. This immunological background has been suggested to play a role in the susceptibility of SLE patients to infection. Moreover, drugs (most of them immunosuppressive or immunomodulating agents) used in the treatment of moderate and severe lupus give rise to a tendency for infections, including opportunistic ones. Infections may mimic the exacerbations of SLE, leading to confusion over the diagnosis and appropriate treatment. Despite increased awareness of this problem, infections remain a major source of morbidity and mortality in SLE. There are various strategies which can be applied to try and reduce the risk of infection in SLE patients. Options include vaccinations, antibiotic/antiviral prophylaxis and intravenous immunoglobulins.

Management of hypogammaglobulinaemia occurring in patients with systemic lupus erythematosus

OBJECTIVES Systemic lupus erythematosus (SLE) is typically associated with hypergammaglobulinaemia but has been described in the setting of hypogammaglobulinaemia as well. The purpose of this article is to describe various cases of SLE and hypogammaglobulinaemia, review the literature and present management strategies for hypogammaglobulinaemia in SLE. METHODS We describe five patients with SLE and antibody deficiency, and review the literature exploring the relationship between the two. RESULTS Various types of antibody deficiency syndromes, including common variable immunodeficiency (CVID), IgA deficiency, IgM deficiency, drug-induced hypogammaglobulinaemia and hypogammaglobulinaemia secondary to nephrotic syndrome can occur in SLE. Antibody deficiency states can be treated with antibiotics and replacement immunoglobulin therapy (particularly CVID) but sometimes close monitoring is all that is required. CONCLUSION Measurement of immunoglobulin levels is useful in SLE to identify coexisting antibody deficiency and the later development of hypogammaglobulinaemia. This allows monitoring and appropriate treatment to be instituted.

Hypertension as the presenting feature of the antiphospholipid syndrome

The antiphospholipid or Hughes syndrome is the association between antiphospholipid antibodies (aPL), venous and arterial thromboses and pregnancy morbidity.1 Antiphospholipid syndrome (APS) commonly coexists with autoimmune diseases usually systemic lupus erythematosus (SLE), when it is known as secondary APS. When present in isolation it is known as primary APS (PAPS). Although the kidney may be affected in APS, its involvement is perhaps not as well described as that of other organs. Thrombotic microangiopathy (TMA) affecting the kidney has been reported as a manifestation in both primary and secondary APS. This report describes hypertension related to underlying renal TMA as a presenting symptom of APS.

Clinical importance of autoantibodies in lupus nephritis

Renal involvement is a serious clinical feature of systemic lupus erythematosus and can present at any stage of the disease. Although its treatment and outcome have improved, lupus nephritis is still a major contributor to morbidity. Autoantibodies, particularly those directed toward nuclear antigens, are a major feature of systemic lupus erythematosus. With respect to nephritis, there are several aspects of lupus autoantibodies that merit attention, including their use in diagnosis and monitoring, and their role in pathogenesis. Anti-dsDNA antibodies are well known, but other important autoantibodies include anti-C1q, antinucleosomal and antiactinin. There has also been interesting work on the relationship of antiphospholipid antibodies with renal disease.