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We read with great interest the leader by Gilliland and Tsokos on the prophylactic use of antibiotics and immunisation in systemic lupus erythematosus (SLE).1 We strongly agree that prophylactic treatment against tuberculosis should be considered in certain groups of patients with SLE, and in particular that co-trimoxazole prophylaxis should be used in patients receiving potent cytotoxic treatment such as cyclophosphamide.
However, the important relationship between hypocomplementaemia, splenic dysfunction, and infection in SLE should also be emphasised. In Western countries, pyogenic infection in SLE is a major cause of morbidity and mortality.2 Infection with Streptococcus pneumoniae and Neisseria meningitidis appears to be particularly important.3–5 We have recently seen in our unit six patients with SLE who died in the past five years. Of these, five had overwhelming infection with S pneumoniae.
Defective clearance of bacteria by the spleen as a result of functional hyposplenism is likely to be the cause of the increased risk of infection with S pneumoniae and N meningitidis in SLE. Corticosteroids and other immunosuppressive drugs are also likely to play a part. The spleen is important in the clearance of particulate immune complexes, such as bacteria opsonised with antibody and complement component C3. Its unique microvascular anatomy and perisinusoidal macrophages bearing Fc and complement receptors are essential in this process. Defective splenic clearance of particulate immune complexes has previously been seen in SLE.6 Furthermore, patients with SLE often have chronic hypocomplementaemia, even when their disease is inactive, with low levels of C3 and C4 resulting in defective opsonisation of immune complexes. This, together with an acquired reduction in levels of complement receptor type 1 on the surface of erythrocytes, impairs delivery of immune complexes to the spleen.
Also important to mention, although only representing a small group of patients with SLE, are those with homozygous deficiencies of early components of the classical complement pathway. Not only do these deficiencies predispose to the development of SLE but they also increase the risk of infection. For example, among 41 patients with C1q deficiency, 13 had recurrent bacterial infections, including meningitis and pneumonia.7 Complement is known to have a vital role in host defence against infection, and may also be important in the processing of Gram negative organisms.8 Gram negative infection is also an important cause of death in certain cohorts of patients with SLE.9
An increased risk of infection with S pneumoniae, N meningitidis, and Haemophilus influenzae type B is also seen after surgical splenectomy. Such patients should receive lifelong prophylaxis with penicillin V and immunisation with pneumococcal polysaccharide vaccine. Children and adults with asplenia or severe splenic dysfunction due, for example, to coeliac disease, should also receive a single dose of H influenzae type B vaccine. We have previously recommended that patients with SLE and chronic hypocomplementaemia should also receive similar prophylaxis10 and wish to reiterate the importance of these measures in order to prevent life threatening infection in this disease.
We appreciate the opportunity to respond to comments generated by our leader entitled “Prophylactic use of antibiotics and immunisations in patients with systemic lupus erythematosus”. Hepburn and Davies address several important issues about the prophylactic use of antibiotics in treating patients with systemic lupus erythematosus (SLE) who also have hypocomplementaemia or functional asplenia, or both. They suggest that the increased incidence of infections with encapsulated organisms in patients with SLE is related to defective clearance secondary to functional hyposplenism, immunosuppressive treatment, and defective opsonisation. All these potential explanations seem plausible, but it is important to note that not all patients with SLE and neisserial infections are receiving immunosuppressive agents at the time of their infection.1
As emphasised in our article, we agree that it is important to recognise cohorts of patients who are at risk of developing certain infections.2 However, in the case of neisserial infections, the evidence to support prophylactic antibiotics for patients with SLE and hypocomplementaemia is not clear. In a small case series of patients with SLE and neisserial infections, Mitchell and colleagues suggested the following possible risk factors: female sex, young age, renal disease, and persistent hypocomplementaemia.1 Although it is clear that in children with haemoglobinopathies and splenic dysfunction who receive oral penicillin prophylaxis, pneumococcal bacteraemia is reduced dramatically,3 little information supports the use of this strategy in asplenic adults.4
In summary, optimal strategies to decrease the incidence of infections should remain a priority for all doctors caring for patients with SLE. However, in those who are asplenic, we reiterate the importance of vaccinations against pneumococcus and Haemophilus influenzae type B. Currently, no data support the role of prophylactic penicillin or other antibiotics in patients with SLE who are asplenic or have persistent hypocomplementaemia, but this should be further investigated with more definitive studies. For now, the best approach for doctors caring for patients with SLE is to immunise them with appropriate vaccinations, consider antibiotic prophylaxis in certain situations, and maintain a high degree of awareness for the diagnosis of bacteria and other pathogens, especially those that are prevalent in the community in which you care for the patients.
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