Autoimmune diseases occur when the body’s defense mechanism mistakenly produces antibodies against some part of the body itself. For most of us, for most of the time, antibodies are helpful. They are usually produced in response to foreign material (such as bacteria or viruses), allowing the body to quickly recognize the problem, and activate defense mechanisms. When antibodies are mistakenly produced against something that is part of our body, those same defense mechanisms are again activated, but this time our own body is attacked. A wide variety of diseases can result, including arthritis or inflammatory bowel disease.
In autoimmune hemolytic anemia, antibodies are produced against red blood cells, meaning these are targeted and destroyed (or hemolysed) and the patient becomes anemic. Depending on how rapidly anemia develops, a patient’s symptoms may vary. Someone who experiences a very rapid drop in haemoglobin may feel short of breath, dizzy and may even develop heart failure. More commonly in AHI, the anemia develops over a longer period, meaning patients will be more non-specifically unwell; they may feel very tired, be pale or perhaps jaundiced (caused by the liver becoming overloaded trying to process and excrete large numbers of hemolyse blood cells) and will often have an intermittent fever.
AHIA is rare, affecting one to three people per 100,000 each year . It seems to be even rarer in children, with the highest reported prevalence being 1 per 100,000, and many reports suggesting fewer children are affected . Cases may be either primary – where the disease occurs without any other conditions – or secondary to conditions including leukaemia or some infections.
Disease differences in children
AHIA in children can affect any age-group, younger children seem to suffer more with a rapid disease onset, whereas teenagers more commonly present with a chronic condition. In general, younger children will have a lower haemoglobin level at presentation – with the average being somewhere around 6 g/dl. Most children will present with a non-specific illness, often including a fever, lasting a few weeks to months running up to the diagnosis.
Much remains to be discovered about childhood autoimmune anemia, with some papers suggesting primary disease (where AHIA occurs alone, without any obvious trigger or associated disease) is most common, and others suggesting AHIA secondary to infection is more likely. The largest observational study on the disease comes from a French National Register. In 2011 they reported on 265 children who had been entered into a National database . They found that patients presented at an average of around 4 years of age and 15% of patients had a family history of immunological disease. 37% of patients had primary AHI, and 15% developed the disease following an infection. 37% of children were found to have Evans’ syndrome – where AHIA is found alongside immune thrombocytic purpura (ITP) – another autoimmune disease, where antibodies target the platelets, meaning blood does not clot as well as it ought to.
Children’s response to treatment
Treatment for AHI in children (similarly to adults) is based mostly on experience rather than large medical trials. Most children will receive steroids as the primary treatment. These act to generally ‘damp-down’ the immune system, so reduce the production of auto-antibodies and allow the patient to recover. Most children will respond to steroid treatment, with most studies showing over 80% success rates [2,3,4]. Steroids tend to be given in high doses until a response is seen. Response is variably defined, although a rise in haemoglobin, and achieving a level over 8-10 g/dl of haemoglobin is often used. Once a response is achieved, or after high doses have been given for 2 weeks, the dose starts to be slowly weaned. Particularly in children, it is important not to give high dose steroids for too long, as side-effects including weight gain, mood swings, thinning of the bones and effects on growth may be seen if the medication is continued for too long. However, this needs to be balanced against the knowledge that patients are more likely to experience a relapse of AHI if steroids are stopped too quickly. Patients seem to do better if steroids are continued for at least 6 months.
In patients who do not respond, or in those whose condition relapses, additional treatment is sometimes needed. Various options exist, and the evidence is really not there to support one or the other. Some centres use cyclosporin A – a powerful immune suppressant, more routinely used for example following organ transplantation. Where this has been used, good results have been reported . However, given the condition is rare, and most children respond well to first-line steroid treatment, numbers tend to be too small to confidently assess its efficacy. Data from adult series suggest that perhaps cyclosporin works best when used in combination with steroids, and may help prevent relapses.
In other children, a splenectomy is carried out to help treat their AHIA. Particularly in young children, this needs to be undertaken with caution since removing the spleen leaves children vulnerable to infections from encapsulated bacteria. Some centres will also use intravenous immunoglobulin or rituximab as ‘rescue therapy’ for patients not responding to steroids, or after a relapse [2,3].
Although most children will respond well to steroid treatment, a significant number will suffer from disease relapses. It remains difficult to predict who will do well, and who might need more intensive treatment. The French report noted that a particular combination of antibodies present at diagnosis (IgG/IgG+C3d) was more likely to result in a difficult clinical course, although this was far from certain .
Despite a good initial response rate, a significant proportion of children will suffer a relapse of their disease, or go on to need second-line treatment. At a median follow-up of 3 years, the French report found only 39% of patients were in complete continuous remission. Good supportive care means the risk of non-survival is low, at 4% .
It is clear that much remains to be learned about this rare condition in children. Given the small number of cases, large national reports, or even multi-national collaborative databases would help to build a more accurate picture of the problem. This may perhaps allow accurate identification of which children are likely to need second-line treatment, so it might be introduced earlier and result in a more rapid result for the patient and their family.
 Autoimmune hemolytic anemia. Gehrs BC, Friedberg RC. Am J Hematol. 2002 Apr;69(4):258-71.
 New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children. Aladjidi N, Leverger G, Leblanc T, et al. Haematologica. 2011 May;96(5):655-63.
 Autoimmune Hemolytic Anemia in Children: Mayo Clinic Experience. Sankaran J, Rodriguez V, Jacob EK, Kreuter JD, Go RS. J Pediatr Hematol Oncol. 2016 Apr;38(3):e120-4.
 Autoimmune hemolytic anemia in children. Naithani R, Agrawal N, Mahapatra M, Kumar R, Pati HP, Choudhry VP. Pediatr Hematol Oncol. 2007 Jun;24(4):309-15.