Sideroblastische Anämie

The sideroblastic anaemias are a heterogeneous group of inherited and acquired disorders characterised by anaemia of varying severity and the presence of ring sideroblasts in the bone marrow¹. Sideroblastic anaemia is characterised by isolated erythroid dysplasia with <5% blasts and at least 15% ringed sideroblasts in the bone marrow². The International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) has recommended that ring sideroblasts be defined as erythroblasts in which there is a minimum of five siderotic granules covering at least one third of the circumference of the nucleus³.

The sideroblasts form due to reduced haemoglobin synthesis, resulting in the accumulation of iron within red blood cell precursors. Cases may be congenital or acquired. Cases are more often acquired and sometimes represent a stage in the development of myelodysplastic syndromes (MDS).

Epidemiologie

Refractory anaemia with ringed sideroblasts (RARS) may account for 5-15% of all MDS cases⁴.

Ätiologie

Kongenital

• The most common inherited sideroblastic anaemia is X-linked sideroblastic anaemia (XLSA) caused by mutations of the erythroid-specific delta-aminolevulinic acid synthase 2 gene (ALAS2)⁵. Sideroblastic anaemia due to SLC25A38 gene mutations is the next most common inherited sideroblastic anaemia.⁶⁷.

• Congenital causes of sideroblastic anaemia also include Wolfram's syndrome. There are two types, each caused by a genetic error on a different chromasome. Wolfram's syndrome 1 is characterised by DIDMOAD (= DDiabetes Wnsipidus, DDiabetes Mellitus, Optic Atrophy and Deafness). Wolfram's syndrome 2 is characterised by early optic atrophy, diabetes mellitus, deafness, decreased lifespan but not diabetes insipidus⁸.

Erworben

In addition to MDS, sideroblastic anaemia can also occur in other bone marrow diseases including:

• Myelom

• Polycythaemia rubra vera

• Myelosclerosis

• Leukaemias

Secondary causes include⁹:

• Inflammatory conditions - eg, rheumatoid arthritis.

• Systemic lupus erythematosus.

• Chronic infections.

• Drug toxicity - eg, chloramphenicol, cycloserine, antituberculous agents.

• Chronischer Alkoholismus.

• Hämolytische Anämie.

• Nutritional deficiencies - eg, copper, vitamin B6; malabsorption syndromes.

• Hypothyreose.

• Unterkühlung.

• Lead poisoning.

• Zinc overdose.

• Hämodialyse⁵.

• Schwangerschaft.

Präsentation

• Clinical features are those related to anaemia in general. Symptoms reflect the cytopenias, ie anaemia, infection, bruising and haemorrhage.

• There are no specific signs or symptoms related to sideroblastic anaemia alone.

Untersuchungen¹¹⁰

Diagnosis is made from bone marrow examination demonstrating the presence of ring sideroblasts with a generalised increase in iron stores.

• FBC usually shows a moderate degree of anaemia.

• The mean corpuscular volume (MCV) is normal or increased, but can be low.

• High serum iron and transferrin saturation also occur.

• The blood film shows a dimorphic population of both normal and hypochromic red blood cells.

Behandlung¹

Allgemeine Maßnahmen

• Treatment is mainly supportive.

• Red cell transfusion is given for symptomatic anaemia.

• Iron chelation with desferrioxamine should be considered after 20-25 units of red cells have been received.

• Avoid alcohol and reduce vitamin C intake, as these increase iron absorption¹¹.

Pharmakologisch

• The use of recombinant erythropoietin (EPO) and granulocyte colony-stimulating factor has been demonstrated to reduce symptoms and may also increase survival¹².

• Patients with hereditary sideroblastic anaemia may respond to pyridoxine¹².

• Ciclosporin has been shown to give a response rate (ie alteration of disease progression or remission) of 62.5% in patients with MDS including sideroblastic anaemia¹³.

• Emerging therapies include the use of the hypomethylating agents decitabine and azacitidine and the immunomodulatory drugs lenalidomide and azacitidine¹⁴.

Chirurgisch

• Allogenic peripheral stem cell transplantation has been used with success in pyridoxine-refractory hereditary sideroblastic anaemia. Few patients are eligible for transplant¹.

Prognose⁹

• The prognosis is very variable.

• Reversible causes (eg, alcohol or drugs) appear to have no long-term effects if the underlying cause is successfully treated or removed.

• Patients continuing to need regular blood transfusions, those who have conditions unresponsive to treatment, and those with MDS often have a much worse prognosis.

• Patients with idiopathic sideroblastic anaemia and MDS have a median survival of 38 months. Those with pure sideroblastic anaemia (abnormal erythropoiesis only) have a median survival of 60 months.

• Favourable prognostic indicators include thrombocytosis and needing fewer blood transfusions¹⁵.

• Causes of death include haemochromatosis, resulting from transfusions, and leukaemia.