Cold autoimmune haemolytic anaemia (Cold AIHA) is a rare autoimmune disorder associated with either primary a-clonal B-cell lymphoproliferation condition (cold agglutinin disease or CAD) or secondary cold agglutinin syndrome (CAS). Its unresponsiveness to steroids complicates treatment decisions in limited-resource health facilities. A 54-year-old female was diagnosed with AIHA in March 2025 and received treatment of cyclosporin 2x50 mg and methylprednisolone 32 mg/ day without satisfactory responses. Monospecific antigen detected a positive anti-C3d and negative anti-IgG. Reactive cold agglutinin with a titer of 1/16 was detected at a temperature of 20 °C. After 2 months of combination treatment with steroid, cyclosporin, and mycophenolate mofetil, the patient failed to show any responses and reported adverse effect of steroid. A chest CT scan showed nodule in the apical lobe of the right lung. GeneXpert examination from bronchoalveolar lavage showed a trace of Mycobacterium tuberculosis. She was started on antituberculosis treatment. Bone marrow aspiration showed no evidence of cold agglutinin-associated lymphoproliferative disease. Corticosteroid was then discontinued, and the patient received rituximab 375 mg/m2 IV weekly in combination with mycophenolate mofetil 2 x 500 mg and cyclosporin 2 x 50 mg. The cold agglutinin syndromes should raise suspicion of hidden chronic infection or malignancy. This Patient had severe anaemia, evidence of haemolysis, and a positive direct antiglobulin test (DAT). Positive result of anti-C3d and negative anti-IgG concluded as a Cold AIHA. Corticosteroids are ineffective in most cases and are often associated with unacceptable toxicity. The use of rituximab is associated with a 45%–60% response rate, lasting approximately 12 months. Tuberculosis is rarely reported as a comorbid infection related to CAS. Diagnosis and management of cold AIHA are challenging, especially in the setting with limited resources. Secondary conditions, such as infection, malignancy, or autoimmunity, should always be taken into account in managing cold AIHA.
Alfath et al. (Wed,) studied this question.
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