Grand Rounds

Cold agglutinin syndrome associated with a pediatric severe systemic Mycoplasma pneumoniae infection

Sara Geitoeira¹, Inês Paiva Ferreira², Ana Lachado³, Lurdes Morais⁴, Paula Cristina Fernandes⁵, Emília Costa³, Esmeralda Cleto³, Isabel Couto Guerra^3
1Pediatrics, Unidade Local de Saúde de Viseu Dão-Lafões, Viseu, Portugal, ²Pediatrics, Unidade Local de Saúde do Tâmega e Sousa, Penafiel, Portugal, ³Pediatric Hematology, Unidade Local de Saúde de Santo António, Porto, Portugal, ⁴Pediatric Pneumology, Unidade Local de Saúde de Santo António, Porto, Portugal, ⁵Pediatric Intensive Care Unit, Unidade Local de Saúde de Santo António, Porto, Portugal

Address for Correspondence: Sara Geitoeira, Rua Tenente Valadim, 161, 1º posterior, 4400-325 Vila Nova de Gaia, Portugal. Email: sarageitoeira@hotmail.com

Keywords: autoimmune hemolytic anemia, cold agglutinin syndrome, cold agglutinins, Mycoplasma pneunomiae

Clinical Problem:
A healthy 14-year-old boy presented to the emergency department with a 3-day history of fever, dry cough, sore throat and dizziness. On physical examination, peripheral oxygen saturation was 84% (FiO2 0,21), he had a moderate respiratory effort and breathing sounds were decreased on the left lung’s base. A complete blood count (CBC) revealed a normal hemoglobin (16,1 g/dL), lymphopenia (470/µL) and mild thrombocytopenia (118000/µL), and C-reactive protein (CRP) was 291 mg/L. Chest radiograph showed a hypotransparency in the lower 2/3 of the left hemithorax. After ultrasound confirmation of pleural effusion, thoracocentesis was performed, draining 250 ml of serohematic fluid. Bacteriological study of the pleural effusion was negative and nasopharyngeal aspirate did not reveal any respiratory viruses. The patient was admitted to the pediatric ward (PW) and started treatment with intravenous ceftriaxone and clindamycin. By day 3, due to persistent fever and increasing oxygen requirements, vancomycin was added. On the following day, due to the need for noninvasive ventilation, he was transferred to Pediatric Intensive Care Unit (PICU). Previously ordered Mycoplasma pneumonia (MP) PCR test result was positive, so clindamycin was replaced by azithromycin. Nevertheless, fever persisted after a 5-day course of azithromycin and it was decided to start levofloxacin because of possible macrolide resistance. By day 9 in PICU, clinical improvement was observed and he was transferred to the PW. By day 3 in this ward, the patient was afebrile and with no supplemental oxygen need. However, looking at the several CBCs that had been done since admission, a progressive decrease in hemoglobin was noted (16,1 g/dL to 8,2 g/dL) with de novo erythrocyte agglutination in peripheral blood smear (PBS). There was a reticulocyte count of 84000/uL (3,18%) and TGO and DHL were elevated for the first time since hospital admission (131 U/L and 407 U/L, respectively), with normal total bilirubin. The direct antiglobulin test (DAT) was positive (4+), monospecific for the complement component C3d and anti-I IgM autoantibody was identified. Therefore, management started with cold avoidance (room temperature and intravenous solutions at 37ºC and heated food). An improvement was observed, with hemoglobin level of 10,9 g/dL 9 days later, with reticulocytosis. TGO and LDH also returned to normal levels. Globally, he completed an antibiotic regimen of ceftriaxone (10 days), clindamycin (3 days), vancomycin (8 days), azithromycin (5 days) and levofloxacin (10 days). The patient was discharged after a 25-day hospital stay, with positive DAT. Cold avoidance measures were kept at home until negative DAT obtained, three months later. He had normal CBC three weeks after CAS diagnosis. Ten months later, chest radiograph was normal and he had occasional dry cough, with no other respiratory complaints.

Which anemia should be suspected of when approaching this Mycoplasma pneumoniae infection and how can it be treated?