What is the best initial management for a patient with Mycoplasma pneumonia who developed jaundice, anemia, elevated reticulocyte count, and low haptoglobin after starting antibiotics?

Management of Mycoplasma Pneumonia-Associated Autoimmune Hemolytic Anemia

Stop the antibiotic immediately and initiate high-dose corticosteroids (1-2 mg/kg/day prednisone or methylprednisolone) as first-line therapy for this patient with Mycoplasma pneumoniae-induced autoimmune hemolytic anemia (AIHA). 1

Clinical Reasoning

This patient presents with classic features of autoimmune hemolytic anemia triggered by Mycoplasma pneumoniae infection: jaundice, low hemoglobin, elevated reticulocytes (indicating bone marrow compensation), and low haptoglobin (indicating intravascular hemolysis). 2, 3, 4

Immediate Management Steps

First Priority: Discontinue the Antibiotic

• While the pneumonia itself requires treatment, the current antibiotic may be contributing to drug-induced immune hemolytic anemia (DIIHA), which can occur with common antibiotics including cephalosporins, penicillins, and trimethoprim-sulfamethoxazole. 1, 5
• Mycoplasma pneumoniae itself causes cold agglutinin-mediated hemolysis in up to 50% of cases, but antibiotics can compound this through independent mechanisms. 2, 3
• The timing (day 3 of antibiotics) is consistent with both Mycoplasma-associated AIHA and DIIHA. 5

Second Priority: Initiate Corticosteroids

• For Grade 3 autoimmune hemolytic anemia (Hgb <8.0 g/dL), guidelines recommend prednisone 1-2 mg/kg/day (oral or IV depending on severity). 1
• Corticosteroids are first-line therapy for warm autoimmune hemolytic anemia and have demonstrated efficacy in Mycoplasma-associated cases. 1, 2
• Methylprednisolone was successfully used in documented cases of Mycoplasma-associated hemolysis with complete recovery. 2, 5

Why NOT Rituximab as Initial Therapy

• Rituximab is reserved for refractory cases or prevention of additional alloantibody formation in patients requiring repeated transfusions. 1
• Guidelines recommend rituximab primarily for patients with chronic lymphocytic leukemia-associated AIHA or those who fail to respond to corticosteroids. 1
• There is insufficient evidence supporting rituximab as first-line therapy for Mycoplasma-associated AIHA. 1

Additional Management Considerations

Supportive Care:

• Transfuse packed red blood cells only if hemoglobin drops to life-threatening levels (<7-8 g/dL) or if symptomatic. 1
• Provide folic acid supplementation (1 mg daily) to support erythropoiesis. 1
• Maintain warm environment if cold agglutinins are present (common with Mycoplasma). 2, 3

Diagnostic Confirmation:

• Direct antiglobulin test (DAT/Coombs test) should be positive for IgG and/or C3d. 1, 2, 5
• Cold agglutinin titers are frequently elevated (often >1:512) in Mycoplasma-associated cases. 2, 3
• Peripheral smear typically shows spherocytes and may show agglutination. 5

Antibiotic Considerations:

• If continued antimicrobial therapy is needed for pneumonia, switch to a macrolide (azithromycin or clarithromycin) or a respiratory fluoroquinolone, as these are less commonly associated with DIIHA. 1
• Most Mycoplasma pneumoniae cases improve with 7-10 days of appropriate antibiotic therapy. 1

Escalation Criteria

Consider adding IVIG (0.4-1 g/kg/day for 3-5 days) if:

• No improvement within 72 hours of high-dose corticosteroids. 1
• Hemoglobin continues to drop despite steroid therapy. 1
• Patient develops life-threatening complications. 1

Consider rituximab (375 mg/m² weekly × 4 doses) only if:

• Patient fails both corticosteroids and IVIG. 1
• Hemolysis persists beyond 2 weeks of appropriate therapy. 1
• Patient requires repeated transfusions. 1

Critical Pitfalls to Avoid

• Do not delay corticosteroids while waiting for serologic confirmation—clinical presentation is sufficient to initiate therapy. 1
• Avoid excessive transfusions, as they can worsen hemolysis in some cases and should be reserved for symptomatic anemia or hemoglobin <7 g/dL. 1
• Do not use aminoglycosides if restarting antibiotics, as they have no role in Mycoplasma treatment and carry nephrotoxicity risk in the setting of hemoglobinuria. 1
• Monitor for thrombotic complications, as Mycoplasma-associated AIHA has been associated with arterial thrombosis in rare cases. 3

Monitoring Parameters

• Daily hemoglobin, reticulocyte count, LDH, and bilirubin until stabilized. 1, 4
• Repeat DAT at 4 weeks to confirm resolution. 5
• Monitor for steroid-related complications (hyperglycemia, infection risk). 1
• Assess renal function given risk of hemoglobin-induced acute tubular necrosis. 4