RECURRENT ANTI–GLOMERULAR BASEMENT MEMBRANE GLOMERULONEPHRITIS IN A PATIENT WITH HISTORY OF SPLENECTOMY FOR IMMUNE THROMBOCYTOPENIC PURPURA: A CASE SUGGESTING LONG-STANDING IMPACTS OF SPLENECTOMY

A 64-year-old woman with a history of immune thrombocytopenic purpura (ITP) treated by splenectomy and prior aseptic meningitis presented with intermittent fever (Tmax 38.9 °C), malaise, headache, and diffuse myalgia lasting for over ten days. Despite an extensive fever work-up, no infectious or malignant etiology was identified. Laboratory findings showed only leukocytosis (WBC 12,000/μL) and elevated CRP (17 mg/dL), while urinalysis initially revealed no proteinuria or hematuria. However, during the subsequent three weeks, persistent fever prompted repeat testing, which showed newly developed microscopic hematuria (10–19 RBC/HPF), mild proteinuria (0.3 g/gCr), and a positive anti-glomerular basement membrane (anti-GBM) antibody (16.0 U/mL).

 Her serum creatinine at that time was 0.67 mg/dL. Renal biopsy demonstrated crescentic glomerulonephritis consistent with anti-GBM glomerulonephritis—14 of 25 glomeruli exhibited cellular crescents with linear IgG deposition along the GBM. The patient was treated with high-dose methylprednisolone pulse, additional oral prednisolone, plasma exchange (25 sessions total), and cyclophosphamide (POCY), but the anti-GBM titer remained persistently elevated; Rituximab (RTX) was subsequently initiated one month after the initiation of treatment. After that, her serum creatinine (peak 2.24 mg/dL) gradually improved, and the anti-GBM antibody titer decreased and became undetectable by four months. There was no evidence of pulmonary hemorrhage or alveolar involvement throughout the course.

Six months after the disappearance of anti-GBM antibody, the patient developed intermittent fever, bilateral ankle pain, and fatigue, when her prednisolone prescription was tapered from 5 mg to 4 mg/day. Within three weeks of the appearance of these symptoms, the anti-GBM antibody titer rose to 73.4 U/mL, and subsequently to 169 U/mL one week later. Serum creatinine again began to rise acutely. Despite the absence of worsening of hematuria or proteinuria, disease relapse was suspected, and treatment was promptly restarted with steroid pulse, plasma exchange, and rituximab, leading to a decrease in both antibody titer and creatinine levels (Figure 1).

Accessory spleen was not detected with images. Due to her status of post-splenectomy and exposures to immunosuppressants, careful prevention and monitoring of Overwhelming Post Splenectomy Infection (OPSI) was planned. 

Recurrence of anti-GBM glomerulonephritis after the disappearance of antibody is exceptionally rare, with a global recurrence rate below 5%. Recurrence is thought to be associated with ongoing antigen exposure, smoking, coexisting autoimmune diseases, and infectious triggers. In this case, the patient’s background of ITP and aseptic meningitis suggests a predisposition to autoimmunity. Notably, her splenectomy history could not prevent the recurrence of anti-GBM glomerulonephritis, although the splenectomy had been considered to be an option for refractory antibody mediated auto-immune diseases, like ITP, autoimmune hemolytic anemia (AIHA), and myasthenia gravis.

Despite initial refractoriness to standard therapy, the patient showed a rapid serologic and clinical response to rituximab, consistent with B-cell–driven disease activity. Repeated plasma exchange was required to accelerate antibody clearance, highlighting the necessity of individualized immunosuppressive sequencing in refractory or relapsing cases and in patients with a history of splenectomy.

This case underscores three clinically important observations:

1.           Recurrence despite initial remission can occur even in the absence of active urinary findings, suggesting that serologic monitoring may be crucial after treatment cessation.

2.           Rituximab can be effective for both initial refractory anti-GBM disease and relapse, and it can be used even when a patient received splenectomy or cumulative toxicity is a concern.

3.           The coexistence of anti-GBM disease and ITP history may represent shared autoimmune susceptibility. Splenectomy, by altering immune homeostasis and long-term B-cell regulation, could not prevent recurrence of anti-GBM disease and could have further contributed to the risk of secondary autoantibody formation.

We report what appears to be the first documented case of recurrent anti-GBM nephropathy in a patient with prior immune thrombocytopenic purpura treated by splenectomy. This case suggests that:

•             immune dysregulation following splenectomy may predispose to secondary autoimmune diseases, and it could not prevent a recurrence of anti-GBM disease

•             rituximab should be considered early in cases with aggressive or relapsing serologic activity even when a patient received splenectomy.

Meticulous planning to minimize immunosuppressants while controlling the severe autoimmune disease is mandatory to prevent the patient from having OPSI. Further studies are warranted to clarify the effectiveness and safety of Rituximab in patients with a history of splenectomy. Establishment of long-term strategies for relapse monitoring for anti-GBM diseases in such autoimmune-prone patients is also essential.