Correspondence

Clinical Problem-Solving: Assembling a Coherent Story

N Engl J Med 1994; 330:1618June 2, 1994

Article

To the Editor:

In their Clinical Problem-Solving article (Jan. 6 issue),1 Oren and Matzner describe a 44-year-old man who apparently had Epstein-Barr virus (EBV) hepatitis, pure red-cell aplasia, and infectious endocarditis due to Haemophilus parainfluenzae1. Since the patient had no overt immunocompromise, the authors propose that the EBV infection was the event that precipitated the red-cell aplasia and endocarditis. They mention other possibilities, including T-cell leukemia. They invite alternative hypotheses.

Although the pathophysiologic chain of events proposed by the authors may be most reasonable, I would like to offer another hypothesis for consideration. Given the information provided, I believe a thymoma is worth considering as an explanation. Thymoma is the most common cause of pure red-cell aplasia, accounting for up to 50 percent of cases2. The authors state that the patient's “hemoglobin level . . . returned to normal,” although the precise length of time it took to do so is not stated. Spontaneous remission of thymoma-associated pure red-cell aplasia is known to occur3.

Thymoma is associated with deficits in both humoral and cell-mediated immunity. There are ample reports documenting the occurrence of a variety of serious opportunistic infections in patients with thymoma who have associated hypogammaglobulinemia (Good's syndrome), including recurrent sinusitis, bronchopneumonia, various forms of viral hepatitis (including that due to herpesviruses), mucocutaneous candidiasis, and bronchiectasis4.

The report states that a chest film showed only bilateral pleural effusions. Thymomas may be missed on routine chest films. One study found that routine posteroanterior and lateral chest roentgenograms had a sensitivity of only 50 percent in detecting thymomas5.

Thymoma is therefore a reasonable alternative explanation for the red-cell aplasia and unusual infections in the patient. It is not uncommon for patients to have more than one parathymic syndrome concurrently. This would have been a particularly relevant consideration during the time the patient had pure red-cell aplasia and unusual infections. Was a computed tomographic scan of the chest, which detects nearly 100 percent of thymomas, obtained at any point during the patient's illness?

Manfred Hauben, M.D., M.P.H.
Sterling Winthrop, New York, NY 10016

5 References

1. 1

   Oren R, Matzner Y. Assembling a coherent story. N Engl J Med 1994;330:48-50
   Full Text | Web of Science | Medline

2. 2

   Verstandig AG, Epstein DM, Miller WT Jr, Aronchik JA, Gefter WB, Miller WT. Thymoma -- report of 71 cases and a review. Crit Rev Diagn Imaging 1992;33:201-230
   Medline

3. 3

   Ito M, Imoto S, Nakagawa T, Murotani A, Tsubota N. Spontaneous remission in pure red cell aplasia associated with thymoma. Int J Hematol 1991;54:209-212
   Web of Science | Medline

4. 4

   Fox MA, Lynch DA, Make BJ. Thymoma with hypogammaglobulinemia (Good's syndrome): an unusual cause of bronchiectasis. AJR Am J Roentgenol 1992;158:1229-1230
   Web of Science | Medline

5. 5

   Ellis K, Austin JH, Jaretzki A III. Radiologic detection of thymoma in patients with myasthenia gravis. AJR Am J Roentgenol 1988;151:873-881
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We know that the patient did not have thymoma because he underwent open-heart surgery and a mass was not found. Although Dr. Hauben is correct in raising the possibility of thymoma in a patient with pure red-cell aplasia, we did not consider this diagnosis for several reasons. First, a computed tomographic scan obtained before the operation revealed no masses. Second, an immune deficiency state was not suspected at the time pure red-cell aplasia was diagnosed. Third, the return of the patient's hemoglobin level to normal within two weeks after the mitral-valve replacement could not be attributed to spontaneous remission of thymoma, an extremely rare event. Fourth, the so-called immune deficiency resolved either after surgery and appropriate antibiotic therapy or after the resolution of the EBV infection. We are not aware that immune deficiency is reversible in patients with a thymoma. Finally, no mass was found in the mediastinum when the patient had open-heart surgery.

In summary, though thymoma is an interesting possibility in the differential diagnosis of pure red-cell aplasia and recurrent infections, we believe that the above-mentioned data and the clinical course did not support its presence in this case.

Ran Oren, M.D.
Yaacov Matzner, M.D.
Hadassah University Hospital, Jerusalem, Israel 91240