Ann Thorac Surg 2007;84:2095-2097. doi:10.1016/j.athoracsur.2007.06.070
© 2007 The Society of Thoracic Surgeons
Case Reports
Good Syndrome Coexisting With Leukopenia
Masatsugu Ohuchi, MDa,*,
Shuhei Inoue, MD, PhDa,
Jun Hanaoka, MD, PhDb,
Tomoyuki Igarashi, MDa,
Noriaki Tezuka, MD, PhDb,
Yoshitomo Ozaki, MD, PhDb,
Koji Teramoto, MD, PhDb
a Department of Thoracic Surgery, National Hospital Organization Shiga Hospital, Shiga, Japan
b Department of Thoracic Surgery, National University Corporation, Shiga University of Medical Science, Shiga, Japan
Accepted for publication June 25, 2007.
* Address correspondence to Dr Ohuchi, Department of Thoracic Surgery, National Hospital Organization Shiga Hospital, 255 Gochi-cho, Higashi-ohmi-shi, Shiga, 527-8505, Japan (Email: iky10{at}shiga-hp.jp).
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Abstract
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A 61-year-old man was admitted to our hospital for further examinations of a mediastinal mass. He had underwent an extended thymothymectomy, and had a tumor that was diagnosed as a type B1 thymoma, according to the World Health Organization. One year after surgery he was admitted again for recurrent diarrhea and pneumonia. Laboratory data revealed severe hypogammaglobulinemia with leukopenia. He was diagnosed with Good syndrome with leukopenia. Regular gamma globulin and figrastim injections were successful in keeping the patient symptom free. The prognosis of patients with Good syndrome and leukopenia is very poor; therefore, immediate diagnosis is important. The development of infectious diseases in a patient with thymoma or after the resection of thymoma mandates early and comprehensive immunologic investigation.
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Introduction
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Immunodeficiency with thymoma, which was described by Robert Good [1] in 1954, is a rare disorder and is commonly referred to as Good syndrome [1]. Today, it is classified as a primary immunodeficiency and is included under common variable immunodeficiencies. Immunologic deficits in Good syndrome affect both humoral and cellular immunity. The immunodeficiency manifests as recurrent sinopulmonary infections and occasional opportunistic infections. Certain patients with Good syndrome exhibit autoimmune conditions, such as pure red cell aplasia or hematological abnormalities (such as leukocytopenia), or both. We report a case of Good syndrome with leukopenia after thymothymectomy that was treated with intravenous immunoglobulin (IVIG) infusions and figrastim subcutaneous injections.
In February 2005 a 61-year-old man was admitted to our hospital for the examination of an anterior mediastinal mass (Fig 1). He was previously healthy; however, he presented with a history of cough with sputum production for 3 months. His total lymphocyte count was 4,904/mm3, the C-reactive protein level was high (7.03 mg/dL), and the anti-acetylcholine receptor antibody titer was positive (1.0 nmol/L). The serum gamma globulin level was normal. He was diagnosed with thymoma, and an extended thymothymectomy was performed. Histopathological examination revealed a World Health Organization type B1 Masaoka stage II spindle cell thymoma with a predominance of lymphocytes. He was discharged in good physical condition.
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Fig 1. Chest x-ray film in February 2005 revealed a mass shadow in the mediastinum. Chest computed tomographic scan in February 2006 revealed a right pleural effusion and infiltrative shadows in the left lower lobe. The clinical course of this patient exhibited the aggravation of infectious diseases corresponding to high levels of C-reactive protein (CRP) and decreased leukocyte counts. (IgG = immunoglobulin G; IVIG = intravenous immunoglobulin; RTx = radiation therapy; WBC = white blood cell count.)
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In February 2006 he was readmitted for recurrent diarrhea and pneumonia that had been present for 3 months. His body temperature was 38.9°C and his SpO
2 was 95%. A chest roentgenogram and a computed tomographic scan revealed a right pleural effusion and infiltrative shadows in the left lung field without the signs of recurrence of the thymoma. He was diagnosed with right pleuritis, pneumonia, and enterocolitis, and was treated with antibiotics. Although the symptoms of these disorders improved, meningitis, subcutaneous abscess, and oral fungal infection subsequently developed. With a decrease in the leukocyte count, the course of these disorders tended to deteriorate (Fig 1).
Laboratory data revealed hypogammaglobulinemia (216 mg/dL; normal, 704 to 1,685 mg/dL) with low levels of IgG (80 mg/dL; normal, 800 to 1,600 mg/dL), IgA (13 mg/dL; normal, 80 to 400 mg/dL), and IgM (5 mg/dL; normal, 50 to 180 mg/dL). The peripheral blood B lymphocyte count was low (0.1% of total lymphocytes), and the number of CD4+ T lymphocytes was 30.2% of the total lymphocytes with an inverted CD4/CD8 ratio of 0.49. A delayed-type hypersensitivity skin test for tuberculin purified protein derivative was negative. In vitro mitogen stimulation studies of the T cells revealed an extremely poor response to both phytohemagglutinin and concanavalin A. The pleural fluid cytology was negative. The examination of the aspirated bone marrow smears revealed mild hypercellularity and the deficiency of mature forms after the myelocytic stage. The serum tested negative for the human immunodeficiency virus.
As a result, the patient was diagnosed with Good syndrome concomitant with leukopenia. In March 2006, IVIG infusions and figrastim subcutaneous injections were initiated. The IVIG was administered to maintain serum immunoglobulin G levels greater than 500 mg/dL and figrastim to maintain the leukocyte count between 2,000 and 6,000/mm3. Consequently, his condition gradually improved, and he has been free from infection for more than 1 year.
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Comment
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At least 40% of the patients with thymoma suffer from various parathymic syndromes such as myasthenia gravis, pure red cell aplasia, and immunodeficiency [2]. The association of thymoma with immunodeficiency is called Good syndrome, and it is characterized by hypogammaglobulinemia, low or absent B cells in the peripheral blood, a low level of CD4± T cells, and an inversion of the CD4/CD8 ratio. It is reported that Good syndrome occurs in 4% to 12% of thymoma patients in Western countries and 0.2% to 0.3% of thymoma patients in Japan. In addition, some of the patients with Good syndrome often suffer from various types of immunodeficiencies such as leukopenia. In our patient, periodic leukopenia was manifested as a low B cell count, hypogammaglobulinemia, and T-cell deficiency. It was obvious that the aggravation of the infectious diseases concurred with the decreased leukocyte count.
In general, the symptoms of Good syndrome caused by humoral and cellular immunodeficiency are occasionally complicated by leukopenia. Infections constitute one of the main characteristics of Good syndrome. The most common complication is recurrent sinopulmonary infection. The other complications are recurrent diarrhea and opportunistic infections, which include mucocutaneous candidiasis, herpes zoster, pneumocystis carinii pneumonia, and cytomegalovirus disease [3]. The prognosis of the patient with hypogammaglobulinemia, thymoma, and leukopenia is very poor due to such infectious diseases; therefore, immediate diagnosis is important. In our case, although no signs of immunodeficiency were noticed when the thymoma was detected, 6 months after the thymothymectomy, recurrent pneumonia and diarrhea developed, based on which a diagnosis of Good syndrome was made. It should be noted that immunodeficiency can develop after the resection of thymoma in the absence of recurrence. The development of infectious diseases in a patient with thymoma or after the resection of thymoma mandates early and comprehensive immunologic investigation. It should include the evaluation of the peripheral blood count of B cells, CD4+, and CD8+ T cells by flow cytometry, and the quantitative analysis of serum immunoglobulin subclasses to diagnose and treat the disorder at an early stage [3].
The pathogenesis of this syndrome and the association of thymoma and immunodeficiency remain unclear. Most studies report that hypogammaglobulinemia in Good syndrome did not improve after thymectomy. In fact it was observed to be aggravated in some cases. Thymectomy should be performed in most patients with thymomas to prevent locally invasive growth and metastasis. However, thymectomy should not be expected to lead to the normalization of immune function, given the absence of any reports of resolution of the immunodeficiency in Good syndrome that convincingly demonstrated such a resolution to be related to thymectomy [3]. Therefore, IVIG should be administered to the cases of hypogammaglobulinemia in doses appropriate for the treatment of humoral immunodeficiency. The optimal immunoglobulin G level has been reported to be 200 to 500 mg/dL [4]. However, the treatment of patients with leucopenia or T-cell dysfunction, or both, by IVIG alone is insufficient. Degos and colleagues [5] reported a case of Good syndrome with agranulocytosis in which infectious diseases were controlled by plasmapheresis. In our case, the patient was not only administered IVIG, but also figrastim to maintain a leukocyte count between 2,000 and 6,000/mm3. He has remained symptom free for more than 1 year since the beginning of this therapy.
In conclusion, it should be taken into consideration that immunodeficiency can develop after the resection of thymoma. The development of infectious diseases in a patient with thymoma or after the resection of thymoma mandates an early and comprehensive immunologic investigation. Regular gamma globulin and figrastim injections may be successful in maintaining a symptom-free status in a patient with Good syndrome who also has leukopenia.
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References
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- Good RA. A gammaglobulinemia: provocative experiment of nature Bull Univ Minn Hosp 1954;26:1-19.
- Rosenow EC, Hurley BT. Disorders of the thymus: a review Arch Intern Med 1984;144:763-770.[Abstract/Free Full Text]
- Tarr PE, Sneller MC, Mechanic SL, et al. Infections in patients with immunodeficiency with thymoma (Good syndrome): report of 5 cases and review of the literature Medicine 2001;80:123-133.[Medline]
- Hashizume T. Good’s syndrome and pernicious anemia Intern Med 2002;41:1062-1064.[Medline]
- Degos L, Faille A, Housset M, et al. Syndrome of neutrophil agranulocytosis, hypogammaglobulinemia, and thymoma Blood 1982;60:968-972.[Abstract/Free Full Text]
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Abstract
Introduction
