Thymoma-associated systemic lupus erythematosus, exacerbating after thymectomy. A case report and review of the literature

A. Boonen, R. Rennenberg and S. van der Linden

Department of Internal Medicine and Rheumatology, University Hospital Maastricht, The Netherlands

SIR, Myasthenia gravis (MG), pure red cell aplasia and acquired hypogammaglobulinaemia are well recognized to be associated with thymoma, but systemic lupus erythematosus (SLE) can also be a manifestation of thymoma. The literature on the features of thymoma-associated SLE and the effect of thymectomy on SLE disease activity is conflicting.

A 76-yr-old Caucasian woman presented with malaise and weight loss of 10 kg over the past 6 months. Clinical examination at that time revealed a low body weight of 46 kg and a body length of 160 cm. Laboratory examination showed an erythrocyte sedimentation rate (ESR) of 89 mm and a slight microcytic anaemia of 7.2 mmol/l with a mean corpuscular volume of 82 fl. Chest X-ray demonstrated a mediastinal mass. The patient was admitted for mediastinoscopy. Biopsy showed a thymoma of the spindle cell type. On computed tomography scanning no signs of invasion were found. Shortly after the biopsy, she developed fever, arthralgias with synovitis of the wrists and pleuropericarditis. Laboratory investigations now yielded an ESR of 99 mm, haemoglobin of 6.8 mmol/l, leucopenia of 3.7 x 109/l with 23% lymphocytes, and polyclonal hypergammaglobulinaemia of 15.4 g/l. Antinuclear antibodies tested positive at 1/800 (homogeneous pattern), extractable nuclear antigen immunoblot was negative but double-stranded DNA (dsDNA) antibodies were positive (1/40), as was the direct Coombs test. A diagnosis of SLE was made. A relationship with the thymoma was suspected. Interestingly, the fever, lymphopenia, arthritis and pleuropericarditis disappeared after a course of non-steroidal anti-inflammatory drugs (NSAIDs). The patient underwent thymectomy 4 weeks after the mediastinoscopy. She recovered uneventfully, and at discharge from hospital 10 days after the thymectomy there were no clinical features of SLE. No drugs were started at that time. Three weeks after discharge, however, she presented with a severe skin rash on sun-exposed parts of the body. For a couple of hours she had been sitting in the sun behind the window-glass. She also reported further weight loss and diffuse alopecia. ESR was now 81 mm and dsDNA antibodies had increased to 1/640. Total complement was decreased to 58%, C4 was in the low normal range (18 mg/l) and C3d was increased (61 U/l). Skin biopsy revealed urticarial vasculitis. It was concluded that there was an exacerbation of SLE. A relationship between the thymectomy and the exacerbation seemed likely. Exposure to sunlight might have contributed to the exacerbation. With prednisone (30 mg/day) treatment the malaise and skin condition improved quickly.

Our patient had both thymoma and SLE. The thymoma was proven histologically as a non-invasive spindle cell thymoma and SLE was diagnosed on clinical, biochemical and histological grounds. The description of SLE and thymoma occurring together is certainly not new. The estimated prevalence of SLE among patients with thymoma varies between 1.5 and 2% in clinical studies [1] and between 6 and 10% in studies in which clinical data of biopsy proven thymomas were reviewed retrospectively [2, 3].

In 1975, Cayla et al. [4] reported two cases of SLE and thymoma and reviewed 11 other cases from the literature between 1922 and 1975. To identify cases published after 1975, we performed a Medline search from 1975 to December 1998 with the MESH (medical subject heading) terms (SLE and thymoma or thymectomy), all headings and subheadings. From this search and by working through the references of these papers, we identified another 18 new cases of thymoma and SLE, all fulfilling the 1982 American College of Rheumatology (ACR) criteria. Characteristics of these patients are presented in Table 1Go [13, 513]. Ninety-four per cent were female, the mean age at detection of the tumour was 53 yr (range 24–68) and the mean age at diagnosis of SLE was 52 yr (range 25–76). In 39% of the patients SLE had been diagnosed before detection of the thymoma (mean interval 2.9 yr), in 33% thymoma and SLE were found simultaneously and in 28% SLE had been diagnosed after discovery of the thymoma (mean interval 2.7 yr). The clinical picture of SLE was classical; the most commonly reported symptoms were arthralgia or arthritis in 58%, skin involvement in 25% and pleuritis or pericarditis in 63%. Autoimmune serology was positive in all cases. Three patients had concurrent MG and one patient had pure red cell aplasia. Remarkably, in 78% of patients corticosteroids were necessary to achieve control of SLE disease activity. In the cases with histological data the most common histological type of thymoma was mixed lympho-epithelial (60%), whereas in 47% of cases it was invasive. Eleven of 13 patients in whom the thymoma was discovered before SLE or simultaneously with SLE underwent thymectomy. The effect of thymectomy on SLE disease activity was not reported in three cases [7, 9, 13], in five cases no clear effect could be seen [3, 5, 6, 8], in two cases an exacerbation was reported [5, 13] and in one case SLE improved [12].


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TABLE 1. Characteristics of 19 patients with thymoma-associated SLE

 
In conclusion, SLE can be associated with thymoma, particularly in older patients. Thymectomy is usually recommended for thymoma, but cannot be considered as a cure for SLE. In fact, the effect of thymectomy on SLE disease activity is not clear. A close clinical eye should be kept on patients after thymectomy. Prospective follow-up of patients after thymectomy might prove useful in identifying factors that might predict the effect of thymectomy on SLE.

Notes

Correspondence to: A Boonen, University Hospital Maastricht, Department of Internal Medicine, Rheumatology, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Back

References

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Accepted 24 February 2000