Splenectomy Has a Limited Role in the Management of Lupus with Thrombocytopenia

Dedicated to the memory of Dr. Mucia Alger.

Thrombocytopenia in patients with systemic lupus erythematosus (SLE) may range from a laboratory finding with no apparent clinical consequences to the full blown syndrome of thrombocytopenic purpura that may be fatal. In lupus patients there is a tendency of thrombocytopenic purpura to be associated with hemolytic anemia in what is known as Evans' syndrome, perhaps through the relationship of both to antiphospholipid antibodies^1,2. Lupus patients with either of these hemocytopenias have common characteristics: they tend to have younger disease onset, are more often male, and less frequently have fever, polyarthritis, serositis, cutaneous vasculitis, nephropathy, neurologic manifestations, and persistent hypocomplementemia than SLE patients without the 2 hemocytopenias¹. Indeed, they are often included among those patients who early in their disease fail to fulfill classification criteria for SLE³. Thrombocytopenia of more than 50 ´ 10⁹/l without purpura requires no treatment, only observation.

Treatment of severe thrombocytopenia requires strategies that can be inferred from, but are not spelled out in, the study by Arnal and coworkers in this issue⁴. One of the problems in evaluating management of thrombocytopenia derives from the different therapeutic rationale of different specialists that deal with lupus patients and different centers. Thus, hematologists tend to be largely influenced in their treatment of lupus thrombocytopenia from their experience with idiopathic thrombocytopenic purpura; nephrologists may be influenced by their experience in the treatment of lupus nephritis; and rheumatologists may tend to use milder treatment, a wider range of agents, and a slower pace in the withdrawal of prednisone (perhaps influenced by the peculiar resistance of patients with rheumatoid arthritis to almost any attempt to reduce the dose of prednisone). Even general internists may be influenced one way or another by the setting they were trained in.

It would therefore be difficult to determine how to treat thrombocytopenic purpura in patients with SLE based on a multicentric study unless results from a large center having a uniform way of treating them were compared to those of another large center having a different way of treating them. This has not been done and the multicenter study of Arnal, et al, albeit valuable because of its size, unfortunately does not yield a definitive answer.

The main nugget in their study is their finding of a high longterm remission obtained with prednisone and either danazol or hydroxychloroquine. The most disputable notion would be the role of splenectomy in attaining longterm remission, in part because it is unlikely to be so for thrombocytopenia as a single manifestation of SLE and much less for the disease proper, with all its other manifestations. Whereas prednisone, hydroxychloroquine, and the immunosuppressors simultaneously treat the various manifestations of SLE, splenectomy, an aggressive form of treatment, does not; rather it adds to the burden of immunocompromise derived from it⁵.

The study by Arnal, et al⁴ does not pertain to all SLE patients with severe thrombocytopenia, but only to those with no other concurrent manifestations of SLE. This may be adequate for evaluating the treatment of thrombocytopenia — there is no influence of other manifestations of lupus on the treatment — but it may differ from what is most frequently found in a clinical setting, that is, high activity indices at the time of the purpura. It is therefore of interest that despite having selected their patients based on absence of other lupus manifestations, a lupus flare occurred in 39% of patients who underwent splenectomy, and in nearly half of them this occurred within 6 months of surgery. It is important now to remember that a long time ago, Dameshek and Reeves described patients who had exacerbation of SLE following splenectomy for thrombocytopenic purpura or hemolytic anemia⁶.

Although Arnal, et al select patients who had few manifestations of lupus other than purpura, splenectomy resulted in complete response of the thrombocytopenia in only 60% of their patients. Hall and coworkers⁷ studied SLE patients who underwent splenectomy for severe thrombocytopenia: in 5 of 14 it recurred within one month, in 3 others within 6 months, and in 3 more after 18 to 54 months. They concluded that splenectomy does not cure the thrombocytopenia of SLE and that the results in lupus patients differ from those of patients with idiopathic thrombocytopenic purpura.

However, in these times of evidence based medicine we should refer to the only study where the results of splenectomy for hemocytopenia in SLE patients were controlled by those obtained in similar SLE patients treated medically⁸. There was no significant difference between the 15 splenectomized and the 15 nonsplenectomized patients when their entire course, as well as the presplenectomy and postsplenectomy or their equivalent control periods, were compared by means of a severity index. In fact, splenectomized patients had a significantly higher frequency of cutaneous vasculitis after splenectomy than before splenectomy, as well as when compared to the equivalent period in the nonsplenectomized patients. Splenectomy did not result in a significant reduction in the length of time medical treatment was required and 10 of the 15 splenectomized patients required immunosuppressive treatment in the postsplenectomy period versus only 3 nonsplenectomized patients in the equivalent period (p < 0.05). In addition, 8 of the splenectomized patients had 18 episodes of infection in the postsplenectomy period, while only 2 nonsplenectomized patients had episodes of infection in the equivalent control period, and they had only one episode each (p < 0.05). In this controlled, albeit retrospective, appraisal of the 15 patients who underwent splenectomy there were 3 in whom the splenectomy was prompted by acute, severe, nonresponsive, life threatening hemocytopenia and who were thus considered to have had an absolute indication for splenectomy. The other 12 patients were considered to have a relative indication for splenectomy since it was done because of their persistent requirement for medical treatment. As it turned out splenectomy did not lessen such requirements.

Splenectomy in patients with SLE should be limited to those with an absolute indication for it.

DONATO ALARCÓN-SEGOVIA, MD,

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán,
Calle Vasco de Quiroga 15,
Tlalpan, Mexico DF 14000, Mexico.

Address reprint requests to Dr. Alarcón-Segovia.

REFERENCES

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1. Alger M, Alarcón-Segovia D, Rivero SJ. Hemolytic anemia and thrombocytopenic purpura: two related subsets of systemic lupus erythematosus. J Rheumatol 1977;4:351-7.

2. Deleze M, Oria CV, Alarcón-Segovia D. Occurrence of both hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) in systemic lupus erythematosus. Relationship to antiphospholipid antibodies. J Rheumatol 1988;5:611-5. [MEDLINE]

3. Lom-Orta H, Alarcón-Segovia D, Díaz-Jouanen E. Systemic lupus erythematosus. Differences between patients who do, and who do not, fulfill classification criteria at the time of diagnosis. J Rheumatol 1980;7:831-7. [MEDLINE]

4. Arnal C, Piette J-C, Léone J, et al. Treatment of severe immune thrombocytopenia associated with systemic lupus erythematosus: a report of 59 cases. J Rheumatol 2002:29:75-83.

5. Robinette CD. Splenectomy and subsequent mortality in veterans of the 1939-45 war. Lancet 1977;2:127-9.

6. Dameshek W, Reeves WH. Exacerbation of lupus erythematosus following splenectomy in "idiopathic" thrombocytopenic purpura and autoimmune hemolytic anemia. Am J Med 1956;21:560-6.

7. Hall S, McCormick JL, Greipp PR, Michet CJ Jr, McKenna CH. Splenectomy does not cure the thrombocytopenia of systemic lupus erythematosus. Ann Intern Med 1985;102:325-8. [MEDLINE]

8. Rivero SJ, Alger M, Alarcón-Segovia D. Splenectomy for hemocytopenia in systemic lupus erythematosus. A controlled appraisal. Arch Intern Med 1979;139:773-6.