Correspondence
Breast Implants and Connective-Tissue Diseases
N Engl J Med 1995; 333:1423-1424November 23, 1995
- Article
To the Editor:
In a large cohort study, Sánchez-Guerrero et al. (June 22 issue)1 found no association between silicone breast implants and connective-tissue diseases, defined according to a variety of standardized criteria, or signs and symptoms of these diseases. The study provides further strong evidence that the case definition for silicone-related disorders does not include systemic lupus erythematosus or rheumatoid arthritis. It has been recognized since 1992, however, that most symptomatic women with breast implants have a chronic fatigue and fibromyalgia-like syndrome.2-4 It is unclear why the authors excluded the very syndrome in which they should have been the most interested — namely, fibromyalgia. Case definition is essential to useful epidemiology.
A biologically appropriate induction time and an adequate latent period must be included in the total follow-up period, before any statements about cause and effect can be made. The total follow-up time in the study by Sánchez-Guerrero et al. does not take induction and latency into account, and in their discussion, the authors do not address these issues. We and others have observed a substantial interval between implantation and the onset of symptoms. In our initial retrospective study, the average interval was five years.5
The best evidence supporting the causal link between silicone or amorphous silica and disease in humans is the observation that clinical symptoms stabilize or improve after the removal of the implants. The authors cite our study, conducted before the publicity about breast implants, showing a 70 percent improvement rate two years after implant removal.5
In January 1994, we began a prospective study of symptomatic women with gel implants. After an average of 11 months of follow-up of the first 52 patients, 23 had had their implants removed, and 29 had not. The number, type, and severity of symptoms were similar in the two groups at the beginning of the study. Disease-severity scores obtained at intervals of three to five months were used to determine the degree of improvement or worsening. These scores, based on an instrument with a scoring system of zero to five for 37 common signs and symptoms observed in patients with implants, were significantly different (P<0.001) in the two groups. Eighty-seven percent of the women whose implants had been removed had progressive improvement, whereas 72 percent of those who still had implants had worsening symptoms.
The danger of studies like that of Sánchez-Guerrero et al. is the public perception that silicone implants have now been proved totally safe. Once there is a consensus about case definition, epidemiologic studies that account for the many aspects of this area of inquiry need to be conducted, before any statements about the safety of implants can be made.
Editor's note: Dr. Vasey has received compensation from a company that manufactures breast implants and from lawyers involved in breast-implant litigation.
5 ReferencesFrank B. Vasey, M.D.
Noreen Aziz, M.B., B.S., M.P.H.
University of South Florida, Tampa, FL 33612-47991
Sanchez-Guerrero J ,Colditz GA ,Karlson EW ,Hunter DJ ,Speizer FE ,Liang MH . Silicone breast implants and the risk of connective-tissue diseases and symptoms. N Engl J Med 1995;332:1666-1670
Full Text | Web of Science | Medline2
Goldman JA . Silicone augmentation mammoplasty (SAM): a specific musculoskeletal spectrum due to these implants? Arthritis Rheum 1991;34:Suppl:R35-R35 abstract.
CrossRef | Web of Science3
Blackburn WD Jr ,Grotting J ,Everson MP . Lack of findings of systemic rheumatic disorders in “symptomatic“ women with silicone breast implants. Arthritis Rheum 1992;35:Suppl:S212-S212 abstract.
Web of Science4
Press RI ,Peebles CL ,Kumagai Y ,Ochs RL ,Tan EM . Antinuclear antibodies in women with silicone breast implants. Lancet 1992;340:1304-1307
CrossRef | Web of Science | Medline5
Vasey FB ,Havice DL ,Bocanegra TS , et al. Clinical findings in symptomatic women with silicone breast implants. Semin Arthritis Rheum 1994;24:Suppl 1:22-28
CrossRef | Web of Science | Medline
To the Editor:
The study as reported was not designed to test the “association between breast implants and previously reported signs and symptoms,” since the survey questionnaires (before the more detailed follow-up questionnaire in 1992) asked only about rheumatoid arthritis and systemic lupus erythematosus. The results therefore do not fully support the conclusion that no such association was found. Should not the more detailed questionnaire on connective-tissue disease have been sent to a much broader sample, for an adequate search for cases of unusual or atypical connective-tissue disease?
The mean period that implants were present in the women surveyed was 10 years. Was this period the same in the group of women with self-reported signs or symptoms of connective-tissue disease and the group without signs or symptoms? Is an average period of 10 years adequate, given, at least hypothetically, that silica may have some role in the pathogenesis of connective-tissue disease in women with silicone implants? The dose of silica in such patients is many orders of magnitude lower than the dose in patients with a disease such as silicosis, which is known to be associated with connective-tissue disease.1 In diseases classically related to silica, there is often a latency period of decades.
An analysis of smoking, known to be prevalent among nurses, was not presented. Smoking has been associated with a decreased incidence of certain inflammatory diseases, such as hypersensitivity pneumonitis.2
Editor's note: Dr. Abraham has received grant support from manufacturers of breast implants and compensation from lawyers involved in breast-implant litigation.
2 ReferencesJerrold L. Abraham, M.D.
SUNY Health Science Center, Syracuse, NY 132101
Seaton A. Silicosis. In: Morgan WKC, Seaton A, eds. Occupational lung diseases. 3rd ed. Philadelphia: W.B. Saunders, 1995:238.
2
Warren CP . Extrinsic allergic alveolitis: a disease commoner in non-smokers. Thorax 1977;32:567-569
CrossRef | Web of Science | Medline
To the Editor:
In a cohort of fewer than 100,000 women, 5000 reported that they had a “connective-tissue disease.” Only a minority of the women (1277) had symptoms or signs that could be validated by physicians or rheumatologists, and an even smaller minority (513) had a well-defined disorder. In other words, the study shows that a substantial proportion of the normal population appears to have symptoms that cannot be validated or diagnosed by the medical profession. It is understandable that such a high rate of morbidity without a medical explanation results in the disgruntlement and resentment that are in part the driving forces behind the controversy over silicone breast implants. These findings also underscore the need to acknowledge the high prevalence of unexplained symptoms and signs and to improve our diagnostic and therapeutic abilities in the realm of connective-tissue diseases.
Ronald van Vollenhoven, M.D., Ph.D.
Stanford University Medical Center, Stanford, CA 94305-5111Author/Editor Response
The authors reply:
To the Editor: Drs. Vasey and Aziz suggest that “most symptomatic women with breast implants have a chronic fatigue and fibromyalgia-like syndrome.” This observation is based on uncontrolled reports on selected patients, the majority of whom have been referred to physicians in preparation for legal action. The features of a unique connective-tissue syndrome have not been put into a coherent, valid, or reproducible case definition, which severely limits scientific study. We did not study fibromyalgia or related diagnoses because they were never ascertained in the biennial questionnaires.
Atypical connective-tissue diseases were studied by documenting the prevalence of 41 signs and symptoms of connective-tissue diseases in women who had reported connective-tissue or atypical connective-tissue diseases since 1976. We abstracted objective signs and verifiable symptoms, which represented 60 percent of the verifiable signs and symptoms reported in 376 patients1 plus 35 additional signs and symptoms.
The average induction time reported for classic and atypical connective-tissue diseases is 8.9 years (range, 0.1 to 21).2 Vasey et al. reported an average of five years. In our cohort, the average time of exposure was almost 10 years (range, 1 month to 40 years).
The study of implant removal by Vasey et al. should not be considered definitive. The article cited summarizes reports to 1994 on 9 patients and, in abstract form only, data on 133 patients. This is a small fraction of the number of women who have had implants removed. A majority of the patients described by Vasey et al. who had their implants removed improved, but key information was not provided, such as the criteria for improvement, whether or not the evaluation was blinded, and the duration of follow-up in some patients.
We have not said breast implants are universally safe. We studied major connective-tissue diseases and specifically acknowledged side effects (such as implant rupture).
Dr. Abraham's comments are based on a misunderstanding. A detailed questionnaire about the symptoms of connective-tissue disease was mailed to every woman who had ever reported a rheumatic condition, “connective-tissue disease not further specified,” or connective-tissue disease under “any other disease diagnosis.” We did not limit our request for additional information to women with rheumatoid arthritis or systemic lupus erythematosus.
Dr. van Vollenhoven makes interesting points. We emphasize, however, that in our study we used a variety of standardized case definitions, but women who might not have met the criteria of the American College of Rheumatology may have received a diagnosis from their physicians.
2 ReferencesMatthew H. Liang, M.D., M.P.H.
Elizabeth W. Karlson, M.D.
Jorge Sánchez-Guerrero, M.D.
Harvard Medical School, Boston, MA 021151
Borenstein D . Siliconosis: a spectrum of illness. Semin Arthritis Rheum 1994;24:Suppl 1:1-7
CrossRef | Web of Science | Medline2
Sanchez-Guerrero J ,Schur PH ,Sergent JS ,Liang MH . Silicone breast implants and rheumatic disease: clinical, immunologic, and epidemiologic studies. Arthritis Rheum 1994;37:158-168
CrossRef | Web of Science | Medline
- Citing Articles (3)
Citing Articles
1
Cleora Roberts, Karen E. Wells, Stephanie Daniels. (1997) Outcome Study of the Psychological Changes after Silicone Breast Implant Removal. Plastic & Reconstructive Surgery 100:3, 595-599
CrossRef2
Jack W. Snyder. (1997) Silicone breast implants. Journal of Legal Medicine 18:2, 133-220
CrossRef3
H. James Williams, Michael H. Weisman, Charles C. Berry. (1997) Breast implants in patients with differentiated and undifferentiated connective tissue disease. Arthritis & Rheumatism 40:3, 437-440
CrossRef
